i

Clinico - Basic

PHARMACOLOGY
5th Revised Edition

Comprehensive & Quick Review for Undergraduates & Postgraduates

Based on Lectures, Demonstrations, Tutorials & Practicals of Most Medical

Colleges & Universities of Pakistan, Bangladesh, China, Russia, Saudi Arabia,
UAE, Sudan, Yemen, Egypt & Malaysia.

Author
Dr. Muhammad Shamim
MBBS, FCPS, FRCS, FACS, FICS, JMHPE, PhD (h.c.)
 Assistant Professor of Surgery, College of Medicine, Prince Sattam bin Abdulaziz University, Saudi
Arabia
 Ex. Associate Professor, Dept. of Surgery, Baqai Medical University, Karachi.
 Supervisor & Chief Facilitator, College of Physicians & Surgeons Pakistan.
 Assistant Editor, Journal of Surgery Pakistan

Editors
 Dr. Syeda Ghazala Arfa (BDS)
 Dr. Shumaila Bano (BDS)
 ii

© 6453 — Copy
All rights reserved. This publication can not be reprinted, distributed or sold without prior
written permission of the author.

 First Edition______________________________________________ January, 1992

As 1st Professional PHARMACO-THERAPEUTICS
 Second Edition ___________________________________________ January, 1994
As Clinically-Correlated PHARMACOLOGY
 Third Edition ____________________________________________ December, 1996
As Clinico-Basic PHARMACOLOGY (First Edition)
 Fourth Edition ____________________________________________ December, 2003
As Clinico-Basic PHARMACOLOGY (Second Edition)
Fifth Edition ____________________________________ January, 2009
Fifth Revised Edition _____________________________ January, 2017

Price ------------------------- Rs. 200/= (Free online)

Author
Dr. Muhammad Shamim
E-mail: [email protected]
Web: http://surgeonshamim.com

Editors
Dr. Ghazala Shamim
Dr. Shumaila Bano

Composer
M. Nadeem, Khurram & Brothers, Karachi

Printed At
Qureshi Art Press, Nazimabad No. 2, Karachi

Publisher
Khurram & Brothers, Karachi (ISBN 978-969-8691)
 iii

Preface

Clinico - Basic PHARMACOLOGY has been written in view of changing examination pattern from subjective type to
MCQ type, esp.in Karachi. It has been compiled in a very comprehensive way with the aim of encompassing all details about
Pharmacology & Therapeutics, & it will best serve as a review for students of MBBS, BDS, USMLE, MCPS, FCPS, M Phil,
PhD, FRCS, MRCP, B Pharm, D Pharm, & MSc in the final weeks of examination, & also for doctors practicing privately or,
in hospitals.

Format of this book

* Basic format for the description of each drug or groups of drugs remains the same, which consists of:
1. Classification ——— update & unmatchable.
2. Mechanism of action —— given in a concept - making, easy, arrow - form.
3. Pharmacological effects —— described under subheads of systems & organs.
4. Clinical uses.
5. Adverse effects —— also described under subheads of systems & organs.
6. Contraindications.
7. Dosage.
* A brief description about system or disease has been given, that is affected by a group of drugs.
* Proprietary names are given to get you familiar with market names of drugs.
* Self - assessment questions are given at the end of every chapter (a total of 171 MCQs).
* Two separate chapters on MCQs are added in the end of the book, one consisting of true/false type MCQs (81) & the other
one-best type of MCQs (192).

This book is useful for answering

1. MCQs
* All topics have been discussed in a very comprehensive way, making sure that any MCQ asked in pharmacology will
be answered correctly.
* In addition, T/F types MCQs are given at the end of every chapter, & two additional chapters at the end of book
(making an overall total of 444 MCQs).
2. Short & long questions
* Format of the book adopted is such that any short or long question in Pharmacology will be answered.
* Also comparisons of important drugs are given in chapter 27, Comparative Pharmacology, which will ensure
answering of comparative questions.
3. Viva
* Each drug or group of drugs has been discussed in appropriate subheadings with numbering of matter, which will
ensure better answering in Viva.
* What one should memorize for viva exam. is also given in chapter 31, Get Thru Pharmacology Viva.
* In addition, viva for practical exam. is given in chapter 28, Practical Pharmacology.

Thanks
Our thanks are due to the following persons for every sort of co-operation they have provided: Dr. Syeda Ghazala Arfa, Dr.
Shumaila Bano, M. Ashar Khan, M. Shafiq, Dr. Naved Akthar, M. Aamir Pervez, Dr. Sarwar Hussain, Khurram & Brothers,
Dr. Lubna, Dr. Nuzhat Shama, Dr. Azharuddin, Dr. Azhar Iqbal, Dr. Mumtaz, Dr. Kamal, Dr. Shahid, & Dr. Farah Yasmeen.

Suggestions
Any suggestion for the improvement of this book will be acknowledged with thanks.

Dr. Muhammad Shamim

21st January, 2009
 iv

Dedicated

To

 My Parents
 My Wife
 My Daughter
 My Sons
 My Brothers
 My Sisters &
 My Friends

WHO ALL HAS COOPERATED & HELP ME IN ONE WAY OR THE OTHER.
 v

Contents
1. GENERAL PHARMACOLOGY ___________1-10 (III) Self Assessment __________________ 66
(I) General Pharmacology _______________ 1
(II) Pharmacokinetics____________________ 1 9. NONSTEROIDAL ANTI-INFLAMMATORY
(III) Pharmacodynamics __________________ 7 DRUGS, NON-OPIOID ANALGESICS,
(IV) Self Assessment ____________________ 9 DMARDs & ANTI-GOUT DRUGS _____ 68-74
(I) NSAIDs__________________________ 68
2. SYMPATHETIC NERVOUS SYSTEM (II) Non - Opioid Analgesics_____________ 71
DRUGS ____________________________11-23 (III) DMARDs ________________________ 72
(I) Introduction to Nervous System & its (IV) Anti - Gout Drugs __________________ 73
Sympathetic Division________________ 11 (V) Self Assessment __________________ 74
(II) Sympathomimetics__________________ 14
(III) Sympatholytics _____________________ 18 10. DRUGS AFFECTING BLOOD_________ 75-83
(IV) Self Assessment ___________________ 22 (I) Anti - Anemics ____________________ 75
(II) Anti - Coagulants __________________ 78
3. PARASYMPATHETIC NERVOUS (III) Coagulants _______________________ 80
SYSTEM DRUGS ____________________24-32 (IV) Other Hematologic Drugs____________ 81
(I) Introduction to Parasymp. Nervous (V) Drugs Causing Blood Disorders_______ 82
System ___________________________ 24 (VI) Self Assessment __________________ 83
(II) Parasympathomimetics ______________ 25
(III) Parasympatholytics _________________ 29 11. CARDIOVASCULAR SYSTEM DRUGS _ 84-96
(IV) Self Assessment ___________________ 32 (I) Anti - Hypertensive Drugs ___________ 84
(II) Anti - Anginal Drugs ________________ 88
4. OPHTHALMOLOGICAL DRUGS________ 33-34 (III) Drug Treatment of CCF _____________ 90
(I) Ophthalmological Drugs _____________ 33 (IV) Drug Treatment of Cardiac Arrhythmias
(II) Self Assessment ___________________ 34 ________________________________ 92
(V) Self Assessment __________________ 95
5. CENTRAL NERVOUS SYSTEM
DRUGS ____________________________35-53 12. RENAL DRUGS ___________________ 97-102
(I) Sedative-Hypnotics _________________ 35 (I) Diuretics _________________________ 97
(II) Alcohols (Ethanol) __________________ 39 (II) Other Renal Drugs ________________ 100
(III) Anti-Epileptic Drugs _________________ 40 (III) Drug Induced Renal Diseases _______ 100
(IV) Anti-Parkinsonion Drugs _____________ 43 (IV) Drug Selection in Renal Disease _____ 101
(V) Anti-Psychotic Drugs ________________ 46 (V) Self Assessment _________________ 102
(VI) Anti-Manic Drugs ___________________ 47
(VII) Anti-Depressant Drugs_______________ 48 13. DRUGS AFFECTING RESPIRATORY
(VIII) CNS Stimulants ____________________ 50 SYSTEM________________________ 103-108
(IX) Anti-Migraine Drugs _________________ 51 (I) Anti - Asthmatics _________________ 103
(X) Self Assessment ___________________ 52 (II) Respiratory Stimulants _____________ 105
(III) Anti - Tussives ___________________ 106
6. ANESTHETICS ______________________54-59 (IV) Self Assessment _________________ 108
(I) General Anesthetics_________________ 54
(II) Local Anesthetics ___________________ 58 14. GASTROINTESTINAL DRUGS______ 109-119
(III) Self Assessment ___________________ 59 (I) Anti - Peptic Ulcer Drugs ___________ 109
(II) Anti - Emetics ____________________ 113
7. SKELETAL MUSCLE RELAXANTS ______ 60-62 (III) Anti - Diarrheals __________________ 114
(I) Skeletal Muscle Relaxants ____________ 60 (IV) Laxatives _______________________ 115
(II) Self Assessment ___________________ 62 (V) Miscellaneous GIT Drugs___________ 117
(VI) Self Assessment _________________ 118
8. OPIOID ANALGESICS & ANTAGONISTS
___________________________________ 63-67 15. HEPATO-PANCREATICO-BILIARY
(I) Opioid Analgesics __________________ 63 DRUGS_________________________ 120-122
(II) Opioid Antagonists __________________ 66 (I) Liver & Drugs ____________________ 120
 vi

(II) Biliary & Pancreatic Drugs ___________ 121 Infestations ______________________ 176
(III) Self Assessment __________________ 122 (IV) Self Assessment _________________ 177

16. AUTACOIDS & ITS ANTAGONISTS ___123-128 23. CANCER CHEMOTHERAPY _______ 179-183
(II) Histamine & its Antagonists __________ 123 (I) Anti - Cancers ___________________ 179
(II) Serotonin & its Antagonists __________ 125 (II) Self Assessment _________________ 183
(III) Eicosanoids ______________________ 126
(IV) Self Assessment __________________ 127 24. VITAMINS & MINERALS___________ 184-186

17. ENDOCRINOLOGY _________________129-141 25. DRUG INTERACTIONS____________ 187-188

(I) Hypothalamic & Pituitary Hormones ___ 129
(II) Thyroid & Anti-Thyroid Drugs ________ 131 26. ANTIDOTES_____________________ 189-190
(III) Anti - Diabetic Drugs _______________ 132
(IV) Adrenocorticosteroids & Analogues____ 134 27. COMPARATIVE PHARMACOLOGY _ 191-207
(V) Gonadal Hormones & Analogues _____ 136 (I) Physostigmine & Neostigmine ______ 191
(IV) Self Assessment __________________ 140 (II) Tubocurarine & Suxamethonium ____ 192
(III) Morphine & Codein ______________ 193
18. CHEMOTHERAPY OF BACTERIAL (IV) Chlorpromazine & Meprobamate____ 194
INFECTIONS ______________________142-159 (V) Cocaine & Procaine ______________ 195
(I) Introduction ______________________ 142 (VI) Guanethidine & Reserpine_________ 196
(II) Penicillins ________________________ 143 (VII) Digoxin & Digitoxin_______________ 197
(III) Cephalosporins ___________________ 146 (VIII) ACTH & Corticosteroids___________ 198
(IV) Chloramphenicol, Macrolides & (IX) Halothane & Ether _______________ 199
Clindamycin ______________________ 147 (X) Opioid & Nonopioid Analgesics _____ 200
(V) Tetracyclines _____________________ 149 (XI) Codeine & Aspirin _______________ 201
(VI) Aminoglycosides __________________ 150 (XII) Quinidine & Digitalis______________ 202
(VII) Sulfonamides _____________________ 151 (XIII) Atropine & Hyoscine _____________ 203
(VIII) Trimethoprim & Co - Trimoxazole _____ 152 (XIV) Epinephrine & Norepinephrine______ 204
(IX) Fluoroquinolones __________________ 153 (XV) Ergotamine & Ergometrine ________ 205
(X) Anti - Tuberculous Drugs ____________ 154 (XVI) Morphine & Meperidine ___________ 206
(XI) Anti - Leprotic Drugs _______________ 155 (XVII) Heparin & Warfarin ______________ 207
(XII) Drug Treatment of UTI ______________ 156
(XIII)Self Assessment __________________ 157 28. PRACTICAL PHARMACOLOGY ____ 208-212
(I) Pharmacy _______________________ 208
19. CHEMOTHERAPY OF FUNGAL (II) Pharmacodynamic ________________ 211
INFECTIONS ______________________160-162
(I) Anti - Fungal ______________________ 160 29. TRUE / FALSE TYPE MCQs ________ 213-218
(II) Self Assessment __________________ 162
30. ONE - BEST TYPE MCQs __________ 219-236
20. CHEMOTHERAPY OF VIRAL
INFECTIONS ______________________163-165 31 GET THRU PHARMACOLOGY VIVA _ 237-239
(I) Anti - Virals _______________________ 163
(II) Self Assessment __________________ 165 32 ANSWERS OF SELF-
ASSESSMENT QUESTIONS _______ 240-241
21. CHEMOTHERAPY OF PROTOZOAL
INFECTIONS ______________________166-173
(I) Drug Treatment of Malaria ___________ 166
(II) Drug Treatment of Amebiasis ________ 169
(III) Drug Treatment of Leishmaniasis _____ 171
(IV) Drug Treatment of Trypanosomiasis ___ 172
(V) Self Assessment __________________ 173

22. CHEMOTHERAPY OF HELMINTIC

INFECTIONS ______________________174-178
(I) Drug Treatment of Schistosomiasis ____ 174
(II) Drug Treatment of Tapeworm
Infestations _______________________ 175
(III) Drug Treatment of Roundworm
 vii

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4. Clinicobasic Microbiology
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7. Essentials of Ophthalmology
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M. Shamim’s PHARMACOLOGY 1

01 GENERAL PHARMACOLOGY

Drug Nomenclature
Unit I Any drug has 3 names:
(1) Chemical name: Based upon chemical structure of
drug, & is unsuitable for prescribing.
General Pharmacology (2) Generic (approved) name: Official name that is used
in pharmacopoeias.
(3) Proprietary name: Market name that is given by
pharmaceutical company.
PHARMACOLOGY Examples
Imipramine, an antidepressant, is named as:
PHARMACOLOGY (1) Chemical name  3 - (10, 11 - dihydro - 5H - dibenz [b,f]
(1) It refers to the study of substances that interacts with - azepin - 5 - yl).
living systems thru chemical processes, esp. by (2) Generic name  Imipramine.
binding to regulatory molecules & activating or (3) Proprietary name  Tofranil.
inhibiting normal body processes.
(2) It is also defined as the study of biochemical & PRODRUGS
physiologic aspects of drug effects, including absorption, It refers to compounds that, on administration, must undergo
distribution, metabolism, elimination, toxicity, & chemical conversion by metabolic processes before
specific mechanism of drug action. becoming an active pharmacological agent.
Examples
BRANCHES OF PHARMACOLOGY Methyldopa, an antihypertensive, is first converted into  -
(1) Pharmacokinetics methylnorepinephrine to produce its pharmacological
It refers to the way the body handles drug absorption, effects.
distribution, biotransformation, & excretion.
(2) Pharmacodynamics PLACEBO
It refers to the study of biochemical & physiologic It refers to an inactive substance or preparation given to
effects of drugs & their mechanism of action. satisfy the patient's symbolic need (psychic need) for drug
(3) Pharmacognosy therapy, & used in controlled studies to determine the
It refers to the study of biological, biochemical, & efficacy of medicinal substances.
economic features of natural drugs & their constituents.
(4) Pharmacotherapeutics (Medical Pharmacology)
It refers to the science of substances used to prevent,
diagnose, & treat diseases. Unit II
(5) Toxicology
It refers to the study of adverse (undesirable, untoward,
or side) effects of chemicals on living systems, from
individual cells to complex ecosystems.
Pharmacokinetics
(6) Pharmacy
It refers to the science of preparation, dispensing, &
proper utilization of drugs. DOSAGE FORMS OF DRUGS

DRUG ORAL PREPARATIONS

(1) Liquids
DRUG (a) Mixtures
It refers to any substance that brings about a change in Drugs dissolved or suspended in water.
biologic function thru its chemical actions. (b) Emulsions
M. Shamim’s PHARMACOLOGY 2

Mixture of 2 immiscible liquids (eg oil & water) (5) Eye, Ear, & Nose Drops
by means of an emulsifying agent (eg gum acacia). Aqueous solutions for local applications.
(c) Syrups (6) Mouth - washes & Gargles
Concentrated sol. of sugar containing flavoring, (7) Powders
coloring, & therapeutically active substances. (8) Vaginal Douches
(d) Elixirs Aqueous solution with cleansing or antiseptic
Sweetened, flavored hydroalcoholic sol. properties.
containing drug, or without any drug (for use as a
vehicle).
DOSAGE
(e) Tinctures
Alcoholic or hydroalcoholic sol. of vegetable drugs.
(2) Solids It refers to the determination & regulation of size, frequency,
(a) Tablets & number of doses (quantity to be administered at one time).
Solid discs prepared by compressing the drug in
granular form. DOSAGE TYPES
Enteric coated tablets: Coated with substances (1) Therapeutic Dose
which resist dissolution in acidic gastric juice, but Average dose for an adult to produce a therapeutic
dissolves in alkaline juice of intestine. effect.
(b) Capsules (2) Loading Dose (LD)
Shells of gelatin containing drug. It may be enteric A dose that promptly & quickly raises the conc. of drug
coated. in plasma to target conc. (that will produce the desired
therapeutic effect).
RECTAL PREPARATIONS LD = Vd x TC
(1) Suppositories [Vd = Vol. of distribution, TC = Target conc.]
Solid preparations for insertion into rectum. (3) Maintenance Dose (MD) or Dosing Rate
(2) Enemas A dose that maintains a steady state of drug in body,
Liquid preparations for insertion into rectum. ie, just enough dose of drug that replace the drug
eliminated since preceding dose.
PARENTERAL PREPARATIONS MD = CL x TC
Solution or suspension containing drug, that may be [CL = Clearance of drug]
dispensed in: (4) Maximal Tolerated Dose
(1) Ampoules: Containing single dose. Largest dose of a drug that can be taken safely.
(2) Vials: Rubber-capped bottles containing a (5) Fatal Dose
number of doses. A dose that produces death.

INHALATIONAL PREPARATIONS DOSAGE FOR CHILDREN

(1) Gases Children require smaller doses of drugs than adults.
Administered thru special devices. (1) Young's Formula
(2) Volatile Liquids Child dose = Adult dose x Age in years
(3) Steam Inhalation Age + 12
(4) Aerosols (2) Dilling's Formula
Released into respiratory passages in the form of a fine Child dose = Adult dose x Age in years
mist of liquid droplets. 20
(3) Clark's Formula
TOPICAL PREPARATIONS Child dose = Adult dose x Wt. in Ib
150
(1) Ointments
Semi - solid preparations for cutaneous or mucosal
applications. ROUTES OF DRUG ADMINISTRATION
(2) Liniments
Preparations of various substances in an oily, ENTERAL
soapy, or alcoholic vehicle intended to be applied to
It involves drug administration via alimentary tract.
skin by rubbing.
(1) Oral
(3) Lotions
Advantages
Aqueous suspensions intended for application to skin
(a) Most convenient, & most acceptable.
without rubbing.
(b) Used for local as well as systemic actions of drugs.
(4) Lozenges
Tablet-like formulations for slow dissolution in mouth.
01: General Pharmacology 3

(c) Dosage forms do not require sterile techniques for (3) Can be used when alimentary route is not feasible (eg in
administration. unconscious pts).
(d) Delivery of drug into circulation is slow, so (4) Suitable for drugs that are not absorbed from GIT, or are
that rapid, high blood conc. are avoided & too irritant to be given by other routes.
adverse effects are less. Disadvantages
Disadvantages (1) More rapid absorption can lead to increased
(a) Rate of absorption is variable. adverse effects.
(b) Irritation of mucosal surfaces can occur. (2) A sterile formulation, & an antiseptic technique are
(c) Extensive hepatic metabolism (first-pass required.
effect) may occur before the drug reaches its (3) Local irritation may occur at the site of injection.
site of action.
(d) Onset of action is delayed, thus unsuitable in MISCELLANEOUS ROUTES
emergency situations. (1) Inhalational
(e) Impractical in unconscious or uncooperative pts. It involves drug administration directly into the
(f) Drugs destroyed by digestive enzymes (insulin, respiratory tract.
pituitary hormones) or by gastric acidity Advantages
(benzyl penicillin) can not be administered. Drugs as gases or aerosols can be rapidly taken up or
(2) Sublingual (Beneath Tongue) eliminated.
Advantages Disadvantages
(a) Rapid absorption & effect (eg, glyceryl trinit-rate in (a) Special apparatus is needed.
angina). (b) Drug must be non-irritant for conscious pts.
(b) Effect can be terminated by spitting out tablet. (2) Topical
Disadvantages It involves application of drugs over skin or mucus
(a) Inconvenient for frequent use. membrane, to produce local effects.
(b) Irritation of oral mucosa, & excessive salivation. Advantages
(3) Rectal High local conc. can be achieved without systemic
Advantages effects.
(a) Drug irritant to stomach can be given by Disadvantages
suppository (eg aminophylline, indomethacin). Absorption can occur, esp. when there is tissue
(b) Suitable in vomiting, motion sickness, destruction, that results in systemic effects.
migraine, or when a pt can not swallow, &
when cooperation is lacking.
(c) Used for local effects, eg in proctitis, or colitis, & DRUG ABSORPTION
for bowel evacuation.
Disadvantages It refers to passage of a drug from its site of administration
(a) Psychological in that the pt may be embarrassed. into bloodstream.
(b) Rectal inflammation may occur with repeated use.
MECHANISM OF ABSORPTION
PARENTERAL See 'Drug Permeation' below.
It involves drug administration via injection into a
blood vessel, soft tissue, or a body cavity. FACTORS AFFECTING DRUG ABSORPTION
Examples (A) Drug Factors
(1) Intravenous (IV). (1) Lipid - Water Partition Coefficient
(2) Intramuscular (IM). Directly proportional to drug absorption.
(3) Intradermal (ID). (2) Degree of Ionization
(4) Subcutaneous (SC). Inversely proportional to drug absorption.
(5) Intraperitoneal (IP). (3) Chemical Nature (ie, Organic or Inorganic)
(6) Intra-arterial (IA). Eg, inorganic iron preparations are better absorbed
(7) Intracardiac (IC). from GIT.
(8) Intrathecal (IT). (4) Dosage Forms
(9) Intra-articular or joint (IJ). Solutions are better absorbed than suspensions.
(10) Intra-bone marrow (IBM). (B) Patient Factors
Advantages (1) Route of Administration
(1) Drugs get to the site of action more rapidly, providing a (a) First - order (Exponential) Kinetics
rapid response, which may be required in an emergency. A constant 'fraction' of drug is absorbed, eg
(2) Dose can be more accurately delivered. following administration via any route except
intravenous.
M. Shamim’s PHARMACOLOGY 4

(b) Zero - order Kinetics (ii) Weak bases (BH) dissociates as;
A constant 'amount' (ie, 100%) of drug is BH+ (protonated)  B (unprotonated) + H+
absorbed, after intravenous administration. Diffusing State
(2) Area & Vascularity of Absorbing Surface (i) For weak acids  Protonated form.
Directly proportional to drug absorption. (ii) For weak bases Unprotonated form.
(3) State of Health of Absorbing Surface Handerson - Hasselbalch Equation
(4) Rate of General Circulation According to it, the relative conc. of protonated
This influences the rate of transport of drug. & unprotonated form is determined by pH
(5) Specific Factors at the site of diffusion & by the strength of
Eg, intrinsic factor is necessary for vit. B12 weak acid or base (pKa).
absorption. log Protonated = pKa - pH
Unprotonated
BIOAVAILABILITY (i) Lower the pH relative to pKa, the greater
It refers to the extent of absorption of a drug following its will be the fraction of drug in protonated
administration by routes other than IV injection. form  absorption of weak acids, &
Factors Affecting Bioavailability  absorption of weak bases.
(1) First-pass hepatic metabolism. (ii) Similarly  pH relative to pKa 
(2) Solubility of drug. unprotonated form absorption of weak
(3) Chemical instability. bases, & absorption of weak acids.
(4) Nature of drug formulation. (2) Filtration
(5) Dietary patterns. It refers to passage of molecules (eg, water, ions, &
some polar & nonpolar molecules of low molecular
DRUG PERMEATION weight) thru memb. via pores or channels (eg, in
glomerulus).
(B) Carrier Mediated Transport
It refers to movement of drug molecules thru various barriers It refers to drug movement across the memb. mediated
into the body from site of administration (absorption), by a macromolecule (carrier protein) in the memb. It is a
between different compartments of body (distribution), & saturable process, & is selective for the chemical
out of body (excretion). structure of a drug.
(1) Facilitated Diffusion
MECHANISM OF DRUG PERMEATION Movement is driven by conc. gradient, for which
(A) Passive Diffusion no energy is required.
It refers to passage of drug molecules by diffusing as (2) Active Transport
un-ionized moiety thru lipid memb. It depends on Movement occur against a conc. gradient (an active
molecule's size & charge, lipid-water partition co- process), that requires energy which is generated
efficient, & conc. gradient. by Na+ - K+ - ATPase.
(1) Simple Diffusion (C) Endocytosis & Exocytosis
Passive diffusion of un-ionized molecules thru lipid (1) Endocytosis refers to the process by which drug
memb., driven by conc. gradient. molecule is engulfed by cell memb. & carried into
(a) Fick's Law of Diffusion cell by pinching off of newly formed vesicles
It states that the passive flux (F) of unionized inside the memb.  Molecule is then released
molecules across lipid memb. is; inside the cytosol by breakdown of vesicle memb.
(i) Directly proportional to conc. gradient (2) Reverse process (exocytosis) is responsible for
(C1 – C2), area across which diffusion secretion of many substances from cells.
occurs (A), & permeability coefficient (P).
(ii) Inversely proportional to thickness of
diffusion path (T). DRUG DISTRIBUTION
F (molecules per unit time) =
(C1 – C2) x A x P It refers to the extent of localization of drug after absorption,
T eg confined to plasma, whole ECF, both ICF & ECF, or to
Note: P is directly proportional to temperature, specific areas such as brain or placenta.
& inversely related to molecular size.
(b) Diffusion of Weak Acids & Bases FACTORS AFFECTING DISTRIBUTION
Many drugs are either weak acids or weak (A) Physical & Chemical Characteristics of Drug
bases. (1) Molecular Weight
(i) Acidic drugs (HA) dissociates as; eg, high mol. wt. drugs such as dextran is largely
HA (protonated)  H+ + A- confined to plasma.
01: General Pharmacology 5

(2) Ionization Lungs, kidneys, & adrenal glands can also metabolize
eg, unionized drug readily move across most drugs.
biological membranes including blood-brain barrier.
(B) Capillary Permeability PHASES OF BIOTRANSFORMATION
It varies widely in various tissues, eg; (A) Phase I Reactions
(1) In brain, capillary endothelial cells are continuous It alters chemical reactivity & increases aqueous
& have no slit junctions; so that only lipid - soluble solubility of drugs.
(unionized) drug can cross. (1) Oxidation
(2) In liver & spleen, a large part of basement memb. It involves addition of oxygen or removal of
is exposed by large discontinuous capillaries  hydrogen from drug.
Large plasma proteins can cross. (a) Microsomal Mixed Function Oxidase System
(C) Blood Flow It causes drug oxidation by oxidative drug -
Blood flow to brain, liver, & kidneys is greater than metabolizing enzymes, located in lipophilic
that to skeletal muscles & adipose tissue  More drug is memb. of smooth endoplasmic reticulum of
delivered to greater blood flow areas. liver & other tissues.
(D) Binding of Drugs to Plasma Proteins Components
Some drugs can bind non-specifically & reversibly to (i) NADPH - cytochrome P450 reductase.
various plasma proteins, eg albumin & globulin. (ii) Cytochrome P450.
(1) Bound & free drug reach an equilibrium. Reaction Examples
(2) Only the free drug exerts a biologic effect. (i) Aromatic hydroxylations, eg of propra-
(3) Bound drug stays in vascular space, & is not nolol, phenytoin, warfarin.
metabolized or eliminated. (ii) Aliphatic hydroxylations, eg of chlorpro-
(E) Tissue Affinity pamide, ibuprofen, digitoxin.
Some drugs are localized in specific tissues which (iii) Epoxidation, eg of aldrin.
possess specific drug receptors, eg iodine in thyroid (iv) Oxidative dealkylation, eg of theophylline,
gland, & chloroquine in liver. codeine, acetaminophen.
(v) S - oxidation, eg of thioridazine,
APPARENT VOLUME OF DISTRIBUTION (VD) cimetidine, chlorpromazine.
It is a quantitative estimate of tissue localization of drug, & (vi) Deamination, eg of diazepam.
is expressed as, (vii)Desulfuration, eg of thiopental.
Vd = Total amount of drug in body (viii) Dechlorination, eg of CCl4.
Conc. of drug in plasma Enzyme Induction
Note: A high Vd indicates high lipophilicity or many Some drugs induce (inc. activity of)
receptors for drug. cytochrome P450 by enhancing its rate of
synthesis & / or reducing its rate of degradation
BIOTRANSFORMATION  Acceleration of metabolism & usually a dec.
in pharmacological action of inducer & also of
co-administered drugs.
It refers to the process of chemical alteration of drugs in Drug examples: Phenobarbital, polycyclic
body.
aromatic hydrocarbons, glucocorticoids,
SITES OF BIOTRANSFORMATION macrolide antibiotics, antiepileptics, steroids,
(1) Liver isoniazid, clofibrate, chronic ethanol
First - Pass Effect administration.
Following oral administration, many drugs are absorbed Enzyme Inhibition
intact from small intestine & transported via portal Some drugs inhibit cytochrome P450 enzyme
system to liver, where they undergo extensive activity.
metabolism referred as first - pass effect. Drug examples: Cimetidine, ketoconazole,
Example of Drugs: Isoproterenol, Meperidine, chloramphenicol, ethinyl estradiol, nore-
Pentazocine, Morphine, etc. thindrone, spironolactone, fluroxene, seco-
(2) Gastrointestinal Tract barbital, allobarbital, ethchlorvynol, carbon
Some orally administered drugs are more extensively disulfide, propylthiouracil.
metabolized in GIT than in liver, by intestinal (b) Non-Microsomal (Cytochrome P450
microorganisms, gastric acid, & digestive enzymes. Independent) Oxidation
Examples of Drugs: Clonazepam, Chlorpromazine, It involves drug oxidation by soluble enzymes
Penicillin, Insulin, Catecholamines. found in cytosol or mitochondria of cells.
(3) Other Sites Examples
M. Shamim’s PHARMACOLOGY 6

(i) Alcohol dehydrogenase  Converts It may alter enzyme level &/or cause polymorphism, eg
ethanol to acetaldehyde. of enzymes involved in;
(ii) Aldehyde dehydrogenase  Converts (a) Hydrolysis of succinylcholine.
acetaldehyde to acetate. (b) Acetylation of isoniazid.
(iii) Xanthine oxidase  Converts hypoxan- (c) Hydroxylation of warfarin.
thine to xanthine, & xanthine to uric acid. (2) Chemical Properties of Drug
(iv) Tyrosine hydroxylase  Converts Certain drugs may stimulate or inhibit the metabolism
tyrosine to dopa. of other drugs (see above).
(v) Monoamine oxidase  Metabolizes (3) Route of Administration
catecholamines, & serotonin. Oral route can result in extensive first - pass effect.
(vi) Flavin monooxygenase  Metabolizes (4) Diet
chlorpromazine, amitriptyline, nortrip- Starvation depletes glycine, & alters glycine conjuga-
tyline, desipramine, methimazole, & tion.
propylthiouracil. (5) Dosage
(2) Reduction Toxic doses can deplete enzymes.
It occur in both microsomal & non - microsomal (6) Age
metabolizing system. Liver cannot detoxify drugs as well in neonates than in
Examples adults.
(a) Azo reduction, eg of prontosil, tartrazine. (7) Sex
(b) Nitro reduction, eg of chloramphenicol, Young males are more prone to sedation from
clorazepam, dantrolene. barbiturates than females.
(c) Carbonyl reduction, eg of metyrapone, (8) Disease
methadone, naloxone. (a) Liver disease dec. drug metabolism.
(3) Hydrolysis (b) Kidney disease dec. drug excretion.
It involves nonmicrosomal hydrolases present in
various body systems including plasma. DRUG ELIMINATION (EXCRETION)
Examples
(a) Esterases  Metabolizes acetylcholine, It refers to the process by which a drug or its metabolite is
succinylcholine, procaine, aspirin, etc. eliminated from body.
(b) Amidases  Metabolizes procainamide,
lidocaine, indomethacin. ROUTES OF ELIMINATION
(B) Phase II Reactions (Conjugation)
(1) Kidney
It involves coupling or conjugation reactions of parent
Excretion of drugs & their metabolites into urine
drugs or their phase I metabolites with an endogenous
involves;
substance to yield drug conjugates, & is catalyzed by
(a) Glomerular filtration, eg of water-soluble & polar
various transferases, located in microsomes or in
compounds.
cytosol. Conjugates are polar molecules that are readily
(b) Active tubular secretion, eg of penicillins, quinine.
excreted, & often inactive.
(c) Passive tubular reabsorption.
Examples
(2) Liver
(1) Glucoronidation, eg of morphine, acetaminophen,
It can secrete drugs or their metabolites (eg, glucoronide
diazepam, meprobamate, digoxin.
conjugates of opioids) into bile, that are lost in feces.
(2) Acetylation, eg of sulfonamides, isoniazid,
However, some drug may be reabsorbed in intestine to
clonazepam, dapsone.
again enter the circulation, referred as entero-hepatic
(3) Glutathione conjugation, eg of ethacrynic acid,
circulation.
bromobenzene.
(3) GIT
(4) Glycine conjugation, eg of salicylic acid, cholic
Some drugs are excreted thru GIT, eg;
acid, deoxycholic acid.
(a) Thiocynates, iodides, & mercury in saliva.
(5) Sulfate conjugation, eg of estrone, phenol,
(b) Morphine thru passive diffusion in stomach (when
acetaminophen, methyldopa.
its blood level is high).
(6) Methylation, eg of dopamine, epinephrine, hista-
(4) Lungs
mine.
Gaseous & volatile general anesthetic are excreted in
(7) Water conjugation, eg of benzopyrene epoxide,
expired air.
carbamazepine epoxide, leukotriene A4.
(5) Other Routes
(a) Sweat.
FACTORS AFFECTING BIOTRANSFORMATION (b) Tears.
(1) Genetics (c) Breast milk.
01: General Pharmacology 7

DRUG CLEARANCE STEADY - STATE CONCENTRATION (CSS)

It refers to the ratio of rate of drug elimination by all routes A steady-state plasma concentration of drug occurs
to the conc. of drug in a biologic fluid (C). when the rate of drug elimination is equal to the rate of
CL = Rate of elimination / C administration, & is expressed as,
Total Body Clearance Css = Ro / CLTotal
Drug is eliminated via several routes. Dividing the rate of [Ro = Infusion rate].
elimination at each organ by conc. of drug presented to it
Note: Approx.. 5 t 1/2 are required to reach a steady-state
yields respective clearance at that organ, & sum of these is
total body clearance. conc.
(1) CLrenal = Rate of elimination renal / C
(2) CLliver = Rate of elimination liver / C
Unit III
(3) CLother = Rate of elimination other / C
(4) CLtotal = CLrenal + CLliver + CLother
Rate of Elimination
For most drugs elimination is not saturable, & rate of drug
Pharmacodynamics
elimination is directly proportional to conc.
Rate of elimination = CL x C
This is referred as first - order elimination. RECEPTORS
(1) Capacity - Limited (Saturable) Elimination
Elimination pathways of some drugs (eg ethanol, It refers to specific drug-binding sites in a cell or on its
phenytoin, aspirin) become saturated if the dose is surface, which mediate the action of drug.
high enough. Provided that the blood flow to an organ Note: Some drugs (eg, mannitol) do not require receptor for
does not limit elimination, its rate is expressed as; its action.
Rate of elimination = ( Vmax x C ) / ( Km + C )
[ Vmax = maximum elimination capacity, Km = drug conc. NATURE OF DRUG RECEPTORS
at which rate of elimination is 50% of Vmax ]. (1) Regulatory proteins, which mediate the actions of
Thus, increment in elimination rate becomes less as endogenous chemical signals eg neurotransmitters,
conc. increases, & at conc. higher than Km, the autacoids, & hormones.
elimination rate is almost independent of conc. & is (2) Enzymes, eg dihydrofolate reductase.
referred as ' pseudo - zero order ' elimination. (3) Transport proteins, eg Na+ / K+ ATPase.
(2) Flow - Dependent Elimination (4) Structural proteins, eg tubulin.
Some drugs are very readily cleared by organ of
elimination & they eliminated on first pass to the organ. RECEPTOR REGULATION
Their elimination will thus depends on blood flow thru (1) Down - Regulation
the organ. Receptors become desensitized or dec. in number, when
Drug Examples of Hepatic Blood flow -Limited exposed to an agonist repeatedly.
Clearance (2) Up - Regulation
Alprenolol, amitriptyline, isoniazid, lidocaine, Receptors become supersensitive to agonists via
pentazocine, morphine, propranolol, verapamil. synthesis of additional receptor, on chronic
administration of an antagonist.
HALF - LIFE
It is the time required to change the amount of drug in body RECEPTOR LIGANDS
by one - half during elimination (or during a constant (1) Agonist
infusion), & is expressed as; A drug that produces some of the effects of endo-
t 1/2 = 0.693 x Vd genous compounds when it interacts with receptor, eg
CL isoproterenol at  - adrenoceptors.
Factors Increasing Drug Half - Life Note: Drug must have affinity & intrinsic activity to be
(1) Dec. renal plasma flow, eg in cardiogenic shock, cardiac an agonist.
failure, hemorrhage. (2) Antagonist
(2) Addition of a second drug, that displaces first from A drug that binds to receptor without activating it,
albumin, increasing its Vd. thereby blocking endogenous agonist from exerting its
(3) Dec. extraction ratio, eg in renal disease. effect, eg propranolol at  - adrenoceptors.
(4) Dec. metabolism, eg when another drug inhibits its Note: Drug must have affinity but no intrinsic activity
biotransformation. to be an antagonist.
(3) Partial Agonist
M. Shamim’s PHARMACOLOGY 8

A drug that binds to receptor blocking access of natural Antagonist bind to receptors preventing an agonist from
agonist, & also capable of a low degree of activation interacting with its receptors to produce an effect.
(ie, affinity + some intrinsic activity), eg pindolol & (a) Competitive Antagonism
oxprenolol at  - adrenoceptors. Antagonist compete with agonists in a reversible
(4) Inverse Agonist fashion for the same receptor site.
A drug that on binding to receptor produces effects (i) High antagonist conc. prevent agonist's
which are specifically opposite to those of agonist, eg response completely.
 - carbolines at benzodiazepine receptors. (ii) Sufficiently high conc. of agonist can com-
pletely surmount the effect of a given conc. of
SPARE RECEPTORS antagonist.
Maximal pharmacological response can be elicited by an Drug example: Propranolol at - adrenoceptors.
agonist at a conc. that does not result in occupancy of full (b) Irreversible Antagonism
complement of available receptors, & the receptors which Antagonist binds irreversibly to receptor site, &
left un-occupied are referred as spare receptors. this antagonism can not be overcome, no matter
Note: Spare receptors are not hidden or unavailable, & how much agonist is given.
when they are occupied, they can be coupled to response. Drug example: Phenoxybenzamine at  -
adrenoceptors.
(2) Physiologic Antagonism
DRUG - RECEPTOR INTERACTIONS Two drugs acts on different receptors, & produces
effect exactly opposite to each other.
MECHANISM OF ACTION Example
(1) Via Intracellular Receptors Drugs acting on cholinoceptors & adrenoceptors are
Lipid - soluble drug crosses the plasma memb. & acts physiologic antagonists of each other.
on intracellular receptors, that may results in; (3) Chemical Antagonism (Neutralization)
(a) Stimulation of intracellular enzymes, eg guanyl Two drugs combine with one another to form an
cyclase by nitric oxide. inactive compound, without involving any receptor.
(b) Stimulation of gene transcription by binding to Example
specific DNA sequences (response elements) Protamine & heparin.
whose expression is regulated, eg by corticosteroids,
sex steroids, vit D, & thyroid hormone. DOSE - RESPONSE RELATIONSHIPS
(2) Via Transmemb. Receptor Protein
Drug bind to a site on protein's extracellular domain,
resulting in a conformational change in & activation of GRADED - DOSE RESPONSE
cytoplasmic enzyme domain which may be a protein As the dose of drug administered is increased,
tyrosine kinase, a serine kinase, or a guanyl cyclase. pharmacological effect will also increase, & at a certain dose,
Drug examples: Insulin. the resulting effect will reach a maximum level.
(3) Via Transmemb. Ion Channels Expressed as;
Drug bind to a transmemb. ion channel that can be E = ( Emax x C ) / ( C + EC50 )
induced to open or close. [where E = effect, C = conc. Emax = maximal response, EC50
Drug example: Acetylcholine at nicotinic receptors. = conc. of drug that produces 50% of maximal effect].
(4) Via G Proteins & Second Messengers (1) Efficacy
Drug binds to a transmemb. receptor protein to It is the maximum effect of a drug (Emax).
stimulate a GTP - binding signal transducer protein (G (2) Potency
protein) that in turn generates an intracellular second It refers to different doses of two drugs that are needed
messenger or inhibits its generation. to produce the same effect. It is measured by EC50 or
Types of Second Messengers
ED50.
(1) Cyclic adenosine monophosphate (cAMP).
(2) Calcium ions. Note: Clinical effectiveness of a drug depends on its
(3) Phosphoinositides. efficacy, & not on its potency.
(4) Cyclic Guanosine monophosphate (cGMP).
Drug Examples ENHANCEMENT OF DRUG EFFECT
Acetylcholine at muscarinic receptors, catecholamines,
FSH, LH, ACTH, histamine, PGE2, etc.
(1) Addition
Two drugs with same effect, when given together,
ANTAGONISM produce an effect that is equal in magnitude to the sum
(1) Pharmacological Antagonism of effects when the drugs are given individually
(ie, 1 + 1 = 2).
01: General Pharmacology 9

(2) Synergism It refers to decreased responsiveness to a drug as a

Two drugs with same effect, when given together, consequence of continued administration of a given
produce an effect that is greater in magnitude than the dose of drug.
sum of effects when the drugs are given individually (6) Tachyphylaxis
(ie, 1 + 1 > 2). It refers to a rapid decrease in responsiveness after
(3) Potentiation administration of a drug.
A drug lacking an effect of its own increases the effect
of a second, active drug (ie, 0 + 1 > 1).
Unit IV
EVALUATION OF DRUG SAFETY & USEFULNESS

(1) Therapeutic Index

Self - Assessment (T/F)
It is a ratio b/w doses of a drug required to produce
(See answers on page no. 240)
undesired & desired effects. Expressed as;
TI = LD50 / ED50 (1) Following are mechanisms of drug permeation
[where LD50 = minimum dose that is lethal for 50% of (A) Aqueous diffusion.
(B) Aqueous hydrolysis.
population, ED50 = minimum dose that is effective for
(C) Lipid diffusion.
50% of population]. (D) Pinocytosis or endocytosis.
(2) Standard Margin of Safety (E) Active (carrier) transport.
It shows the percentage by which ED99 (dose effective in
(2) Following statements about routes of drug
99% of population) must be increased to cause lethal
administration are correct
effects in 1% of population (LD1). Expressed as;
(A) Conc. in blood often rise faster after IM injection
SMS = ( LD1 / ED99 ) - 1 x 100 than after oral dosing.
(B) First - pass effect is more likely to occur in sub-
VARIATION IN DRUG RESPONSIVENESS lingual administration than in oral.
(C) Bioavailability of most drugs is lower with rectal
(suppository) administration than with IV route.
(1) Idiosyncrasy (D) Oral route can be used in comatose pts or in pts
It refers to an unusual drug response in an individual with emergency.
than in most individuals. (E) Sterile formulation & aseptic technique are required
Causes in parenteral administration.
(a) Genetic differences in drug metabolism.
(b) Immunologic mechanism, including allergic (3) Distribution of drugs to tissues
reactions. (A) Is independent of blood flow to the organ.
(2) Hyporeactivity (B) Is independent of solubility of drug in a given
It refers to decreased intensity of effect of a given tissue.
dose of drug, in comparison to effect seen in most (C) Depends on conc. gradient b/w blood & tissue.
individuals. (D) Is increased for drugs that are strongly bound to
(3) Hyperreactivity plasma proteins.
It refers to increased intensity of drug's effect for a (E) Has no effect on half - life of drug.
given dose, in comparison to effect seen in most (4) Drugs bound to plasma proteins
individuals. (A) Cannot leave vascular space.
(4) Hypersensitivity (B) Is not metabolized.
It refers to allergic or other immunologic responses to (C) Is eliminated early.
drugs. (D) Is active pharmacologically.
Clinical Manifestations (E) Forms a storage depot from which a small
(a) Skin reactions: Urticaria, rashes, angioneurotic proportion of active drug is freed constantly.
edema. (5) Following are sites of biotransformation
(b) Blood dyscrasias: Thrombocytopenia, granulo-
cytopenia, aplastic anemia, hemolysis. (A) Liver.
(c) Others: Anaphylaxis, asthma, serum-sickness, (B) GIT.
fever, systemic lupus erythematosus, hepatitis, (C) Spleen.
cholestatic jaundice, nephropathy.
(5) Tolerance (D) Kidneys.
(E) Brain.
M. Shamim’s PHARMACOLOGY 10

(6) Examples of phase I biotransformation reactions are (A) Additions.

(A) Hydrolysis. (B) Antagonism.
(C) Synergism.
(B) Reduction. (D) Potentiation.
(C) Cytochrome P450 independent oxidation. (E) Increased excretion.
(D) Carboxylation.
(E) Conjugation.
(7) Regarding absorption of drugs
(A) Unionized form is readily absorbed.
(B) Suspensions are better absorbed than solutions.
(C) Intrinsic factor is necessary for absorption of vit B12.
(D) In first - order kinetics 100% drug is absorbed into
blood.
(E) In zero - order kinetics a constant fraction of drug
is absorbed into blood.
(8) First - pass effect occur in following routes of
administration
(A) Oral.
(B) Sub - lingual.
(C) Rectal.
(D) Intravenous.
(E) Subcutaneous.
(9) Induction of drug metabolism
(A) Results in increased production of rough
endoplasmic reticulum.
(B) Results in increased production of smooth
endoplasmic reticulum.
(C) Requires 3 - 4 months to reach completion.
(D) Results in decreased pharmacologic actions of
inducer.
(E) Is irreversible.
(10) Most drug receptors are
(A) Small molecules with a molecular weight b/w 100
& 1000.
(B) Lipids arranged in a bilayer configuration.
(C) Proteins located on cell memb. or in cytosol.
(D) DNAs.
(E) RNAs.
(11) Following statements are correct
(A) Maximum efficacy of a drug is directly correlated
with its potency.
(B) Therapeutic index is LD50 divided by ED50.
(C) A partial agonist has no effect on its receptors
unless another drug is present.
(D) Antagonist has affinity but no intrinsic activity.
(E) Agonist has both affinity & intrinsic activity.
(12) Major organs for drug excretion are
(A) Kidneys.
(B) Liver.
(C) GIT.
(D) Lungs.
(E) Breast.
(13) Administration of 2 or more drugs simulta-neously
may results in
02: Sympathetic Nervous System Drugs 11

02 SYMPATHETIC NERVOUS
SYSTEM DRUGS
(c) Enteric nervous system (ENS)
Unit I It is a collection of neurons located in gut
wall, & sometimes considered a 3rd division
of ANS;
Introduction (i) Consists of  Myenteric plexus (of
Auerbach), & submucus plexus (of
Meissner).
(ii) Receives  Preganglionic parasympa-
NERVOUS SYSTEM thetic fibres, postganglionic sympathetic
fibres, & also sensory input from within
It is a system that, along with endocrine system, the gut wall.
coordinates the regulation & integration of body (iii) Fibres from its cell bodies go to smooth
functions. muscle & secretory cells of gut, & control
motility & secretions respectively.
DIVISIONS OF NERVOUS SYSTEM
(A) Central Nervous System SYMPATHETIC NERVOUS SYSTEM (SNS)
It includes;
(1) Brain.
(2) Spinal cord. ANATOMY
(B) Peripheral Nervous System Efferent (motor) portion of SNS consists of:
It includes neurons (or nerves) located outside the (1) Preganglionic Neurons
brain & spinal cord. Cell bodies of preganglionic neurons are found in
(1) Somatic Nervous System spinal cord (ie CNS), in the lateral grey horn of all the
It is concerned with consciously controlled thoracic & upper two lumbar segments. Their axons
functions (voluntary activities), eg movement, constitute the preganglionic fibres.
respiration, & posture. (2) Preganglionic Fibres
It consists of ; Leave the CNS, from T1 to L2 segments of spinal cord,
Two components, afferent & efferent, both con- & travel upto sympathetic ganglia.
tained in; (3) Ganglia
(a) Cranial nerves 12 pairs. Preganglionic fibres terminate by synapsing with the
(b) Spinal nerves 31 pairs. cell bodies of sympathetic ganglia (paravertebral chain
(2) Autonomic Nervous System of ganglia & prevertebral ganglia).
It is concerned with activities that are not under (4) Postganglionic Fibres
direct conscious control (ie visceral functions), eg These are axons of cell bodies in sympathetic ganglia,
cardiac output, blood flow to various organs, extending to the effector organs (viscera & glands).
digestion, etc.
Components NEUROTRANSMITTERS
(a) Afferent fibres that run from periphery to Transmission of nerve impulse across a synapse occurs
integrating centres (enteric plexuses in gut, thru the release of specific chemical signals, called neuro-
autonomic ganglia, & CNS). It evokes reflex transmitters, from nerve terminals. These substances rapidly
visceral activities. diffuse across the synapse b/w nerve endings & combine
(b) Efferent fibers (see below). with specific receptors on postsynaptic (target) cell.
Sub-divisions Sympathetic Neurotransmitters
(a) Sympathetic nervous system (Thoracolumbar (1) Acetylcholine
or Adrenergic system). Released by;
(b) Parasympathetic nervous system (Craniosacral (a) Preganglionic fibres at ganglionic synapses.
or cholinergic system). (b) Postganglionic fibres at neuroeffector synapses, of;
M. Shamim’s PHARMACOLOGY 12

(i) Eccrine (thermoregulatory) sweat glands. receptors on effector organs or to presynaptic

(ii) Skeletal muscle blood vessels. receptors on nerve terminal  Triggers formation
(2) Norepinephrine & Epinephrine of intracellular 2nd messengers, eg cAMP, IP3, etc.
(a) Norepinephrine is released by postganglionic fibres (See Box 2.1 below).
at most neuroeffector synapses. (5) Removal of Norepinephrine ( & Epinephrine)
(b) A mixture of epinephrine & norepinephrine is Termination of action of released norepinephrine
released by adrenal medullary cells (embryolo- can results from:
gically analogous to postganglionic sympathetic (a) Diffusion
neurons). Simple diffusion of norepinephrine away from
(3) Dopamine the receptor site, with eventual metabolism in
Released by postganglionic fibres in renal blood plasma or liver.
vessels. (b) Reuptake
(4) Cotransmitters (i) Uptake I
These are substances other than primary transmitters Norepinephrine is taken back into the
(mentioned above) that may provide a slow, long- same nerve terminal, where it may re-enter
lasting action to supplement or modulate the more synaptic vesicle via amine transporter
transient effects of primary transmitters. They may system or, oxidized by MAO (present in
have feedback inhibitory effect. neuronal mitochondria).
Examples (ii) Uptake II
Adenosine triphosphate (ATP), Calcitonin gene-related Norepinephrine is taken back into
peptide (CGRP), Neuropeptide Y, Serotonin, etc. perisynaptic glia or smooth muscle cells.
(c) Metabolism (Degradation)
SYMPATHETIC NEUROTRANSMISSION (i) Oxidation
Neurotransmission refers to the transmission of nerve By monoamine oxidase (MAO) present in
impulse from one neuron to another neuron or to an effector neuronal mitochondria.
organ by releasing neurotransmitters. Basically, two (ii) Methylation
types of neurotransmission occur in SNS, depending on By catechol-O-methyltransferase (COMT)
the type of neurotransmitter released. present in postsynaptic memb.
(A) Cholinergic Transmission
Here acetylcholine is the neurotransmitter, eg at AUTO- & HETERO-RECEPTORS
ganglionic synapses, some sympathetic neuro-effector These are meant for feedback control at presynaptic level,
synapses, & all parasympathetic neuro-effector in both sympathetic & parasympathetic nervous system.
synapses. (See chapter 3, unit I). Autoreceptors
(B) Adrenergic Transmission These are presynaptic receptors that respond to the
Here norepinephrine is the neurotransmitter, found at transmitter substances released by the nerve ending.
most of the sympathetic neuro-effector synapses. It Examples
involves 5 steps: (A) Inhibitory Autoreceptors
(1) Synthesis of Norepinephrine (1) Alpha-2 at adrenergic terminals  Activated by
Tyrosine is transported into cytoplasm of adrener- norepinephrine, & in turn diminishes further
gic neuron  Hydroxylated to DOPA by tyrosine release of norepinephrine.
hydroxylase  Decarboxylated to form dopamine. (2) D2 at adrenergic terminals  Activated by
(2) Storage of Norepinephrine in Vesicles dopamine, inhibits further transmitter release.
Dopamine is transported into synaptic vesicles (B) Excitatory Autoreceptors
using an amine transporter system  Hydroxylated (1) Beta-1 at adrenergic terminals  Activated by
to form norepinephrine ( Methylated to form epinephrine, stimulates further transmitter release.
epinephrine in adrenal medulla). (2) NM at somatic motor cholinergic terminals 
(3) Release of Norepinephrine Activated by acetylcholine, stimulates further
Arrival of action potential at presynaptic nerve transmitter release.
terminal  Triggers Ca++ influx into cytoplasm of Heteroreceptors
neuron  Inc. Ca++ destabilizes the storage These are also presynaptic receptors that respond to many
vesicles by interacting with a special protein other substances, which diffuses to the receptor sites from
"synaptotagmin" in vesicular memb.  Vesicular blood or from nearby tissues. It may also be activated by
memb. fuses with the terminal memb.  Exocytotic substances released from nerve terminals that synapse with
expulsion of norepinephrine occur in synaptic cleft. the nerve ending.
(4) Binding to Receptors Examples
Released norepinephrine diffuses across the (A) Inhibitory Heteroreceptors
synaptic cleft, & binds to either postsynaptic
02: Sympathetic Nervous System Drugs 13

Box 2.1 ADRENOCEPTORS ------- Location & Effects

Receptors Location Pharmacological Effects 2nd Messenger Effects
1 Postsynaptic effector cells   IP3,  DAG
1) Most vascular smooth muscle Contraction  Vasoconstriction,  (common to all sub-
(innervated) peripheral resistance &  BP types)
2) Radial muscle of iris Contraction  Mydriasis (dilatation of   Ca++ influx (-
pupil) 1B,1D)
3) Pilomotor smooth muscle Contraction  Hair erection
4) GIT sphincters Contraction
5) Prostate & bladder sphincter Contraction
6) Heart Increases force of contraction
2 1) Presynaptic adrenergic & Inhibition of transmitter release  Inhibition of adenyl
cholinergic nerve terminals cyclase  cAMP
2) Some vascular smooth muscle Contraction (common to all sub-
(non-innervated) types)
3) Platelets Aggregation   K+ channels,
4) Lipocytes Inhibition of lipolysis   Ca++ channels
5) CNS (post-synaptically) Probably multiple
1 1) Presynaptic adrenergic nerve Stimulation of transmitter release Stimulation of adenyl
terminals cyclase  cAMP
2) Heart (postsynaptic)
a) SA node Acceleration (+ve chronotropic effect)
b) Ectopic pacemakers Acceleration (+ve chronotropic effect,
arrhythmias)
c) Contractility Increases (+ve inotropic effect)
3) Kidneys (postsynaptic) Stimulation of renin release
2 Postsynaptic effector cells Stimulation of adenyl
1) Bronchiolar smooth muscle Relaxation cyclase  cAMP
2) GIT wall smooth muscle Relaxation
3) Bladder wall smooth muscle Relaxation
4) Pregnant uterus Relaxation
5) Vascular smooth muscle in Relaxation (vasodilatation)
skeletal muscle
6) Liver Stimulation of glycogenolysis &
gluconeogenesis
7) Skeletal muscle Promotion of K+ uptake
 3 Lipocytes (postsynaptic) Stimulation of lipolysis Stimulation of adenyl
cyclase  cAMP
D1 1) Brain Associated with motor function Stimulation of adenyl
a) Putamen (presynaptic) control cyclase  cAMP
b) Zona compacta of substantia
nigra (postsynaptic)
2) Vascular smooth muscle esp of Relaxation (renal vasodilation)
renal vascular bed (postsynaptic)
D2 1) Brain  Both pre- & Associated with motor function control Inhibition of adenyl
postsynaptically on neurons in cyclase  cAMP, 
caudate - putamen, nucleus K+ conductance
accumbens, & olfactory tubercle
2) Presynaptic adrenergic nerve Inhibition of transmitter release
terminals
D3 Brain  Frontal cortex, medulla, & Inhibition of adenyl
midbrain cyclase  cAMP
D4 Brain Inhibition of adenyl
cyclase  cAMP
D5 Brain  Hippocampus, & Stimulation of adenyl
hypothalamus cyclase  cAMP
M. Shamim’s PHARMACOLOGY 14

(1) EP3 at adrenergic terminals  Activated by CLASSIFICATION OF SYMPATHOMIMETICS

prostaglandin E1, E2.
(2) M2 at adrenergic terminals  Activated by
ACCORDING TO CHEMICAL NATURE
acetylcholine.
(1) Catecholamines
(3) 5-HT1, 5-HT2, & 5-HT3, at cholinergic pregangli- Norepinephrine (Noradrenaline), Epinephrine (Adrena-
onic terminals  Activated by serotonin (5-HT). line), Isoproterenol (Isoprenaline), Dopamine,
(B) Excitatory Heteroreceptors Dobutamine, Ibopamine.
A II-1 at adrenergic terminals  Activated by (2) Non-Catecholamines
angiotensin II. Phenylephrine, Methoxamine, Ephedrine, Pseudoephe-
drine, Albuterol (Salbutamol), Terbutaline, Metapro-
ADRENERGIC RECEPTORS (ADRENOCEPTORS) terenol (Orciprenaline), Ritodrine, Amphetamine,
These are receptors that mediate the actions of sympathetic Hydroxyamphetamine, Methamphetamine, Xylometa-
nervous system, by interacting with primary neurotransmit- zoline, Oxymetazoline, Phenmetrazine, Methyl-
ter or exogenously administered drugs. Three classes phenidate, Pemoline, Phenylpropanolamine, Mephen-
(types) of adrenoceptors are identified with many sub- teramine, Clonidine, Naphazoline, Tetrahydrozoline.
types, based on affinity for various agonists & antagonists,
& molecular cloning. Box 2.2
(A) Alpha Adrenoceptors
Exhibits following series of agonist's potency: CHARACTERISTICS OF CATECHOL- &
Epinephrine Norepinephrine  Isoproterenol. NONCATECHOLAMINES
Sub-Types
Two sub-types are identified with antagonist (blocker) Catecholamines
 Presence of catechol ( a 3 ,4 – dihydroxybenzene
drugs, & each have further sub-types as well ;
group ) in the structure
(1) Alpha-1  Blocked by Prazosin.
 Rapid onset of action
(a) Alpha - 1A  Brief duration of action
(b) Alpha - 1B  Can not be administered orally
(c) Alpha - 1C  Do not penetrate blood - brain barrier
(d) Alpha - 1D
(2) Alpha-2  Blocked by Yohimbine. Non - Catecholamines
(a) Alpha - 2A  Longer duration of action
(b) Alpha - 2B  All can be administered orally
(c) Alpha - 2C
(B) Beta Adrenoceptors ACCORDING TO MECHANISM OF ACTION
Exhibits following series of agonist's potency : (1) Direct - Acting Agonists
Isoproterenol  Epinephrine  Norepinephrine. These drugs act directly on adrenoceptors
Sub-Types Examples
(1) Beta-1  Exhibits approx. equal affinity for Epinephrine, Norepinephrine, Isoproterenol, Dobu-
epinephrine & norepinephrine. tamine, Phenylephrine, Methoxamine, Albuterol,
(2) Beta-2  Exhibits higher affinity for epinephrine Terbutaline, Ritodrine, Metaproterenol, Clonidine.
than for norepinephrine. (2) Indirect - Acting Agonists
(3) Beta-3  Recently demonstrated on the basis of These drugs causes release of catecholamines.
molecular cloning, & shows agonist activity for Examples
BRL 37344. Amphetamine, Tyramine, Modafinil.
(C) Dopamine Receptors (3) Mixed-Acting Agonists
Exhibits agonist activity for dopamine. Dopamine, Ephedrine, Methamphetamine, Hydroxy-
Sub-Types amphetamine, Metaraminol.
Five sub-types are identified  D1, D2, D3, D4, & D5. (4) Inhibitors of catecholamine reuptake
Dexmethylphenidate.
Unit II
ACCORDING TO RECEPTOR SELECTIVITY
(1) Alpha Selective
Sympathomimetics (a) Alpha-1 Selective
Phenylephrine, Methoxamine, Midodrine.
(b) Alpha-2 Selective
[Adrenoceptors - Activating Drugs, Sympathetic
Agonists, or Adrenoceptor Agonists]
02: Sympathetic Nervous System Drugs 15

Clonidine, Aproclonidine, Brimonidine, Dexmede- PHARMACOLOGICAL EFFECTS OF

tomidine, Methylnorepinephrine, Guanabenz, SYMPATHOMIMETICS
Guanfacine. .
(2) Beta Selective
(a) Beta-1 Selective CARDIOVASCULAR SYSTEM (CVS)
Dobutamine. (1) Blood Vessels
(b) Beta-2 Selective (a) Vasoconstriction of cutaneous & splanchnic
Albuterol, Terbutaline, Ritodrine, Metaproterenol, vessels (effect).
Bitolterol, Procaterol, Fenoterol, Pirbuterol, (b) Vasoconstriction () or vasodilation ( 2) of vessels
Salmeterol. in skeletal muscle, depending on whether  or
(c) Beta-1 & -2 Non-Selective 2 receptors are activated.
Isoproterenol.
(c) Vasodilation of renal, splanchnic, coronary, &
(3) Alpha & Beta Non-Selective
Epinephrine, Norepinephrine. cerebral arteries (D1 effect).
(4) Dopamine Selective (2) Heart
Dopamine (D non-selective), Fenoldopam(D1 selective).  1 adrenoceptor activation results in increased
Ca++ influx in cardiac cells, that results in ;
(a) Increased pacemaker activity, both normal (SA
MECHANISM OF ACTION OF SYMPATHOMIMETICS
node) & abnormal (eg Purkinje fibres) ↑ heart
rate (+ve chronotropic effect). However,
Sympathomimetics bind to adrenoceptors, which are normally due to reflux vagal response to BP
coupled with G proteins ( Gs stimulatory, Gi inhibitory, or Gq changes, the heart rate is decreased.
phospholipase C related)  GDP dissociates from  (b) Increased conduction velocity in AV node, &
subunit of appropriate G protein  GTP then binds to this decreased refractory period.
G protein & subunit dissociates from -  unit  (c) Increased intrinsic contractility (+ve inotropic
Activated GTP - bound subunit then regulate the activity effect), accelerated relaxation  Intraventricular
of its effector ( ie, adenyl cyclase, cGMP phosphodiesterase, pressure rises & falls more rapidly, &
phospholipase C, ion channels). ejection time is decreased.
(Note : One or more effector mechanism is associated with (3) Blood Pressure
each receptor type [See Box 2-1], that results in final (a) Alpha Effect eg, by Phenylephrine
cellular effect). (i) Vasoconstriction  Increased arterial
(A) Alpha-1 Adrenoceptors resistance & decreased venous capaci- tance
A rise cytosolic Ca++ conc. occurs, thru ;  Inc. blood pressure (BP).
(1) Opening of receptor-operated Ca++ channels (-1A (ii) However, normally, a rise in BP elicits
& -1D) baroreceptor-mediated vagal response 
(2) Gq mediated phospholipase C  Breakdown of Decreases heart rate; but cardiac output may
not diminish, due to increased venous return &
polyphosphoinositides into inositol triphosphate
modest +ve inotropic effect.
(IP3) & diacylglycerol (DAG)  IP3 promotes
(b) Beta Effect eg, by Isoproterenol
release of Ca++ from intracellular stores. Net effect is:
(B) Alpha-2 Adrenoceptors (i) A fall in diastolic pressure due to
(1) Gi mediated inhibition of adenyl cyclase  decreased peripheral resistance from
Dec. intracellular cAMP level. skeletal muscle vasodilation (2).
(2) Activation of K+ channels (-2A). (ii) Slight increase or no change in systolic
(3) Closing of Ca++ channels (-2A,-2B). pressure due to increased cardiac output ( 1).
(C) Beta Adrenoceptors
(iii) Decreased mean blood pressure.
Gs mediated activation of adenyl cyclase  Inc. intra-
cellular cAMP level. EYE
(D) D1 & D5 Adrenoceptors
(1) Alpha Effect eg, by Phenylephrine
Activation of adenyl cyclase ↑ cAMP. (a) Contraction of radial pupillary dilator muscle of iris
(E) D2, D3 & D4 Adrenoceptors  Dilatation of pupil (mydriasis).
(1) Inhibition of adenyl cyclase  cAMP. (b) Increase in outflow of aqueous humor 
(2) Opening of K+ channels ( D2, D4 ). Decrease intra-ocular pressure.
(3) Closing of Ca++ channels ( D2, D4 ). (2) Beta Effect
(a) Relaxation of ciliary muscle to a minor degree 
Insignificant decrease in accommodation.
M. Shamim’s PHARMACOLOGY 16

(b) Increased production of aqueous humor  Increases K+ uptake into the cells ( 2 effect) 
Increased intra-ocular pressure. Hypokalemia.

RESPIRATORY TRACT ENDOCRINE SYSTEM

(1) Alpha-1 Effect eg, by Phenylephrine (1) Insulin Secretion
Vasoconstriction in mucosal vessels of upper (a) Stimulation ( effect).
respiratory tract  Decongestion. (b) Inhibition (2effect).
(2) Beta-2 Effect eg, by Albuterol
(2) Renin Secretion
Relaxation of bronchial smooth muscles 
Bronchodilation. (a) Stimulation ( 1 effect).
(b) Inhibition (2 effect).
GASTROINTESTINAL TRACT (GIT)
(1) Alpha-2 Effect CENTRAL NERVOUS SYSTEM (CNS)
(a) GI smooth muscle relaxation by indirectly Here effects are not due to  or  mediated actions, but
decreasing muscle activity, thru presynaptic probably represent enhancement of dopamine-mediated
inhibition of acetylcholine release. processes in CNS.
(b) Decrease salt & water flux into intestinal (1) Catecholamines
lumen. They have almost no effect except, for nervousness to a
(2) Beta-2 Effect feeling of impending disaster, noted at
Direct relaxation of GI smooth muscles via highest rates of infusion.
hyperpolarization & decreased spike activity in smooth (2) Non-Catecholamines
muscle cells. (a) Mild alerting, with improved attention to boring
tasks.
GENITOURINARY TRACT (b) Elevation of mood, insomnia, euphoria, &
(1) Uterus anorexia.
(a)  effect  Smooth muscle contraction. (c) Psychotic behavior at very highest level.
(b) 2 effect  Smooth muscle relaxation in
pregnant uterus. CLINICAL USES OF SYMPATHOMIMETICS
(2) Urinary Bladder
(a) Alpha-1 Effect
EPINEPHRINE
Contraction of urethral sphincter, bladder
base, & prostate  Promote continence. (1) To treat bronchospasm, eg in acute asthma &
(b) Beta-2 Effect anaphylactic shock.
Relaxation of bladder wall. (2) As primary treatment of anaphylaxis, to relieve
(3) Male Genitalia hypersensitivity reactions.
Alpha effect on ductus deferens, seminal vesicles, (3) To reduce regional blood flow (via vasoconstriction);
prostate, & penis  Ejaculation. (a) For achieving hemostasis in surgery.
(b) For reducing diffusion of local anesthetics
away form administration site.
EXOCRINE GLAND
(c) For reducing mucous memb. congestion.
(1) Salivary Glands (4) To restore cardiac activity in cardiac arrest.
(a) Regulation of amylase & water secretion, via (5) To facilitate aqueous drainage in chronic open- angle
adrenoceptors contained in them. glaucoma.
(b) Dry mouth, via central effect eg by clonidine.
(2) Apocrine (Stress, or Nonthermoregulatory)
NOREPINEPHRINE
Sweat Glands
As a pressor agent in hypotension, to preserve cerebral &
Increased sweat production (effect).
coronary blood flow, eg in;
(1) Severe hemorrhage.
METABOLIC EFFECTS
(2) Spinal cord injury.
(1) Lipocytes (3) Overdosage of antihypertensives or CNS depres-sants.
(a) Activation of lipolysis ( 3 effect). (4) During anesthesia.
(b) Inhibition of lipolysis (2 effect).
(2) Liver OTHERS
Activation of glycogenolysis & gluconeogenesis ( Isoproterenol
or 2 effect. depending on species). (1) As a cardiac stimulant, eg in cardiogenic shock,
(3) Skeletal Muscle complete heart block, & cardiac arrest.
(2) As a bronchodilator, eg in asthma.
02: Sympathetic Nervous System Drugs 17

Dopamine (2) CVS

(1) Shock esp. cardiogenic shock. Hypertension, cardiac arrhythmias, angina.
(2) Chronic refractory congestive heart failure. (3) Resp. Tract
Dobutamine Pulmonary edema.
To improve myocardial function in congestive heart failure
& cardiogenic shock. OTHERS
Fenoldopam (1) Norepinephrine & Isoproterenol
As an antihypertensive agent postoperatively, to treat Similar to epinephrine.
hypertensive crisis. (2) Dopamine
Apraclonidine & Brimonidine (a) CVS
For the lowering of intraocular pressure in patients with Anginal pain, arrhythmias, hypertension.
open-angle glaucoma or ocular hypertension. (b) GIT
Phenylephrine Nausea.
(1) As a pressor agent. (c) Overdosage
(2) As a local mucous memb. decongestant, eg in nose to Results in excessive sympathomimetic effects.
relieve hay fever & common cold. (3) Dobutamine
(3) As an adjunct for local anesthesia (to reduce Similar to epinephrine.
regional blood flow). Precaution
(4) To treat paroxysmal atrial tachycardia. Used with caution in atrial fibrillation, because it
(5) As a mydriatic agent to facilitate examination of retina, increases AV conduction.
& in diagnosis of Horner's syndrome. (4) Phenylephrine
Methoxamine (a) CNS
(1) As a pressor agent. Headache.
(2) To treat paroxysmal atrial tachycardia. (b) CVS
Ephedrine Hypertension, cardiac irregularities.
(1) As a nasal decongestant. (c) Resp. Tract
(2) To treat bronchial asthma. Rebound nasal congestion (with chronic use).
(3) As a pressor agent in spinal anesthesia. Precaution
(4) As a mydriatic. It can be systemically absorbed from topical sites; so,
(5) To treat stress incontinence. their use in pts. taking  blockers increases the risk of
Amphetamine, Methamphetamine & Methyl- cardiac irregularities, myocardial infarction, & intra-
phenidate cranial hemorrhage.
(1) To treat narcolepsy. (5) Methoxamine
(2) To treat attention-deficit hyperkinetic syndrome of (a) CNS
children. Headache.
Hydroxyamphetamine (b) CVS
(1) As a mydriatic Hypertension.
(2) As a decongestant (c) GIT
(3) As a pressor agent Vomiting.
(4) To diagnose Horner's syndrome. (6) Ephedrine
Metaraminol Similar to epinephrine.
To treat hypotension. Precaution
Metaproterenol & Albuterol Used with caution in pts. with CVS disease or
To treat bronchospasm, eg in asthma. hyperthyroidism, because it is a powerful heart
Terbutaline & Ritodrine stimulant.
(1) To treat bronchospasm. (7) Amphetamine
(2) To reduce uterine contractions in premature labor. (a) CNS
Xylometazoline, Oxymetazoline, & Toxic psychosis, mental depression, fatigue,
Phenylpropanolamine restlessness, insomnia.
As a topical decongestant. (b) CVS
Tachycardia, hypertension.
ADVERSE EFFECTS OF SYMPATHOMIMETICS (c) Eye
Mydriasis.
(d) GIT
EPINEPHRINE Vomiting.
(1) CNS (f) Tolerance &, psychic & physical
Anxiety, fear, tension, headache, tremor, cerebral dependence.
hemorrhage.
M. Shamim’s PHARMACOLOGY 18

(8) Beta-2 Agonists (E) Phenylephrine

(a) CNS (1) IV  10 mg in 250 ml of 5% Dextrose or NS &
Fine tremor, tension, headache. titrated; given at a rate of 0.04 - 0.08 mg/min.
(b) CVS (2) Eye drops  10% sol. in HCl; 1-2 drops 2-3 hourly
Peripheral vasodilatation, tachycardia. for 2 days, then one instillation TDS for 5-6 days.
Precaution (3) Nasal drops  0.25 % / 0.50 % sol; 2-3 drops, 4-6
Used with caution in pts. with CVS disease or hourly daily.
hyperthyroidism, because they can still stimulate
(though minimally) 1 receptors of heart. GENERIC & TRADE NAMES

CONTRAINDICATIONS OF SYMPATHOMIMETICS (A) Catecholamines

Epinephrine: Xylocaine*, Medicaine*.
EPINEPHRINE Dopamine: Dopamine, Intropin, Tropin.
(1) Coronary disease, as it may induce anginal attacks. Dobutamine: Buta, Dobuject, Dobutrex, Dobutamine.
(2) Hyperthyroidism, because of enhanced drug effect due (B) Non-Catecholamines
to increased production of adrenergic receptors in Phenylephrine: Bronex, Ethifrin, Fenox, Isonefrine,
hyperthyroid individuals. Mediphrine, Oculoforte*, Zincfrin*......
(3) Hypertension Ephedrine: Alcof D*, Amcodrin*, Davenol*, Efed.
(4) Chloroform, cyclopropane, trichloroethylene, & Pseudoephedrine: Actified P*, Arinac*, Dexodine*,
halothane anesthesia. Rondex*……….
(5) Pts. receiving digitalis therapy. Albuterol (Salbutamol): Aerolin, Asthamol,
Bronchilate, Butamol, Clenil*, Ventide, Ventolin ......
AMPHETAMINE Terbutaline: Bricanyl, Terbulin, Terbutil…...
Ritodrine: Yutopar.
(1) Pts with cardiovascular diseases.
Xylometazoline: Nasavin, Rhezole, Xoline, Xynosine.
(2) Pts receiving MAO inhibitors or guanethidine.
Oxymetazoline: Rinerge.
(3) Insomnia.
Methylphenidate: Phenida.
(4) Anorexia.
Naphazoline: Curin, Deltarhinol*, Efemoline*,
(5) Mentally unstable pts.
Nafamine*, Naphcon-A*.
Tetrahydrozoline: Famecon*, Murin Plus*,
DOSAGE OF SYMPATHOMIMETICS Vasoflam*.
Procaterol: M-butamol, Meptin air.
(A) Epinephrine Salmeterol: Axinat, Serevent.
(1) In Bronchospasm
(a) 0.4 ml of 1:1000 sol., SC.
(b) 320 g per puff, inhaled as a microaerosol Unit III
from a pressurized container.
(2) In Anaphylaxis
0.3-0.5 mg (0.3-0.5 ml of 1: 1000 sol.), SC. Sympatholytics
(3) As an Adjunct to Local Anesthesia
0.5 ml of 1: 80,000 or 1: 200,000 sol., 1M. [Adrenoceptor-Blocking Drugs, Sympathetic
(B) Norepinephrine Antagonists, or Adrenoceptor Antagonists]
(1) Diluted in  5% Dextrose water.
(2) Concentration (1 amp = 4 mg)  4 mg /250 ml = CLASSIFICATION OF SYMPATHOLYTICS
16 g/ml.
(3) Administered IV at a rate of 2 g/min (8 ml/hr),
& may be increased upto 4 g/min (15 ml/hr). (A) Alpha - Adrenoceptor Antagonists
(C) Isoproterenol (1) Alpha-1 Antagonists
Isoproterenol HCl is given in 2 dosage forms: Alfuzosin, Prazosin, Terazosin, Doxazosin,
(1) IV  1 mg in 250 ml 5% dextrose or NS, & Tamsulosin, Phenoxybenzamine, Indoramin,
Uradipil.
titrated; given at a rate of 1-4 g/min.
(2) Alpha-2 Antagonists
(2) Oral  30 mg sustained-release tabs.
Tolazoline, Yohimbine, Rauwolscine.
(D) Dopamine
(3) Alpha-1 & -2 Antagonists
Dopamine HCl 400 mg is diluted in 250 ml of 5%
Phentolamine, Ergot derivatives eg ergotamine,
dextrose or NS, & titrated; given IV at a rate of 2
dihydroergotamine.
g/Kg/min. & may be increased upto 5-10 g/Kg/min.
(B) Beta-Adrenoceptor Antagonists
02: Sympathetic Nervous System Drugs 19

(1) Beta-1 Antagonists (a) In pts. with prostatic hypertrophy (by partial
Metoprolol, Acebutolol, Alprenolol, Atenolol, reversal of smooth muscle contraction in prostate
Betaxolol, Celiprolol, Esmolol, Bisoprolol. or in bladder base).
(2) Beta-2 Antagonists (b) In pts with spinal cord injury (by relieving bladder
Butoxamine. neck hypertonus).
(3) Beta-1 & -2 Antagonists (4) To control autonomic hyperreflexia due to spinal cord
Propranolol, Metipranolol, Carteolol, Penbutolol, transection.
Pindolol, Timolol, Nadolol, Carvedilol, Adverse Effects
Levobunolol, Sotalol, Cloranolol, Medroxalol, (1) CNS: Fatigue, Sedation.
Bucindolol. (2) Eye: Miosis.
(C) Mixed (&  ) Adrenoceptor Antagonists (3) CVS: Postural hypotension, reflex tachycardia.
Labetalol (1=2 1  2 ). (4) Resp. Tract: Nasal stuffiness.
(D) Centrally Acting Sympatholytics (5) GIT: Nausea & vomiting (with oral administration).
Methyldopa, Clonidine, Guanfacine, Guanabenz. (6) Reproduction: Inhibition of ejaculation.
(E) Adrenergic Neuron Blockers (7) Local: Local tissue irritation by injection.
Guanethidine, Reserpine, Bretylium, Guanadrel. Dosage
(F) Inhibitors of Catecholamine synthesis (1) 10-20 mg/day, orally; may be increased to 200 mg,
Metirosine. gradually.
(2) 1 mg/kg, diluted in 5% dextrose or 0.9% saline, by IV
infusion.
ALPHA-ADRENOCEPTOR ANTAGONISTS
PRAZOSIN, TERAZOSIN, & DOXAZOSIN
PHENOXYBENZAMINE Mechanism of Action
Mechanism of Action Selective blocked of postsynaptic 1-adrenoceptors.
(1) It binds covalently to alpha-adrenoceptors (1 >2) Pharmacological Effects
 Irreversible blockade of long duration (14 - 48 hrs). (A) CVS
Note: Block can be overcome only by the synthesis of (1) Dilatation of both resistance & capacitance
new adrenoceptors. vessels  Decreases blood pressure, more in
(2) It inhibits reuptake of released norepinephrine by upright than in supine position.
presynaptic adrenergic terminals. (2) Only minimal changes in cardiac output.
(3) It also blocks histamine (H), acetylcholine, & serotonin (3) No reflex tachycardia.
receptors. (B) Kidneys
Pharmacological Effects (1) Retention of salts & fluid when administered
(A) CNS without a diuretic or during long- term therapy.
Stimulates CNS, producing; (2) Only minimal changes in renal blood flow &
(1) Nausea glomerular filtration rate.
(2) Hyperventilation Clinical Uses
(3) Loss of time perception (1) Mild to moderate chronic hypertension (more effective
(B) CVS when used in combination with a diuretic or
(1) Blocks catecholamine-induced vasoconstriction  propranolol).
Decrease in total peripheral resistance & BP. It will (2) Acute congestive heart failure ( Prazosin).
reduce BP more when sympathetic tone is high, eg (3) To relieve urinary obstruction ( Terazosin).
as a result of upright posture (postural Adverse Effects
hypotension) or, b/c of reduced blood volume. (1) CNS: Dizziness, headache, lassitude.
(2) Increases cardiac output, due to; (2) CVS: Postural hypotension , first-dose phenomenon
(a) Reflex effects (a precipitous drop in standing BP after the first dose
(b) Some blockade of presynaptic 2 receptors in that results in syncope, & occur esp. in pts who are
cardiac sympathetic nerves. salt- & volume-depleted ).
Clinical Uses (3) Resp. Tract: Nasal congestion.
(1) For controlling hypertension in pheochromocytoma, (4) GIT: GI hypermotility.
esp. in preoperative management &, in cases of (5) Kidneys: Salt & fluid retention.
inoperable or metastatic tumor. Dosage
(2) To relieve vasospasm in Raynaud's phenomenon, & (1) Prazosin
other conditions involving excessive reversible (a) First dose  0.5 mg at bed time, orally.
vasospasm in peripheral circulation. (b) Then 0.5 mg BD or TDS, for 3-7 days.
(3) To relieve urinary obstruction; (c) Followed by 1 mg BD or TDS, for 3-7 days.
M. Shamim’s PHARMACOLOGY 20

(d) Thereafter increases gradually as required, upto ERGOT DERIVATIVES

max. of 20 mg /day. Examples
(2) Terazosin Ergotamine tartrate, Dihydroergotamine, Ergonovine
(a) Initially 1 mg at bed time, orally. maleate, Methylergonovine maleate, Methysergide,
(b) Titrate by approx. doubling dose at weekly Bromocriptine, Lysergic acid diethylamide (LSD).
intervals.
.(c) Usual maintenance dose is 2-10 mg OD. Box 2.3 EFFECTS OF ERGOT DERIVATIVES AT
SEVERAL RECEPTORS
PHENTOLAMINE Ergot - adreno- Dopamine Serotonin
Mechanism of Action Derivatives ceptors Receptors ( 5-HT2 )
(1) Competitive blockade of alpha-adrenoceptors (1 =2). Receptors
(2) Inhibits response to serotonin. Ergotamine - - ( PA ) 0 + ( PA )
(3) Stimulates muscarinic &, H1 & H2 histamine receptors. Ergonovine + + - ( PA )
Pharmacological Effects Methysergide +/0 +/0 - - - ( PA )
(A) CVS Bromocriptine - +++ -
(1) Vasodilatation thru both -adrenoceptor blockade LSD 0 +++ --
& an additional nonadrenergic action on vascular [ + = Agonist, - = Antagonist, 0 = No effect, PA = Partial
smooth muscle  Dec. peripheral resistance, & agonist, Relative affinity is indicated by no. of + or - signs ]
inc. venous capacitance.
(2) Cardiac stimulation thru, Mechanism of Action
(a) Reflex effect Each member have varying effects on several receptors
(b) 2-adrenoceptor blockade. (see box 2.3); include,
(B) Glands (1) Agonist, partial agonist, & antagonist actions at -
Stimulate lacrimal, salivary, pancreatic, & respiratory adrenoceptors.
tract secretions. (2) Agonist, partial agonist, & antagonist actions at
Clinical Uses serotonin receptors.
(1) Diagnosis of pheochromocytoma & other clinical (3) Agonist action at CNS dopamine receptors.
situations associated with excess release of Pharmacological Effects
catecholamines. (A) CNS
(2) Hypertensive emergencies from pheochromocytoma, (1) They stimulate CNS & may cause:
sympathomimetics overdosage or, clonidine withdrawal. (a) Confusion
(3) Raynaud's phenomenon (b) Irregular respiration
(4) Frost-bite (c) Anxiety
(5) To reverse intense local vasoconstriction caused by (2) LSD acts as a powerful hallucinogen.
inadvertent infiltration of -agonists into subcutaneous (3) Bromocriptine directly suppresses prolactin
tissue during IV administration. secretion from pituitary cells by activating
(6) To cause erection in male sexual dysfunction. regulatory dopamine receptors.
Adverse Effects (B) CVS
(1) CVS: Severe tachycardia, arrhythmias, angina, postural Effects are drug-, species-, & vessel-dependent.
hypotension. (1) Ergotamine & related compounds constrict most
(2) GIT: Diarrhea, increased gastric acid production. human blood vessels in a predictable, prolonged, &
Precautions potent manner, & is due to partial agonist effect.
(1) Pts with coronary artery disease. (2) Different vascular beds have different sensitivities,
(2) Pts with peptic ulcer. & cerebral vessels esp cerebral arteriovenous
anastomotic vessels are most sensitive.
TOLAZOLINE (3) Blood pressure is elevated, due to vasoconstriction.
Similar to phentolamine, but is some what less potent & its (C) Uterine Smooth Muscle
receptor affinity is2 > > 1. Stimulate uterine smooth muscle esp. of pregnant
Clinical Uses uterus, due to combine alpha & serotonin agonists
(1) Peripheral vasospastic disease, eg Raynaud's effect.
phenomenon. Clinical Uses
(2) Pulmonary hypertension in neonates with respiratory (1) Ergotamine tartarate  Migraine.
distress syndrome. (2) Dihydroergotamine  Intractable migraine.
Adverse Effects (3) Ergonovine maleate 
Similar to phentolamine, except that it may cause (a) To control late uterine bleeding (post-partum
paradoxical hypertension. hemorrhage).
(b) Prophylaxis of migraine.
02: Sympathetic Nervous System Drugs 21

(c) Diagnosis of variant angina. (2) Angina pectoris & prophylaxis of myocardial infarction.
(4) Methylergonovine maleate  Post-partum hemorrhage. (3) Supraventricular & ventricular arrhythmias.
(5) Methysergide  Prophylaxis of migraine. (4) Ventricular ectopic beats, esp if precipitated by
(6) Bromocriptine  Hyperprolactinemia. catecholamines.
(5) Obstructive cardiomyopathy (to increase stroke
Adverse Effects volume).
(1) CNS: Drowsiness. (6) Dissecting aortic aneurysm (to decrease rate of
(2) CVS: Gangrene (due to prolonged vasoconstriction). development of systolic pressure).
(3) GIT: Nausea, vomiting, diarrhea. (7) Hyperthyroidism.
(8) Prophylaxis of migraine.
(9) Anxiety (to reduce somatic manifestations).
BETA-ADRENOCEPTOR ANTAGONISTS
(10) Cirrhosis (to reduce portal vein pressure).
Adverse Effects
PROPRANOLOL (1) CNS: Sedation, sleep disturbances, depression.
Mechanism of Action (2) CVS: Peripheral arterial insufficiency, cardiac failure,
Blocks both  1 - &  2 - adrenoceptors. bradycardia, cardiac conduction abnormalities.
Pharmacological Effects (3) Resp. Tract: Bronchoconstriction.
(A) CVS (4) GIT: Nausea, vomiting, constipation, diarrhea.
(1) Anti-Hypertensive Effect (5) Metabolism: Hypoglycemia.
(a) Initially, due to decreased cardiac output (6) Allergy: Rash, fever, purpura.
associated with bradycardia. (7) Withdrawal Symptoms: Abrupt discontinuing after
(b) With continued use, due to decreased chronic use causes up-regulation of number of-
peripheral resistance resulting from inhibition adrenoceptors, which can provoke anginal attacks,
of renin secretion. arrhythmias, or myocardial infarction.
(2) Anti-Anginal Effect Precautions
Decreases heart rate, contractility, & BP  Dec. (1) Pts with asthma.
myocardial O2 requirements at rest & during (2) Pts with diabetes mellitus esp IDDM.
exercise. Contraindications
(3) Anti-Arrhythmic Effect (1) Cardiogenic shock
(a) Decreases SA nodal firing. (2) Right ventricular failure secondary to pulmonary
(b) Increases AV nodal refractory period. hypertension
(c) Increases PR interval. (3) Congestive cardiac failure
(4) Effect on Peripheral Blood Vessels & Flow (4) Asthma
(a) Blocks  2-mediated vasodilation  Initially (5) Greater than 1st degree heart block
(6) Hypotension
inc. peripheral resistance from unopposed  (7) Raynaud's phenomenon
effects. (8) Pts on MAO inhibitors
(b) Inhibition of renin secretion  Dec. peripheral Dosage
resistance. (1) 20-80 mg TDS or QID, orally.
(c) A favorable redistribution of coronary blood (2) In emergency treatment of dysarrhythmias  1 mg over
flow to ischemic myocardium. 1 min, IV; repeated at 2 min. interval to a maximum of
(B) Respiratory Tract 10 mg.
Increases airway resistance, esp. in pts with asthma
(2-blockade). OTHER BETA ANTAGONISTS
(C) Kidneys Clinical Uses
(1) Increases Na+ retention, due to a fall in renal Atenolol
perfusion that results from low BP. (1) Hypertension
(2) Antagonizes renin release ( 1-blockade). (2) Angina pectoris
(D) Metabolism (3) Cardiac dysarrhythmias
(1) Inhibit lipolysis ( 1-blockade). Note: Safe in pts with diabetes, or peripheral vascular
(2) Partially inhibit glycogenolysis in liver ( 2- disease.
blockade)  Hypoglycemia. Metoprolol
(3) Chronic use is associated with inc. plasma VLDL, (1) Hypertension
dec. HDL, & a variable decline in HDL/LDL ratio. (2) Angina pectoris
(3) Supraventricular arrhythmias
Clinical Uses
Note: Safe in pts with diabetes, or peripheral vascular
(1) Hypertension (most often used with either a diuretic
disease.
or a vasodilator).
M. Shamim’s PHARMACOLOGY 22

Esmolol (B) Beta Blockers

(1) Supraventricular arrhythmias Metoprolol: Betalock Zok, Mepresor, Meprol, Merol.
(2) Perioperative hypertension Atenolol: Atelor, Atenolol, Atenorm, Blokium*,
(3) Myocardial infarction Cardiolite, Normitab, Tenormin..........
Bisoprolol Betaxolol: Betaxen, Betoptic, Vistagan.
(1) Hypertension Esmolol: Brevibloc.
(2) Angina pectoris Bisoprolol: Biscot, Concor, Corbis.
Pindolol Propranolol: Betanol, Beta prograne, Blockonol,
(1) Hypertension Cardinol, Inderal, Oprinol.
(2) Angina pectoris Carteolol: Carteol, Mikelan.
Note: Safe in asthmatics. Pindolol: Vikaldix*.
Timolol Timolol: Betalol, Milosol, Optimol, Timop- tol,
(1) Glaucoma Timosol.
(2) Hypertension Nadolol: Corgard.
(3) Migraine prophylaxis Carvedilol: Carveda, Vadil.
Nadolol Cloranolol: Tobanum.
(1) Hypertension Methyldopa: Aldomet, Normet.
(2) Angina pectoris Bretylium: Bretylol.
(3) Cardiac tachyarrhythmias
(4) Migraine prophylaxis
Carteolol Unit IV
(1) Hypertension
(2) Angina pectoris
(3) Cardiac arrhythmias
(4) Glaucoma
Self-Assessment (T/F)
(See answers on page no. 240)
MIXED ADRENOCEPTOR ANTAGONIST (14) Following are beta-2 selective agonists
(A) Albuterol.
LABETALOL (B) Prenalterol.
Mechanism of Action (C) Terbutaline.
Reversible adrenoceptor blockade: (D) Fenoterol.
(1) Non-selective  - blockade, with potency somewhat (E) Ritodrine.
lower than that of propranolol. (15) Dilatation of vessels in muscle, constriction of
(2) Relatively 1 - selective blockade, with potency less cutaneous vessels, & positive inotropic & chronotropic
than that of phentolamine. effects on heart are all actions of
Clinical Uses (A) Metaproterenol.
Hypertension (B) Norepinephrine.
Note: Safe in pts with peripheral vascular disease. (C) Acetylcholine.
(D) Epinephrine.
(E) Isoproterenol.
OTHER SYMPATHOLYTICS
(16) An indirect sympathomimetic agent sometimes used
orally for asthma is
Centrally Acting Sympatholytics (A) Epinephrine.
See chapter 11, CVS. (B) Ephedrine.
Adrenergic Neuron Blockers (C) Dobutamine.
See chapter 11, CVS. (D) Isoproterenol.
(E) Phenylephrine.
GENERIC & TRADE NAMES (17) Selective beta-2 stimulants frequently cause
(A) Skeletal muscle tremor.
(A) Alpha Blockers (B) Tachycardia in direct proportion to bronchodilation.
Alfuzosin: Xatral SR (C) Vasodilation in skin.
Prazosin: Minipress. (D) Increased cGMP in mast cells.
Terazosin: Hytrin. (E) Palpitations.
Doxazosin: Cardura, Prosdura. (18) Phenylephrine
Yohimbine: Vigrol Forte. (A) Increases skin temperature.
Ergotamine: Migranil, Migril*, Tagril*. (B) Causes mydriasis in eye.
02: Sympathetic Nervous System Drugs 23

(C) Constricts small vessels in nasal mucosa. (A) Pheochromocytoma.

(D) Increases gastric secretion & motility. (B) Essential hypertension.
(E) Causes all of the above. (C) Raynaud's phenomenon.
(19) Beta-2 agonists are effective in (D) Angina pectoris.
(A) Raynaud's syndrome. (E) Shock.
(B) Delayed or insufficiently strong labor. (28) Adverse effects of propranolol includes
(C) Ischemic ulcers of skin. (A) Tachycardia
(D) Bronchial asthma. (B) AV block.
(E) Coronary insufficiency manifested by angina. (C) Depression.
(20) Epinephrine is clinically used in (D) Hypoglycemia.
(A) Bronchial asthma. (E) Hypersensitivity reactions .ion.
(B) Primary treatment of anaphylaxis.
(C) Chronic open-angle glaucoma.
(D) Paroxysmal atrial tachycardia.
(E) Narcolepsy.
(21) Which of the following structures are more
responsive to beta agonists than to alpha
agonists
(A) Bronchial smooth muscle.
(B) Radial muscle of iris.
(C) Vasculature of skeletal muscle.
(D) Vasculature of skin.
(E) Pregnant uterus.
(22) Following drugs are both alpha & beta
receptor stimulator
(A) Ephedrine.
(B) Isoproterenol.
(C) Epinephrine.
(D) Methoxamine.
(E) Dopamine.
(23) Following are alpha-2 antagonists
(A) Prazosin.
(B) Yohimbine.
(C) Tolazoline.
(D) Phentolamine.
(E) Butoxamine.
(24) Following are centrally acting sympatholytics
(A) Methyldopa.
(B) Clonidine.
(C) Guanfacine.
(D) Reserpine.
(E) Guanadrel.
(25) Phentolamine & tolazoline
(A) Are beta-blockers.
(B) Induce vasospasm when administered in large doses.
(C) Causes tachycardia.
(D) Cause hypertension.
(E) Used in Raynaud's phenomenon.
(26) Propranolol is useful in
(A) Hypertension.
(B) Angina pectoris.
(C) Congestive heart failure.
(D) Hypertrophic obstructive cardio-myopathies.
(E) Hyperthyroidism.
(27) Phenoxybenzamine is used in the treatment of
M. Shamim’s PHARMACOLOGY 24

03 PARASYMPATHETIC NERVOUS
SYSTEM DRUGS

Unit I
PARASYMPATHETIC NEUROTRANSMISSION

Introduction CHOLINERGIC TRANSMISSION

It involves 6 steps:
(1) Synthesis of Acetylcholine
Choline is transported into cytoplasm of cholinergic
ANATOMY
neuron by a carrier system that cotransports Na+ 
Reacts enzymically with acetyl CoA to form
EFFERENT (MOTOR) PORTION OF PNS acetylcholine.
(1) Preganglionic Neurons (2) Storage of Acetylcholine in Vesicles
Cell bodies of preganglionic neurons are found in CNS Acetylcholine is transported into synaptic vesicles
&, their axons constitutes the preganglionic fibres. where it is stored in granules
(a) Cranial Part (3) Release of Acetylcholine
Cell bodies are found in Edinger-Westphal nucleus, Similar to norepinephrine release (see unit I , chapter 2).
superior & inferior salivary nucleus, & dorsal (4) Binding to Receptors
motor nucleus of vagus. Similar to norepinephrine binding (see unit I, chapter 2).
(b) Sacral Part (5) Degradation of Acetylcholine
Cell bodies are found in lateral grey horn of sacral Released acetylcholine is rapidly degraded into choline
segments 2-4 of spinal cord. & acetate by :
(2) Preganglionic Fibres (a) Acetylcholinesterase (found in synaptic cleft &
Leave the CNS from brainstem (cranial part) & 2-4 RBCs).
sacral segments of spinal cord (sacral part) & travel (b) Pseudocholinesterase (found in plasma, liver, glia)
upto the parasympathetic ganglia near or on the contribute to a smaller extent.
effector organs. (6) Recycling of Choline
(3) Ganglia Choline may be recaptured by a high affinity transport
Preganglionic fibres terminates by synapsing with cell system into the neuron, where it is acetylated & stored
bodies of parasympathetic ganglia. until release by subsequent action potential.
(a) Cranial Parasympathetic Ganglia
(i) Edinger-Westphal fibres Ciliary ganglion. CHOLINOCEPTORS (CHOLINERGIC RECEPTORS)
(ii) Superior salivary fibres  Pterygopalatine &
submandibular ganglion.
These are receptors that mediate the actions of parasympa-
(iii) Inferior salivary fibres  Otic ganglion.
thetic nervous system, by interacting with acetylcholine or
(iv) Vagal fibres  Postganglionic cell bodies in
exogenously administered drugs. Two classes (types) of
the visceral wall (heart, lungs, & gut).
cholinoceptors are identified, with further sub-types.
(b) Sacral Parasympathetic Ganglia
(A) Muscarinic Cholinoceptors
Postganglionic cell bodies in the wall of pelvic
(1) Agonist  Muscarine
viscera.
(4) Postganglionic Fibres (2) Antagonist  Atropine
These are axons of cell bodies in parasympathetic (3) Sub-types M1 , M2, M3, M4, & M5.
ganglia, extending to effector organs (viscera & gland). (B) Nicotinic Cholinoceptors
(1) Agonist  Nicotine (first stimulates, then block).
PARASYMPATHETIC NEUROTRANSMITTERS (2) Antagonist  d-Tubocurarine.
Both preganglionic & postganglionic parasympathetic (3) Sub-types NG (ganglionic), & NM (muscular end-
fibres release acetylcholine at their nerve terminals. plates).
03: Parasympathetic Nervous System Drugs 25

Box 3.1 CHOLINOCEPTORS ------- Location & Effects

Receptors Location Pharmacological Effects 2nd Messenger Effects
Muscarinic 1) CNS neurons Probably multiple Formation of IP3 & DAC,
M1 2) Sympathetic post-ganglionic Onward impulse transmission
 Ca++ influx
neurons
3) Some pre-synaptic sites Inhibition of transmitter release
4) GIT myenteric plexus Activation
M2 1) Heart (postsynaptic) Opening of K+ channels,
a) SA node Deceleration inhibition of adenyl
b) Contractility Decreases cyclase
2) Some presynaptic sites Inhibition of transmitter release
3) Smooth muscle Contraction
M3 1) Smooth muscle of eye Formation of IP3 & DAG,
a) Iris circular muscle Contraction
 Ca++ influx
b) Ciliary muscle Contraction
2) Bronchiolar smooth muscle Contraction
3) GIT
a) Smooth muscle of walls Contraction
b) Smooth muscle of Relaxation
sphincters
c) Exocrine glands & secretory Increases secretions
cells
4) Genitourinary smooth muscle
a) Bladder wall Contraction
b) Sphincters Relaxation
c) Pregnant uterus Contraction
d) Penis, seminal vesicles Erection
5) Vascular smooth muscle
a) Skeletal muscle vessels Relaxation
b) Endothelium (uninnervated) Releases EDRF  Vasodilation
6) Thermoregulatory sweat glands Increases secretions
M4 CNS neurons, possibly vagal nerve Probably multiple Inhibition of adenyl
endings cyclase
M5 1) Vascular endothelium, esp. Releases EDRF  Vasodilation Formation of IP3 & DAC,
cerebral vessels
 Ca++ influx
2) CNS neurons Probably multiple
Nicotinic 1) Autonomic ganglion Opening of Na+, K+
NG a) Sympathetic ganglion Predominantly CVS effects (vaso- channels, & depolari-
constriction, tachycardia &  BP) zation
b) Parasympathetic ganglion Predominantly GIT effects ( inc.
tone & motility )
2) Some presynaptic cholinergic
terminals
NM Skeletal muscle neuromuscular Skeletal muscle contraction Opening of Na+, K+
endplates channels, & depolari-
zation

DIRECT ACTING
(1) Muscarinic Agonists
Unit II (a) Choline Esters
Bethanechol, Cevimeline.
(b) Alkaloids
Parasympathomimetics Muscarine, Pilocarpine.
(2) Nicotinic Agonists
[ Cholinoceptor-Activating Drugs, Parasympathetic (a) Choline Esters
Agonists, or Cholinoceptor Agonists] Varenicline.
(b) Alkaloids
Nicotine, Lobeline.
CLASSIFICATION OF PARASYMPATHOMIMETICS (3) Mixed Agonists
Choline Esters
M. Shamim’s PHARMACOLOGY 26

Acetylcholine, Methacholine, Carbachol. (1) Quaternary Alcohols, eg Edrophonium

Bind reversibly to enzyme's active site Prevent
INDIRECT ACTING (ANTI-CHOLINESTERASE) access of acetylcholine to enzyme's active site. It is
(1) Reversible short lived (2-10 minutes).
(a) Quaternary Alcohols (2) Carbamate Esters, eg Neostigmine
Edrophonium. Bind to enzyme's active site  Form covalent
(b) Carbamate Esters carbamoylated enzyme. It is more resistant (lasting 30
Neostigmine, Physostigmine, Pyridostigmine, min. to 6 hours).
Rivastigmine, Ambenonium, Demecarium, (3) Organophosfates, eg Echothiofate
Galantamine, Tacrine, Donepezil. Bind to enzyme's active site  Result in covalent
(2) Irreversible phosphorylated active site (extremely stable)  Further
Organophosfate compounds strengthening of phosphorus-enzyme bond by aging
Echothiofate, lsoflurofate, Paraoxon, Parathion process, in which one of the oxygen- phosphorus
(converted to active form paraoxon), Malaoxon bonds of inhibitor is broken.
Malathion, Soman.
PHARMACOLOGICAL EFFECTS OF PARASYM-
DRUGS POTENTIATING ACETYLCHOLINE
PATHOMIMETICS
Metoclopramide (see chapter 14, unit II ).

DIRECT ACTING PARASYMPATHOMIMETICS

MECHANISM OF ACTION OF PARASYMPATHO-
(A) Eye
MIMETICS
(1) Contraction of smooth muscle of iris sphincter 
Miosis (pupillary constriction).
DIRECT ACTING PARASYMPATHOMIMETICS (2) Contraction of ciliary muscle  Accommodation
(1) Muscarinic Cholinoceptors of lens for near vision.
It involves G proteins coupled mechanisms similar to (3) Both effects facilitate outflow of aqueous humor
that of adrenoceptors (see unit II, chapter 2), that result
into canal of Schlemm  Dec. intraocular pressure.
in various 2nd messenger effects (see box 3.1) which
(B) Cardiovascular System
causes final cellular effects.
(1) Blood vessels & BP
(a) Activation of IP3, DAG cascade  DAG open Vasodilation via release of endothelium-derived
smooth muscle Ca++ channels, & IP3 evokes Ca++ relaxing factor (EDRF)  Reduction in peripheral
release from endoplasmic & sarcoplasmic reticulum. vascular resistance  Dec. BP, often accompanied
(b) Increase in intracellular cGMP. by a reflex (sympathetic) tachycardia.
(c) Increase in K+ flux across cell memb. (2) Heart
(d) Inhibition of adenyl cyclase. (a) Dec. pacemaker rate (negative chronotropism).
(2) Nicotinic Cholinoceptors (b) Dec. atrial contractility (negative inotropism).
(a) Depolarization Note: Ventricular contractility dec. to a small
Nicotinic agonists acts on nicotinic cholinoceptors extent.
 Conformational change in protein ( channel (c) Dec. atrial refractory period, & inc. AV nodal
opening)  Na+ & K+ ions diffuse rapidly down their refractory period.
conc. gradients  Depolarization of nerve cell or (d) Dec. conduction velocity in AV node (negative
neuromuscular endplate  Nerve cell excitation or dromotropism).
muscle contraction. Cardiac Effects Results From
(b) Depolarizing Blockade (a) Inc. K+ flux in atrial, pacemaker, & AV nodal
Prolonged agonist occupancy of nicotinic cells.
cholinoceptors prevents electrical recovery of (b) Dec. slow inward Ca++ current in heart cells.
postjunctional memb.  Postganglionic (c) Dec. hyperpolarization-activated current that
neurons stops firing & skeletal muscle cells underlies diastolic depolarization.
relaxes Depolarizing Blockade. Reflex Modification
Direct slowing of pacemakers rate & AV conduc-
INDIRECT ACTING PARASYMPATHOMIMETICS tion is often opposed by reflex sympathetic dis-
Acts by inhibiting acetylcholinesterase (& also charge, elicited by dec BP. Therefore, net cardiac
pseudocholinesterase), & there by increasing conc. of effects depends on local conc. of agonist in heart &
endogenous acetylcholine in the vicinity of cholinoceptors. in vessels & on the level of reflex responsiveness.
However, their interaction with enzymes varies, according to (C) Respiratory Tract
the chemical subgroups. (1) Contraction of bronchial smooth muscle.
(2) Stimulation of glands of tracheobronchial mucosa.
03: Parasympathetic Nervous System Drugs 27

(D) Gastrointestinal Tract (b) Activation of parasympathetic ganglia tend to

(1) Inc. secretions of salivary, gastric, pancreatic & dec. vascular resistance & BP.
small intestinal glands. (2) Heart
(2) Inc. peristalsis thru-out the gut (due to Parasympathetic effect predominate ;
depolarization of smooth muscle cell memb. & inc. (a) Dec. heart rate.
Ca++ influx). (b) Dec. AV conduction velocity.
(3) Relaxation of sphincters. (c) Dec. atrial contractility.
(E) Genitourinary Tract (d) Dec. cardiac output.
(1) Contraction of detrusor muscle. (3) Net CVS Effects
(2) Relaxation of trigone & sphincter muscles. (a) Moderate doses  Modest bradycardia, dec.
(3) Both effects promote voiding of urine. cardiac output, & no change or modest fall in
(F) Miscellaneous Secretory glands BP.
Inc. secretions of sweat, lacrimal & nasopharyngeal (b) Large (toxic) doses  More marked brady-
glands. cardia & hypotension.
(G) Central Nervous System (C) Resp. , Gastrointestinal, & Urinary Tracts
There is usually stimulation followed by depression, Similar to direct-acting.
but variation b/w drugs is great, eg: (D) Central Nervous System
(1) Nicotine causes; (1) Low conc. causes;
(a) Mild alerting action. (a) Diffuse activation of EEG.
(b) Tremor, emesis & respiratory centre (b) Subjective alerting response.
stimulation (at higher doses). (2) Higher conc. causes;
(c) Convulsion & coma (at more higher doses). (a) Generalized convulsions.
(2) DMPP is relatively free of CNS effects b/c it (b) Coma.
doesn't cross the blood-brain barrier. (c) Respiratory arrest.
(H) Peripheral Nervous System (E) Peripheral Nervous System
Nicotinic agonist causes marked activation of Similar to direct-acting.
autonomic ganglia Simultaneous discharge of both (F) Neuromuscular Junction
sympathetic & parasympathetic nervous system : (1) At Low ( Therapeutic) Conc.
(1) In CVS, effects are sympathomimetic; Inc. strength of muscle contraction, esp. in muscle
(a) Hypertension weakened by curare-like neuromuscular blockers
(b) Sympathetic tachycardia, alternating with or by myasthenia gravis.
vagally mediated bradycardia. (2) At Higher Conc.
(2) In GIT & urinary tract, effect are (a) Fibrillation of muscle fibres.
parasympathomimetic; (b) Depolarizing blockade
(a) Nausea Note: Neostigmine have an additional direct nicotinic
(b) Vomiting agonist effect at neuromuscular junction.
(c) Diarrhea
(d) Voiding of urine
CLINICAL USES OF PARASYMPATHOMIMETICS
(I) Neuromuscular Junction
Nicotinic cholinoceptor stimulation causes :
(1) Immediate depolarization of endplate (due to inc. DIRECT - ACTING PARASYMPATHOMIMETICS
Na+ & K+ flux)  Disorganized fasciculation to (A) Acetylcholine
strong muscular contraction, depending on No clinical use.
synchronization of endplate depolarization. (B) Methacholine & Carbachol
(2) Continued presence of nicotinic agonists results in (1) Chronic glaucoma
depolarization blockade  Flaccid paralysis. (2) Accommodative esotropia
(3) As a miotic agent (carbachol).
INDIRECT ACTING PARASYMPATHOMIMETICS (C) Bethanechol
(A) Eye (1) Postoperative ileus
Similar to direct acting. (2) Congenital megacolon
(B) Cardiovascular System (3) Reflux esophagitis (to inc. tone of lower
(1) Blood vessels & BP esophageal sphincter).
Effects are less marked than direct-acting agonists (4) Urinary retention.
&, it also depends on the balance of sympathetic & (D) Pilocarpine
parasympathetic nervous system. (1) Chronic glaucoma.
(a) Activation of sympathetic ganglia tend to inc. (2) Acute angle-closure glaucoma (in combination
vascular resistance & BP. with physostigmine).
(E) Cevimeline
M. Shamim’s PHARMACOLOGY 28

Dry mouth associated with Sjögren's syndrome. (c) Skeletal muscle endplate: Depolarization blockade,
(F) Varenicline respiratory paralysis.
Smoking cessation. Treatment
(a) Atropine.
INDIRECT - ACTING PARASYMPATHOMIMETICS (b) Anticonvulsants eg diazepam.
(A) Edrophonium (c) Mechanical respiration.
(1) Diagnosis of myasthenia gravis. (2) Chronic Nicotinic Toxicity
(2) Assessment of treatment adequacy in myasthenia Caused by chronic tobacco smoking.
gravis. (a) CVS : Inc. risk of vascular disease & sudden
(3) Antagonism of non-depolarizing neuromuscular coronary death.
blockers. (b) GIT : High incidence of peptic ulcer recurrence.
(B) Neostigmine
(1) Myasthenia gravis. INDIRECT - ACTING PARASYMPATHOMIMETICS
(2) Antagonism of non-depolarizing neuromuscular (1) Acute Toxicity
blockers. Usually caused by pesticides used in agriculture & in
(3) Postoperative ileus. home:
(4) Congenital megacolon. (a) CNS : Anxiety, headache, convulsions, respiratory
(5) Reflux esophagitis. arrest.
(6) Urinary retention. (b) Eye : Miosis.
(C) Physostigmine (c) CVS : Bradycardia.
(1) Chronic glaucoma. (d) Resp Tract: Broncho-constriction, inc. bronchial
(2) Acute angle-closure glaucoma (in combination with secretion.
pilocarpine). (e) GIT : Salivation, vomiting, diarrhea.
(3) Intoxication of atropine, tricyclic antidepressants, & (f) Skeletal system: Weakness, twitching,
phenothiazine. depolarization blockade.
(D) Pyridostigmine (g) Skin : Sweating.
(1) Myasthenia gravis. Treatment
(2) Paralytic ileus. (a) Maintenance of vital signs esp. respiration.
(E) Ambenonium (b) Decontamination to prevent further absorption.
Myasthenia gravis. (c) Atropine parenterally in large doses.
(F) Demecarium, Isoflurofate & Echothiofate (d) Pralidoxime
Chronic glaucoma. (2) Chronic Toxicity
(G) Galantamine, Rivastigmine, Donepezil & Neuropathy associated with demyelination of axons.
Tacrine
mild to moderate Vascular Dementia and Alzheimer’s.
CONTRAINDICATIONS OF PARASYMPATHO-
MIMETICS
ADVERSE EFFECTS OF PARASYMPATHO-
MIMETICS
DIRECT-ACTING PARASYMPATHOMIMETICS
(1) Coronary insufficiency
DIRECT - ACTING MUSCARINIC AGONISTS (2) Hyperthyroidism
(1) CVS : Cutaneous vasodilation. (3) Asthma
(2) Resp. Tract : Bronchial constriction. (4) Peptic ulcer
(3) GIT : Nausea, vomiting, diarrhea, salivation.
(4) Skin : Sweating.
DOSAGE OF PARASYMPATHOMIMETIC
Mushroom Poisoning
(1) Caused by : Ingestion of mushrooms of genus Inocybe,
that contain muscarinic alkaloids. DIRECT-ACTING PARASYMPATHOMIMETICS
(2) Results in : Typical adverse effects (see above). (A) Methacholine
Treatment (1) 10 - 25 mg, SC.
Atropine 1-2 mg, parenterally. (2) 200 - 500 mg, orally.
(B) Carbachol
DIRECT - ACTING NICOTINIC AGONISTS (1) 0.25 - 0.5 mg, SC.
(1) Acute Nicotinic Toxicity (2) 0.5 - 1 mg, orally.
(a) CNS : Convulsions, coma, respiratory arrest. (C) Bethanechol
(b) CVS : Hypertension, cardiac arrhythmias. (1) 5 mg SC; repeated in 30 minutes, if necessary.
(2) 10 - 25 mg orally, TDS or QID.
03: Parasympathetic Nervous System Drugs 29

(D) Pilocarpine Flavoxate.

1, 2, or 4% eye drops ; 2 drops TDS.
ANTI- NICOTINIC DRUGS
INDIRECT-ACTING PARASYMPATHOMIMETICS (1) Ganglion Blockers
(A) Neostigmine (a) Depolarizers
(1) Oral  15 - 30 mg TDS; in myasthenia gravis Nicotine.
75 - 300 mg in divided doses 2-4 hourly. (b) Competitive
(2) Parenteral (SC or IM)  0.5 - 2.5 mg as required. (i) Secondary Amines
(B) Physostigmine Mecamylamine.
0.5 - 1% eye drops or ointment. (ii) Tertiary Amines
(C) Pyridostigmine Pempidine.
300 - 1200 mg orally, in 3-4 divided doses. (iii) Quaternary Amines
Hexamethonium, Trimethaphan.
(2) Neuromuscular Blockers
GENERIC & TRADE NAMES
(a) Depolarizers
Suxamethonium (Succinylcholine), Decametho-
(A) Direct-Acting nium.
Pilocarpine: Medicarpine, Orbacarpine, Pilocar. (b) Competitive
(B) Indirect-Acting Tubocurarine, Atracurium, Cisatracurium, Doxacu-
Neostigmine: Neostigmine, Prostigmin, Stigma. rium, Mivacurium, Metocurine, Pancuronium,
Tacrine: Congnex. Rocuronium, Vecuronium, Gallamine.

CHOLINESTERASE REGENERATORS
Unit III Pralidoxime, Diacetylmonoxime.

Parasympatholytics ANTI - MUSCARINIC DRUGS

[Cholinoceptor- Blocking Drugs, Parasympathetic MECHANISM OF ACTION

Antagonists, or Cholinoceptor Antagonists] Anti-muscarinic drugs causes reversible blockade of the
actions of parasympathomimetics at muscarinic
cholinoceptors, via competition for a common binding site.
CLASSIFICATION OF PARASYMPATHOLYTICS Selectivity
Atropine does not distinguish b/w different muscarinic
ANTI-MUSCARINIC DRUGS cholinoceptors; whereas, other antimuscarinic drugs may
(1) Natural Alkaloids have moderate selectivity (See Box 3.2).
Atropine, Scopolamine (Hyoscine), Hyoscyamine.
Box 3.2 SELECTIVITY OF ANTI-MUSCARINIC DRUGS
(2) Synthetic
(a) Mydriatic Muscarinic Primary Antagonists
Homatropine, Tropicamide, Cyclopentolate. Cholinoceptors Location
(b) Anti-Parkinsonism M1 Nerves Pirenzepine,
Tertiary Amines Telenzepine,
Benztropine. Dicyclomine,
(c) Anti-Asthmatics Trihexyphenidyl
Quaternary Amines
Ipratropium, Tiotropium. M2 Heart, nerves, Gallamine,
smooth muscles Methoctramine
(d) Gastrointestinal & Genitourinary
(i) Tertiary Amines M3 Glands, smooth Darifenacin,
Pirenzepine, Dicyclomine, Darifenacin, muscles, Solifenacin,
Oxyphencyclimine, Oxybutynin, Propiverine, endothelium Oxybutynin,
Solifenacin, Tolterodine. Tolterodine
(ii) Quaternary Amines
Propantheline, Glycopyrrolate, Isopropamide, PHARMACOLOGICAL EFFECTS
Mepenzolate, Clidinium, Anisotropine, (A) Central Nervous System
Tridihexethyl, Trospium, Methantheline, (1) At Therapeutic Doses
Methscopolamine, Oxyphenonium, (a) Stimulation of vagal nucleus that causes
(iii) Others bradycardia, which is later supplanted by
M. Shamim’s PHARMACOLOGY 30

tachycardia due to antimuscarinic effects at (G) Sweat Glands

SA node. (1) Suppression of thermoregulatory sweating.
(b) Slower, longer-lasting sedation. (2) Inc. body temperature (atropine fever in children).
(c) Drowsiness & amnesia (with scopolamine).
(d) Dec. tremors of Parkinsonism. CLINICAL USES
(e) Prevent vestibular disturbances esp. motion (A) Atropine
sickness. (1) As cycloplegic, for accurate measurement of
(2) At Toxic Doses refractive error.
(a) Excitement. (2) As mydriatic, to facilitate ophthalmoscopic
(b) Agitation. examination of retina.
(c) Hallucination. (3) As preoperative medication, to dec. upper & lower
(d) Coma. resp. tract secretions.
(B) Eye (4) In myocardial infarction, to treat SA node
(1) Paralysis of pupillary constrictor muscle  bradycardia or a high-grade A-V block.
Unopposed sympathetic dilator activity  (5) In hyperactive carotid sinus reflexes, to treat
Mydriasis (dilatation of pupil). faintness or syncope
(2) Paralysis of ciliary muscle, or cycloplegia  Loss of (6) As anti-diarrheal (combined with an opioid).
accommodation for near vision. (7) As anti-spasmodic to treat ureteric & biliary colic
(3) Above 2 effects may precipitate acute glaucoma in (combined with an opioid).
pts with narrow anterior chamber angle. (8) In minor inflammatory bladder disorders, to treat
(4) Dec. lacrimal secretion (dry & sandy eyes). urinary urgency.
(C) Cardiovascular System (9) In anti-cholinesterase poisoning, to reverse
(1) Heart muscarinic effects.
(a) Initial bradycardia due to central (10) In rapid-onset type mushroom poisoning, to
parasympathetic (vagal) stimulation. reverse muscarinic effects.
(b) Later, tachycardia due to anti-muscarinic (B) Scopolamine
effect at SA node. Similar to atropine; in addition, it is used in :
(c) Dec. PR interval due to anti-muscarinic effect (1) Prophylaxis of motion sickness
at AV node. (2) Anesthetic procedures esp. during childbirth, to
(d) Blockade of muscarinic effects on atrial muscle produce amnesia.
(of value only in atrial flutter & fibrillation). (C) Other Anti-Muscarinics
(2) Blood Vessels (1) Homatropine
(a) Blockade of skeletal muscle vasodilation (a) As cycloplegic
caused by sympathetic cholinergic nerves. (b) As mydriatic
(b) Blockade of vascular uninnervated muscarinic (c) In uveitis & iritis, to prevent synechia
cholinoceptors  Dec. EDRF release. (adhesion) formation.
(c) Cutaneous vasodilation esp. in blush area. (2) Tropicamide, & Cyclopentolate: As mydriatic &
(D) Respiratory Tract cycloplegic.
(1) Bronchodilation. (3) Benztropine, & Trihexyphenidyl: Parkinsonism.
(2) Dec. bronchial secretions. (4) Ipratropium, & Tiotropium: Asthma
(E) Gastrointestinal Tract (5) Pirenzepine: Peptic ulcer.
(1) Secretions (6) Flavoxate, Oxybutynin, Tolterotine, &
(a) Dec. salivary secretions  Dry mouth. Darifenacin: To reduce urgency, spasm, &
(b) Dec. gastric secretions esp. basal. incontinence.
(c) Pancreatic & intestinal secretions are less (7) Other tertiary & quaternary amines:
effected, b/c they are primarily under hormonal Gastrointestinal & genitourinary conditions (see
control. Atropine above).
(2) Wall & Motility
Relaxation of GIT wall  Dec. tone & propulsive ADVERSE EFFECTS
movements  Prolonged gastric emptying & (A) Atropine
intestinal transit times. (1) CNS: Restlessness, confusion, hallucinations,
(F) Genitourinary Tract delirium.
(1) Relaxation of smooth muscle of ureters & bladder (2) Eye: Mydriasis, blurred vision.
wall. (3) CVS: Tachycardia.
(2) Precipitate urinary retention in elderly men, esp. (4) GIT: Dry mouth.
with prostatic hypertrophy. (5) Skin: Hot & flushed skin.
(3) No significant effect on uterus. (6) Body Temp: Elevated esp. in children.
03: Parasympathetic Nervous System Drugs 31

Treatment (b) Tremor.

(1) Antidote  Physostigmine, 1-4 mg, slowly IV. (c) Choreiform movements.
(2) Temp control with cooling blankets. (d) Mental aberrations.
(3) Seizure control with diazepam. (B) Eye
(B) Scopolamine (1) Cycloplegia with loss of accommodation.
Similar to atropine. (2) Modest mydriasis.
(C) Quaternary Amines (C) Cardiovascular System
Similar to atropine, except ; (1) Dec. arteriolar tone  Dec. peripheral vascular
(1) CNS: Little or no effect. resistance.
(2) CVS: Orthostatic hypotension (due to ganglion (2) Dec. venomotor tone  Dec. venous return.
blockade). (3) Dec. BP due to above 2 effects, esp. marked in
upright position (orthostatic or postural hypo-
CONTRAINDICATIONS tension) b/c postural reflex that normally prevent
(1) Pts with glaucoma, esp. angle-closure glaucoma. venous pooling are blocked.
(2) Pts with prostatic hypertrophy. (D) Gastrointestinal Tract
(1) Dec. secretions.
DOSAGE (2) Markedly dec. motility.
(A) Atropine Sulfate (E) Genitourinary Tract
(1) Anti-cholinesterase & mushroom poisoning  1-2 (1) Hesitancy in urination  Precipitate urinary
mg, IV, every 5-15 minutes; upto a maximum of retention in men with prostatic hypertrophy.
1 gm/day for as long as one month. (2) Impaired erection & ejaculation.
(2) Other systemic use  0.4 mg, TDS or QID, orally or Clinical Uses
parenterally. (A) Trimethaphan
(3) Eye 1% eye drops; 1 drop TDS, or 1-2 drops (1) Hypertensive emergencies.
before examination. (2) For controlled hypotension during surgery, to
(B) Scopolamine reduce bleeding in operative field.
0.5-1 mg, TDS, orally or parenterally. (3) In acute pulmonary edema, to reduce pulmonary
(C) Others vascular pressure.
(4) Autonomic hyperreflexia.
(1) Dicyclomine  10-20 mg, QID.
(B) Mecamylamine
(2) Isopropamide  5 mg, BD.
Hypertension.
(3) Propantheline  15 mg, QID. Adverse Effects
(4) Homatropine  2% eye drops; 1 or more drops as Limited to the autonomic effects (described above).
required.
NEUROMUSCULAR BLOCKERS
ANTI-NICOTINIC DRUGS See chapter 7, Skeletal Muscle Relaxants.

NICOTINE CHOLINESTERASE REGENERATORS

See unit II, in association with parasympathomimetics.
Mechanism of Action
COMPETITIVE GANGLION BLOCKERS (1) Hydrolyze phosphorylated enzyme from organophos-
Examples phorus-cholinesterase complex, if the complex has not
Mecamylamine, Pempidine, Hexamethonium, Trimethaphan. aged.
Mechanism of Action (2) Most effective in regenerating cholinesterase asso-
Non-depolarizing competitive blockade of ganglia. ciated with skeletal muscle neuromuscular junction.
(A) Hexamethonium (3) Pralidoxime does not enter CNS; however,
Produces blockade by occupying sites in or on the ion diacetylmonoxime does enter CNS & can regenerate
channels that is controlled by nicotinic cholinoceptors, some of the CNS cholinesterase.
not by occupying the cholinoceptor itself. Clinical Uses
(B) Trimethaphan For the treatment organophosfate poisoning.
Block nicotinic cholinoceptors, not the channels. Dosage
Pharmacological Effects Pralidoxime 1 gm IV, repeated every 3-4 hours as needed or
(A) Central Nervous System preferably as a constant infusion 250-400 mg/hour.
(1) Hexamethonium & Trimethaphan
No effect.
(2) Mecamylamine GENERIC & TRADE NAMES
(a) Sedation.
M. Shamim’s PHARMACOLOGY 32

(A) Antimuscarinic Drugs (D) Pyridostigmine is used in early stages of

Atropine: Atrosol, Ethiatropine, Isopto atropine, Opta- Alzheimer's disease
atropine, Orbatropin, Lomotil*, Motilex*. (E) Acetylcholine is used as mydriatic in cataract
Scopolamine: Anapaz, Hyoscine, Buscopan*, surgery
Geospasmocin*, Hyscopan*, Spasler*, Spasmogin.......
Homatropine: Homatropine. (33) Typical symptoms of cholinesterase inhibitor toxicity
Tropicamide: Mydolate, Mydriacyl, Mydriaticum. include
Cyclopentolate: Cyclopen. (A) Anorexia, vomiting, diarrhea
Ipratropium: Ipratee, Optra. (B) Salivation, sweating
Pirenzepine: Gastrozepin. (C) Miosis
Dicyclomine: Blisscolic, Colenticon, Infacol*. (D) Paralysis of skeletal muscles
Oxybutynin: Butyn, Cystrin, Oxitrin. (E) Paralysis of accommodation
Tolterodine: Detrusitol. (34) Pilocarpine
Glycopyrrolate: Pyrolate. (A) Is used to dec. intraocular pressure in glaucoma
Isopropamide: Stelabid*. (B) Selectively binds to nicotinic receptors
(B) Anti- Nicotinic Drugs (C) Is not cleaved by acetylcholinesterase
Neuromuscular Blockers: See chapter 7. (D) Causes profuse sweating
(E) Is an alkaloid
(35) Ganglion blocking anti-nicotinic drugs include
Unit IV (A) Hexamethonium
(B) Tropicamide

Self-Assessment (T/F)
(C) Propantheline
(D) Mecamylamine
(E) Trimethaphan
(See answers on page no. 240) (36) Competitive neuromuscular blockers include
(29) Nicotinic receptor sites includes (A) Pempidine
(A) Parasympathetic ganglia. (B) Suxamethonium
(B) Sympathetic ganglia. (C) Tubocurarine
(C) Skeletal muscle. (D) Gallamine
(D) Excitatory receptors on Renshaw cells in spinal (E) Atracurium
cord. (37) Atropine overdosage may cause
(E) Bronchial smooth muscle. (A) Disorientation
(B) Relaxation of gastrointestinal smooth muscle
(30) Following are both muscarinic & nicotinic (C) Decrease in gastric secretion
receptor stimulants
(D) Pupillary constriction
(A) Acetylcholine. (E) Tachycardia
(B) Lobeline.
(C) Methacholine. (38) Which one of the following drugs most closely
resembles atropine in its pharmacological actions
(D) Carbachol.
(A) Scopolamine
(E) Bethanechol. (B) Trimethaphan
(31) In the treatment of myasthenia gravis, best agent for (C) Physostigmine
distinguishing b/w myasthenic crisis (D) Acetylcholine
(insufficient therapy) & cholinergic crisis (E) Carbachol
(excessive therapy) is (39) Atropine is clinically used in
(A) Atropine. (A) Anti-cholinesterase poisoning
(B) Physostigmine. (B) Prophylaxis of motion sickness
(C) Echothiofate. (C) Glaucoma
(D) Pralidoxime. (D) High-grade AV block
(E) Edrophonium. (E) Asthma
(32) Regarding clinical uses of parasympatho- mimetics,
following are correct
(A) Methacholine & carbachol are used in glaucoma
(B) Edrophonium is used in the treatment of
myasthenia gravis
(C) Neostigmine is used in paralytic ileus
M. Shamim’s PHARMACOLOGY 33

04 OPHTHALMOLOGICAL DRUGS

Epinephrine, Norepinephrine, Ephedrine, Phenylephrine.

Unit I (B) Parasympatholytics
Atropine, Scopolamine (Hyoscine), Homatropine,
Tropicamide, Cyclopentolate.
Ophthalmological Drugs (C) Centrally Acting Drugs
Cocaine, Pethidine, Chloroform, Thiopentone.

MIOTICS ANTI-GLAUCOMA DRUGS

It refers to drugs that produce constriction of pupil. GLAUCOMA

It refers to a disease characterized by increased intraocular
DRUG CLASSIFICATION pressure.
(A) Parasympathomimetics Types
(1) Direct Acting (1) Primary
Acetylcholine, Bethanechol, Carbachol, Pilocarpine. (a) Angle closure glaucoma.
(2) Anti- Cholinesterases (b) Open angle glaucoma.
(a) Reversible (2) Secondary
Neostigmine, Physostigmine, Demecarium. eg, glaucoma caused by surgical procedures.
(b) Irreversible
Diisopropyl fluorophosfate, Echothiofate. CLASSIFICATION OF ANTI - GLAUCOMA DRUGS
(B) Sympatholytics (A) Drugs used in Angle Closure Glaucoma
(1) Alpha - Adrenoceptor Blockers Pilocarpine, Physostigmine, Acetazolamide, Mannitol.
Tolazoline, Phentolamine. (B) Drugs used in Open Angle, & Secondary
(2) Adrenergic Neuron Blockers glaucoma
Guanethidine, Reserpine. (1) Parasympathomimetics
(C) Centrally Acting Drugs Pilocarpine, Carbachol, Demecarium, Physo-
Morphine, Codeine. stigmine, Echothiofate.
(2) Sympathomimetics
CLINICAL USES (a) Unselective
(1) Glaucoma. Epinephrine, Dipivefrin.
(2) To counteract effect of mydriatic cycloplegic drugs, (b) Alpha-2 selective
eg homatropine. Apraclonidine, Brimonidine.
(3) In alternation with mydriatics to break adhesions (3) Beta - Adrenoceptor Blockers
between iris &lens. Timolol, Betaxolol, Carteolol, Levobunolol,
Metipranolol.
(4) Diuretics
MYDRIATICS Dorzolamide, Brinzolamide, Acetazolamide,
Dichlorphenamide, Methazolamide.
It refers to drugs that produce dilatation of pupil by; (5) Prostaglandins
(1) Stimulation of dilator pupillae muscle (active mydriasis). Latanoprost, Bimatoprost, Travoprost, Unoprostone.
(2) Paralysis of sphincter pupillae muscle (passive
mydriasis). DRUGS THAT PRECIPITATE GLAUCOMA
(1) Atropine.
DRUG CLASSIFICATION (2) Amyl nitrate.
(A) Sympathomimetics (3) Histamine.
Alpha-adrenoceptor agonists, eg; Note: These drugs are "contraindicated" in glaucoma.
M. Shamim’s PHARMACOLOGY 34

ANTI - INFECTIVES
Self-Assessment (T/F)
DRUG CLASSIFICATION (See answer on page no. 240)
(A) Antibiotics (40) Which one of the following drugs does not
(1) Quinolones (topically) Ciprofloxacin, produce miosis
Gatifloxacin, Levofloxacin, Moxifloxacin, (A) Carbachol.
Ofloxacin. (B) Isoflurofate.
(2) Tetracyclines Gentamicin, Tobramycin. (C) Atropine.
(3) Chloramphenicol (D) Pilocarpine.
(4) Erythromycin (E) Neostigmine.
(5) Sulfonamides
(41) Which of the following dilates pupil & dec. intra-
(a) Systemically  Sulfadiazine, Sulfamethoxy- ocular pressure
pyridazine. (A) Atropine.
(b) Topically  Sulfacetamide. (B) Timolol.
(6) Bacitracin zinc (C) Pilocarpine.
(7) Polymyxin B (D) Phenylephrine.
(B) Antivirals (E) Tolazoline.
(1) Topical  Trifluridine, Vidarabine.
(42) In human eye, Echothiofate can cause
(2) Oral  Acyclovir, Valacyclovir, Famciclovir.
(A) Miosis.
(3) Intravenous  Acyclovir, Foscarnet, Ganciclovir. (B) Ciliary spasm.
(4) Intravitreal  Cidofovir, Foscarnet, Ganciclovir. (C) Reversal of cycloplegic action of atropine.
(C) Antifungals (D) Dec. incidence of cataract.
Amphotericin B, Miconazole. (E) Dec. intraocular pressure.
(D) Others
(1) Boric acid. (43) All of the following may cause cycloplegia, when
(2) Zinc sulfate. used topically in eye
(3) Silver nitrate. (A) Atropine.
(4) Mercuric oxycyanide. (B) Physostigmine.
(C) Tropicamide.
(D) Cyclopentolate.
DRUGS TOXIC TO EYE (E) Scopolamine.
(44) Following drugs may be used in glaucoma
DRUG CLASSIFICATION (A) Carbachol.
(A) Conjunctival Irritants (B) Bethanechol.
(1) Ethylmorphine. (C) Phenylephrine.
(2) Chloroacetophenone (Tear gas). (D) Physostigmine.
(B) Special Drugs (E) Isoflurofate.
(1) Methyl Alcohol
Has toxic effects on optic nerve, & retina.
(2) Cardiac Glycosides
Causes visual disturbances.
(3) Oxygen in High Conc.
Causes retrolental fibroplasia.
(4) Chloroquine
Causes retinopathy.
(5) Corticosteroids
Causes cataract.

Unit II
M. Shamim’s PHARMACOLOGY 35

05 CENTRAL NERVOUS SYSTEM

DRUGS
Bromazepam, Chlordiazepoxide, Clorazepate,
Unit I Clonazepam, Clobazam, Diazepam, Desmethyl-
diazepam, Flurazepam, Halazepam, Ketazolam,
Nitrazepam, Prazepam, Quazepam.
Sedative - Hypnotics (2) Intermediate Acting Benzodiazepines
Elimination half-life (t ½)  Upto 30 hrs., eg;
Alprazolam, Estazolam, Flunitrazepam, Lorazepam,
INTRODUCTION Oxazepam, Temazepam.
(3) Short Acting Benzodiazepines
Sedative (Anxiolytic) Elimination half-life (t ½)  Upto 8 hrs., eg;
It refers to a drug that reduces anxiety & exerts a calming Midazolam, Triazolam.
effect, with little or no effect on motor or mental functions. (B) Barbiturates
Hypnotic (1) Long Acting Barbiturates
It refers to a drug that produces drowsiness, & encourages Duration of Action  Greater than 6 hrs., eg;
the onset & maintenance of a state of sleep that as far as Barbital, Phenobarbital, Mephobarbital.
possible resemble the natural sleep state. (2) Intermediate Acting Barbiturates
Insomnia Duration of Action  3 to 5 hrs., eg;
Belief or feeling on the part of pts. that they are not Amobarbital (Amylobarbital), Aprobarbital,
getting enough sleep, is referred as insomnia. Its complaints Butabarbital, Cyclobarbital, Talbutal.
include difficulty in falling asleep, frequent awakenings, (3) Short Acting Barbiturates
short duration of sleep, & unrefreshing sleep. Duration of Action  About 2 hrs., eg;
Sleep Pentobarbital, Hexobarbital, Secobarbital
It is an active, circadian, physiological depression of (Quinalbarbital).
consciousness characterized by cyclical EEG & eye (4) Ultra Short Acting Barbiturates
movement changes. Duration of Action  30 min. eg;
Types Thiopental, Methohexital, Thiamylal.
Two, occurring cyclically over an interval of about 90 min.; (C) Miscellaneous
(1) NREM (Non-Rapid Eye Movement) Sleep (1) Chlorinated Compounds
It progresses thru 4 stages (1-4), with 50% of sleep Chloral hydrate, Ethchlorvynol, Trichloroethanol.
being spent in stage 2. This is followed by delta or (2) Heterocyclic Compounds
slow-wave sleep (stages 3 & 4), in which Glutethimide, Methyprylon, Methaqualone.
somnambulism & night terrors occur. Heart rate, BP, & (3) Aldehyde Group
respiration are steady or decline, muscles are relaxed & Paraldehyde.
growth hormone secretion is maximal. (4) Alcohol
(2) REM (Rapid Eye Movement) Sleep Ethyl Alcohol.
In this stage most recallable dreams occur. Heart rate, (5) Propanediol Carbamate
BP & respiration are fluctuant, cerebral blood flow Meprobamate.
inc., penis is erect (unless there is dream anxiety), & (6) Anti-histamines
skeletal muscles are relaxed. Hydroxyzine, Promethazine.
(7) Newer Anxiolytics
(a) Piperazinyl pyrimidine derivative eg Buspirone.
DRUG CLASSIFICATION (b) Imidazopyridine derivative, eg Zolpidem.
(c) Pyrazolopyrimidines, eg Zaleplon.
(A) Benzodiazepines (d) Cyclopyrrolones, eg Eszopiclon.
(1) Long Acting Benzodiazepines (e) Melatonin receptor agonist, eg Ramelteon.
Elimination half-life (t ½)  Upto 100 hrs., eg;
M. Shamim’s PHARMACOLOGY 36

BENZODIAZEPINES (3) At toxic levels, myocardial contractility & vascular

tone is dec. both by central & peripheral effects 
Circulatory collapse.
BENZODIAZEPINE RECEPTORS (C) Respiration
High-affinity receptor sites for benzodiazepines are located (1) Upto hypnotic doses, no significant effects in
at GABA-ergic synapses, & are functionally coupled to healthy individuals.
GABA- responsive chloride channels but are separate (2) In pts. with obstructive pulmonary disease, even
macromolecules from either GABA receptors or chloride normal dose can cause profound respiratory
channels. depression.
Benzodiazepine Receptor Ligands (3) At toxic levels, depression of medullary respira-
(1) Classic Agonists tory center may occur causing death.
These are clinically useful benzodiazepines which (D) Skeletal Muscle
causes anxiolytic, hypnotic, & antiepileptic effects. Relaxation occurs due to inhibitory effect on
(2) Antagonists polysynaptic reflexes, & internuncial transmission. High
eg Imidazodiazepine, Flumazenil. They block the action doses may depress transmission at skeletal myoneural
of benzodiazepines. junction.
(3) Inverse agonists
eg  - carbolines. They block the effects of classic CLINICAL USES
agonists, & when administered alone produce anxiety, (1) Anxiety.
& seizures. (2) Hypnosis.
(3) For sedation & amnesia before medical & surgical
MECHANISM OF ACTION procedures.
Benzodiazepines enhances inc. chloride ion conductance (4) Epileptic disorders.
induced by interaction of GABA with its receptors, due to (5) Anesthetic premedication.
inc. frequency of Cl- channel opening. This effect occur at (6) For control of ethanol or other sedative-hypnotic
postsynaptic receptors at all level of neuroaxis, including withdrawal states.
cerebral cortex, cerebellar cortex, substantia nigra, (7) For skeletal muscle relaxation in specific neuromuscular
hypothalamus, hippocampus, & spinal cord. disorders.
(8) Night terrors.
PHARMACOLOGICAL EFFECTS (9) As diagnostic aids or for treatment in psychiatry.
(A) Central Nervous System
(1) Sedation ADVERSE EFFECTS
Responsiveness to a constant level of stimulation (1) CNS
is dec., with dec. in spontaneous activity & (a) Ataxia, drowsiness, sedation, impaired judgement,
ideation. diminished motor skills, lethargy.
(2) Hypnosis (b) Paradoxically inc. anxiety including psychosis
(a) Latency of sleep onset is dec. esp. with high doses.
(b) Duration of stage 2 NREM sleep is inc. (2) CVS
(c) Duration of REM sleep is dec. Myocardial depression.
(d) Duration of slow-wave sleep is dec. (3) Respiration
(e) Withdrawal after continued use results in a Respiratory depression.
"rebound" inc. in the frequency of occurrence (4) Hypersensitivity Reactions
& duration of REM sleep. Skin rashes.
(3) Anticonvulsant Effects (5) Withdrawal Syndromes
Inhibits the development & spread of epileptiform Withdrawal of the drug after continued use results in;
activity in the CNS. Anxiety, restlessness, weakness, hyperreactive reflexes,
(4) Anesthesia & generalized seizures.
In large dose, may causes anesthesia due to CNS
depression. CONTRAINDICATIONS
(B) Cardiovascular System (1) Previously known hypersensitivity reactions.
(1) Upto hypnotic doses, no significant effect in (2) Psychoses.
healthy individuals. (3) Acute narrow angle glaucoma.
(2) In hypovolemic states, congestive cardiac failure or
other diseases impairing cardiovascular function, DOSAGE
normal doses may cause CVS depression due to (1) For Sedation
actions on medullary vasomotor centres.
(a) Diazepam  5 mg twice daily.
(b) Lorazepam  1-2 mg once or twice daily.
05: Central Nervous System Drugs 37

(c) Alprazolam  0.25 - 0.5 mg 2-3 times daily. (a) Anesthetic doses lead to depression of smooth
(2) For Hypnosis muscle of uterus, ureter, & urinary bladder.
(a) Diazepam  1-5 mg at bed - time. (b) Barbiturates pass thru placental barrier, & may
(b) Lorazepam  2-5 mg at bed - time. depress respiratory centre of the newborn.
(c) Triazolam  0.5 - 1 mg at bed - time. (9) Blood
Barbiturate-induced porphyria can occur.
WHY BENZODIAZEPINES PREFERRED AS
SEDATIVE - HYPNOTICS ? CLINICAL USES
Because of (1) Anxiety.
(1) Relatively high therapeutic index. (2) Hypnosis.
(2) Low risk of drug interactions based on enzyme (3) Convulsions.
induction. (4) As IV adjuncts to surgical anesthetics (ultra-short
(3) Slow elimination rates, which may favor persistence of acting barbiturates).
useful CNS effects. (5) Cerebral edema due to surgery or trauma.
(4) Low risk of physical dependence with minor withdrawal (6) During cerebral ischemia to protect cerebral infarction.
symptoms. (7) Hyperbilirubinemia & kernicterus in the neonate (due
to the ability of barbiturates to stimulate hepatic
glucuronyl transferase).
BARBITURATES
ADVERSE EFFECTS
MECHANISM OF ACTIONS (1) CNS
(1) It either have a GABA-like action or enhance the effects Oversedation, dec. in REM sleep.
of GABA ( inhibitory neurotransmitter); by inhibiting (2) Blood
the neuronal uptake system for GABA or by stimu- Porphyria.
lating the release of GABA or by binding directly to the (3) Skin
receptors at GABA -ergic synapses. Skin eruptions.
(2) It also depresses the actions of excitatory neuro- (4) Withdrawal Symptoms
transmitters. Grand mal seizures, tremors, vivid hallucinations,
psychoses.
PHARMACOLOGICAL EFFECTS (5) Acute Barbiturate Overdosage
(1) Central Nervous System Results in;
Similar to benzodiazepines. Coma, dec. reflexes (although deep tendon reflexes are
(2) Cardiovascular System intact), severe respiratory depression, circulatory
(a) At sedative doses, no significant effect. collapse, & renal failure.
(b) As the dose is inc., depressed ganglionic Treatment
transmission results in dec. BP & heart rate. (a) Support respiration & circulation.
(c) Toxic doses cause circulatory collapse due to (b) Alkalinize urine & promote diuresis, to inc.
medullary vasomotor centre depression. elimination of drug.
(3) Respiration (c) Hemodialysis or peritoneal dialysis.
(a) Potent respiratory centre depression, directly.
(b) Dec. sensitivity of respiratory center to CO2. CONTRAINDICATIONS
(4) Skeletal Muscle (1) Acute intermittent porphyria, variegate porphyria,
Large doses have a mild curare - like effect. hereditary coproporphyria, symptomatic porphyria.
(5) Gastrointestinal Tract (2) Respiratory obstruction, resp. depression, bronchial
Dec. tone & motility, either due to a direct action or to asthma.
an action on intrinsic nervous mechanisms. (3) Shock.
(6) Kidney (4) Advance liver disease.
Large doses lead to dec. urine formation due to (5) Advance kidney disease.
hypotension & release of ADH.
(7) Liver CHLORAL HYDRATE
Barbiturates, esp. phenobarbital, induces hepatic micro-
somal drug-metabolizing enzyme system. This results in;
(a) Inc. degradation of barbiturates leading to ACTIVE METABOLITE
barbiturate tolerance. In liver chloral hydrate is metabolized by alcohol dehydro-
(b) Inc. inactivation of anticoagulants, phenytoin, genase to active metabolite "Trichloroethanol" that
digitoxin, theophylline, & glucocorticoids. produces CNS effects.
(8) Uterus, Ureter, & Urinary Bladder
M. Shamim’s PHARMACOLOGY 38

PHARMACOLOGICAL EFFECTS (1) Relieves anxiety without causing marked sedative,

(1) Central Nervous System hypnotic, or euphoric effects.
It induces sleep in half an hour, lasting for about (2) No rebound anxiety or withdrawal signs on abrupt
6 hours, with relatively small reduction in REM sleep discontinuance.
& with little effect on respiration or BP. (3) Less psychomotor impairment than benzodiazepines, &
(2) Local Sites does not affect driving skills.
It is irritant to the skin & mucus memb. & is quite bad (4) No anticonvulsant or muscle relaxant effects.
tasting. Clinical Uses
Generalized anxiety states.
CLINICAL USES Adverse Effects
(1) As hypnotic for children & elderly. (1) CNS: Nervousness, paresthesias.
(2) Preanesthetic medication in the old where barbiturates (2) CVS: Tachycardia, palpitations.
are contraindicated. (3) GIT: Gastrointestinal distress.
Dosage
ADVERSE EFFECTS 5-10 mg, 2-3 times daily.
(1) CNS: Depressant effect leading to coma, respiratory
depression & hypotension. GENERIC & TRADE NAMES
Note  Alcohol potentiates the CNS depressant effects.
(2) Eye: Pinpoint Pupil. (1) Benzodiazepines
(3) GIT: Gastritis. Alprazolam: ALP, Alpram, Azolex, Nervin, Neuxam,
(4) Skin: Skin eruptions. Xanax, Zolarem.
Bromazepam: Anxit, Anxolite, Brexotanil, Broma,
PARALDEHYDE Calmease, Lexilium, Lexotanil, Rektonil, Relaxin,
Relaxitil, Sedonil.
Chlordiazepoxide: Elenium, Chlobrium.
Pharmacological Effects
Clobazam: Frisium.
(1) Central Nervous System
Clorazepate: Tranxene.
(a) Produces hypnosis in about 15 min., which lasts
Clonazepam: Clonatril, Klozepam, Rivotril.
4 to 8 hours.
Diazepam: Anglopam, Apaurin, Cerelium, Diazepam,
(b) Some anticonvulsant effect.
Neopam, Relax, Relaxipam, Valium.
(2) Gastrointestinal Tract
Estazolam: Esilgan.
Produces an irritant action.
Lorazepam: Ativan, Avor, Tenzil, Tranquil.
Clinical Uses
Midazolam: Dormicum, Hypozam.
It is useful for pts. with hepatic or renal disease, b/c it is
Nitrazepam: Mogadon.
mainly eliminated by the lung.
Prazepam: Verstran.
(1) Hypnosis.
Temazepam: Calm, Restoril.
(2) Tetanus.
Triazolam: Halcion.
(3) Eclampsia.
(2) Barbiturates
(4) Status epilepticus.
Phenobarbital: Fenton, Phenobarbitone, Phenotab*,
(5) For pts. undergoing withdrawal from alcohol.
Phenotone.
Adverse Effects
Thiopental: Pentothal sodium,Thiopentone.
(1) CNS: Depression (resemble that of alcohol, barbi-
(3) Miscellaneous
turates, & chloral hydrate).
Chloral Hydrate: Apnotek, Chloral Hydrate.
(2) GIT: Nausea, vomiting.
Meprobamate: Meprogesic*.
Contraindications
Hydroxyzine: Meditrax, Roxyzin.
(1) Pulmonary disease.
Promethazine: Metharex, Phenergan, Promazine,
(2) Peptic ulcer.
Promethazine.
Buspirone: Busron, Novatil.
BUSPIRONE Zolpidem: Slepzol, Zolp.

Mechanism of Action
It may exert its anxiolytic effects by acting as a partial Unit II
agonist at brain 5-HT1A receptors, but it also has affinity for

Alcohols (Ethanol)
brain D2 receptors.
Pharmacological Effects
Central Nervous System
05: Central Nervous System Drugs 39

METABOLISM (b) In cases of severe overdose, hypothermia due to

vasodilation is marked.
(c) It also relaxes uterus & has been given IV for
Over 90% of alcohol consumed is oxidized in liver, while suppression of premature labor.
the rest is excreted thru lungs & in urine. Typical adult can
metabolize 7-10 gm of alcohol per hour.
Alcohol Dehydrogenase Pathway CONSEQUENCES OF CHRONIC ETHANOL
It involves the enzyme "alcohol dehydrogenase" that CONSUMPTION
catalyzes conversion of alcohol to acetaldehyde.
C2H5OH + NAD+  CH3CHO + NADH + H+ (1) Central Nervous System
Note: Alcohol dehydrogenase is found only in liver. (a) Impairment of intellectual & motor functions,
Microsomal Ethanol Oxidizing System emotional liability, reduced perceptual acuity, &
It uses NADPH instead of NAD as cofactor; amnesia.
C2H5OH + NADPH + H+ + O2  CH3CHO + NADP+ + 2H2O (b) Generalized symmetric peripheral nerve injury, that
begins with distal paresthesias of the hands & feet.
At low alcohol conc. alcohol dehydrogenase is the main
oxidizing system, while at higher conc. & during chronic (c) Wernicke-Korsakoff Syndrome
alcohol consumption MEOS plays more significant role. It is associated with thiamine def. & is
characterized by paralysis of external eye muscles,
Acetaldehyde Metabolism
ataxia, altered mentation & amnesia (esp. for recent
(1) Over 90% of acetaldehyde formed from alcohol is
events).
also oxidized in liver.
(d) Withdrawal Symptoms on CNS
(2) Mitochondrial NAD-dependent aldehyde dehydro-
genase is involved in acetaldehyde oxidation. It consists of discomfort & hyperexcitability in
mild cases, & convulsions, toxic psychosis &
(3) Acetate is produced, that is metabolized to CO2 & water.
delirium tremens in severe ones.
(4) Chronic alcohol consumption results in dec. rate of (2) Cardiovascular System
acetaldehyde oxidation in intact mitochondria. (a) Direct injury to myocardium, due to contaminants
in alcoholic beverages or due to simultaneous
MECHANISM OF ACTION thiamine def.
(b) Arrhythmias may occur.
(c) Elevated blood pressure directly related to the
(1) Ethanol reduces the viscosity of (fluidizes) the memb.
amount of alcohol intake.
of many types of cells.
(d) Withdrawal symptoms on CVS consists of
(2) Fluidizing effect causes changes in specific memb.
arrhythmias, & syncope.
functions, including;
(3) Gastrointestinal Tract
(a) Neurotransmitter receptors for dopamine,
(a) Ethanol inc. gastric & pancreatic secretion, &
norepinephrine, glutamate, & opioids.
alters mucosal barriers that enhance the risk of
(b) Enzymes, eg Na+-K+-ATPase, Ca++ ATPase, 5-
gastritis & pancreatitis.
nucleotidase, acetylcholinesterase, & adenyl
(b) Acute gastrointestinal bleeding may result from
cyclase.
alcoholic gastritis.
(c) Mitochondrial electron transport chain.
(c) It also injures the small intestine, leading to
(d) Ion channels, eg Ca++ channels.
diarrhea, weight loss & multiple vitamin def.
(3) Acute ethanol exposure inc. the number of GABA-
(4) Liver
receptors.
(a) Inc. ratio of NADH to NAD leads to metabolic
abnormalities, including reduced gluconeogenesis,
CONSEQUENCES OF ACUTE ETHANOL ABUSE hypoglycemia, ketoacidosis & accumulation of
fat in liver parenchyma.
(1) Central Nervous System (b) Essential factors, eg glutathione is dec. in
It produces a state of drunkenness characterized by malnourished alcoholics.
sedation, relief of anxiety, slurred speech, ataxia, (c) Alcoholic fatty liver may progress to alcoholic
impaired judgment, & uninhibited behavior. hepatitis, & finally to cirrhosis.
(2) Heart (d) Hepatic failure may occur causing death.
Significant depression of myocardial contractility (at a (5) Endocrine System
blood conc. of 100 mg/dL). (a) Gynecomastia & testicular atrophy may occur in
(3) Smooth Muscle alcoholics with cirrhosis.
(a) Ethanol is a vasodilator as a result of both (b) Ascites, edema, & effusions may occur due to
vasomotor centre depression, & direct smooth disturbances in fluid & electrolyte balance.
muscle relaxation caused by acetaldehyde. (c) Ketosis occurs, & is caused by excessive lipolytic
factors esp. inc. cortisol & growth hormone.
M. Shamim’s PHARMACOLOGY 40

(d) Hypokalemia occurs due to secondary hyper- are preferred, eg chlordiazepoxide, clorazepate &
aldosteronism, & due to vomiting & diarrhea. diazepam.
(6) Blood Drugs To Treat Alcoholism
(a) Anemia due to folic acid def. (1) Naltrexone, an orally active opioid receptor antagonist
(b) Iron def. anemia due to gastrointestinal bleeding. that blocks the effects at  opioid receptors of
(c) Hypoplasma-proteinemia due to gastritis & GIT exogenous & endogenous opioids.
bleeding. (2) Acamprosate, a weak NMDA-receptor antagonist & a
(d) Abnormalities in platelets & leukocytes function. GABAA-receptor activator.
(7) Eye (3) Disulfiram, an inhibitor of aldehyde dehydorgenase.
(a) Ethanol impairs visual acuity with painless bilateral
blurring.
CLINICAL USES
(b) This may be followed by optic nerve degeneration.
(8) Fetal Alcohol Syndrome
Chronic maternal alcohol abuse during pregnancy (1) As skin disinfectant.
causes 'Fetal Alcohol Syndrome' characterized by; (2) Trigeminal neuralgia, to relieve pain.
(a) Retarded body growth.
INHIBITOR OF ALCOHOL DEHYDROGENASE
(b) Microencephaly.
(c) Underdevelopment of midfacial region. Fomepizole
(d) Poor coordination. It is a potent inhibitor of alcohol dehydrogenase, & is used
(e) Minor joint anomalies. as an antidote in methanol & ethylene glycol poisoning.
(f) Congenital heart defects & mental retardation in (3) As stomachics to improve appetite & digestion.
more severe cases. (4) As carminative to relieve flatulence.
(9) Increased Risk of Cancer (5) As antifoaming agent in acute pulmonary edema.
Chronic alcoholism inc. the risk for cancer of mouth, (6) For pyrexia.
pharynx, larynx, esophagus, liver, & breast. (7) For hypnosis.

ALCOHOL - DRUG INTERACTIONS

Unit III

These occur b/c of proliferation of smooth endoplasmic

reticulum of liver.
(1) Additive effect with other sedative - hypnotics.
Anti - Epileptic Drugs
(2) Potentiates the effects of vasodilators & oral hypo-
glycemic agents.
(3) Enhances the anti-platelet action of aspirin. INTRODUCTION

MANAGEMENT OF ALCOHOLISM EPILEPSY

It refers to a heterogeneous symptom complex characterized
Acute Ethanol Intoxication by recurrent seizures.
(1) To prevent severe respiratory depression.
(2) Aspiration of vomitus. SEIZURES
(3) To support cardiovascular system. It refers to finite episodes of brain dysfunction resulting
(4) Administration of glucose for hypoglycemia & ketosis. from abnormal discharge of cerebral neurons.
(5) Administration of electrolyte solutions in pts who are Classification of Seizures
dehydrated & vomiting. (A) Partial Seizures
(6) Administration of K for hypokalemia. Attack begins in a specific locus in brain, & the
(7) Administration of pyridoxine to accelerate the localized onset can be ascertained, clinically or by EEG.
metabolism of alcohol. (1) Simple Partial Seizures
It is characterized by minimal spread of abnormal
discharge such that normal consciousness &
Alcohol Withdrawal Syndrome awareness are preserved.
(1) Restoration of potassium, magnesium & phosphate For examples, the pt. have a sudden onset of clonic
balance. jerking of an extremity lasting 60 - 90 sec.,
(2) Thiamine therapy. followed by residual weakness lasting for 15 - 30
(3) Substituting a long-acting sedative-hypnotic drug for min. Pt. is completely aware of the attack & can
alcohol, & then gradually reducing it. Benzodiazepines describe it in detail.
(2) Complex Partial Seizures
05: Central Nervous System Drugs 41

(a) It also has a localized onset, but the discharge (6) Tonic Seizures
becomes more widespread (usually bilateral), Characterized by tonic rigidity of all extremities.
& almost always involves the limbic system. (7) Status Epilepticus
(b) Most of it arise from one of the temporal lobes It is a condition where grandmal epilepsies follow
b/c of inc. susceptibility of this area to hypoxia one after another without return of consciousness.
or infection, & so-called temporal lobe
epilepsy..
DRUG CLASSIFICATION
(c) Clinically, the pts. have a brief warning
followed by an alteration of consciousness
during which some pts. may even fall. They (A) Drugs Used In Partial Seizures & Generalized
demonstrate automatism, eg lip smacking, Tonic - Clonic Seizures
swallowing, fumbling, scratching or even (1) Hydantoins
walking about. After 30 - 120 sec., pts. make a Phenytoin, Mephenytoin, Fosphenytoin, Ethotoin,
gradual recovery to normal consciousness but Phenacemide.
may feel tired or ill for several hrs after (2) Iminostilbenes
attack. Carbamazepine.
(3) Secondarily Generalized Partial Seizures (3) Barbiturates
(a) Also called Jacksonian epilepsy. Phenobarbital, Mephobarbital, Metharbital,
(b) It includes those seizures in which a partial Primidone.
seizure immediately precedes a generalized (4) Benzodiazepines
tonic-clonic seizure. Diazepam, Lorazepam, Chlorazepate dipotassium,
(B) Generalized Seizures Clonazepam, Clobazepam, Nitrazepam.
It refers to seizures in which there is no evidence of (5) GABA Analog
localized onset. Gabapentin, Pregabalin.
(1) Generalized Tonic - Clonic Seizures (6) Piracetams
(a) Also called grand mal epilepsy. Levetiracetam.
(b) It is characterized by tonic rigidity of all (7) Others
extremities, followed in 15 - 30 sec. by a Oxcarbazepine, Vigabatrin, Lamotrigine, Felbamate,
tremor (relaxation phase). As the relaxation Tiagabine, Topiramate, Zonisamide.
phase becomes longer, the attack enters (B) Drugs Used In Generalized Seizures Other
clonic phase with massive jerking of body. Than Gen. Tonic-Clonic Seizures
Clonic jerking slows over 60 - 120 sec. & the (1) Succinimides
pt. is usually left in a stuporous state. Ethosuximide, Phensuximide, Methsuximide.
(c) Tongue or cheek may by bitten & urinary (2) Valproates
incontinence is common. Valproic acid, Na Valproate.
(2) Absence Seizures (3) Oxazolidinediones
(a) Also called petit mal epilepsy. Trimethadione, Paramethadione, Dimethadione.
(b) Characterized by both sudden onset, & abrupt (4) Benzodiazepines
cessation. Clonazepam, Nitrazepam, Clobazepam, Diazepam.
(c) Duration is usually less than 10 sec., & rarely (5) Sulfonamide Derivatives
more than 45 sec. Acetazolamide, Sulthiame.
(d) Consciousness is altered.
(e) Associated with mild clonic jerking of the PHENYTOIN
eyelids or extremities, with postural tone
changes, autonomic phenomenon &
automatism. MECHANISM OF ACTION
(3) Atonic Seizures (1) Phenytoin blocks posttetanic potentiation by raising
Characterized by sudden loss of postural tone, eg memb. potentials, & suppressing burst activity &
standing pt. falls to the floor & may be injured. repetitive firing, causing inhibition of development &
(4) Myoclonic Seizures spread of epileptiform discharges.
It consists of myoclonic jerkings, that occurs in a (2) At therapeutic conc., it suppresses repetitive action
variety of seizures including generalized tonic- potentials by blocking Na channels & dec. influx of Na.
clonic seizures, partial seizures, absence seizures (3) At high conc., it also inhibits the release of serotonin
& infantile spasms. & norepinephrine, promotes uptake of dopamine, &
(5) Infantile Spasms inhibits MAO activity.
Characterized by brief, recurrent myoclonic jerks (4) At high conc., it dec. GABA uptake & induce
of the body of infants with sudden flexion or proliferation of GABA receptors.
extension of body & limbs.
M. Shamim’s PHARMACOLOGY 42

(5) It also inhibit Ca influx across the cell memb., thereby (2) It also inhibits uptake & release of norepinephrine
inhibiting a variety of Ca- induced secretory processes. from brain synaptosomes.
Clinical Uses
CLINICAL USES (1) Partial seizures.
(1) Simple partial seizures. (2) Generalized tonic-clonic seizures.
(2) Complex partial seizures. (3) Trigeminal neuralgia.
(3) Secondarily generalized partial seizures. Adverse Effects
(4) Generalized tonic-clonic seizures. (1) CNS: Diplopia, ataxia, drowsiness.
(5) Ventricular arrhythmias, associated with digitalis (2) CVS: Congestive cardiac failure.
toxicity or acute myocardial infarction. (3) GIT: Mild gastrointestinal upset.
(4) Liver: Liver toxicity.
ADVERSE EFFECTS (5) Renal: Kidney toxicity.
(1) CNS: Ataxia, sedation, peripheral neuropathy (6) Blood: Aplastic anemia, agranulocytosis, leukopenia.
(manifested as dec. deep tendon reflexes in lower (7) Hypersensitivity reactions: Erythematous skin rash.
limbs), depression. Dosage
(2) Eye: Nystagmus, loss of smooth extraocular pursuit 1-2 gm.
movements, diplopia. Drug Interactions
(3) CVS: Circulatory collapse. (1) It induces hepatic microsomal drug-metabolizing
(4) GIT: Gingival hyperplasia, gastrointestinal irritation. enzyme system, causing dec. steady-state conc. of its
(5) Liver: Hepatitis. own & inc. metabolism of primidone, phenytoin,
(6) Endo: Hirsutism. ethosuximide, valproic acid & clonazepam.
(7) Blood: Blood dyscrasias. (2) Valproic acid inhibits its clearance & phenobarbital
(8) Hypersensitivity reactions: eg skin rash, fever, dec. its blood level.
lymphadenopathy, agranulocytosis, Stevens-Johnson (3) Phenytoin & phenobarbital dec. its steady-state conc.
synd., systemic lupus erythematosus. thru enzyme induction.
(9) Vitamins: Osteomalacia (b/c vit. D def.),
Megaloblastic anemia (b/c vit. B9 def). BARBITURATES

CONTRAINDICATIONS Phenobarbital
(1) Liver disease. Antiepileptic Mechanism of Action
(2) Absence seizures. (1) It markedly prolongs posttetanic potentiation &
(3) Epilepsy resulting from fever or barbiturate withdrawal. enhances pre-synaptic inhibition.
(2) It selectively suppresses abnormal neurons, inhibiting
DOSAGE spread & suppressing firing from loci.
Begin with 300 - mg/d orally. If seizures continues dosage (3) At therapeutic conc., it antagonizes glutamate excitation
inc. each time by 25 - 30 mg. while at the same time enhancing GABA inhibition.
Primidone
DRUG INTERACTIONS In the body it is converted to phenobarbital, but its
(1) B/c phenytoin is highly plasma protein bound, other mech. of action is more like that of phenytoin.
highly bound drugs eg phenylbutazone, sulfonamides,
benzodiazepines or anticoagulants, can displace ETHOSUXIMIDE
phenytoin from its binding sites causing an inc. free
drug level & intoxication.
(2) It induces microsomal enzymes responsible for Mechanism of Action
metabolism of many drugs. (1) Exact mech. is unknown.
(3) Phenobarbital & carbamazepine dec. its steady-state (2) It inhibits Na+ -K+ -ATPase, depresses cerebral
conc. thru induction of hepatic microsomal enzymes. metabolic rate, & inhibits GABA transaminase.
(4) Isoniazid inhibits metabolism of phenytoin resulting Clinical Uses
in its inc. steady - state conc. Absence seizures.
Adverse Effects
(1) CNS: Transient lethargy, headache, dizziness, euphoria.
CARBAMAZEPINE (2) GIT: Abd. pain, nausea, vomiting.
(3) Blood: Eosinophilia, thrombocytopenia, leukopenia,
Mechanism of Action pancytopenia.
(1) It blocks Na+ channels & inhibit the generation of
repetitive action potentials in epileptic focus. VALPROIC ACID
05: Central Nervous System Drugs 43

Mechanism of Action Phenytoin: Di-Hydan, Dilantin, Fentin, Phenton-S.

(1) Inhibits "GABA - transaminase"Inc. GABA (2) Iminostilbene
level by blocking conversion of GABA to succinic Carbamazepine: Carbanil, Epilepsin, Lexopine, Tegral.
semialdehyde. (3) GABA Analogs
(2) Inc. K+ conductance ( at very high conc. ) Gabapentin: Engaba, Gaba, Gabatin, Gabin.
(3) May cause a whole - body shift towards metabolic Pregabalin: Gabica.
acidosis by stimulating beta oxidation of fatty acids  (4) Piracetams
Inc. circulating ketone bodies  These ketone bodies are Levetiracetam: Kepra.
then utilized to inc. brain glycogen, which might (5) Succinimides
protect against seizures induced by transient stimulation. Ethosuximide: Emeside.
Note: It is active against both pentylenetetrazole seizures (6) Valproates
& maximal electroshock seizures. Valproic acid: Epival, Valep, Valpro.
Clinical Uses (7) Benzodiazepines
(1) Absence seizures. See Unit I.
(2) Myoclonic seizures. (8) Others
(3) Atonic seizures. Oxcarbazepine: Oxalepsy.
(4) Generalized tonic - clonic seizures. Lamotrigine: Lamictal, Lamonil.
Adverse Effects Topiramate: Epimate, Topamax, Topte.
(1) CNS: Sedation, tremor, ataxia. Acetazolamide: Diamox.
(2) GIT: Nausea, vomiting, abd. pain, heartburn, inc.
appetite, weight gain, pancreatitis.
(3) Liver: Hepatotoxicity. Unit IV
(4) Blood: Thrombocytopenia.
(5) Hairs: Alopecia.
(6) Teratogenicity: Inc. incidence of spina bifida in Anti-Parkinsonian Drugs
offspring of women who take the drug during pregnancy.
Dosage
25 - 30 mg/kg/d.
Drug Interactions PARKINSON'S DISEASE
(1) At low doses, inhibits its own metabolism.
(2) At higher doses, there is inc. free fraction of valproic Parkinsonism refers to 2 main disorders with similar
acid. clinical symptoms;
(3) Displaces phenytoin from plasma proteins. (1) Paralysis agitans or idiopathic Parkinson's disease,
(4) Inhibits the metabolism of phenobarbital, phenytoin, & which accounts for 90% of the cases, &,
carbamazepine. (2) Secondary or symptomatic parkinsonism, caused by
past infection with the virus of lethargic encephalitis.
OXAZOLIDINEDIONES Clinical Features
(1) Tremor.
(2) Rigidity.
Examples (3) Bradykinesia.
Trimethadione, Paramethadione, Dimethadione. (4) Postural instability.
Mechanism of Action Role of Acetylcholine & Dopamine in Basal Ganglia
(1) Active against pentylenetetrazole - induced seizures. (1) Normally, dopaminergic neurons originating in
(2) It causes reduction in synaptic transmission in spinal substantia nigra exert an inhibitory effect on neurons,
cord during repetitive stimulation without effecting including cholinergic neurons, in corpus striatum.
single-impulse transmission thru monosynaptic (2) In Parkinson's disease, dopamine is selectively depleted
pathways. in caudate nucleus, putamen & pallidum. This depletion
(3) Also causes an inc. in GABA level. can be correlated with the degree of degeneration of
Adverse Effects substantia nigra. In the presence of a dopamine
(1) CNS: Sedation, hemeralopia. deficiency, the normal balance b/w dopamine &
(2) Renal: Reversible nephrotic syndrome. acetylcholine is disturbed & cholinergic activity
(3) Skin: Rashes, exfoliative dermatitis. predominates.
(4) Metabolic: Mild metabolic acidosis.
DRUG CLASSIFICATION
GENERIC & TRADE NAMES
(A) Dopaminergic Drugs
(1) Hydantoin (1) Levodopa
M. Shamim’s PHARMACOLOGY 44

(a) Levodopa (alone), (b) Behavioral effects: Depression, anxiety, agitation,

(b) Levodopa in combination with dopa- insomnia, somnolence, confusion, delusions,
decarboxylase inhibitor hallucinations, nightmares, euphoria.
(i) Levodopa + Carbidopa  Sinemet. (2) Eye
(ii) Levodopa + Benserazide  Madopar, Mydriasis, precipitation of acute glaucoma.
Prolopa. (3) CVS
(iii) Levodopa + Carbidopa + Entacapone  Tachycardia, ventricular extrasystoles, atrial fibrillation,
Stalevo. orthostatic hypotension, hypertension (in the presence
(2) Ergolines of MAO inhibitors, sympathomimetics, or overdosage).
Bromocriptine, Pergolide. (4) GIT
(3) Non-ergolines Anorexia, nausea, vomiting.
Pramipexole, Ropinirole. (5) Endo
(B) Monoamine Oxidase 'B' Inhibitor Dec. prolactin secretion.
Deprenyl (Selegiline), Rasagiline (6) Repro
(C) Catechole-O-Methyltransferase Inhibitor Priapism (abnormal penile erection), brownish vaginal
Tolcapone, Entacapone. secretion.
(D) Centrally - Acting Anticholinergic Drugs (7) Renal
Benzhexol (Trihexyphenidyl), Benztropine, Biperidine, Brownish urine.
Orphenadrine, Procyclidine. (8) Blood
(E) Others Blood dyscrasias, positive coomb's test.
(1) Amantadine (antiviral). (9) Metabolic
(2) Apomorphine. Elevation of BUN, serum transaminase, alkaline
phosphatase & bilirubin.
(10)Joints
LEVODOPA Aggravation or precipitation of gouts.
(11)Skin
MECHANISM OF ACTION Hot flushes.
Levodopa is the immediate precursor of dopamine. When
administered to pts, a small portion of the dose enters brain CONTRAINDICATIONS
& is converted to dopamine by dopa decarboxylase. (1) Psychosis.
Note: Dopamine can not be administered itself b/c it will (2) Angle - closure glaucoma.
not cross the blood - brain barrier. (3) Pts. with a history of melanoma.

PHARMACOLOGICAL EFFECTS DRUG INTERACTIONS

(1) It is the immediate precursor of dopamine, & converted (1) Pyridoxine inc. extracerebral conversion of levodopa
to dopamine thru-out the body. to dopamine, & reduce its therapeutic effectiveness.
(2) Dopamine is a less potent sympathomimetic than (2) MAO inhibitors impair dopamine & norepinephrine
epinephrine & norepinephrine. metabolism, & inc. both the central & peripheral effects
(3) Effects of dopamine are due to stimulation of central of levodopa. As a result pts. may experience a
& peripheral dopamine receptors, as well as 1 &  1 hypertensive crisis or hyperpyrexia.
adrenoceptors. (3) Antipsychotics block dopamine receptors in the brain,
(4) It causes release of norepinephrine from sympathetic & reduce or abolish the effects of levodopa.
nerve endings. (4) Concomitant use of tricyclic antidepressant can cause
(5) Levodopa is effective in relieving all of the clinical orthostatic hypotension.
features of parkinsonism particularly bradykinesia &
any disability resulting from it. SINEMET, MADOPAR, PROLOPA & STALEVO

CLINICAL USES
MECHANISM OF ACTION
Treatment of moderate to severe parkinson's disease.
(1) Carbidopa & benserazide are dopa decarboxylase
inhibitors.
ADVERSE EFFECTS
(2) They do not cross the blood - brain barrier, so reduce
(1) CNS only peripheral metabolism of levodopa to dopamine.
(a) Dyskinesias: Chorea, ballismus, athetosis, (3) Formation of dopamine in the brain is not affected.
dystonia, myoclonus, tics, & tremor may occur (4) A higher percentage of administered levodopa is
individually or in any combination in face, trunk or converted to dopamine in the brain.
limbs.
05: Central Nervous System Drugs 45

(5) By using carbidopa or benserazide it is possible to DOSAGE

administer lower doses of levodopa, thereby reducing 7.5 - 30 mg/day.
its peripheral adverse effects.
(6) Entacapone prolong the action of levodopa by
diminishing its peripheral metabolism. AMANTADINE

CLINICAL USES Mechanism of Action

Replace levodopa as the most useful agents for parkinsonism. (1) An antiviral agent, it is of some help in the treatment of
parkinsonism.
DOSAGE (2) It releases dopamine from remaining intact neurons,
Sinemet contains carbidopa & levodopa in fixed proportion delays re-uptake into these neurons, & exerts an anti-
(1:10 or 1:4). cholinergic action.
Treatment is started with sinemet 25 mg/100 mg 3 times Pharmacological Effects
daily, & gradually inc. the dose upto sinemet 25mg/250mg (1) Exerts an antiparkinsonian effect.
3 or 4 times daily. (2) Acts as a prophylactic against A2 influenza virus.
Clinical Uses
See Chapter 20.
BROMOCRIPTINE Adverse Effects
See Chapter 20.
MECHANISM OF ACTION
Its anti-parkinsonian effect is due to its partial agonist CENTRALLY-ACTING ANTICHOLINERGIC DRUGS
activity at presynaptic dopamine D2 receptors.
Examples
PHARMACOLOGICAL EFFECTS Benzhexol (Trihexyphenidyl), Benztropine, Biperidine,
(1) Stimulates D2 receptors in corpus striatum. Chlorphenoxamine, Orphenadrine, Procyclidine.
(2) Inhibits synthesis & release of prolactin. Mechanism of Action
(3) Lowers elevated secretion of growth hormone in pts. They block the central cholinergic receptors, & reduce
with acromegaly. excessive cholinergic stimulation in basal ganglia.
Clinical Uses
CLINICAL USES Parkinsonism, where it improves its tremor & rigidity.
As an alternative to levodopa in parkinson's disease. Adverse Effects
(1) CNS: Drowsiness, mental slowness, inattention,
ADVERSE EFFECTS restlessness, confusion, agitation, delusions,
(1) CNS hallucinations, mood changes, dyskinesias.
(a) Dyskinesias: Same as in levodopa. (2) Eye: Blurred vision, mydriasis, inc. intraocular
(b) Mental disturbances: Confusion, hallucination, pressure.
delusions & other psychiatric reactions. (3) CVS: Tachycardia, palpitation, cardiac arrhythmias.
(c) Headache, inc. arousal (4) Resp: Tachypnea.
(2) CVS (5) GIT: Dry mouth (which may cause acute suppurative
Orthostatic hypotension, cardiac arrhythmias, painless parotitis), nausea, vomiting, constipation.
digital vasospasm. (6) Renal: Urinary retention.
(3) GIT Contraindications
Anorexia, nausea, vomiting, constipation, dyspepsia, (1) Prostatic hypertrophy.
reflux esophagitis, bleeding from peptic ulcer. (2) Pyloric stenosis.
(4) Resp. Tract (3) Paralytic ileus.
Nasal congestion. (4) Angle - closure glaucoma.
(5) Erythromelalgia
It consists of red, tender, painful swollen feet & hands DRUGS CAUSING PARKINSONISM
associated with arthralgia.
(1) Reserpine, which depletes biogenic amines from
CONTRAINDICATIONS
storage sites.
(1) Pts. with recent myocardial infarction. (2) Haloperidol, which block dopaminergic receptors.
(2) Pts. with a history of psychotic illness. (3) Phenothiazine, which also block dopaminergic
(3) Peptic ulcer. receptors.
(4) Peripheral vascular disease.
M. Shamim’s PHARMACOLOGY 46

GENERIC & TRADE NAMES (4) Diphenylbutyl piperadine: Pimozide.

(5) Benzamides: Sulpiride, Remoxipiride.
(6) Thienobenzodiazepine: Olanzapine.
(1) Dopaminergic Drugs (7) Dibenzothiazepine: Quietiapine.
Carbidopa + Levodopa: Sinedopa, Sinemet, Validopa. (8) Dihydrocarbostyril: Aripiprazole.
Carbidopa + Benserazide: Madopar. (9) Benzisoxazole: Risperidone.
Bromocriptine: Brotin, Parlodel.
Pergolide: Celance.
Ropinirole: Requip. MECHANISM OF ACTION OF ANTIPSYCHOTICS
(2) Centrally - Acting Anticholinergic Drugs
Benzhexol: Pacitane. (1) Block D2 receptors in mesolimbic & mesofrontal
Orphenadrine: Norflex, Orphenalax. systems, that accounts for its antipsychotic effects.
Procyclidine: Kemadrin. (2) Also blocks muscarinic cholinoceptors.
(3) Monoamine Oxidase 'B' Inhibitor (3) At high doses, blocks 1- adrenoceptors & histamine
Selegiline: Jumex, Selgin.
H1 receptors.
(4) Others
Amantadine: PK-Merz, Virofral.
PHARMACOLOGICAL EFFECTS OF ANTI-
PSYCHOTICS
Unit V
(1) Effects Due to D2 Receptor Blockade

Anti - Psychotic Drugs (a) Antipsychotic Effect

This is due to blockade of D2 receptors in
mesolimbic & mesofrontal systems.
[ Neuroleptics, Major tranquilizers ]
(b) Other Effects
(i) D2 receptors blockade in the nigrostriatal
INTRODUCTION pathway results in unwanted parkinsonian
effects.
Psychosis (ii) D2 receptor blockade in pituitary gland
It is a general term for any major mental disorder of organic results in hypersecretion of prolactin.
&/or emotional origin, characterized by derangement of the (iii) D2 receptor blockade in chemoreceptor
personality & loss of contact with reality, often with trigger zone & stomach results in antiemetic
delusions, hallucinations, or illusions. effect.
Schizophrenia (2) Other Effects
It is a particular kind of psychosis characterized by a clear (a) Higher doses esp. of phenothiazines & thioxan-
sensorium, but a marked thinking disturbance. thene produce pronounced sedation, due to
blockade of H1 receptors.
DRUG CLASSIFICATION (b) Generalized inhibition of parasympathetic function,
due to blockade of muscarinic cholinoceptors.
(c) Hypotension, most pronounced with high dose
(A) Phenothiazine Derivatives phenothiazines & thioxanthene, due to blockade of
(1) Aliphatic derivatives: Chlorpromazine, Promazine,
1-adrenoceptors.
Promethazine, Trimeprazine.
(2) Piperadine derivatives: Thioridazine, Mesorida-
zine, Piperacetazine. CLINICAL USES OF ANTIPSYCHOTICS
(3) Piperazine derivatives: Prochlorperazine,
Trifluoperazine, Perphenazine, Fluphenazine,
(A) Psychiatric Uses
Thiopropazate.
(1) Schizophrenia.
(B) Thioxanthene Derivatives
(2) Manic episode in bipolar affective disorder.
Thiothixene, Chlorprothixene, Clopenthixol,
(3) Non - manic excited states.
Zuclopenthixol, Fluphenthixol.
(4) Tourette syndrome.
(C) Butyrophenone Derivatives
(5) For controlling disturbed behavior in pts. with
Haloperidol, Droperidol, Benperidol, Trifluperidol.
senile dementia of Alzheimer type.
(D) Miscellaneous
(6) Alcoholic hallucinosis.
(1) Dibenzoxazepine: Loxapine.
(7) Paranoid states.
(2) Dihydroindolone: Molindone, Ziprasidone.
(B) Nonpsychiatric Uses
(3) Dibenzodiazepine: Clozapine.
05: Central Nervous System Drugs 47

(1) As antiemetic (except thioridazine). GENERIC & TRADE NAMES

(2) As antipruritics (due to H1 blocking effect).
(3) Neuroleptanesthesia (Droperidol).
(4) Hiccup (Chlorpromazine). (1) Phenothiazine Derivatives
Chlorpromazine: Chlorotil, Largactil.
Fluphenazine: Fluphan, Flucate, Modrin*, Motival*.
ADVERSE EFFECTS OF ANTIPSYCHOTICS Promethazine: Phenergan, Promazine, Semozin.
Prochlorperazine: Prochlor, Stemetil.
(1) CNS Trifluoperazine: Stelabid*, Stelazine.
(a) Neurologic effects: Extrapyramidal reactions Thioridazine: Melliril.
include typical parkinson synd., akathisia, acute (2) Thioxanthene Derivatives
dystonic reactions (eg facial grimacing, torticollis); Zuclopenthixol: Clopenia, Clopixol.
tardive dyskinesia, lethargy, drowsiness. Fluphenthixol: Fluanoxol.
(b) Behavioral effects: Pseudo-depression due to (3) Butyrophenone Derivatives
akinesia; toxic-confusional states. Haloperidol: Halpol, Phrenia, Serenace.
(c) Neuroleptic malignant synd: Characterized by (4) Miscellaneous
muscle rigidity, impaired sweating, hyperpyrexia, Clozapine: Clozaril, Glipin.
altered BP & pulse rate, & raised creatinine Olanzapine: Nozapin, Olanzin, Ozapine.
phosphokinase level. Aripiprazole: Aripip, Zedan.
(2) Eye Risperidone: Espidone, Risperal.
Loss of accommodation, deposits in the cornea & lens
(with chlorpromazine), retinal deposits (with
thioridazine). Unit VI
(3) CVS
Orthostatic hypotension, syncope, reflex tachycardia,
arrhythmia, conduction block. Anti - Manic Drugs
(4) GIT
Dry mouth, constipation. [Drugs Treatment of Bipolar Affective Disorder,
(5) Endo Mood - Stabilizing Drugs ]
Hyperprolactinemia in women results in amenorrhea-
galactorrhea synd, & in men gynecomastia.
(6) Repro BIPOLAR AFFECTIVE DISORDER
In women infertility & inc. libido; in men infertility,
impotence & loss of libido. (1) Also called manic-depressive illness.
(7) Renal (2) It is a very serious emotional disorder. Pts have cyclic
Urinary retention. attacks of mania with symptoms of paranoid schizo-
(8) Allergic Reactions phrenia consisting of grandiosity, bellicosity, paranoid
Cholestatic jaundice, agranulocytosis, skin eruption. thoughts, & overactivity.
(9) Pregnancy (3) Inc. catecholamine activity is found in bipolar affective
Dysmorphogenesis. disorder.

DOSAGE DRUGS FOR BIPOLAR AFFECTIVE DISORDER

(1) Lithium.
(2) Anti-epileptics: Valproic acid, Carbamazepine,
(1) Chlorpromazine  100 -1000 mg/d. Lamotrigine (see Unit III).
(2) Thioridazine  100 - 800 mg/d. (3) Antipsychotics (see Unit V).
(3) Trifluoperazine  5 - 60 mg/d.
(4) Fluphenazine  2 - 20 mg/d.
LITHIUM
(5) Zuclopenthixol  20 - 150 mg/d.
(6) Haloperidol  2 - 20 mg/d.
MECHANISM OF ACTION
(1) Substitute for sodium in generating action potential.
DRUG INTERACTIONS
(2) Enhances some of the actions of serotonin.
(3) Dec. norepinephrine & dopamine turnover, that may
Additive effects occur when these drugs are used with contribute to its antimanic action.
sedative-hypnotics, alpha adrenoceptor blockers & anti-
cholinergics.
M. Shamim’s PHARMACOLOGY 48

(4) Blocks the development of dopamine receptor super- (1) It is a psychiatric syndrome consisting of dejected
sensitivity, that may accompany chronic therapy with mood, psychomotor retardation, insomnia & weight
antipsychotics. loss, sometimes associated with guilt feelings &
(5) Enhance the synthesis of acetylcholine by inc. choline somatic preoccupations, often of delusional proportions.
uptake into nerve terminals. (2) It is an alteration of mood characterized by sadness,
(6) Inhibits norepinephrine sensitive adenylate cyclase, worry, anxiety, & losses of weight, libido & enthusiasm.
contributing to its antidepressant & antimanic effects. Types
(7) Inhibits the conversion of IP2 to IP1  Depletion of (1) Reactive (Secondary) Depression
phosphatidylinositol - 4, 5 - biphosphate (PIP2 which is It occurs in response to a real stimuli, eg grief, illness,
the memb. precursor of IP3 & diacylglycerol). etc or in response to drugs, eg antihypertensive,
alcohol, hormones.
(2) Endogenous (Major Depressive) Depression
CLINICAL USES It is a genetically determined biochemical disorder
(1) Bipolar affective disorders. manifested by inability to cope with ordinary stress.
(2) Acute mania. (3) Bipolar Affective (Manic-Depressive)
(3) Recurrent endogenous depressions. Depression
(4) Excited phase in schizo-affective disorders. It is associated with bipolar affective disorder.
(5) Alcoholic mania & depression.
(6) Management of aggressive violent behavior in
prisoners. DRUG CLASSIFICATION

ADVERSE EFFECTS (A) Tricyclics

(1) CNS: Tremor, choreoathetosis, ataxia, dysarthria, (1) Neutral: Imipramine, Dothiepin.
aphasia, confusion, withdrawal or bizarre motor (2) Sedative: Amitriptyline, Clomipramine,
movements, seizures. Trimipramine, Doxepin.
(2) CVS: SA nodal depression, hypotension, arrhythmias. (3) Stimulant: Desipramine, Nortriptyline, Protrip-
(3) GIT: Anorexia, vomiting, diarrhea. tyline, Mianserin.
(4) Endo: Dec. thyroid function, goitre, hypothyroidism. (B) Heterocyclics (2nd Generation Agents)
(5) Repro: Disturbed sexual function in men. Amoxapine, Maprotiline, Trazodone, Bupropion.
(6) Renal: Polydipsia, polyuria, nephrogenic diabetes (C) 3rd Generation Agents
insipidus, edema. Venlafaxine, Mirtazapine, Nefazodone, Duloxetine.
(7) Blood: Leukocytosis. (D) Monoamine Oxidase Inhibitors
(8) Skin: Acneiform eruptions. (1) Hydrazide derivatives: Phenelzine, Isorcarbo-
(9) Teratogenicity: Cardiovascular anomalies, esp. xazid.
Ebstein's anomaly. (2) Non-hydrazide derivatives: Tranylcypromine,
(10) Pregnancy: Lithium toxicity in newborn manifested by Moclobemide.
lethargy, cyanosis, poor suck, Moro reflexes, & (E) Sympathomimetic Stimulants
hepatomegaly. Dextroamphetamine, Methylamphetamine, Methly-
phenidate.
DOSAGE (F) Selective Serotonin Reuptake Inhibitors
600 to 3600 mg/day. Fluoxetine, Paroxetine, Sertraline, Fluvoxamine,
Citalopram, Escitalopram.
GENERIC & TRADE NAMES
TRICYCLIC ANTIDEPRESSANTS
Lithium
Lithium Carbonate: Camcolit, Carlit, Neurolith SR, MECHANISM OF ACTION
Priadel. (1) They have both H1-receptor blocking &  adrenergic
properties.
(2) They potentiate the action of biogenic amines by
Unit VII blocking the inactivating re-uptake of amines after
release from presynaptic neuron.
(3) They also possess antimuscarinic action, & block
Anti - Depressant Drugs re-uptake of serotonin.
(4) Alpha-2 receptors which are found on adrenergic
nerve terminals are blocked by tricyclics, resulting in
inc. neurotransmitter release.
DEPRESSION
05: Central Nervous System Drugs 49

(5) One or more of the above mention action could CLINICAL USES
contribute to elevation of mood in depressed pts. Similar to tricyclics.

CLINICAL USES ADVERSE EFFECTS

(1) Depression. Similar to tricyclics; except that it does not causes
(2) Enuresis. antimuscarinic adverse effect (blurred vision, aggravation
(3) Chronic pain. of glaucoma, constipation, paralytic ileus, urinary hesitancy,
(4) Obsessive compulsive phobic states. urinary retention, delirium).
(5) Cataplexy associated with narcolepsy.
(6) Acute pain attacks. CONTRAINDICATIONS
(7) School phobia. (1) Hypersensitivity.
(8) Attention deficit disorders in children. (2) Pheochromocytoma.

ADVERSE EFFECTS WHY MAO INHIBITORS CAUSES HYPERTENSIVE

(1) CNS: Lassitude, fatigue, sleepiness, agitation, insomnia, CRISIS OR CHEESE SYNDROME?
aggravation of psychosis, tremor, delirium, confusion,
paresthesias, seizures, neuropathy. MAO inhibitors can interact with foods containing a
high tyramine content, eg cheese, beer & chicken liver.
(2) Eye: Blurred vision, aggravation of glaucoma.
1) High conc. of tyramine absorbed form these foods
(3) CVS: Tachycardia, orthostatic hypotension, delayed cannot undergo oxidative deamination.
cardiac conduction, arrhythmias. 2) Tyramine can therefore induce release of large
(4) GIT: Constipation, paralytic ileus. amounts of stored catecholamines from nerve
(5) Liver: Cholestatic jaundice. terminals which can precipitate a hypertensive
(6) Endo: Sexual disturbances, gynecomastia, amenorrhea, crisis or cheese syndrome.
weight gain.
(7) Renal: Urinary hesitancy, urinary retention. (3) Congestive cardiac failure.
(8) Blood: Agranulocytosis, hemolytic anemia. (4) Liver disease.
(9) Skin: Sweating, rashes. (5) Impaired renal function.
(6) Hypertension.
CONTRAINDICATIONS
DOSAGE
(1) Prior sensitivity.
(2) Acute recovery phase of myocardial infarction. Phenelzine  45 - 75 mg/day.
(3) Concomitant use of MAO inhibitors. Isocarboxazid  20 - 50 mg/day.
Tranylcypromine  10 - 30 mg/day.
DOSAGE
Amitriptyline  75 - 200 mg/day. GENERIC & TRADE NAMES
Desipramine  75 - 200 mg/day.
Doxepin  75 - 300 mg/day. (1) Tricyclics
Imipramine  75 - 200 mg/day. Amitriptyline: Amitryp, Amyline, Tryptanol.
Protriptyline  20 - 40 mg/day. Clomipramine: Clomipril, Depramine.
Nortriptyline  75 - 150 mg/day. Dothiepin: Prothiaden.
Imipramine: Imiprol, Tofranil.
MONOAMINE OXIDASE INHIBITORS Mianserin: Lantanon.
Nortriptyline: Notrilin, Sensival.
Trimipramine: Surmontil.
MECHANISM OF ACTION (2) Heterocyclics
(1) They form stable complex with the enzyme monoamine Maprotiline: Ludiomil.
oxidase, irreversibly inactivating it & thereby Bupropion: Zylexx SR.
preventing oxidative deamination of biogenic amines, (3) 3rd Generation Agents
eg norepinephrine, epinephrine, dopamine, serotonin & Venlafaxine: Venaxin, Venalax, Vexor.
tyramine. Mirtazapine: Mirtazep, Remeron.
(a) These biogenic amines are thus inc. significantly (4) Monoamine Oxidase Inhibitors
in brain, intestines, heart, & blood. Moclobemide: Aurorix.
(b) Inc. biogenic amine levels in brain is responsible (5) Sympathomimetic Stimulants
for their antidepressant effects. Methylphenidate: Phenida, Ritalin.
(2) Tranylcypromine also release norepinephrine centrally, (6) Selective Serotonin Reuptake Inhibitors
which accounts for its relatively rapid action. Fluoxetine: Alert, Faxetine, Flux, Prozac.
Paroxetine: Froxtin, Paraxyl, Seroxat.
M. Shamim’s PHARMACOLOGY 50

Sertraline: Pertral, Reline. (e) Depress appetite & reduce food intake thru a
Fluvoxamine: Flomin, Voxamine. central action on hypothalamic feeding centre, &
Citalopram: Celesta, Cipramil, Citalo. by reduction of acuity of smell & taste.
Escitalopram: Cipralex, Depram, Eslopram. (f) Facilitates monosynaptic & polysynaptic
transmission in the spinal cord.
(2) Eye
Unit VIII Mydriasis upon local application.
(3) Cardiovascular System
(a) Inc. both systolic & diastolic BP.
CNS Stimulants (b) Reflex slowing of heart rate.
(c) Large doses may produce cardiac arrhythmias.
(4) Gastrointestinal Tract
Relaxation in spastic states.
DRUG CLASSIFICATION (5) Urinary Bladder
Relaxation of detrusor, & contraction of sphincter.
(A) Cerebral Cortex Stimulants
(1) Xanthines: Caffeine, Theophylline, Theobromine. CLINICAL USES
( See Unit I, Chapter 13 ). (1) Narcolepsy.
(2) Sympathomimetics: Amphetamine, Dextroam- (2) Hyperkinetic synd. in children.
phetamine, Methamphetamine, Methylphenidate. (3) Nocturnal enuresis.
(3) Others: Atropine, Cocaine. (4) As mydriatic (locally).
(B) Medullary Stimulants (Analeptics) (5) As nasal decongestant (locally).
(1) Acting directly on medullary centre: Leptazol,
Nikethamide, Ethamivan, Doxapran, Picrotoxin, ADVERSE EFFECTS
Amiphenazole. (1) CNS: Dysphoria, headache, confusion, dizziness,
(2) Acting reflexly thru chemoreceptors in carotid fatigue, mental depression, delirium, psychosis,
body: Nikethamide, Bemigride. convulsions, coma.
(Note: For detail on Analeptics see Unit II, Chapter 13.) (2) Eye: Mydriasis.
(C) Spinal Cord Stimulants (3) CVS: Hypertension, arrhythmias.
Strychnine, Brucine. (4) GIT: Dry mouth.
(D) Antidepressant Drugs (5) Tolerance, psychic, & physical dependence
(E) Hallucinogenic Drugs
Lysergic acid diethylamide, Mescaline, Psilocybin, CONTRAINDICATIONS
Psilocin, Adrenochrome, Cannabis. (1) Pts with cardiovascular diseases.
(2) Pts receiving MAO inhibitors or guanethidine.
AMPHETAMINE (3) Insomnia.
(4) Anorexia.
(5) Mentally unstable pts.
MECHANISM OF ACTION
(1) It stimulates both alpha - & beta - adrenoceptors thru DOSAGE
an indirect mechanism (ie thru the release of 5 - 10 mg orally, IM or IV.
catecholamines).
(2) It stimulates cerebral cortex, reticular activating
system, medullary centre, & spinal cord. GENERIC & TRADE NAMES

PHARMACOLOGICAL EFFECTS Caffeine: Amtalidin*, Panadol extra*.

(1) Central Nervous System Theophylline: Asthalin, Theograd.
(a) Psychic stimulation consisting of euphoria, Theobromine: Urodonal.
wakefulness, alertness, & inc. mental & physical Methylphenidate: Phenida, Ritalin.
activity; usually followed by a sense of depression. Atropin: Atrosol, Ethiatropin.
(b) Antifatigue action.
(c) Analeptic action.
(d) Mild analgesic properties of its own; enhances Unit IX
analgesic effect of morphine & meperidine, while
dec. that of nitrous oxide.
Anti - Migraine Drugs
05: Central Nervous System Drugs 51

MIGRAINE (2) It is also a partial agonist at  - adrenoceptors, &

agonists at tryptaminergic & dopaminergic receptors.
Pharmacological Effects
(1) Migraine headache consists of periodic attacks of (1) Anti - Migraine Effect
vascular headache, usually temporal & unilateral in Vasoconstriction of cranial arteries induced by
onset, commonly associated with irritability, nausea, ergotamine, with consequent reduction in the amplitude
vomiting, constipation, or diarrhea, & often photophobia; of their pulsation is responsible for the relief of acute
attacks are preceded by constriction of cranial migraine attacks.
arteries, usually with resultant prodromal ocular (2) Effect on Uterine Smooth Muscle
symptoms, & is followed by vasodilation. (a) In small doses, evokes rhythmic contraction &
(2) Migraine headache, is characterized by a brief 'aura' relaxation of uterus.
that may involve visual scotomas or even hemianopia (b) At higher doses, induce powerful & prolonged
& speech abnormalities, followed by a severe throbbing contractions.
unilateral headache that lasts for a few hrs to 1-2 Clinical Uses
days. Acute migraine attacks.
(3) The attacks are usually precipitated by stress & occur Adverse Effects
after stressful episodes. (1) CNS: Drowsiness.
Pathophysiology (2) CVS: Prolonged vasospasm resulting in gangrene, eg
(a) Some vascular mech. is involved b/c onset of head- of arms, legs & bowel.
ache is associated with inc. amplitude of temporal artery (3) GIT: Nausea, vomiting, diarrhea.
pulsations, & relief of pain by ergotamine is (4) Others: Fibroplastic changes in the retroperitoneal
accompanied by dec. pulsation. space, pleural cavity, & endocardial tissue of heart.
(b) Onset of migrainous aura is associated with an Contraindications
abnormally inc. release of serotonin from platelets. (1) Obstructive vascular disease.
(c) Arterial throbbing phase is associated with dec. of (2) Collagen disease.
platelets & serum serotonin level below normal. Dosage
(d) Other chemical triggers include falling levels of (1) 6 mg, orally.
estrogen in women whose headache is linked to (2) 0.25 - 0.5 mg, intravenously or intramuscularly.
menstrual cycle, & elevated levels of prostaglandin E1.
OTHER ANTIMIGRAINE DRUGS
DRUGS USED IN MIGRAINE
(1) Aspirin & Paracetamol
(A) In Acute Attacks See 'Chapter 9'.
(1) Ergotamine tartarate. (2) Metoclopramide
(2) Dihydroergotamine. It is used in acute migraine attack for treating nausea
(3) Aspirin. & vomiting ; it also enhances aspirin absorption.
(4) Paracetamol. Note: For detail see 'Chapter 14'.
(5) Metoclopramide. (3) Methysergide
(B) For Prophylactic Use Mechanism of Action
(1) Beta - adrenoceptor blockers, eg propranolol, It is a strong antagonist of serotonin, inhibiting its
atenolol, timolol, metoprolol. vasoconstrictor & presser effect.
(2) Methysergide. Clinical Uses
(3) Cyproheptadine. Prophylactic treatment of migraine.
(4) Pizotifen. Adverse Effects
(5) Clonidine. Similar to ergotamine tartarate.
(6) Amitriptyline. (4) Cyproheptadine
(7) Verapamil. Mechanism of Action
(8) Sandomigran. It is a competitive antagonist of serotonin, blocking its
vascular effects; also has weak anticholinergic activity.
ERGOTAMINE TARTARATE & Clinical Uses
DIHYDROERGOTAMINE (1) Prophylaxis of migraine.
(2) Pruritic dermatoses.
Adverse Effects
Mechanism of Action (1) CNS: Drowsiness.
(1) It is a strong serotonin antagonist, as well as a weak (2) GIT: Dry mouth.
 - adrenoceptor blocker. (5) Pizotifen
M. Shamim’s PHARMACOLOGY 52

It blocks serotonin receptors, as well as have some (C) Activation of glycine receptors in spinal cord.
H1 - antihistamine & anticholinergic actions. (D) Facilitation of GABA - mediated inc. in Cl ion
(6) Sandomigran conductance.
It is an antagonist of serotonin, histamine, bradykinin, (E) Inc. in dopamine - stimulated adenyl cyclase
& acetylcholine. activity.
Clinical Uses (49) All of the following respond to treatment with
Prophylaxis of migraine. benzodiazepines
Adverse Effects (A) Tetanus.
CNS: Drowsiness. (B) Schizophrenia.
(C) Epileptic seizure.
GENERIC & TRADE NAMES (D) Insomnia.
(E) Anxiety.
Ergotamine tartarate: Cafergot*. (50) All of the following may occur after acute
administration of ethanol
(A) Myocardial depression.
Unit X (B) Sedation, slurred speech.
(C) Contraction of uterine smooth muscle.
(D) Alcoholic hepatitis.
Self - Assessment (T/F) (E) Hypothermia.
(51) All of the following are signs or symptoms of chronic
(See answers on page no. 240) ethanol use
(A) Distal paresthesias.
(45) Following statements concerning benzo-diazepines are (B) Gynecomastia & testicular atrophy.
correct (C) Fatty liver & hepatitis.
(A) Seizures occur with abrupt discontinuance after (D) Gastric irritation & bleeding.
chronic use. (E) Dec. liver alcohol dehydrogenase levels.
(B) Produces anxiety.
(C) In low doses, causes anesthesia. (52) Drugs used in the treatment of partial seizures include
(D) Contraindicated in psychoses. (A) Valproic acid.
(E) Has relatively high therapeutic index. (B) Phenytoin.
(C) Ethosuximide.
(46) Following statements concerning barbiturates are (D) Carbamazepine.
correct (E) Primidone.
(A) Have a GABA - like action or enhances the effect
of GABA. (53) Which of the following drugs is most likely to be
(B) Induces hepatic microsomal drug metabolizing effective in myoclonic seizures
enzyme system. (A) Valproic acid.
(C) Acute barbiturate overdosage can be treated by (B) Phenobarbital.
acidification of urine. (C) Phenytoin.
(D) Phenobarbital is a short acting barbiturate. (D) Ethosuximide.
(E) Contraindicated in advanced liver & renal disease. (E) Carbamazepine.

(47) Concerning the clinical uses of sedative-hypnotics, (54) Following drugs are effective in absence
following are correct (petit mal) seizures
(A) Diazepam is used for muscle spasticity in pts. (A) Clonazepam.
with cerebral palsy. (B) Ethosuximide.
(B) Chlordiazepoxide is useful in detoxification of (C) Phenytoin.
alcoholic pts. (D) Valproic acid.
(C) Pentobarbital is used as IV adjuncts to surgical (E) Phenobarbital.
anesthetics. (55) All of the following statements concerning
(D) Chloral hydrate is used for hypnosis in young adults. antiepileptic drugs are correct
(E) Barbiturates are used for hyperbilirubinemia & (A) Anticoagulants can displace phenytoin from its
kernicterus in neonate. plasma protein binding sites.
(B) Carbamazepine induces hepatic microsomal drug -
(48) Which one of the following best describes the
metabolizing enzyme system.
mechanism of action of benzodiazepines
(A) Blockade of excitatory actions of glutamic acid. (C) Mechanism of action of carbamazepine involves
(B) Inhibition of GABA transaminase leading to inc. block of Na ion channels in neuronal memb.
level of GABA.
05: Central Nervous System Drugs 53

(D) Gastrointestinal distress is a common adverse (A) Sympathomimetic actions.

effect of valproic acid. (B) Alpha - adrenoceptor blockade.
(E) Sedation & development of physical dependence (C) Atropine - like effects.
are serious problems with chronic use of (D) H1 - receptor blockade.
ethosuximide in treatment of seizures states. (E) Elevation of seizure threshold.
(56) All of the following statements concerning levodopa (63) Clinical uses of antidepressant drugs include
are correct (A) Anxiety.
(A) Choreoathetosis of face & distal extremities is an (B) Depression.
important adverse effect. (C) Obsessive compulsive phobic states.
(B) Fluctuations in clinical response occur with (D) School phobia.
increasing frequency as treatment continues. (E) Bipolar affective disorders.
(C) It effectively antagonizes akinesia & tremor
(64) Monoamine oxidase inhibitors include
caused by antipsychotic drugs.
(A) Isocarboxazid.
(D) It should be avoided in pts with a history of
(B) Imipramine.
melanoma.
(C) Nortriptyline.
(E) Pyridoxine increases its therapeutic effectiveness.
(D) Tranylcypromine.
(57) Which of the following statements about carbidopa is (E) Amoxapine.
accurate
(65) Which of the following statements about
(A) It is dopa decarboxylase inhibitor.
amphetamine is correct
(B) It cross the blood-brain barrier.
(A) It acts on alpha & beta adrenergic presynaptic
(C) It is converted to false transmitter, carbidopamine.
terminals.
(D) When used with levodopa, it reduces the peripheral
(B) It depresses hunger centre in hypothalamus.
adverse effects of levodopa.
(C) It is effective in narcolepsy.
(E) It decreases the formation of dopamine in brain.
(D) It causes miosis.
(58) All of the following statements about (E) It is contraindicated in pts. receiving MAO
bromocriptine are accurate inhibitors.
(A) It should not be administered to pts on anti-
(66) Following drugs are used for migraine
cholinergic drugs.
prophylaxis
(B) It is contraindicated in pts with a history of
(A) Ergotamine tartarate.
psychosis.
(B) Aspirin.
(C) It has partial agonist activity at D2 receptors.
(C) Methysergide.
(D) It inhibits synthesis & release of prolactin. (D) Propranolol.
(E) It may cause dyskinesias. (E) Imipramine.
(59) Clinical uses of antipsychotic drugs include
(A) Schizophrenia.
(B) Manic episode in bipolar affective disorder.
(C) Epilepsy.
(D) Tourette syndrome.
(E) Amenorrhea - galactorrhea syndrome.
(60) Adverse effects of antipsychotic drugs include
(A) Tardive dyskinesia.
(B) Orthostatic hypotension.
(C) Diarrhea.
(D) Altered endocrine function.
(E) Urinary retention.
(61) Regarding lithium, following statements are correct
(A) It substitutes for Na in generating action
potential.
(B) It stimulates norepinephrine sensitive adenyl
cyclase.
(C) It is effective in bipolar affective disorders.
(D) Tremor is a common adverse effect.
(E) It may cause hypertension.
(62) Effects of tricyclic antidepressant drugs
include all of the following
M. Shamim’s PHARMACOLOGY 54

06 ANESTHETICS

(4) Incontinence & struggling may occur.

Unit I (5) Pulse becomes rapid.
(6) BP inc. due to inc. level of circulating catechol-
amines.
General Anesthetics (C) Stage of Surgical Anesthesia
It begins with recurrence of regular respiration &
normal BP, & extends to complete cessation of sponta-
neous respiration. Subdivided into 4 planes ;
INTRODUCTION (1) Plane I
(a) Moving eyeballs.
General Anesthesia (b) Pupils normal in size.
It is a state which includes analgesia, amnesia, loss of (c) Conjunctival reflex is abolished.
consciousness, inhibition of sensory & autonomic reflexes, (d) Respiration is regular.
& skeletal muscle relaxation. (2) Plane II
Balanced Anesthesia (a) Fixed eyeballs.
It includes administration of medication preoperatively (b) Pupils constricted at first, but become dilated
for sedation & analgesia, use of neuromuscular blocking in lower plane II.
drugs intra-operatively & use of both intravenous & (c) Corneal reflex is abolished.
inhaled anesthetic drugs. (d) Respiration is regular, but shallower than in
Surgical Anesthesia plane I.
It is a degree of CNS depression sufficient to allow surgical (3) Plane III
operations to be performed. (a) Pupils are dilated.
Basal Anesthesia (b) Light reflex is abolished.
It represents a degree of anesthesia short of surgical stage, (c) Lagging of thoracic respiration behind
ie, the pt. is unconscious but yet not sufficiently depressed abdominal respiration.
for surgical operations. (4) Plane IV
Neuroleptanesthesia (a) Pupils are completely dilated.
It is a state of neuroleptanalgesia & unconsciousness, (b) Light reflex is lost.
produced by the combined administration of a narcotic (c) At first, there is lagging of thoracic respiration
analgesic & a neuroleptic agent, together with the behind the abdominal resp., & later cessation
inhalation of nitrous oxide & oxygen. of respiration ensue.
Dissociative Anesthesia (D) Stage of Medullary Depression
It is a state of catatonia, amnesia & analgesia; pts feel It starts by the cessation of respiration, & ends with
totally dissociated from their surroundings. the failure of circulation.

SIGNS & STAGES OF ANESTHESIA DRUG CLASSIFICATION

(A) Stage of Analgesia
It begins with administration of anesthetics & lasts till
consciousness is lost. INHALATIONAL AGENTS
(1) Initially there is analgesia without amnesia. (1) Volatile liquids
(2) Later, both analgesia & amnesia ensue. (a) Ether
(B) Stage of Excitement Diethylether, Divinylether.
It start after loss of consciousness & proceeds to the (b) Halogenated Agents
beginning of surgical anesthesia. Halothane, Desflurane, Sevoflurane Enflurane,
(1) Pt appears to be delirious & excited but is amnesic. Isoflurane, Methoxyflurane, Chloroform, Trichloro-
(2) Respiration is irregular both in volume & rate. ethylene, Ethyl chloride.
(3) Retching & vomiting may occur.
06: Anesthetics 55

(2) Gases (3) Ventilatory response to CO2 is dec. due to depres-

Nitrous oxide, Cyclopropane. sion of central chemoreceptors.
(4) Bronchodilation occurs.
INTRAVENOUS AGENTS (5) Depresses airway mucociliary function, thus
(1) Thiobarbiturates prolonged anesthesia may lead to pooling of mucus
Thiopental, Thiamylal, Methohexital.  Atelectasis & respiratory infections.
(2) Benzodiazepines (D) Kidney
Midazolam, Diazepam, Lorazepam. Dec. glomerular filtration rate & effective renal plasma
(3) Opioid Analgesics flow, as renal vascular resistance is increased.
Fentanyl, Alfentanil, Remifentanil. (E) Liver
(4) Arylcyclohexylamines (1) Dec. hepatic blood flow.
Ketamine. (2) Dec. hepatic function.
(5) Phenols (F) Skeletal Muscle
Disoprofol (Propofol). (1) Relaxation occur by both central & peripheral
(6) Imidazole mechanisms.
Etomidate. (2) Triggers malignant hyperthermia, in which in
(7) Miscellaneous response to anesthesia, a sudden rapid rise in body
Dexmedetomidine, Propanidid. temp. & signs of inc. muscle metabolism occur.
(G) Uterine Smooth Muscle
MECHANISM OF ACTION OF GENERAL Relaxes uterine smooth muscle.
ANESTHETICS
ADVERSE EFFECTS
(1) ''Halothane hepatitis'' can occur 2-5 days postopera-
(1) Inc. the threshold of cells to firing, resulting in dec. tively, characterized by fever, anorexia, vomiting,
activity. eosinophilia & biochemical abnormalities.
(2) Dec. the rate of rise of action potential by interfering (2) Postoperative jaundice.
with sodium influx. (3) Hepatic necrosis.

HALOTHANE ADVANTAGES
(1) Non-inflammable & non-explosive.
PHARMACOLOGICAL EFFECTS (2) Non-irritant to respiratory passages.
(A) Central Nervous System (3) Useful in pts. with asthma, due to its bronchodilating
(1) Cerebral blood vessels dilate, increasing cerebral action.
blood flow & CSF pressure. (4) Useful in plastic surgery to produce a "bloodless
(2) As halothane anesthesia deepens, fast, low-voltage area" thru inducing controlled hypotension.
EEG waves are replaced by slow, high-voltage (5) Safe for children.
waves.
(3) Shivering occur during recovery. DISADVANTAGES
(B) Cardiovascular System (1) Inadequate muscle relaxation.
(1) Dec. arterial blood pressure.
(2) CVS disturbances ie, hypotension, arrhythmias &
(2) Inc. cutaneous blood flow, as blood vessels dilate.
(3) Depressed myocardial contractility. bradycardia.
(4) Depressed cardiac sympathetic activity, resulting (3) Inhibition of uterus & dec. response to ergot &
in bradycardia. oxytocin; therefore, contraindicated during labor.
(5) Interferes with norepinephrine action, thus (4) Poor analgesics; so, commonly supplemented with
antagonizes the sympathetic response to arterial nitrous oxide or ether.
hypotension. (5) Expensive.
(6) Increases cardiac automaticity, esp. in the presence (6) Potential hepatotoxicity.
of adrenergic agonists, cardiac disease, hypoxia (7) Respiratory depression.
& electrolyte abnormalities.
Note: Surgical stimulation, hypercarbia & inc.
anesthesia duration will lessen depressant effects of ENFLURANE
inhaled anesthetics.
(C) Respiratory System Pharmacological Effects
(1) Respiration becomes rapid & shallow. (A) Central Nervous System
(2) Minute volume is reduced. (1) Cerebral blood vessels dilate, increasing cerebral
blood flow & CSF pressure.
M. Shamim’s PHARMACOLOGY 56

(2) Enflurane anesthesia lead to an EEG pattern (4) Good skeletal muscle relaxation.
characteristic of seizure activity or to frank seizures. (5) Cheap.
(B) Cardiovascular System Disadvantages
(1) Dec. arterial BP & dec. sympathetic response to (1) Narrow margin of safety.
arterial hypotension, similar to halothane. (2) In induction stage, vagal bradycardia & cardiac arrest
(2) Depresses myocardial contractility, similar to may occur.
halothane. (3) During excitement stage, myocardial sensitization to
(3) Inc. in cardiac automaticity is less marked than catecholamines may produce ventricular fibrillation.
with halothane. (4) During surgical anesthesia, high conc. of chloroform
(4) Tachycardia, either by altering sinus node in blood may directly depress myocardium with
depolarization or by shifting balance of ANS progressive fall in BP.
activity. (5) During medullary paralysis, vasomotor centre is
(C) Respiratory System affected before the respiratory centre leading to
Similar to Halothane. circulatory insufficiency.
(D) Kidney (6) Postoperatively vomiting, urinary retention & paralytic
Similar to Halothane. ileus may occur.
(E) Liver (7) Delayed chloroform poisoning occurs 24 hour after
(1) Lower incidence of liver impairment, usually operation due to liver necrosis, characterized by
reversible. vomiting, jaundice, acidosis & coma.
(2) Hepatic necrosis less commonly, esp. after
repeated administration of enflurane.
DIETHYL ETHER
(F) Skeletal Muscle
Similar to Halothane.
(G) Uterine Smooth Muscle Pharmacological Effects
Similar to Halothane. (A) Central Nervous System
Advantages Dec. metabolic rate of brain, but inc. cerebral blood
(1) Non inflammable. flow due to dec. cerebral vascular resistance.
(2) Produces good muscle relaxation. (B) Cardiovascular System
(3) Does not produce hepatotoxicity. (1) Depresses myocardium, directly.
(4) Causes a lower incidence of arrhythmias. (2) Cardiac output & arterial BP are maintained b/c of
Disadvantages sympathetic stimulation.
Causes seizure activity. (3) Tachycardia due to vagal blockade.
(C) Respiratory System
ISOFLURANE (1) Bronchodilation due to inc. sympathetic activity.
Similar to Enflurane, except that it has no seizures activity. (2) Respiratory response to CO2 is reduced, but is
maintained spontaneously by reflex excitation at
peripheral sites.
METHOXYFLURANE
(D) Gastrointestinal Tract
(1) Nausea & vomiting during induction & recovery.
Advantages (2) Inhibition of tone & motility proportional to depth
(1) Non inflammable. & duration of anesthesia.
(2) Non irritant to respiratory passages. (E) Kidney
(3) Excellent muscle relaxant & analgesic properties. Stimulate antidiuretic hormone release.
(4) Little or no postoperative vomiting. (F) Liver
Disadvantages Inc. glycogenolysis due to sympathetic stimulation.
(1) Slow induction & recovery. (G) Skeletal Muscle
(2) Hypotensive action. (1) Relaxation b/c it causes CNS depression at
(3) Sensitization of myocardium to catecholamines. synaptic pathways in the spinal cord.
(4) Postoperative diuresis, due to a specific (2) Also has a curare-like action.
nephrotoxicity affecting distal convoluted tubules. Advantages
(1) Wide safety margin.
(2) Good muscle relaxation.
CHLOROFORM
(3) No significant CVS effects.
(4) Sufficiently potent to allow good oxygenation.
Advantages (5) Cheap.
(1) Non inflammable & non explosive. Disadvantages
(2) Non irritant to respiratory passages. (1) Inflammable & explosive.
(3) Rapid pleasant induction. (2) Irritant to respiratory passages causing laryngospasm.
06: Anesthetics 57

(3) Unpleasant slow induction & delayed recovery. (3) Postoperative hypotension.
(4) Inc. salivation & vomiting. (4) Atelectasis.
(5) Pulmonary complications. (5) Bronchospasm & respiratory centre depression leading
(6) Acidosis & hyperglycemia. to CO2 accumulation.
(7) Convulsions. (6) Nausea & vomiting.
Contraindications
(1) Acute pulmonary disease or tuberculosis.
(2) Cautery of diathermy. NEUROLEPTANESTHETICS
(3) Acidosis.
(4) Advanced renal or hepatic disease. Examples
(5) Shock from trauma or hemorrhage. (1) Droperidol & Fentanyl citrate.
(2) Innovar (a premixed combination of droperidol &
NITROUS OXIDE fentanyl citrate).
Note: Nitrous oxide & Oxygen are added to these
neuroleptanalgesics to produce neuroleptanesthesia.
Alone, it is not effective as general anesthetic; so, usually Pharmacological Effects
supplement with opioids, thiopental & neuromuscular (A) Cardiovascular System
blockers. (1) Droperidol produce mild  - adrenergic blockade 
Pharmacological Effects Hypotension.
(A) Cardiovascular System (2) Fentanyl has parasympathomimetic effect 
Activation of symp. nervous system (when used with Bradycardia & hypotension.
potent inhalational anesthetics)  Inc. total peripheral (B) Respiratory System
resistance & BP, & dec. cardiac output. (1) Droperidol dec. respiratory rate but inc. tidal
(B) Respiratory System volume.
Similar to halothane except that, it causes dec. (2) Fentanyl dec. both respiratory rate & tidal volume.
respiratory rate & inc. tidal volume. (3) Both has marked respiratory depressant effect.
Advantages Adverse Effects
(1) Non explosive but supports combustion. (1) Post operative respiratory depression.
(2) Nonirritant to respiratory passages. (2) Confusion & mental depression.
(3) Rapid induction & recovery. (3) Extrapyramidal symptoms.
(4) No adverse effects on circulation & respiration.
(5) Good general analgesic.
Disadvantages KETAMINE
(1) Not effective general anesthetic.
(2) Inadequate muscle relaxation. Produces dissociative anesthesia.
(3) Diffusion hypoxia, during recovery. Pharmacological Effects
(4) Distension of bowel, expansion or rupture of pulmonary (A) Central Nervous System
cyst, rupture tympanic memb. in occluded middle ear, (1) Inc. cerebral blood flow.
pneumocephalus. (2) Inc. cerebral oxygen consumption.
(5) Air emboli. (3) Inc. intracranial pressure.
(6) Post operative nausea & vomiting. (B) Cardiovascular System
Contraindications Heart rate, arterial BP & cardiac output are significantly
(1) Pregnancy. inc. b/c of central symp. nervous system stimulation.
(2) Immunosuppressed pts. (C) Respiratory System
(3) Pernicious anemia. (1) Dec. respiratory rate slightly for 2-3 min.
(2) Upper airway muscle tone is well maintained.
CYCLOPROPANE (3) Upper airway reflexes are usually active.
Advantages
(1) Good analgesic & amnesic.
Advantages (2) No effect on laryngeal reflexes.
(1) Rapid induction & recovery. (3) Respiratory cycle is maintained near normal.
(2) Nonirritant to respiratory passages. (4) Useful in pts with shock b/c of cardiostimulatory effect.
(3) Wide safety margin. (5) Used in outpatient anesthesia.
(4) Have little effect on CVS; so, it is the anesthetic of Disadvantages
choice in shock. Recovery is accompanied by emergence delirium &
Disadvantages psychomotor activity.
(1) Explosive & inflammable. Contraindications
(2) Sensitizes myocardium to catecholamines. (1) Psychiatric disorders.
M. Shamim’s PHARMACOLOGY 58

(2) Cerebrovascular disease. DRUG CLASSIFICATION

(3) Respiratory infections.

(1) Esters
ETOMIDATE Cocaine, Procaine (Novocaine), Tetracaine
(Amethocaine), Benzocaine, Chloroprocaine,
Advantages Oxybuprocaine.
(1) Rapid induction. (2) Amides
(2) Minimal cardiovascular & respiratory effects. Lidocaine (Xylocaine, Lignocaine), Mepivacaine,
Disadvantages Bupivacaine, Levobupivacaine, Etidocaine, Prilocaine,
(1) Myoclonia. Dibucaine, Ropivacaine, Proxymetacaine (Proparacaine).
(2) Pain during injection. (3) Both ester & amide
(3) Postoperative nausea & vomiting. Articaine.
(4) Embryocidal effect. (4) Ethers
Pramoxine.
(4) Ketones
PROPANIDID
Dyclonine.
(5) Phenetidin Derivatives
Advantages Phenacaine.
Rapid induction & rapid recovery. (6) Alcohols
Disadvantages Ethyl alcohol, Benzyl alcohol.
(1) Hypotension, due to peripheral vasodilation & negative (7) Miscellaneous
inotropic effect. Ethylchloride, Eugenol (clove oil), Phenol.
(2) Major epileptiform convulsion occur.
MECHANISM OF ACTION OF LOCAL
PROPOFOL ANESTHETICS

Advantages Local anesthetics bind to receptors near intracellular ends

Rapid induction & rapid recovery. of Na-channels  This result in blockade of Na current 
Disadvantages Resulting in;
(1) Causes nausea, vomiting, & dreaming. (1) Inc. threshold for excitation.
(2) Muscle movement, hypotonus & tremors may occur. (2) Slow impulse conduction.
(3) Hypersensitivity reactions, eg hypotension, flushing (3) Declining of rate of rise of action potential.
& bronchospasm may occur. (4) Dec. action potential amplitude.
(5) Blockade of ability to generate action potential.
GENERIC & TRADE NAMES
PHARMACOLOGICAL EFFECTS OF LOCAL
(A) Inhalational Agents ANESTHETICS
Enflurane: Ethrane.
Halothane: Fluothane, Halothane. (1) Differential Nerve Block
Isoflurane: Forane. (a) Fibres with smallest diameter are blocked first.
Sevoflurane : Sevorane. Usual sequence is:
(B) Intravenous Agents Type B (preganglionic fibres)  Type C (dorsal
Benzodiazepines: See Chapter 5, Unit I. root pain fibres & sympathetic postganglionic
Fentanyl: Durogesic TTS, Fentyl. fibres)  Type A delta (pain & temperature fibres)
Ketamine: Calypsol, Ketasol. Type A gamma ( muscle spindle fibres)  Type A
Propofol: Diprivan, Propofol. beta (touch & pressure fibres)  type A alpha
Thiopental: Pentothal Na. (motor & proprioception fibres).
Etomidate: Etomidate Lipuro. (b) Myelinated nerves blocked before unmyelinated
nerves, eg, B fibres are blocked before the C fibres.
(c) In large nerve trunks, motor nerves are blocked
Unit II first b/c they are located circumferentially.
(d) In extremities, proximal sensory fibres (located in

Local Anesthetics
mantle of nerve) are blocked before the distal
sensory fibres (located in core).
(2) Effects on Other Excitable Membranes
06: Anesthetics 59

(a) Weak neuromuscular blocker (See answers on page no. 240)

(b) Similar depressant effect on cardiac cell memb. (67) All of the following statements about halogenated
anesthetics are accurate
CLINICAL USES OF LOCAL ANESTHETICS (A) All cause dec. hepatic & renal blood flow.
(B) All facilitate contraction of uterine smooth muscle.
(C) All cause dec. arterial pressure.
(1) For Topical Anesthesia
(D) All cause inc. in ventilatory response to CO2.
Lidocaine, Tetracaine, Dibucaine, Procaine.
(2) For Infiltration Anesthesia (E) Halothane is useful in pts. with asthma.
Lidocaine, Procaine, Prilocaine, Etidocaine, (68) All of the following statements about inhalational
Mepivacaine, Articaine (specifically for dental local agents are correct
anesthesia). (A) Postoperative hepatitis is associated mostly with
(3) For Nerve Block Anesthesia the use of isoflurane.
Lidocaine, Procaine, Mepivacaine, Chloroprocaine. (B) Mild, generalized muscle twitching occurs with
(4) For Spinal Anesthesia high doses of enflurane.
Lidocaine, Procaine, Tetracaine, Prilocaine, (C) Nitrous oxide is often used as a single agent in
Mepivacaine. anesthesia.
(5) For Epidural Anesthesia (D) Induction & recovery are rapid with nitrous
Etidocaine. oxide.
(6) For Regional Anesthesia (E) Methoxyflurane may causes postoperative
Prilocaine, Etidocaine, Mepivacaine, Bupivacaine. diuresis.
(7) For Treating Arrhythmias (69) All of following statements concerning intravenous
Lidocaine. anesthetics are correct
(A) Droperidol produces dissociative anesthesia.
ADVERSE EFFECTS OF LOCAL ANESTHETICS (B) Ketamine is a cardiovascular depressant.
(C) Ketamine inc. cerebral blood flow.
(D) Propanidid may causes major epileptiform
(1) CNS
convulsions.
Euphoria, sleepiness, light headedness, visual &
(E) Ketamine is used in outpatient anesthesia.
auditory disturbances, restlessness, nystagmus,
shivering, convulsions, depression. (70) Action of local anesthetics include
(2) CVS (A) Blockade of voltage- dependent Na+ channels.
Hypotension, cardiovascular collapse. (B) Preferential binding to resting channels.
Note: Cocaine doesn't cause hypotension b/c it has (C) Slowing of axonal impulse conduction.
vasoconstricting effect. (D) Inc. in threshold for excitation.
(3) Respiratory System (E) Blockade of slow Ca++ channels.
Respiratory failure secondary to CNS depression. (71) Regarding the clinical uses of local anesthetics,
(4) Blood following are correct
Methemoglobinemia (prilocaine). (A) Lidocaine is useful for epidural anesthesia.
(5) Allergic Reactions (B) Tetracaine is useful for topical anesthesia.
(C) Mepivacaine may be used for nerve block
GENERIC & TRADE NAMES anesthesia.
(D) Lidocaine is useful for treating arrhythmias.
(E) Etidocaine is useful for spinal anesthesia.xcretion.
(1) Procaine : Cardioplegia*.
(2) Benzocaine : Hitogen*.
(3) Oxybuprocaine: Medicaine, Novesin.
(4) Lidocaine: Anacaine, Epocain, Lignocain, Xylocaine.
(5) Bupivacaine: Abocain, Bupicain.
(6) Proparacaine : Alcaine.
(7) Ethylchloride : Ethylchloride spray.

Unit III

Self - Assessment (T/F)

M. Shamim’s PHARMACOLOGY 60

07 SKELETAL MUSCLE
RELAXANTS

Unit I
NEUROMUSCULAR BLOCKERS

Skeletal Muscle Relaxants MECHANISM OF ACTION

(A) Depolarizers
(1) Phase I Block (Depolarization)
The drug reacts with nicotinic receptors  Na-
DRUGS CLASSIFICATION channels are opened causing endplate
depolarization  This depolarization spreads
(A) Neuromuscular Blockers causing fasciculations  B/c drugs is not
(1) Drugs Preventing Action of Released metabolized rapidly, a flaccid paralysis results
Acetylcholine (b/c excitation- contraction coupling requires
(a) Depolarizers repolarization & repetitive firing to maintain
Suxamethonium (Succinylcholine), Decame- muscle tension)
thonium. Note: Phase I block is potentiated by
(b) Non - Depolarizers cholinesterase inhibitors & antagonized by
(i) Isoquinoline derivatives: Tubocurarine, tubocurarine.
Atracurium, Cisatracurium, Metocurine, (2) Phase II Block (Desensitization)
Doxacurium, Mivacurium. With continued drug exposure, memb. becomes
(ii) Steroid derivatives: Pancuronium, repolarized again by acetylcholine as longs as
Vecuronium, Pipecuronium, Rocuronium. blocking drug is present.
(iii) Others: Gallamine. Reason: A nonexcitable area develops in investing
(2) Drugs Depressing Acetylcholine Output muscle memb. which becomes repolarized shortly
(a) Inhibitors of Acetylcholine Synthesis after drug arrival. This impedes centrifugal spread
Hemicholinium, Triethylcholine. of impulses initiated by acetylcholine action on
(b) Inhibitors of Acetylcholine Release receptors.
Inc. Mg & PO4 ions, lack of Ca++, Procaine, Note: Phase II block is potentiated by tubocurarine
Botulinum toxin. & antagonized by cholinesterase inhibitors.
(B) Spasmolytics (Central Muscle Relaxants) (B) Non-depolarizers
(1) Diazepam (See Chapter 5, Unit I). They act by competing with acetylcholine for nicotinic
(2) Baclofen (GABA-mimetic at GABAB receptors). receptor sites at muscle end plate.
(3) Tizanidine (2 agonist). Note: Paralysis by nondepolarizers is potentiated by
(4) Gabapentin & pregabalin (GABA analogs). further administration of drug & antagonized by
(5) Progabide (GABAA & GABAB agonists) suxamethonium & cholinesterase inhibitors.
(6) Glycine (an inhibitory amino acid neurotransmitter).
(7) Idrocilamide & Riluzole (inhibitors of PHARMACOLOGICAL EFFECTS
glutamatergic transmission). (1) Skeletal Muscle
(8) Drugs used to treat acute local muscle spasm: Skeletal muscle paralysis;
Chlorphenesin, Carisoprodol, Chlorzoxazone, (a) Depolarizers
Cyclobenzaprine, Metaxalone, Methocarbamol, (i) Initially, transient muscle fasciculations occur
Orphenadrine. esp. over the chest & abdomen.
(C) Direct Skeletal Muscle Relaxants (ii) This is followed by spreading paralysis. Arm,
(1) Hydantoins: Dantrolene. neck & leg muscles are involved before the
(2) Botulinum toxin. facial & pharyngeal muscle. Respiratory
muscle involvement occurs lastly.
07: Skeletal Muscle Relaxants 61

(b) Non-depolarizers ADVERSE EFFECTS

Muscle are paralyzed in following order: (1) All Neuromuscular Blockers
(i) Muscles innervated by cranial nerves. (a) Resp: Prolonged apnea.
(ii) Muscles of limbs & trunk. (b) Muscle: Skeletal muscle pain.
(iii) Intercostal muscles. (2) Depolarizers
(iv) Diaphragm. (a) Eye: Inc. intraocular pressure.
Note : Recovery from muscle paralysis occurs in (b) CVS: Bradycardia, arrhythmias, cardiac arrest.
the reverse order. (c) Resp. tract: Inc. bronchial secretion.
(2) Cardiovascular System (d) GIT: Inc. intragastric pressure, emesis.
(a) Depolarizers (e) Temp: Malignant hyperthermia (when given
Succinylcholine stimulates nicotinic receptors in with halothane).
both sympathetic & parasympathetic ganglia, & (3) Tubocurarine, Metocurine, Atracurium &
muscarinic receptors in SA-node. This causes; Mivacurium
(i) In low doses, negative inotropic & chrono- (a) CVS: Hypotension.
tropic effects. (b) Resp. tract: Bronchospasm.
(ii) With large doses, positive inotropic & (4) Gallamine & Pancuronium
chrono- tropic effects. CVS: Tachycardia, hypertension.
(b) Non-depolarizers
(i) Vecuronium, Doxacurium & Pipecuronium DOSAGE
have no CVS effect. (1) Succinylcholine  0.5 - 1 mg/kg body weight, IV.
(ii) Tubocurarine & to a much lesser extent Meto-
(2) Tubocurarine  0.12 - 0.4 mg/kg body weight, IV.
curine, Atracurium & Mivacurium produce
(3) Gallamine  Initially 80-120 mg by IV inj., & if
"hypotension." This result from histamine
necessary further doses of 20-40 mg may be given.
release & in larger doses from ganglionic
blockade. (4) Pancuronium  Initial doses 0.02-0.06 mg/kg, IV;
incremental dose 0.01-0.02 mg/kg.
(iii) Gallamine & Pancuronium increases heart
rate, primarily by vagolytic action & (5) Atracurium  0.3-0.6 mg/kg, IV.
secondarily by sympathetic stimulation.
(3) Eye BACLOFEN
Succinylcholine causes an inc. in intraocular pressure,
which may be due to contraction of tonic myofibrils or
Pharmacological Effects
transient dilatation of choroidal blood vessels.
(1) It is an active spasmolytic & acts as a GABA agonist
(4) Gastrointestinal Tract
at GABAB receptors.
In muscular pts, fasciculations associated with
succinylcholine cause an inc. in intragastric pressure. (2) Also reduces pain in spasticity by inhibiting release
This may result in emesis. of substance P in the spinal cord.
(5) Histamine Release Adverse Effects
Tubocurarine causes moderate while succinylcholine, (1) CNS: Drowsiness, to which tolerance develops.
metocurine, atracurium & mivacurium causes slight (2) CVS: Hypotension, CV depression.
increase in histamine release. (3) Resp: Respiratory depression.
(6) Hyperkalemia (4) Muscle: Fatigue.
Succinylcholine causes inc. release of K+ into blood, (5) Renal: Dysuria, frequency of micturition.
that may result in cardiac arrest.
MEPHENESIN
CLINICAL USES
(1) As surgical adjuvants to general anesthesia, for Pharmacological Effects
promoting skeletal muscle relaxation.
(1) Skeletal muscle relaxation without inducing, sleep or
(2) For facilitation of endotracheal intubation, laryngo-
scopy, bronchoscopy, & esophagoscopy. loss of consciousness, by depressing transmission thru
(3) With electro-convulsant shock therapy, to prevent spinal & supraspinal polysynaptic pathways.
trauma. (2) Local anesthetic action preceded by local irritation.
(4) Treatment of tetanus & other convulsive states. Adverse Effects
(5) Diagnosis of myasthenia gravis. (1) CNS: Dizziness, lassitude, muscle weakness, ataxia.
(6) For control of ventilation, in pts with ventilatory (2) Eye: Nystagmus, diplopia.
failure to eliminate chestwall resistance & ineffective (3) GIT: Nausea, vomiting.
spontaneous ventilation. (4) Blood: Hemolysis.
(5) Renal: Hemoglobinuria.
M. Shamim’s PHARMACOLOGY 62

DANTROLENE (C) Atracurium.

(D) Succinylcholine.
(E) Vecuronium.
Mechanism of Action
(74) Regarding adverse effects of neuromuscular blockers,
It reduces skeletal muscle strength by interfering with
following are correct
excitation-contraction coupling in muscle fibre, by inhibiting
(A) Tubocurarine causes hypertension.
the release of activator Ca++ from sarcoplasmic reticulum.
(B) All causes skeletal muscle pain.
Note: Motor units that contract rapidly are more sensitive
(C) Succinylcholine causes arrhythmias.
to drug.
(D) Atracurium causes bronchodilation.
Clinical Uses
(E) All causes prolonged apnea .
(1) To reduce spasticity.
(2) In malignant hyperthermia.
Adverse Effects
(1) CNS: Sedation.
(2) Skeletal muscle: Generalized muscle weakness.
(3) Liver: Hepatitis.
Dosage
Begin with 25 mg daily as a single dose orally, increasing
to max. of 100 mg QID.

GENERIC & TRADE NAMES

(1) Neuromuscular Blockers

Succinyl choline: Leptosuccine, Muscolax, Pantolax,
Suxamethonium.
Atracurium: Atrelax, Tracrium.
Pancuronium: Pancron, Pavulon.
Vecuronium: Norcuron, Veronium.
Rocuronium: Esmeron.
Procaine: Cardioplegia*.
(2) Spasmolytics
Diazepam: See Chapter 5, Unit I.
Baclofen: Baclorax, Lioresal.
Tizanidine: Azanid, Movax, Tizadin.
Gabapentin: Engaba, Entin, Gabin.
Pregabalin: Gabica.
Orphenadrine: Duragesic*, Flexar*, Medigesic*,
Norflex, Norgesic*, Samerol N*.

Unit II

Self - Assessment (T/F)

(See answers on page no. 240)
(72) Characteristics of phase I depolarizing
neuromuscular blockade include
(A) Well- sustained tetanic tension.
(B) Marked muscarinic blockade.
(C) Muscle fasciculations in later stages of block.
(D) Potentiation by cholinesterase inhibitors.
(E) Antagonization by tubocurarine.
(73) All of the following may cause histamine release
(A) Tubocurarine.
(B) Pancuronium.
M. Shamim’s PHARMACOLOGY 63

08 OPIOID ANALGESICS &

ANTAGONISTS
MECHANISM OF ACTION
Unit I Opioid analgesics bind with & stimulate specific opioid
receptors in brain (ie, they mimic actions of endogenous
chemicals, known as opiopeptins)  This results in
Opioid Analgesics inhibition of release of excitatory neurotransmitters from
terminals of nerves containing nociceptive stimuli.
Neurotransmitters Showing Depressed Release
Acetylcholine, norepinephrine, dopamine, 5- hydroxy-
DRUG CLASSIFICATION
tryptamine & substance P.
Endogenous Opioid Peptides
OPIOID AGONISTS Methionine-enkephalin, leucine-enkephalin, dynorphine,
(1) Natural Opium Alkaloids neo-endorphins, dynorphine B, & -endorphin
(a) Phenanthrene Group Opioid Receptor Types
Morphine, Codeine. (1) Mu (  )
(b) Benzylisoquinoline Group Mediates supraspinal analgesia, respiratory depression,
Papaverine, Narcotine (Noscapine). euphoria & physical dependence, & is associated with
(2) Semi-Synthetic Opium Derivatives morphine-like analgesia & euphoria.
(a) Morphine Derivatives Subtypes: 1 & 2
Hydromorphone, Oxymorphone, Heroin (Diacetyl
(2) Kappa (  )
morphin).
Mediates analgesia, miosis & sedation, & is associated
(b) Codeine Derivatives with pentazocine-like analgesia, sedation & miosis.
Hydrocodone, Oxycodone, Dihydrocodeine,
(3) Delta (  )
Pholcodine.
Associated with alteration in effective behavior
(3) Synthetic Opium Substitutes
(a) Phenylpiperidines (4) Sigma (  )
(i) Strong agonists: Meperidine, (Pethidine), Associated with dysphoric, hallucinogenic & cardiac
Fentanyl, Sufentanil, Alfentanil, Remifentanil. stimulant effects
(ii) Mild to moderate agonists: Diphenoxylate, Opioid Receptor Distribution
Loperamide, (1) Limbic system including amygdaloid nucleus & hypo-
thalamus.
(b) Phenylheptylamines
Methadone, Propoxyphene, Levomethadyl acetate. (2) Medial & lateral thalamus, & area postrema.
(3) Nucleus of tractus solitarius.
(c) Morphinans
Levorphanol, Dextromethorphan. (4) Substantia gelatinosa, & other areas of spinal cord.

OPIOID AGONIST - ANTAGONISTS & PARTIAL PHARMACOLOGICAL EFFECTS

AGONISTS (1) Central Nervous System
(1) Phenanthrenes (a) Analgesia
(i) By raising threshold for pain sensation.
Nalbuphine, Buprenorphine.
(ii) By changing pain perception, & reaction of pt.
(2) Morphinans
Butorphanol. to pain.
(3) Benzomorphans (b) Euphoria
Pentazocine, Dezocine. (i) Pt. in pain or addict experiences a pleasant
floating sensation, & freedom from anxiety &
(4) Miscellaneous
distress.
Tramadol.
(ii) Normal subjects experience dysphoric effects.
(c) Sedation
OPIOID AGONISTS
M. Shamim’s PHARMACOLOGY 64

It consists of drowsiness, clouding of mentation, results from opioids central effects as well as histamine
& some impairment of reasoning ability. release causing cutaneous vasodilation.
(d) Respiratory Depression
(i) It results from reduced responsiveness of CLINICAL USES
respiratory centre in brainstem to blood levels (1) Analgesia
of CO2. Used for relief of pain resulting from myocardial
(ii) Inc. arterial CO2 retention causes cerebral vaso- infarction, terminal illness, surgery, obstetrical
dilation resulting in inc. intracranial pressure. procedures, cancer &, biliary & renal colics.
(e) Cough Suppression Note: For Biliary & renal colics strong agonist in inc.
It results from suppression of cough centre located dose is used.
in nucleus of tractus solitarius. (2) For relief of dyspnea from pulmonary edema associated
(f) Miosis with left ventricular failure.
It results from stimulation of Edinger-Westphal (3) Cough.
nucleus, causing pin-point pupils. (4) Diarrhea.
(g) Truncal Rigidity (5) As premedicant drugs before anesthesia & surgery.
Intensification of tone in large trunk muscles
occur as a result of opioids' stimulating action at ADVERSE EFFECTS
spinal cord level Dec. thoracic compliance, & (1) CNS
interference with respiration. Inc. intracranial pressure, behavioral restlessness,
(h) Emesis tremulousness, hyperactivity (in dysphoric reaction).
Stimulation of brainstem chemoreceptor trigger (2) CVS
zone results in nausea & vomiting. Postural hypotension esp. in hypovolemia.
(2) Neuroendocrine (3) GIT
(a) Stimulate release of ADH, prolactin & Nausea, vomiting, constipation.
somatotropin. (4) Resp
(b) Inhibit release of luteinizing hormone. Respiratory depression.
(3) Cardiovascular System (5) Renal
(a) No significant direct effect on CVS. Urinary retention.
(b) Hypotension may occur if CVS is already stressed. (6) Skin
This is due to peripheral arterial & venous dilation Urticaria, itching (around nose).
resulting from histamine release & central (7) Tolerance
depression of vasomotor centre. Manifests clinically after 2-3 weeks of frequent
(c) Cerebral vasodilation due to respiratory depression therapeutic doses:
causes inc. intracranial pressure. (a) High degree of tolerance occur for analgesia,
(4) Gastrointestinal Tract euphoria, dysphoria, mental clouding, sedation,
(a) Dec. intestinal propulsive peristalsis & stomach resp. depression, antidiuresis, nausea, vomiting, &
motility  Constipation. cough suppression.
(b) Spasmodic nonpropulsive contractions of gastro- (b) No tolerance occur for miosis & constipation.
intestinal smooth muscle. (c) Cross-tolerance may occur among different opioid
(c) Dec. gastric HCl secretion. analgesics.
(5) Biliary Tract (8) Physical dependence
(a) Constriction of biliary smooth muscles  Biliary It results in withdrawal (abstinence) syndrome, if there
colic. is failure to continue administer drug.
(b) Constriction of sphincter of Oddi  Inc. biliary Symptoms & signs: Rhinorrhea, lacrimation, yawning,
pressure, reflux of biliary & pancreatic secretions, chills, goose pimples, hyperventilation, hyperthermia,
& elevated plasma amylase & lipase levels. mydriasis, muscular aches, vomiting, diarrhea, anxiety,
(6) Urinary Tract & hostility.
(a) Dec. renal plasma flow  Depressed renal function. (9) Psychologic dependence
(b) Inc. ureteral & bladder tone. Effects such as euphoria, indifference to stimuli,
(c) Inc. urethral sphincter tone  Urinary retention sedation & a peculiar abdominal experience linked to
esp. in postoperative pts. intense sexual orgasm, leads to psychologic
(7) Uterus dependence.
Dec. uterine tone  Prolong labor.
(8) Skin CONTRAINDICATIONS
Opioids produce flushing & warming of skin, sometime
(1) With mixed agonist-antagonists opioids.
accompanied by sweating & itching. These effects
(2) Pts with head injuries.
08: Opioid Analgesics & Antagonists 65

(3) Pregnancy. (4) Unlike pentazocine & butorphanol, it does not cause
(4) Pts with impaired pulmonary function adverse cardiac effects.
(5) Liver disease. (5) Both physical & psychological dependence can occur.
(6) Pts with endocrine disease eg Addison's disease,
myxedema. TRAMADOL
(1) It is a centrally acting analgesic, predominantly via
DOSAGE blockage of serotonin reuptake.
(2) Also a weak mu-receptor agonist.
(1) Morphine  10 mg; SC, IM.
(3) No clinically significant effect occurs on respiratory or
(2) Oxymorphone  1.5 mg; SC, IM. cardiovascular systems.
(3) Methadone  120 mg; Orally, SC. (4) Used as an adjunct with pure opioid agonists in the
(4) Meperidine  60-100 mg; oral, SC, IM, IV. treatment of chronic neuropathic pain.
(5) Fentanyl  0.1 mg; I M, IV. (5) Adverse effects include nausea & dizziness.
(6) Levorphanol  2-3 mg; oral, IM. (6) Contraindicated in epileptics.
(7) Codeine  30-60 mg; oral, IM.
(8) Oxycodone  4.5 mg; oral, IM.
HEROIN

OPIOID AGONIST – ANTAGONISTS & PARTIAL

(1) It is diacetylated morphine.
AGONIST
(2) It has more rapid onset & shorter duration of action
than morphine.
Examples (3) Its analgesic potency is greater than morphine.
Pentazocine, Butorphanol, Buprenorphine, Nalbuphine, (4) It is the most potent of all dependence producing drugs.
Tramadol.
Mechanism of Action SIGNS & SYMPTOMS OF HEROIN POISONING
They competitively block mu receptors &, act as agonists (1) Sleepiness, lethargy, or coma, depending on dose.
on kappa & sigma receptors. (2) Bradycardia & hypotension.
(1) Produce analgesia in the absence of opioid agonists. (3) Hypoventilation or apnea.
(2) In the presence of agonists, they block many of the (4) Pin-point pupils.
actions of latter drugs. (5) Skin cool; may show signs of IV or IM drug abuse with
associated infectious disease complications.
PENTAZOCINE (6) Dec. bowel sounds.
(1) It is kappa-agonist, with mu-antagonist properties. (7) Muscle tone flaccid; occasionally twitching, & rigidity.
(2) Pharmacological effects are nearly similar to morphine
but has one-fifth analgesic properties. TREATMENT OF HEROIN POISONING
(3) Produce psychomimetic effects eg, anxiety & (1) Administration of antagonist Naloxone; 1- 2 mg by IV,
hallucination. IM or SC inj., & repeated every 2-3 min. for 2-3 doses.
(4) Cause less nausea & constipation. (2) Airway support.
(5) Unlike opioid agonists, it inc. pulmonary artery pressure
& cardiac work, & causes hypertension & tachycardia. TREATMENT OF HEROIN ADDICTS
(6) Respiratory depression is less pronounced. (1) Drug Treatment
(7) Due to its antagonistic activity, it is capable of precipi- (a) Stop heroin & start giving methadone. Methadone
tating withdrawal in agonist addicts. suppress withdrawal symptoms which occur after
(8) Tolerance to analgesia can develop. stopping heroin, & it also satisfy craving for heroin
(9) Both physical & psychological dependence can occur, without producing euphoria or somnolence.
but less than with agonists. (b) Then gradually reduce the dose of methadone, &
finally withdraw it.
BUTORPHANOL (2) Psychiatric Treatment
(1) It is kappa agonist. (a) Effects are made to remove the causes responsible
(2) Pharmacological effects similar to Pentazocine. for addiction.
(3) Unlike Pentazocine, it does not ppt. withdrawal synd. in (b) Contacts of addict with his antisocial associates
opioid addicts. should be stopped.
(c) He should be engaged in some job to keep him
NALBUPHINE busy &, divert his mind to useful occupations.
(1) It is kappa-receptor agonist, & mu-receptor antagonist. (d) He is informed about the harmful effect of
(2) Produce analgesia equal to morphine. addiction on his health & the ruin it brings to his
(3) Produce withdrawal state in opioid addict.
M. Shamim’s PHARMACOLOGY 66

family besides entailing risk of going to jail for CLINICAL USES

his criminal acts. (1) Acute opioid overdosage.
(2) As maintenance drug for addicts in treatment programs.
GENERIC & TRADE NAMES (3) Cerebrovascular disease, eg stroke.

DOSAGE
(1) Opioid Agonists
Naloxone  0.1-0.4 mg IV, which can be repeated as
Papaverine: Spasmogin*.
necessary.
Noscapine, Dextromethorphan, & Pholcodine: See
Chapter 13, Unit III.
Fentanyl: Durogesic, Fentyl. GENERIC & TRADE NAMES
Diphenoxylate, & Loperamide: See Chapter 14, Unit
III. Naloxone: Nalox, Narcan.
Dextropropoxyphene: Draphene, Paradecaphen, Naltrexone: Trexan.
Algaphan*, Analphene*, Darvin*, Diagesic*,
Distalgesic*, Femidol*, Jalgesic*.
Morphine: Magnus Mr, Morphine inj.
Unit III
Codeine: Codar, Codogesic, Tempol C.
Pethidine: Pethidine inj.
(2) Opioid Agonist- Antagonists
Nalbuphine: Nalbine, Nalbinor, Nubain. Self - Assessment (T/F)
Buprenorphine: Buepron, Bunorfin, Bupregesic,
Dorfene, Temgesic. (See answers on page no. 240)
Butorphanol: Deocalm. (75) All of the following statements about opioid
Pentazocine: Fortagesic*, Panto, Pentagesic, analgesics are correct
Pentazogon, Penzocine, Sosegon. (A) They have no significant direct effects on heart
Tramadol: Nopa, Tamadol, Tradol, Tramal. (B) They stimulate chemoreceptor trigger zone
(C) They relax the smooth muscle of bladder
(D) They dec. intestinal peristalsis
Unit II (E) They produce flushing & warming of skin
(76) Interaction of opioid analgesic with kappa

Opioid Antagonists receptors leads to all of the following

(A) Sedation
(B) Cerebral vascular dilatation
(C) Euphoria
OPIOID ANTAGONISTS (D) Spinal analgesia
(E) Miosis
(77) With continued use of strong opioid analgesics,
DRUG CLASSIFICATION
tolerance develops to all of the following effects
(1) Phenanthrene (A) Constipation
Nalorphine, Naloxone, Naltrexone, Nalmefene. (B) Analgesia
(2) Morphinans (C) Sedation
Levallorphan. (D) Cough suppression
(E) Miosis
PHARMACOLOGICAL EFFECTS
(1) When given in absence of opioid agonists, they are (78) Which of the following statements about
almost inert at therapeutic doses; however, at higher pentazocine is incorrect
dose antagonizes endogenous opiopeptins. (A) It is a mixed agonist-antagonist
(2) When given to opioid-treated subject, they completely (B) It precipitates withdrawal in agonist addicts.
reverse opioid effects within 1-2 min. (C) It produces less euphoria than morphine.
(3) In acute opioid overdosage, they effectively normalize (D) It is often combined with morphine for maximal
respiration, level of consciousness, pupil size, bowel analgesic effects.
activity, etc. (E) High doses of pentazocine causes hypertension.
(4) In dependent subjects who appear normal while taking (79) Opioid antagonists include
opioids, they almost instantaneously ppt. withdrawal (A) Naloxone.
synd. (B) Nalorphine.
(5) There is no tolerance to their antagonistic actions. (C) Levallorphan.
08: Opioid Analgesics & Antagonists 67

(D) Levorphanol.
(E) Nalbuphine.
M. Shamim’s PHARMACOLOGY 68

NONSTEROIDAL ANTI-INFLAMMATORY
09 DRUGS, NONOPIOID ANALGESICS, &
ANTI-RHEUMATOID & ANTI-GOUT DRUGS

(3) Enolcarboxamide
Unit I Meloxicam.
(4) Isoxazole
Valdecoxib.
NSAIDs
ASPIRIN

DRUG CLASSIFICATION MECHANISM OF ACTION

It irreversibly blocks both isoforms of cyclooxygenase
(A) Nonselective COX Inhibitors (COX-1 & COX-2), thereby decreasing prostaglandin &
(1) Salicylates thromboxane synthesis thru-out the body.
Acetyl salicylic acid (Aspirin), Salicylic acid, Na Note: COX-1 is primarily expressed in non-inflammatory
salicylate, Methyl salicylate, Choline salicylate, Mg cells, whereas COX-2 is expressed in activated lymphocytes,
salicylate, Na thiosalicylate. polymorphs & other inflammatory cells.
(2) Propionic Acid Derivatives
Ibuprofen, Fenoprofen, Ketoprofen, Flurbiprofen, PHARMACOLOGICAL EFFECTS
Indoprofen, Fenbufen, Carprofen, Tiaprofen, (1) Anti-inflammatory
Naproxen, Oxaprozin. (a) Inhibits prostaglandin biosynthesis by irreversibly
(3) Substituted Anthranilic Acids blocking 'cyclooxygenase' which catalyzes reaction
Meclofenamate, Mefenamic acid, Flufenamic acid, of arachidonic acid to endoperoxide compounds.
Tolfenamic acid. (b) In high dose, also inhibits thromboxane A2
(4) Phenylacetic Acids formation, by the same enzyme (cyclooxygenase)
Diclofenac Na, Diclofenac K. inhibition.
(5) Acetic Acid Derivatives (c) Inhibits granulocyte adherence to damaged vascu-
Ketorolac, Etodolac. lature, stabilizes lysosomes, & inhibits migration of
(6) Indole Acetic Acids polymorphonuclear leukocytes & macrophages into
Indomethacin. inflammation site.
(7) Sulfoxides (d) Interferes with chemical mediators of kallikrein
Sulindac. system.
(8) Pyrrolealkanoic Acid (2) Analgesic
Tolmetin. Aspirin reduces mild to moderate pain of varying cause,
(9) Pyrazolone Derivatives eg, of muscular, vascular & dental origin, postpartum
Phenylbutazone, Apazone, Oxyphenbutazone, states, arthritis & bursitis.
Dipyron (Metamizol). Mechanism
(10)Oxicams (a) Due to its anti-inflammatory effects.
Piroxicam,Tenoxicam. (b) Due to depression of pain stimuli at subcortical site.
(11)Difluorophenyl Derivatives (3) Antipyretic
Diflunisal. Aspirin reduces only elevated temperature.
(12)Naphthylacetic Acid Prodrug Mechanism
Nabumetone. (a) Inhibition of PGE2 synthesis.
(B) COX-2 Selective Inhibitors (b) Blockade of CNS response to interleukin-1.
(1) Sulfonamide (c) Vasodilation of superficial blood vessels causing
Celecoxib, Nimesulide. inc. dissipation of heat.
(2) Bipyridine Derivatives (4) Platelets
Etoricoxib.
09: Nonsteroidal Anti-Inflammatory Drugs, Nonopioid Analgesics, & Anti-Gout Drugs 69

Inc. bleeding time due to inhibition of platelet (a) With higher doses 'Salicylism' occur characterized
aggregation secondary to thromboxane synthesis by tinnitus, dec. hearing, vertigo, headache,
inhibition. confusion, lassitude, drowsiness, hyperthermia,
(5) Cardiovascular System sweating, thirst.
(a) Peripheral vasodilation, at large doses. (b) Still higher doses, causes hypernea.
(b) Vasomotor paralysis, at toxic doses. (c) At toxic doses, respiratory alkalosis & later
(6) Respiration acidosis.
(a) Inc. depth of respiration due to inc. in alveolar (2) CVS
ventilation, resulting from inc. oxygen Depressed cardiac function & peripheral vasodilation at
consumption, & CO2 production in skeletal muscle. toxic doses.
(b) At higher doses, hyper-ventilation leading to (3) GIT
respiratory alkalosis; however, compensation occur Gastric intolerance, gastritis, upper gastrointestinal
thru kidneys. bleeding, vomiting (of central origin).
(c) At toxic doses, medullary respiratory centre (4) Renal
depression resulting in uncompensated respiratory Dec. glomerular filtration rate.
acidosis. (5) Liver
(7) Gastrointestinal Tract Hepatitis.
(a) Aspirin stimulate chemoreceptor trigger zone in (6) Hypersensitivity Reactions
CNS, causing emesis. Bronchoconstriction & shocks, occur in pts with
(b) Produce dose-related gastric ulceration & asthma & nasal polyps.
hemorrhage. Treatment of Salicylate Poisoning
(c) Inhibits gastric mucus secretion. (1) Induce emesis with ipecac syrup, or perform gastric
(d) Inc. gastric acid secretion, as it inhibits synthesis lavage.
of PGI2. (2) Correct abnormal electrolyte imbalance & dehydration.
(8) Renal (3) Urine alkalinization.
(a) Inc. excretion of Na-urate resulting in uricosuria, at (4) Dialysis.
dosage above 5 g.
(b) Dec. excretion of Na-urate resulting in CONTRAINDICATIONS
hyper-uricemia, at dosage below 2 g. (1) Hemophilia.
(9) Endocrine (2) Pregnancy.
(a) In very large doses, stimulates adrenal cortex (3) Peptic ulcer.
steroid secretion, thru an action on hypothalamus.
(b) Causes competitive displacement of thyroxin & DOSAGE
triiodothyronine from prealbumin leading to their (1) Analgesic or antipyretic dose  300-600 mg, every 4
enhanced rate of disappearance. hours orally.
(c) Prolong gestational period during pregnancy, due (2) Anti-inflammatory dose  4 g daily, orally, in 3 divided
to delay in onset of labor b/c of prostaglandin doses taken after meal.
synthesis inhibition.
(10)Metabolic DRUG INTERACTION
(a) Aspirin uncouple oxidative phosphorylation. (1) Acetazolamide, NH4CL & alcohol enhance salicylate
(b) Large doses produce hyperglycemia & glycosuria.
intoxication.
(c) Reduce lipogenesis by blocking incorporation of
(2) Aspirin displaces drugs from protein binding sites,
acetate into fatty acids.
eg, tolbutamide, chlorpropamide, NSAIDs, phenytoin,
probenecid.
CLINICAL USES (3) It reduces pharmacologic activity of spironolactone, &
(1) Mild to moderate pain eg, headache, arthritis, antagonize effects of heparin.
dysmenorrhea. (4) It competes with penicillin G for renal tubular secretion.
(2) Rheumatoid arthritis & other inflammatory joint
conditions.
(3) Fever esp. acute rheumatic fever. PROPIONIC ACID DERIVATIVES
(4) Unstable angina (as prophylactic agent).
(5) Cataract. Examples
(6) Gout. Ibuprofen, Fenoprofen, Ketoprofen, Naproxen, Flurbiprofen,
Indoprofen, Fenbufen, Carprofen, Oxaprozin..
ADVERSE EFFECTS Pharmacological Effects
(1) CNS (1) Anti-inflammatory (non-selective reversible blockage of
cyclooxygenase).
M. Shamim’s PHARMACOLOGY 70

(2) Analgesic (non-selective reversible blockage of (1) Nasal polyps.

cyclooxygenase). (2) Angioedema.
(3) Antipyretic (non-selective reversible blockage of (3) Asthma.
cyclooxygenase). (4) Pregnancy.
(4) Inhibits platelet aggregation. (5) Psychiatric disorders.
(5) Inhibits prothrombin synthesis. (6) Peptic ulcer.
Clinical Uses Dosage
(1) Mild rheumatoid arthritis. (1) Indomethacin  Initially 200 g BD, IM or IV; then
(2) Ankylosing spondylitis. 200 g either daily or every other day in chronic cases.
(3) Osteoarthrosis. (2) Sulindac  200 mg BD, orally.
(4) Seronegative arthropathies.
(5) Periarticular disorders eg, bursitis, capsulitis of shoulder,
tenosynovitis, sprains, strains & low back pain. PHENYLBUTAZONE
(6) Soft tissue injuries.
(7) Mild to moderate pain eg, dental pain, dysmenorrhea. Pharmacological Effects
(8) Acute gout (Naproxen). Similar to propionic acid derivatives.
Adverse Effects Clinical Uses
(1) CNS: Headache, dizziness, tinnitus, anxiety, aseptic (1) Rheumatoid arthritis.
meningitis. (2) Ankylosing spondylitis.
(2) GIT: Gastrointestinal irritation and bleeding ( less (3) Acute gouty arthritis.
severe than with aspirin). (4) Musculoskeletal disorders.
(3) Renal: Acute renal failure, interstitial nephritis, (5) Osteoarthritis.
nephrotic syndrome. Adverse Effects
(4) Skin: Rash, pruritus. (1) Eye: Optic neuritis.
(5) Blood: Agranulocytosis, aplastic anemia. (2) Ear: Deafness.
Contraindications (3) Renal: Nephrotic synd., renal tubular necrosis.
(1) Active peptic ulcer. (4) Liver: Hepatic necrosis.
(2) Nasal polyps. (5) Skin: Exfoliative dermatitis.
(3) Angioedema. (6) Blood: Agranulocytosis, aplastic anemia, hemolytic
(4) Bronchospastic reactivity to aspirin. anemia.
Dosage (7) Allergic reactions
(1) Ibuprofen  1200 - 1800 mg daily, orally in divided Dosage
doses; max. 2400 mg. 100 - 200 mg, TDS.
(2) Fenoprofen  300 - 600 mg orally, TDS or QID; max.
3g KETOROLAC
(3) Naproxen  250 - 500 mg orally, BD.

Mechanism Of Action
INDOMETHACIN Like most NSAIDs, ketorolac is a non-selective COX
inhibitor.
Pharmacological Effects Pharmacological Effects
Similar to propionic acid derivatives. Similar to propionic acid derivatives.
Clinical Uses Clinical Uses
(1) Patent ductus arteriosus (Indomethacin). Short-term management of pain (up to five days maximum).
(2) Acute gouty arthritis. Adverse Effects
(3) Ankylosing spondylitis. Similar to other NSAIDs.
(4) Osteoarthritis of hip. Contraindications
(5) Pericarditis. (1) Hypersensitivity to ketorolac.
(6) Rheumatoid arthritis. (2) In patients with nasal polyps, angioedema,
(7) Bartter's syndrome. bronchospastic reactivity or other allergic
(8) Not routinely used for analgesia or antipyresis. manifestations to aspirin or other NSAIDs.
Adverse Effects (3) Renal dysfunction.
(1) CNS: Headache, dizziness, confusion, depression,
psychosis, hallucinations. CELECOXIB
(2) CVS: Coronary vasoconstriction.
(3) GIT: Abd. pain, diarrhea, GI bleeding, pancreatitis.
(4) Blood: Thrombocytopenia, aplastic anemia. Mechanism Of Action
Contraindications
09: Nonsteroidal Anti-Inflammatory Drugs, Nonopioid Analgesics, & Anti-Gout Drugs 71

It is a highly selective COX-2 inhibitor (inhibition of (2) For analgesia in aspirin allergic pts.
prostaglandin production). (3) Fever.
Pharmacological Effects Adverse Effects
COX-2 selectivity allows celecoxib (& other COX-2 (1) CNS
inhibitors) to reduce inflammation & pain, while minimizing Dizziness, excitement, disorientation.
gastrointestinal adverse effects that are common with non- (2) Renal
selective NSAIDs. Acute tubular necrosis.
Clinical Uses (3) Liver
(1) Osteoarthritis. (a) At therapeutic doses, a mild inc. in hepatic enzymes.
(2) Rheumatoid arthritis. (b) Ingestion of 15 g or more causes severe hepato-
(3) Acute pain. toxicity with central lobular necrosis. Early
(4) Painful menstruation and menstrual symptoms. symptoms of hepatic damage include nausea,
(5) To reduce the number of colon & rectal polyps in vomiting, diarrhea & abd. pain.
patients with familial adenomatous polyposis. (4) Endocrine
Adverse effects Hypoglycemic coma.
(1) Significantly lower incidence of gastrointestinal (5) Hypersensitivity Reactions
ulceration than traditional NSAIDs. Skin rashes, drug fever.
(2) Allergic reactions Treatment of Overdosage
(3) Increased risk for heart attack & stroke (a) Stomach wash & administering activated charcoal.
Dosage (b) Hemodialysis, if begun within first 12 hrs of ingestion.
100 to 200 mg once or twice a day. (c) Paracetamol antidote eg, Methionine, Acetylcysteine,
Cysteamine HCI.
Contraindications
Unit II (1) Hypersensitivity to acetaminophen.
(2) Impaired hepatic functions.
Dosage
Nonopioid Analgesics 325 - 500 mg QID, orally.

GENERIC & TRADE NAMES (NSAIDS &

DRUG CLASSIFICATION NONOPIOID ANALGESICS)

(A) Aniline Derivatives (1) Nonselective COX Inhibitors

Acetaminophen ( Paracetamol ), Phenacetin. Aspirin: Anaprin, Ascard, Aspirin, Aspro, Dispirin,
(B) Nonsteroidal Anti-inflammatory Drugs Empirin-S, Empirin comp, Epalcin*, Irzapyrin*,
(1) Salicylates. Lopirin, Meprogesic, Trigesic*.............
(2) Propionic acid derivatives. Methyl salicylate: Methyl salicylate, Wintogeno.
(3) Indole acetic acids. Choline salicylate: Bonjela*.
(4) Substituted anthranilic acids. Ibuprofen: Anglofen, Brufen, Dolofen, Ibugen, Ibu-
(5) Pyrrolealkanoic acids. slow, Inflam, Profen, Ruberin, Rumafen......................
(6) Pyrazolone derivatives. Ketoprofen: Ketonal, Mobifen, Oruvail, Profenid.
(7) Oxicams. Flurbiprofen: Ansaid, Froben, Lubifen, Ocufen.
(8) Difluorophenyl derivatives. Tiaprofen: Surgam.
(9) Carbazole derivatives. Naproxen: Aproxen, Flexin, Naprosyn, Naprox,
(10) Phenylacetic acids. Naptrol, Nepexen, Proxen, Synflex, Xenar CR.
Note: For detail of each drug group see previous unit. Oxaprozin: Daypro.
Meclofenamate: Meclomen.
Mefenamic acid: Befenac, Dologin, Dolor, Doloran,
ACETAMINOPHEN Mefenamic acid, Mefgesic, Ponstan............
Diclofenac K: Cataflam, Caflam, Deflam, Dolo K.
Pharmacological Effects Diclofenac Na: Alcazar, Almiral, Artifen, Diclofen,
(1) It is an effective analgesic & antipyretic agent. Diclogesic, Dicloran, Diclozaf, Phlogin, Voltaren,
Mechanism: Thru inhibition of prostaglandin synthesis Voren, Vurdon........................................
in brain. Ketorolac: Toradol, Torapan.
(2) It has no anti-inflammatory effect. Indomethacin: Anglocid, Camcocid, Elmetacin,
Clinical Uses Incin, Indocin, Indobid, Liometacen.
(1) Mild to moderate pain eg, headache, myalgia, post- Phenylbutazone: Pharmazone, Wilzolid.
partum pain. Dipyron: Dipyron, Elkopyron, Fibrex, Javalgin.
M. Shamim’s PHARMACOLOGY 72

Piroxicam: Brexin, Feldene, Limbar, Paldon, Riacen, (8) Auranofin inhibits release of PGE2 from synovial cells
Rosiden, Roxicam. &, release of leukotriene B4 & C4 from polymorphs.
Tenoxicam: Tenoxam, Tenoxim, Tenoxitil. Clinical Uses
Nabumetone: Relifex. Active progressive rheumatoid arthritis inadequately
(2) COX-2 Selective Inhibitors controlled by other NSAIDs.
Celecoxib: Articoxib, Celoxib, Nuzib, Osteoxib. Adverse Effects
Nimesulide: Amsolide, Mesulid, Nimsulid, Nise. (1) CNS: Nitritoid reactions characterized by headache,
Meloxicam: Articam,Melocam, Mobex, Synlox. faintness, sweating & flushing; peripheral neuropathy.
Valcecoxib: Vorteil. (2) Eye: Corneal deposits of gold.
(3) Aniline Derivatives (3) GIT: Stomatitis, metallic taste in mouth, diarrhea,
Acetaminophen: Anamol, Calpol, Coldene*, Coldrex*, neuropathy.
Diagesic*, Disprol, Duragesic*, Kaypol, Medigesic*, (4) Resp. Tract: Pulmonary infiltrates.
Panadol, Panaram, Paracetamol, Samerol*.................. (5) Renal: Proteinuria, nephrotic synd.
(6) Liver: Cholestatic jaundice.
(7) Skin: Pruritic dermatitis, skin pigmentation.
Unit III (8) Blood: Thrombocytopenia, leukopenia, pancytopenia,
eosinophilia, aplastic anemia.
Contraindications
Disease Modifying Anti- (1) Previous toxicity.
Rheumatic Drugs (DMARDs) (2) Pregnancy.
(3) Serious liver impairment.
(4) Serious renal impairment.
(5) Blood dyscrasias.
DRUG CLASSIFICATION Dosage
(1) Aurothiomalate & aurothioglucose  50 mg IM
weekly until a total of 1000 mg has been injected.
(1) Immunosuppressive Drugs (2) Auranofin  6 mg orally daily, increasing to 9 mg/d
Methotrexate, Mechlorethamine, Chlorambucil, if a response is not seen after 3 months.
Cyclophosphamide, Cyclosporine, Azathioprine,
Mycophenolate mofetil.
(2) 4- Aminoquinolines INFLIXIMAB
Chloroquine, Hydroxychloroquine.
(3) Gold It is known as a "chimeric monoclonal antibody" (the term
Aurothiomalate, Aurothioglucose, Auranofin. "chimeric" refers to the use of both mouse & human
(4) Penicillin Metabolite components of the drug i.e. murine binding Fab domains &
Penicillamine. human constant Fc domains).
(4) TNF- Blockers Mechanism Of Action
Adalimumab, Infliximab, Etanercept. It blocks the action of the pleiotropic proinflammatory TNFα
(5) Others (tumor necrosis factor alpha) by binding to it & preventing it
Sulfasalazine, Abatacept, Rituximab, Leflunomide, from signaling the receptors for TNFα on the surface of cells.
Anakinra. Note: TNFα is one of the key cytokines that triggers &
sustains the inflammation response.
GOLD Pharmacological Effects
COX-2 selectivity allows celecoxib (& other COX-2
inhibitors) to reduce inflammation & pain, while minimizing
Examples gastrointestinal adverse effects that are common with non-
Aurothiomalate, Aurothioglucose, Auranofin. selective NSAIDs.
Pharmacological Effects Clinical Uses
(1) Alter morphologic & functional capabilities of macro- (1) Rheumatoid arthritis.
phages. (2) Ankylosing spondylitis.
(2) Inhibit lysosomal enzyme activity. (3) Juvenile chronic arthritis.
(3) Reduces histamine release from mast cells. (4) Psoriatic arthritis.
(4) Inactivates first component of complement. (5) Psoriasis.
(5) Suppress phagocytic activity of polymorphs. (6) Ulcerative colitis.
(6) Inhibits Shwartzman phenomenon. (7) Crohn's disease.
(7) Aurothiomalate reduces number of circulating (8) Wegener’s granulomatosis.
leukocytes. (9) Giant cell arteritis.
09: Nonsteroidal Anti-Inflammatory Drugs, Nonopioid Analgesics, & Anti-Gout Drugs 73

(10) Sarcoidosis. (1) It relieves pain & inflammation of gouty arthritis in

Adverse effects 12-24 hrs without altering metabolism or excretion of
(1) CNS: Headache, demyelinating syndromes. urates, & without other analgesic effects.
(2) CVS: Vaculitis. (2) It produces anti-inflammatory effects by binding to
(3) Resp: Upper respiratory tract infections, sinusitis, micro-tubular protein 'tubulin', thereby preventing its
cough. polymerization & leading to inhibition of leukocyte
(4) GIT: Nausea, hepatitis. migration & phagocytosis.
(5) Blood: Leukopenia, activation of latent tuberculosis. (3) It also inhibits leukotriene B4 formation.
(6) Skin: Rash, infusion site reaction. Clinical Uses
Dosage (1) For prophylaxis & treatment of acute gouty arthritis.
3-5 mg/kg every 8 weeks, as an intravenous infusion. (2) Mediterranean fever.
(3) Sarcoid arthritis.
GENERIC & TRADE NAMES Adverse Effects
(1) GIT: Nausea, vomiting, abd. pain.
(2) Appendages: Hair loss (alopecia).
Immunosuppressive drugs: See Chapter 23. (3) Bone marrow: Bone marrow depression.
4- Aminoquinolines: See Chapter 21. (4) Skeletal muscle: Myopathy.
Penicillamine: Vistamin. (5) Acute intoxication: Results from over dosage, &
Infliximab: Remicade. characterized by burning throat pain, bloody diarrhea,
Sulfasalazine: Salazine, Salazodine, Salazopyrin. shock, hematuria, oliguria & CNS depression.
Rituximab: Mabthera. Dosage
Leflunomide: Ariva, Flunomid, Lenomide. (1) For treatment of acute attack  Initially 0.5 - 1 mg,
followed by 0.5 mg every 2 hrs until pain is relieved
or nausea & diarrhea appear.
Unit IV (2) For prophylaxis  0.5 mg 1-3 times/d.

Anti - Gout Drugs URICOSURIC AGENTS

Examples
Probenecid, Sulfinpyrazone.
GOUT
Pharmacological Effects
(1) They lowers serum levels of uric acid by inhibiting
It is a familial metabolic disease characterized by recurrent proximal tubular reabsorption of uric acid.
episodes of acute arthritis due to deposits of monosodium (2) As a general inhibitor of tubular secretion of organic
urate in joints & cartilages. It is associated with high acids, probenecid will also inc. serum levels of other
serum level of uric acid & formation of uric acid calculi in organic acids, eg penicillin.
kidneys. (3) Sulfinpyrazone also inhibits prostaglandin synthesis &
interferes with a number of platelet functions, including
DRUG CLASSIFICATION adherence to subendothelial cells.
Clinical Uses
(1) Chronic gout.
(1) Colchicum Alkaloid (2) To prolong effects of penicillin. (probenecid).
Colchicine. (3) As antithrombotic agent. (Sulfinpyrazone).
(2) Nonsteroidal Anti-inflammatory Drugs Adverse Effects
Aspirin, Naproxen, Indomethacin, Phenylbutazone, (1) GIT: Gastrointestinal irritation.
Ibuprofen. (2) Renal: Nephrotic synd. (probenecid).
(3) Uricosuric Agents (3) Blood: Aplastic anemia.
Probenecid, Sulfinpyrazone. (4) Allergy: Rash, dermatitis.
(4) Urate Synthesis Inhibitor Contraindications
Allopurinol, Febuxostat. Oliguria.
Dosage
COLCHICINE (1) Probenecid  Started at 0.5 g orally daily in divided
doses, progressing to 1 g daily after 1 week.
(2) Sulfinpyrazone  Started at 200 mg orally daily,
Pharmacological Effects progressing to 400 - 800 mg daily.
M. Shamim’s PHARMACOLOGY 74

ALLOPURINOL (81) All of the following statements concerning ibuprofen

are correct
(A) It increases prothrombin synthesis.
Mechanism of Action (B) It is useful in ankylosing spondylitis.
Allopurinol & its metabolite alloxanthine, prevents terminal (C) It relieves dental pain & dysmenorrhea.
steps in uric acid synthesis by inhibiting xanthine oxidase, (D) Agranulocytosis may occur as an adverse reaction.
which converts xanthine or hypoxanthine to uric acid. (E) It is contraindicated in active peptic ulcer.
Hyperuricemia is thus reversed by blockade of uric acid
(82) Drugs that are useful in dysmenorrhea includes
production.
(A) Colchicine.
Clinical Uses
(B) Chloroquine.
(1) Chronic gout.
(C) Ibuprofen.
(2) Chronic myelogenous leukemia.
(D) Aspirin.
(3) Chronic lymphogenous leukemia.
(E) Naproxen.
(4) As antiprotozoal.
Adverse Effects (83) Drugs used in treatment of gout includes
(1) CNS: Peripheral neuritis. (A) Indomethacin.
(2) Eye: Cataracts. (B) Allopurinol.
(3) GIT: Nausea, vomiting, diarrhea. (C) Colchicine.
(4) Liver: Hepatotoxicity. (D) Probenecid.
(5) Renal: Interstitial nephritis. (E) Auranofin.
(6) Blood: Aplastic anemia. (84) Acetaminophen has all of the following
(7) Skin: Pruritic maculopapular rash, exfoliative dermatitis, properties
necrotizing vasculitis. (A) It has anti-inflammatory effect similar to aspirin.
(8) Bone marrow: Bone marrow depression. (B) It reduces fever..
(9) Acute attacks of gout: Occur during initial therapy (C) It is useful for analgesia in pts. with hepatic
with allopurinol, due to active dissolution of disease.
microcrystalline deposits of sodium urate within (D) It may cause acute tubular necrosis .
subcutaneous tissue, resulting in transient periods of
hyperuricemia & crystal deposition in joint tissue. (E) It is an aspirin substitute in pts. with peptic ulcer.
Note: To prevent this, colchicine is given
simultaneously.
Dosage
100-300 mg/day, orally.

GENERIC & TRADE NAMES

Colchicine: Colchicine.
Allopurinol: Progout, Zyloric, Zynol.
NSAIDs: See Unit II.

Unit V

Self - Assessment (T/F)

(See answers on page no. 240)
(80) Important effects of aspirin includes
(A) Reduction of fever.
(B) Reduction of prostaglandin synthesis in inflamed
tissue.
(C) Medullary respiratory centre depression at toxic
doses.
(D) Reduction of bleeding tendency.
(E) Tinnitus & vertigo.
M. Shamim’s PHARMACOLOGY 75

10 DRUGS AFFECTING BLOOD

Unit I
CLASSIFICATION OF ANTI - ANEMICS

Anti - Anemics (A) Drugs for Iron - Deficiency Anemia

(1) Oral Iron Preparations
Ferrous sulfate, Ferrous gluconate, Ferrous
fumarate, Ferric ammonium citrate, Ferric choline
ANEMIA citrate, Ferrous succinate, Ferric pyrophosphate,
Sodium iron edetate, Iron polymaltose,
DEFINITION (2) Parenteral Iron Preparations
It is a reduction in O2 transporting capacity of blood, due Iron dextran, Iron-sorbitol-citric acid complex, Iron
sorbitol, Iron polysaccharide complex, Iron protein
to a reduction below normal limits of total circulating red
succinylate, Iron sucrose.
cell mass & hemoglobin concentration.
(B) Drugs for Megaloblastic Anemia
(1) Vit B12 (Cyanocobalamin & Hydroxocobalamin).
CAUSES OF ANEMIA (CLASSIFICATION )
(2) Folic acid.
(A) Blood Loss
(C) Hematopoietic Growth Factors
(1) Acute, eg due to trauma.
(1) Erythropoietin.
(2) Chronic, eg due to GIT lesions.
(2) Darbepoetin alfa.
(B) Inadequate RBCs Production
(1) Deficiency of essential factors:
(a) Iron deficiency Hypochromic microcytic IRON (Fe)
anemia.
(b) Intrinsic factor deficiency  Pernicious anemia. DAILY IRON REQUIREMENTS
(c) Vit B12 or Folic acid deficiency  Megalo- (1) Men: 0.5 - 1 mg.
blastic anemia. (2) Menstruating women: 2 mg.
(2) Endocrine deficiency: (3) Pregnant women: 5 - 6 mg.
Dec. erythropoietin production
(3) Bone marrow invasion: PHARMACOKINETICS
(a) Leukemia. (A) Absorption
(b) Secondary carcinoma. (1) Form
(4) Stem cells failure: Ferrous (Fe+2) is more readily absorbed than ferric
Aplastic anemia. (Fe+3).
(5) Drugs: (2) Site
(a) Chloramphenicol. Duodenum & proximal jejunum.
(b) Thiouracil. (3) Process
(C) Increased RBCs Destruction (Hemolytic By active transport across the intestinal mucosal
Anemia) cells.
(1) Intra - erythrocytic defects: Note: In the intestinal mucosal cells Fe+2 is
(a) Hereditary spherocytosis. converted into Fe+3.
(b) Thalassemias. (4) Fate
(2) Extra - erythrocytic abnormalities: (a) Transported to plasma via transferrin.
(a) Erythroblastosis fetalis. (b) Converted to ferritin & stored in mucosal cells.
(b) Transfusion reactions. (B) Distribution
(c) Malaria. (1) Iron is transported in the plasma bound to
transferrin, from intestinal mucosal cells or from
M. Shamim’s PHARMACOLOGY 76

storage sites in liver or spleen, to developing (f) Hypersensitivity: Anaphylaxis.

erythroid cells in bone marrow. (B) Acute Iron Toxicity
(2) Transferrin receptors present on proliferating Seen in young children who have accidently ingested
erythroid cells, bind the transferrin-iron complex iron tablets.
& internalize iron, releasing it within the cells. Fatal Dose
(C) Storage 10 tablets.
(1) Forms Clinical Features
(a) Ferritin. (1) Necrotizing gastroenteritis, with vomiting,
(b) Hemosiderin. abdominal pain, & bloody diarrhea.
(2) Sites (2) Followed by shock, lethargy, & dyspnea.
Macrophages in liver, spleen, & bone marrow. (3) Followed by improvement or, severe metabolic
(D) Elimination acidosis, coma, & death.
(1) About 1 mg Fe is lost by exfoliation of intestinal Treatment
mucosal cells into stool. (1) Gastric aspiration.
(2) Trace amounts are excreted in bile, urine, & sweat. (2) Gastric lavage with carbonate solution.
(E) Regulation of Pharmacokinetics (3) Antidote: Deferoxamine, parenterally.
(1) By the amount of storage Fe present (inversely (4) Supportive therapy for GIT bleeding, metabolic
related). acidosis, & shock.
(2) By the rate of erythropoiesis (directly related). (C) Chronic Iron Toxicity
Occur in pts with hemochromatosis or, with many red
MECHANISM OF ACTION cell transfusions.
Fe combines with protoporphyrin IX & forms heme  Clinical Features
4 heme combines with polypeptide (globin) to form Hemochromatosis & Hemosiderosis
hemoglobin chain (  or ) 2 combines with 2 chains Excess iron deposition occur in heart, liver, pancreas
to form hemoglobin A. & other organs  Organ failure & death.
Treatment
CLINICAL USES (1) Intermittent phlebotomy.
Treatment or prevention of iron deficiency anemia. (2) Drugs: Deferasirox, Deferoxamine.
(A) Oral Iron Preparations
Used for Fe deficiency in; DOSAGE
(1) Infants. (1) Oral Preparations
(2) Children during rapid growth periods. Ferrous sulfate (325 mg tab), Ferrous gluconate (320 mg
(3) Pregnant & lactating women. tab), or Ferrous fumarate (200 mg tab)  3-4 tab per day.
(B) Parenteral Iron Preparations (2) Parenteral Preparations
Reserved for; Iron-sorbitol-citric acid complex  1.5 mg/Kg IM as
(1) Pts with documented Fe def., unable to tolerate or single daily dose; max. 100 mg per inj.
absorb oral Fe.
(2) Pts with extensive chronic blood loss, due to; VITAMIN B12
(a) Postgastrectomy conditions.
(b) Small bowel resection.
(c) Inflammatory bowel disease involving DAILY B12 REQUIREMENTS
proximal small bowel. 2 g in both sexes.
(d) Malabsorption syndromes.
(e) Hereditary hemorrhagic telangiectasia. PHARMACOKINETICS
(A) Absorption
ADVERSE EFFECTS
(1) Vit. B12 binds with intrinsic factor, a glycoprotein
(A) Adverse Effects With Usual Dosage
secreted by parietal cells of gastric mucosa.
(1) Oral Iron Preparations
(2) Intrinsic factor- B12 complex is absorbed in distal
GIT: Nausea, epigastric discomfort, abdominal
cramps, constipation, diarrhea. ileum by a highly specific receptor-mediated
(2) Parenteral Iron Preparations transport system.
(a) CNS: Headache, light-headedness. (B) Distribution
(b) Resp tract: Bronchospasm. Vit. B12 is transported to various body cells bound to a
(c) GIT: Nausea, vomiting. plasma glycoprotein, transcobalamin II.
(d) Musculo-skeletal: Local pain & tissue staining, (C) Storage
arthralgia, back pain. Excess vit. B12 (upto 300-500 g) is stored in liver.
(e) Skin: Fever, flushing, urticaria. (D) Elimination
10: Drugs Affecting Blood 77

(1) Only trace amounts of vit. B12 are normally lost in DAILY FOLIC ACID REQUIREMENTS
urine & stool. 50 g in both sexes.
(2) Significant amount of vit. B12 are excreted in urine,
when large amounts are given parenterally. PHARMACOKINETICS
(A) Absorption
MECHANISM OF ACTION (1) Form
(1) Act as a cofactor in the conversion of methylmalonyl- Dietary folates in polyglutamte forms, first undergo
CoA to succinyl -CoA by the enzyme methylmalonyl- hydrolysis by conjugase (present in brush border
CoA mutase. of intestinal mucosa) &, form monoglutamate
Effects of B12 Deficiency 5 - CH3 - H4 folate that is readily & completely
Methylmalonyl -CoA accumulates  Abnormal fatty absorbed.
acid synthesis & incorporation into cell memb.  (2) Site
Demyelination of neurons. Proximal jejunum.
(2) Act as a cofactor in the conversion of 5 - CH3 - H4 folate (B) Distribution
Widely distributed thru-out the body via blood stream.
& homocysteine, to H4 folate & methionine, by the
(C) Storage
enzyme 5 - CH3 - H4 folate - homocysteine methyl- Normally, 5 - 20 mg is stored in liver & other tissues.
transferase. (D) Elimination
Effect of B12 Deficiency Excreted in urine & stool, & also destroyed by
5 - CH3 - H4 folate accumulates  Deficiency of folate catabolism.
cofactors  Dec. DNA synthesis  Megaloblastic
anemia. MECHANISM OF ACTION
Folic acid (H4 folate) is a precursor of several folate
CLINICAL USES cofactors, which are essential for one-carbon transfer
reactions necessary for DNA synthesis, eg:
Box 10.1 CAUSES OF VIT B12 DEFICIENCY (1) Synthesis of thymidylic acid from deoxyuridylate.
(2) Synthesis of purine.
1) Deficiency of intrinsic factor (as in gastric atrophy)
Pernicious anemia CLINICAL USES
2) Defects in absorption of intrinsic factor - B12 complex Treatment or prevention of folic acid deficiency, which
in distal ileum causes megaloblastic anemia.
3) Partial or total gastrectomy
4) Malabsorption syndromes
5) Inflammatory bowel disease
ADVERSE EFFECTS
6) Small bowel resection No; b/c it is promptly excreted in urine.
7) Nutritional deficiency (seen in strict vegetarian)
8) Congenital absence of transcobalamin II Box 10.2 CAUSES OF FOLIC ACID DEFICIENCY
Treatment or prevention of vit B12 deficiency conditions, eg 1) Inadequate dietary intake
(1) Megaloblastic anemia. 2) Liver disease
(2) Pernicious anemia. 3) Pregnancy
(3) Neuropathy. 4) Hemolytic anemia
5) Sprue & other malabsorption syndrome
ADVERSE EFFECTS 6) Cancer , leukemia, & myeloproliferative disorders
7) Pts on renal dialysis
No; b/c large doses are promptly excreted in urine. 8) Drugs eg, Phenytoin, isoniazid, oral contra-
ceptives, methotrexate
DOSAGE
(1) Initially  100 - 1000 g 1M, daily or every other day
DOSAGE
for 1-2 weeks.
(2) Maintenance therapy  100-1000 g 1M, once a month 1 mg orally, daily.
(for life).
(3) In neuropathy  Injections should be given every ERYTHROPOIETIN
1-2 weeks for 6 months before switching to monthly
inj. Pharmacological Effects
Erythropoietin stimulates erythroid proliferation &
FOLIC ACID differentiation, by interacting with specific erythropoietin
receptors on red cell progenitors in bone marrow.
M. Shamim’s PHARMACOLOGY 78

Note: Endogenously it is secreted by kidney in response to (E) Iron-Folic Acid Combinations

hypoxia. Apofer F, Ferlip-F, Ferrum FA, Ferry F, Giofer F,
Clinical Uses Maltofer Fol, Iberet Folic-500 Gradumet*.
Treatment of renal failure pts with significant anemia. (F) Iron - B12 - Folate Combinations
Adverse Effects Iberol-F*, Theragran-H*, Tri-Hemic 600*.
(1) CVS: Hypertension, thrombotic complications. (G) Erythropoietin
(2) Allergic reactions Epokine, Eprex, Hemax.

TREATMENT OF OTHER ANEMIAS

Unit II
Blood Loss Anemia
(1) Acute Loss
Blood volume replacement by transfusion of whole Anti - Coagulants
blood, red cell concentrates, plasma, or plasma
substitutes.
(2) Chronic Loss INTRODUCTION TO HEMOSTASIS
Iron supplements.
Aplastic Anemia
(1) Bone marrow transplantation HEMOSTASIS
(2) Replacement therapy It is the spontaneous arrest of bleeding from a damaged
(a) Red cell concentrates vessel.
(b) Platelet transfusion Hemostatic Response
(c) Antibiotic (1) Vasospasm
(3) Androgenic steroids or erythropoietin Occur immediately following damage to a vessel.
(4) Prednisolone (2) Formation of Platelet Plug
Hemolytic Anemias (a) Within seconds, platelets stick to exposed
(1) Removal of causative agents collagen of damaged endothelium & to each other
(2) Blood transfusion Platelet plug.
(3) Folic acid supplements (b) Platelets releases several factor eg, ADP, TXA2
(4) Prednisolone & serotonin, which cause further platelets
(5) Splenectomy aggregation & vasoconstriction.
(6) Bone marrow transplantation (c) Aggregated platelet plug make available platelet
(7) Antimalarials factor 3 for coagulation sequence to take place.
(3) Fibrin Reinforcement of Platelet Plug
Coagulation system, activated by intrinsic or extrinsic
GENERIC & TRADE NAMES
pathway, leads to cascade of reactions that causes
conversion of proenzymes ( inactive coagulation
(A) Iron factors) into activated enzymes ( activated coagulation
Ferrous Sulfate: Blissferon, Fer-in-sol, Ferrous Sulfate, factors or proteases)  Finally Xa ( activated factor X )
Iberet, Unifer. is produced  Xa converts prothrombin (factor II)
Ferrous Gluconate: Ferrous Gluconate, Feglone. into thrombin (factor IIa) Thrombin converts
Ferrous Fumarate: Ferovis, Givitol. fibrinogen (factor I) into fibrin Fibrin molecules
Na Iron Edetate: Sytron. polymerize to form fibrin threads which cement
Iron-Sorbitol-Citric Acid Complex : Iprafer forte, platelet plug.
Jectosol.
Iron polymaltose: Apofer, Biofer, Fermalose, Indofer. NATURAL ANTICOAGULANTS OF BODY
Iron polysaccharide complex: Ferricure.
(A) Fibrin Inhibition System
Iron protein succinylate: Ferplex, Succiron.
Plasma contains protease inhibitors that rapidly
Iron sucrose: Ivefer, Venofer.
inactivate coagulation proteins as they escape from site
(B) Vit B12
of vessel injury; include,
Cyanocobalamin: Cyanoplex, Cyanovit, Cyomin, (1) Antithrombin III
Cytacon, Cytamen, Elkomin, Vit B12. (2) 1 - antiprotease
(C) Folic Acid
(3) 2 - macroglobulin
Delfol, Folitab, Folic Acid, Folacin.
(D) Iron- Vit B12 Combinations (4) Protein C & S
(B) Fibrinolysin System
Iberet-500, Incremin.
10: Drugs Affecting Blood 79

Plasminogen is activated by factor XII - dependent (c) Rash, alopecia

pathway or by plasminogen activator (eg urokinase - (4) Pregnancy
like PA & tissue - type PA) into plasmin  Plasmin Warfarin readily crosses placenta, & causes
breaks down fibrin (fibrinolysis). hemorrhagic disorders & bony abnormalities in fetus.
Treatment
(1) Stop the drug.
CLASSIFICATION OF ANTI - COAGULANTS
(2) Antidote: Vit K1 (Phytonadione).
(3) Fresh - frozen plasma (FFP), or factor IX concentrates.
These are drugs that prevent coagulation of blood.
(1) Oral Anti-Coagulants CONTRAINDICATIONS
Warfarin Na, Dicumarol, Phenindione. (1) Hemorrhagic conditions.
(2) Indirect Thrombin Inhibitors (2) Impaired renal or hepatic function.
Antithrombotic effect is exerted via antithrombin; eg , (3) Within 24 hours of surgery or labor.
Unfractionated heparin, Low-molecular-weight heparin (4) Pregnancy.
(Dalteparin, Enoxaparin), Fondaparinux, Tinzaparin. (5) Bacterial endocarditis.
(3) Direct Thrombin Inhibitors (6) Active tuberculosis.
Antithrombotic effect is exerted by direct binding to the (7) Recent head trauma.
active site of thrombin; eg , (8) Neurosurgery.
Hirudin, Bivalirudin, Lepirudin, Argatroban,
Ximelagatran.
DRUG INTERACTIONS
(4) Fibrinolytic ( Thrombolytic ) Drugs
Drugs that lyse fibrin or thrombi; eg , (A) Drugs that Inc. Warfarin Effect
Streptokinase, Urokinase, Anistreplase, Tissue (1) Pharmacokinetically
plasminogen activator (t - PA), Reteplase, Tenecteplase. Amiodarone, Cimetidine, Disulfiram,
(5) Anti-Thrombotic Drugs Metronidazole, Miconazole, Phenylbutazone,
Drugs that inhibits platelet aggregation; eg , Sulfinpyrazone, Trimethoprim - sulfamethoxazole.
Aspirin, Clopidogrel, Dipyridamole, Ticlopidine, (2) Pharmacodynamically
Abciximab, Eptifibatide, Tirofiban, Cilostazol. Aspirin, Cephalosporins (3rd generation), Heparin.
(B) Drugs that Dec. Warfarin Effect
(1) Pharmacokinetically
WARFARIN Barbiturates, Cholestyramine, Rifampin.
(2) Pharmacodynamically
MECHANISM OF ACTION Diuretics, Vit K.
It blocks  - carboxylation of several glutamate residues in
prothrombin & factors VII, IX, X, & endogenous DOSAGE
anticoagulant protein C  This results in incomplete (1) Initially: 2-5 mg daily for about 1 week.
molecules that are biologically inactive in coagulation. (2) Maintenance dose: 5-7 mg/day.

CLINICAL USES HEPARIN

Secondary prophylactic treatment of venous thrombosis
& pulmonary embolism. MECHANISM OF ACTION
Heparin bind tightly to plasma protease inhibitor
ADVERSE EFFECTS
antithrombin III & cause a conformational change in it 
(1) CVS This results in exposure of antithrombin's active site, for
Bleeding, purpura, fall in hematocrit. more (about 1000 - fold) rapid interaction with clotting
(2) GIT factor proteases, which forms equimolar stable complexes
Diarrhea. with proteases This causes inhibition of clotting factor
(3) Skin
proteases (thrombin, factor IXa, Xa, XIa & XIIa)  Fibrin
(a) Warfarin necrosis: It is a painful erythematous
formation is abolished.
patch on skin, which can progress to gangrene;
occur during 1st week of therapy.
CLINICAL USES
Note: Same process may causes frank infarction
of breast, fatty tissues, intestine, & extremities. (1) Prophylaxis of venous thrombosis in;
(b) Purple toe syndrome: It is caused by cholesterol (a) Pts undergoing elective surgery.
emboli from atheromatous plaques, following (b) Acute phase of myocardial infarction.
bleeding into plaques; occur 3-8 weeks after (2) Treatment of established venous thrombosis or
starting therapy. pulmonary embolism.
M. Shamim’s PHARMACOLOGY 80

ADVERSE EFFECTS (3) Acute myocardial infarction.

(1) CVS: Bleeding, paradoxical thromboembolism. (4) Acute peripheral arterial thrombosis & emboli.
(2) Blood: Transient thrombocytopenia. (5) For unclotting catheters & shunts.
(3) Bone: Osteoporosis, spontaneous fractures.
(4) Skin: Transient alopecia. ADVERSE EFFECTS
(5) Hypersensitivity reactions: Chills, fever, urticaria, (1) CVS: Bleeding complications (hematoma, intracranial
anaphylaxis. hemorrhage, GIT bleeding), reperfusion atrial or ventri-
Antidote cular dysarrhythmias, hypotension.
Protamine sulfate. (2) Hypersensitivity Reactions: Minor bronchospasm to
anaphylaxis.
CONTRAINDICATIONS (3) Body Temp: Fever.
(1) Pts hypersensitive to heparin.
(2) Pts with active bleeding. CONTRAINDICATIONS
(3) Hemophilia. (1) Recent stroke.
(4) Thrombocytopenia. (2) Craniotomy.
(5) Purpura. (3) Head trauma.
(6) Severe hypertension. (4) Brain tumor .
(7) Intracranial hemorrhage.
(8) Infective endocarditis. DOSAGE
(9) Active tuberculosis. Streptokinase
(10) Ulcerative lesions of GIT. Loading IV dose of 250,000 units, followed by continuous
(11) Threatened abortion. infusion of 100,000 units/hr for 24 - 72 hours.
(12) Visceral carcinoma.
(13) Advanced hepatic or renal disease.
(14) During or after surgery of brain, spinal cord, or eye. GENERIC & TRADE NAMES
(15) Pts undergoing lumbar puncture or regional anesthesia.
Warfarin: Coumadin, Warfarin, Werifrin.
DOSAGE Heparin: Ecfast, Mediparine, Pine.
(1) For Established Disease Dalteparin: Fragmin.
(a) Initial IV bolus inj. of 5000 - 10,000 units. Enoxaparin: Clexan.
(b) Followed by continuous infusion of 900 units/hr Tinzaparin: Innohep.
or 10 - 15 units/Kg/hr, Streptokinase: Amikase, Durakinase, Streptase.
or Aspirin: Anapirin, Ascard, Lopirin.
Intermittent IV administration of 75-100 units/kg Clopidogrel: Clogrel, Clopeg, Lowplat.
every 4 hours. Dipyridamole: Damopres, Persantin.
Note: This therapy is continued for 7-10 days, with a Ticlopidine: Clopidine, Ticlid, Ziclodin.
3-5 day overlap with warfarin; then warfarin is Abciximab: Reopro.
continued for 6 weeks to 6 months. Eptifibatide: Integrilin.
(2) For Prophylaxis Tirofiban: Aggrastat.
5000 units SC, TDS or BD. Cilostazol: Lostaz, Pletaal.

FIBRINOLYTIC (THROMBOLYTIC) DRUGS

Unit III

EXAMPLES
Streptokinase, Urokinase, Anistreplase, t - PA. Coagulants
MECHANISM OF ACTION (Anti-Hemorrhagics)
They act either directly or indirectly (thru proactivator
plasminogen) to convert endogenous plasminogen to
DRUGS CLASSIFICATION
plasmin (a protease) Plasmin cleaves fibrin, & thus
thrombus is dissolved.
These are drugs that promote coagulations & prevent
CLINICAL USES hemorrhage.
(1) Multiple pulmonary emboli. (1) Vitamin K
(2) Central deep vein thrombosis, eg superior vena caval (a) Natural
synd. & ascending thrombophlebitis of iliofemoral vein. Vit. K1 (Phytonadione), & K2.
10: Drugs Affecting Blood 81

(b) Synthetic GENERIC & TRADE NAMES

Acetomenaphthone.
(2) Fibrinolytic Inhibitors
Aminocaproic acid, Tranexamic acid. Vitamin K: Vitamin K.
(3) Serine Protease Inhibitors Tranexamic acid: Tranex, Transamin.
Aprotinin. Aprotinin: Trasylol.
(4) Plasma Fractions
(a) Factor VIII
Cryoprecipitate, Lyophilized factor VIII Unit IV
concentrates.
(b) Factor IX
(c) Fibrinogen Other Hematological Drugs
(d) Fresh frozen plasma (FFP)

VITAMIN K ANTI-METHEMOGLOBINEMICS

Mechanism of Action Methemoglobinemia

It confers biologic activity upon prothrombin & factors It refers to the presence of methemoglobin in blood that
VII, IX, & X by participating in their post-ribosomal results in cyanosis.
modification. Note: Methemoglobin is formed from hemoglobin by
Clinical Uses oxidation of its ferrous iron to ferric ( Fe+3 ) state.
(1) Administered to all newborn, to prevent hemorrhagic Causes
diseases of vit. K deficiency (which is esp. common in (1) Drug induced (see unit V)
premature infants). (2) Defect in NADH methemoglobin reductase.
(2) As antidote of warfarin.
Adverse Effects ANTI-METHEMOGLOBINEMICS
Rapid infusion can produce; Reducing Agents
(1) Dyspnea (1) Ascorbic acid
(2) Chest & back pain (2) Methylene blue
(3) Death Note: Excess methylene blue may itself cause
methemoglobinemia.
FIBRINOLYTIC INHIBITORS
ANTI-HYPERLIPIDEMICS
Examples
Aminocaproic acid, Tranexamic acid. Hyperlipidemias
Mechanism of Action It refers to elevations in plasma lipoproteins & triglycerides
They competitively inhibits plasminogen activator. levels.
Clinical Uses Clinical Sequelae
(1) Adjunct therapy in hemophilia. (1) Atherosclerosis, & its complications.
(2) Bleeding from fibrinolytic therapy. (2) Acute pancreatitis.
(3) Prophylaxis for rebleeding from intracranial aneurysms. (3) Xanthomas.
(4) Postsurgical GIT bleeding .
(5) Postprostatectomy bleeding.
CLASSIFICATION OF ANTI-HYPERLIPIDEMICS
(6) Bladder hemorrhage secondary to radiation & drug-
induced cystitis. (1) Bile Acid Sequestrants
Adverse Effects Cholestyramine, Colestipol, Colesevelam.
(1) CVS: Intravascular thrombosis, hypotension. (2) HMG CoA Reductase Inhibitors
(2) Resp Tract: Nasal stuffiness. Lovastatin, Atorvastatin, Pravastatin, Mevastatin,
(3) GIT: Abdominal discomfort, diarrhea. Simvastatin, Fluvastatin, Rosuvastatin.
(4) Muscles: Myopathy. (3) Niacin (Nicotinic Acid)
Dosage (4) Fibric Acid Derivatives
Clofibrate, Gemfibrozil, Fenofibrate, Bezafibrate.
Tranexamic Acid
Loading dose of 15 mg/kg orally, followed by 30 mg/kg (5) Inhibitors Of Intestinal Sterol Absorption
QID. Ezetimibe.

ANTI-ANAPHYLACTICS
M. Shamim’s PHARMACOLOGY 82

Anaphylaxis DRUG CAUSING APLASTIC ANEMIA

It refers to an exaggerated IgE-mediated allergic reaction
to foreign protein or other substances, in a sensitized
individual. (1) Anti - Cancer Drugs
Clinical Features Mercaptopurine, Busulphan, Cyclophosphamide,
(1) Pruritus, urticaria, angioedema. Doxorubicin, Methotrexate.
(2) Respiratory distress (due to laryngeal edema, (2) Anti - Inflammatory & Anti - Rheumatic Drugs
laryngospasm, or bronchospasm). Phenylbutazone, Oxyphenbutazone, Gold compounds,
(3) Hypotension & shock. Indomethacin.
(4) Abdominal pain. (3) Anti - Epileptics
Phenytoin, Troxidone, Primidone.
ANTI-ANAPHYLACTICS (4) Anti - Diabetics
(1) Epinephrine Tolbutamide, Chlorpropamide.
(2) Inhaled beta-agonists, eg albuterol or metaproterenol. (5) Anti - Thyroid Drugs
(3) Aminophylline Carbimazole, Methythiouracil, Propylthiouracil,
(4) Antihistamines, eg diphenhydramine. Potassium Perchlorate.
(5) Glucocorticoids, eg hydrocortisone. (6) Psychotropics
(6) Glucagon. Chlorpromazine, Prochlorperazine, Promazine,
Mianserin.
(7) Anti - Histamines
Unit V Chlorpheniramine.
(8) Antibiotics
Chloramphenicol, Sulfonamides.
Drugs Causing Blood
DRUGS CAUSING MEGALOBLASTIC ANEMIA
Dyscrasias
(1) Anti - Epileptics
Phenytoin, Primidone.
DRUGS CAUSING HEMOLYTIC ANEMIA (2) Others
Methotrexate, Pyrimethamine, Trimethoprim.
(A) Due to Hypersensitivity
(1) Antimicrobials DRUGS CAUSING SIDEROBLASTIC ANEMIA
Penicillins, Cephalosporins, Rifampin,
Aminoglycosides. (1) Anti - Tuberculous Drugs
(2) Anti - Hypertensives Isoniazid, Cycloserine, Pyrazinamide.
Methyldopa. (2) Antibiotics
(3) Anti - Migraine Chloramphenicol.
Methysergide. (3) Analgesics
(4) Anti - Parkinsonism Phenacetin.
Levodopa.
(5) NSAIDs
Mefenamic acid. DRUGS CAUSING METHEMOGLOBINEMIA
(B) Due to G6PD Deficiency
(1) Analgesics (1) Analgesics
Acetylsalicylic acid, Phenacetin, Acetanilide. Phenacetin, Acetanilide.
(2) Anti - Bacterials (2) Antimicrobials
Sulfonamides, Dapsone, Nitrofurantoin, Sulfonamides, Trimethoprim.
Nitrofurazone, Furazolidine, Chloramphenicol, (3) Antimalarials
Isoniazid. Primaquine.
(3) Anti - Malarials (4) Anti - Anginal Drugs
Chloroquine, Primaquine, Pamaquin, Pyri- Nitrites & nitrates.
methamine, Quinine.
(4) Others
Vit K, Probenecid, Nalidixic acid, Quinidine, DRUGS CAUSING ACUTE INTERMITTENT
Dimercaprol, Phenylhydrazine, p-Aminosalicylic PORPHYRIA
acid.
10: Drugs Affecting Blood 83

(1) Sedative - Hypnotics (87) Anticoagulant activity of warfarin can be

Thiopentone, Meprobamate, Alcohol. potentiated by
(2) Oral Contraceptives (A) Rifampin.
(3) Others (B) Aspirin.
Sulfonamides, Pentazocine, Griseofulvin, Methyldopa. (C) Phenylbutazone.
(D) Cimetidine.
(E) Disulfiram.
DRUGS CAUSING NEUTROPENIA & AGRANULO-
CYTOSIS (88) Concerning anticoagulants, all of the following are
correct
(A) Parenteral administration of heparin provides
(1) Antibiotics
immediate anticoagulation.
Chloramphenicol, Penicillin, Sulfonamides,
(B) Oral administration of warfarin provide delayed
Co - trimoxazole.
anticoagulation.
(2) Anti - Epileptics
(C) Anticoagulant action of heparin require the
Phenytoin.
presence of antithrombin III.
(3) Antithyroid Drugs
(D) Warfarin is the preferred anticoagulant in
Propylthiouracil.
pregnant women.
(4) Antidiabetics
(E) Heparin overdose can be reversed with basic
Chlorpropamide.
protein protamine.
(5) Phenothiazines
Chlorpromazine. (89) Anti - hyperlipidemic agents include
(6) Antimalarials (A) Clofibrate.
Maloprim. (B) Cholestyramine.
(C) Aspirin.
(D) Lovastatin.
DRUGS CAUSING ANAPHYLAXIS
(E) Prednisone.

(1) Penicillins.
(2) Cephalosporins.
(3) Amphotericin B.
(4) Ketoconazole.
(5) Local anesthetics.

Unit VI

Self - Assessment (T/F)

(See answers on page no. 240-241)
(85) Optimal treatment of mild iron deficiency
anemia associated with pregnancy is
(A) A high-fibre diet.
(B) Parenteral iron dextran injections.
(C) Iron dextran tablets.
(D) Ferrous sulfate tablets.
(E) Folic acid supplements.
(86) Regarding toxicity of iron, following are correct
(A) Acute oral ingestion of a large overdose causes
constipation.
(B) Chronic iron overload, as in hemochromatosis,
causes liver disease.
(C) Acute overdose may cause metabolic acidosis.
(D) Chronic toxicity is treated by phlebotomy .
(E) In acute toxicity, deferoxamine may be used as an
antidote.
M. Shamim’s PHARMACOLOGY 84

11 CARDIOVASCULAR SYSTEM
DRUGS

Unit I ANGIOTENSIN BLOCKERS

(1) Angiotensin Receptor Blockers

Anti-Hypertensive Drugs
Candesartan, Eprosartan, Irbesartan, Losartan,
Olmesartan, Telmisartan, Valsartan.
(2) Angiotensin Converting Enzyme Inhibitors
Benzapril, Captopril, Enalapril, Fosinopril, Lisinopril,
Moexipril, Perindopril, Quinapril, Ramipril,
HYPERTENSION
Trandolapril.
(3) Competitive Inhibitors of Angiotensin II
Persistently elevated arterial pressure is called hypertension. Saralasin
Threshold for Hypertension
(1) Systolic Pressure DIURETICS
Ranges from 140 to 200 mm Hg. (1) Thiazide Diuretics
(2) Diastolic Pressure Chlorothiazide, Chlorthalidone.
Ranges from 90 to 110 mm Hg. (2) Loop Diuretics
Furosemide, Ethacrynic acid.
DRUG CLASSIFICATION (3) K+ Sparing Diuretics
Spironolactone, Amiloride.
(4) Nonthiazide Sulfonamide Diuretics
DRUGS THAT ALTER SYMPATHETIC NERVOUS Indapamide.
SYSTEM Note: For detail on diuretics, see chapter 12.
(1) Centrally Acting Sympathoplegic Drugs
Methyldopa, Clonidine, Guanabenz, Guanfacine. DIRECT ACTING VASODILATORS
(2) Ganglionic Blocking Drugs
Diazoxide, Fenoldopam, Hydralazine, Minoxidil, Na
Mecamylamine, Hexamethonium.
nitroprusside.
(3) Adrenergic Neuron Blocking Drugs
Reserpine, Guanadrel, Guanethidine, Bethanidine,
Debrisoquin. CENTRALLY ACTING SYMPATHOLYTICS
(4) Adrenoceptor Blocking Drugs
(a)  - Receptor Blockers METHYLDOPA
Prazosin, Doxazosin, Terazosin, Phenoxybenz- Mechanism of Action
amine, Phentolamine.
(1) Converted into  -methylnorepinephrine which is stored
(b)  - Receptor Blockers in adrenergic nerve granules, where it
Atenolol, Acebutolol, Betaxolol, Bisoprolol, stoichiometrically replaces norepinephrine &, is
Carteolol, Carvedilol, Esmolol, Metoprolol, released by nerve stimulation to interact with
Nadolol, Penbutolol, Propranolol, Pindolol, Timolol.
presynaptic central  2 adrenoceptors  Dec.
(c)  - &  - Blockers
Labetalol. sympathetic outflow  Dec. arterial pressure.
(2) Inhibit dopa decarboxylase  Dec. stores of norepi-
CALCIUM CHANNEL BLOCKERS nephrine in the sympathetic nervous system Dec.
(1) Dihydropyridines BP.
Nifedipine, Nicardipine, Nisoldipine, Amlodipine, (3) Reduces renal vascular resistance, probably -methyl-
Felodipine, Isradipine. norepinephrine being a weaker vasoconstrictor than
(2) Miscellaneous norepinephrine in renal beds
Diltiazem, Verapamil. Clinical Uses
Mild to moderately severe hypertension.
11: Cardiovascular System Drugs 85

Adverse Effects Pharmacological Effects

(1) CNS: Sedation, lassitude, nightmares, depression, (1) Central Nervous System
vertigo, extrapyramidal signs. Sedation due to depletion of biogenic amines centrally.
(2) CVS: Orthostatic hypotension, rebound hypotension (2) Cardiovascular System
on sudden withdrawal. (a) Dec. heart rate, cardiac output & BP, & may dec.
(3) GIT: GI disturbances. peripheral vascular resistance.
(4) Blood: Hemolytic anemia, positive Coombs test. (b) Inhibits cardiovascular reflexes only partially.
(5) Endo: Lactation. Clinical Uses
(6) Liver: Hepatitis. Mild to moderate hypertension.
(7) Metabolic: Drug fever. Adverse Effects
Contraindications (1) CNS: Sedation, lassitude, nightmares, depression,
(1) Pheochromocytoma. extrapyramidal signs.
(2) Acute hepatic disease. (2) CVS: Postural hypotension, bradycardia.
(3) During MAO inhibitor administration.. (3) GIT: Diarrhea, abd. cramps, inc. gastric acid secretion.
Dosage (4) Resp. tract: Nasal congestion.
1-2 g orally in divided doses. Contraindications
(1) Pheochromocytoma
CLONIDINE (2) Peptic ulcer
Mechanism of Action (3) Depression.
It stimulates presynaptic 2 receptors in vasomotor center of (4) During MAO inhibitors administration.
(5) Parkinsonism.
brain  Dec. sympathetic outflow to the peripheral vessels.
Pharmacological Effects
GUANETHIDINE
(1) Cardiovascular System
(a) I/V inj. causes an initial transient inc. in both Mechanism of Action
systolic & diastolic pressure due to direct (1) It is transported across the sympathetic nerve memb.
stimulation of peripheral  - adrenoceptors. by a mech. that transports norepinephrine itself 
(b) This is followed by a fall in BP, resulting from a Concentrated in transmitter vesicles, where it replaces
dec. in cardiac output & heart rate. norepinephrine  Causing a gradual norepinephrine
(c) Vagal discharge is inc. in association with inc. depletion in nerve endings.
baroreceptor reflex sensitivity. (2) It inhibits norepinephrine release from sympathetic
(2) Kidney nerve endings.
(a) Dec. plasma renin activity. Pharmacological Effects
(b) Dec. renal vascular resistance but with no (1) Central Nervous System
alteration in renal blood flow. No effect, b/c it does not cross the BBB.
Adverse Effects (2) Cardiovascular System
(1) CNS: Sedation, drowsiness. (a) Initially, it displaces & releases enough unchanged
(2) CVS: Rebound hypertensive crisis from sudden norepinephrine to cause mild transient hyperten-
withdrawal of clonidine characterized by nervousness, sion & cardiac stimulation.
tachycardia, headache & sweating. (b) Followed by hypotension & bradycardia.
(3) GIT: Dry mouth (c) Orthostatic hypotension, b/c it depresses vaso-
(4) Renal: Fluid retention. constrictor reflexes.
Dosage (d) Inc. sensitivity of tissues to catecholamines.
0.2 - 1.2 mg /d. (3) Skeletal Muscle
It has a direct inhibitory effect on skeletal muscle
contraction.
ADRENERGIC NEURON BLOCKERS Clinical Uses
Moderate to severe hypertension ( usually with a diuretic &
RESERPINE a vasodilator).
Mechanism of Action Adverse Effects
(1) Reserpine blocks the ability of adrenergic transmitter (1) CVS: Orthostatic hypotension & syncope esp. during
vesicles to take up & store biogenic amines by exercise.
interfering with an uptake mechanism that depends on (2) GIT: Diarrhea.
Mg++ & ATP  Depletion of norepinephrine, (3) Sk. muscles: Aching, weakness.
dopamine & serotonin in both central & peripheral (4) Repro: Delayed or retrograde ejaculation.
neurons. Contraindications
(2) Also exerts a direct vasodilating effect on vascular (1) Pheochromocytoma.
smooth muscle when administer intraarterially. (2) Severe coronary artery disease.
M. Shamim’s PHARMACOLOGY 86

(3) Cerebrovascular insufficiency. (1) Decrease in total peripheral resistance (afterload) &
(4) During MAO inhibitor administration. venous return (preload).
(2) Reduction in blood pressure occurs independently of the
status of the renin-angiotensin system. As a result,
ANGIOTENSIN BLOCKERS
plasma renin activity increases due to removal of the
angiotensin II feedback.
SARALASIN Clinical Uses
Mechanism of Action (1) Mild to moderate hypertension.
It acts by competitive inhibition of angiotensin II at its (2) Diabetic nephropathy.
receptors.
Pharmacological Effects
DIRECT ACTING VASODILATORS
(1) It blocks the presser & aldosterone releasing effects of
angiotensin II, & lowers BP in high renin states eg in
renal artery stenosis. DIAZOXIDE
(2) It also has weak agonist activity so that rapid Mechanism of Action
administration to persons without high circulating Relaxes smooth muscle of the arterioles  Dec. systemic
angiotensin II may inc. BP. vascular resistance  Dec. BP.
Pharmacological Effects
ACE INHIBITORS (1) Cardiovascular System
Mechanism of Action It causes a fall in both systolic & diastolic pressure,
They inhibit the converting enzyme peptidyl dipeptidase accompanied by an inc. in heart rate & cardiac output.
that hydrolyzes angiotensin I to angiotensin II, & inactivates (2) Smooth Muscles
bradykinin (a potent vasodilator). It relaxes other smooth muscle in addition to vascular
Pharmacological Effects one.
(1) They cause a reduction in total peripheral resistance (3) Endocrine
& mean arterial BP, & either no change or an inc. in It inhibits release of insulin.
cardiac output. Clinical Uses
(2) They do not cause reflex sympathetic activation & can (1) I/V in hypertensive emergencies.
be used safely in pts. with ischemic heart disease. (2) Orally in hypoglycemia caused by hyperinsulinemia.
Clinical Uses Adverse Effect
(1) Mild to moderate hypertension. (1) CVS
(2) Chronic congestive cardiac failure (a) Severe hypotension which may result in stroke &
Adverse Effects myocardial infraction.
(1) CNS: Headache, dizziness & fatigue (enalapril). (b) Angina.
(2) CVS: Severe hypotension in hypovolemic pts. (c) Cardiac failure in pts. with ischemic heart disease.
(3) Renal: Acute renal failure, hyperkalemia, proteinuria, (2) Endo
angioedema. Hyperglycemia.
(4) Resp. tract: Dry cough, wheezing. (3) Renal
(5) Blood: Neutropenia. Edema.
(6) Skin: Skin rashes. Contraindications
(7) Special senses: Alteration in taste. (1) Congestive cardiac failure.
Contraindications (2) Diabetes mellitus.
(1) Aortic stenosis. Dosage
(2) Bilateral renal artery stenosis. Initially 75 - 100 mg; if necessary 150 mg every 5 min. until
(3) Renal impairment. BP is lowered to normal.
(4) Pregnancy.
(5) Lactation. SODIUM NITROPRUSSIDE
Pharmacological Effects
ANGIOTENSIN RECEPTOR BLOCKERS (1) Cardiovascular System
Examples (a) It directly relaxes both arterial & venous smooth
Candesartan, Eprosartan, Irbesartan, Losartan, Olmesartan, muscles.
Telmisartan, Valsartan. (b) It dec. BP in both supine & upright positions.
Mechanism of Action (c) It causes dec. myocardial oxygen demand due to
They are selective, competitive antagonists of Angiotensin II inc. venous capacitance.
type 1 (AT1) receptor, reducing the end organ responses to (d) Causes a slight inc. in heart rate & dec. in cardiac
angiotensin II. output except in heart failure.
Pharmacological Effects
11: Cardiovascular System Drugs 87

(e) In heart failure, heart rate may dec. & cardiac (3) Endo: Hirsutism (hypertrichosis).
output inc. (4) Skin: Sweating.
(2) Kidney
Renal blood flow is maintained, & renin secretion is
OTHER ANTI- HYPERTENSIVE DRUGS
increased.
Clinical Uses
(1) Hypertensive emergencies. Ganglion Blockers
(2) To minimize bleeding during surgery by producing See chapter 3, Parasympathetic nervous system drugs.
controlled hypotension. Adrenoceptor Blockers
(3) Acute myocardial infarction. See chapter 2, Sympathetic nervous system drugs.
(4) Acute congestive cardiac failure. Ca++ Channel Blockers
Adverse Effects See Unit II of this chapter.
(1) CNS: Headache, restlessness.
(2) CVS: Excessive hypotension, arrhythmias, palpitation, GENERIC & TRADE NAMES
retrosternal pain.
(3) Endo: Delayed hypothyroidism.
(4) Blood: Methemoglobinemia, metabolic acidosis. (1) Diuretics
(5) GIT: Nausea. See Chapter 12.
(6) Thiocynate Poisoning: Manifested as weakness, (2) Centrally Acting Sympathoplegic Drugs
disorientation, psychosis, muscle spasms & convulsions. Methyldopa: Aldomet, Hyergen, Normet.
Dosage (3) Alpha Adrenoceptor Blockers
0.5 - 10 g / kg /min, IV. Prazosin: Minipress.
Doxazosin: Cardura.
HYDRALAZINE Terazosin: Hytrin.
(4) Beta Adrenoceptors Blockers
Mechanism of Action
Atenolol: Atelor, Atenovid, Atenolol, Blokium,
Same as diazoxide. It may reduce diastolic BP more than
Cardiolite, Coxalol, Normitab, Nortenalol, Pulse,
systolic BP.
Tenolol, Tenoret-50*, Tenormin.
Clinical Uses
Betaxolol: Betaxen, Betoptic.
(1) Moderate to severe hypertension.
Bisoprolol: Bison, Concor.
(2) Acute & chronic congestive cardiac failure.
Carteolol: Carteol, Mikelan.
Adverse Effects
Carvedilol: Carveda, Vadil.
(1) CNS: Headache, dizziness, peripheral neuropathy.
Esmolol: Brevibloc.
(2) CVS: Palpitation, flushing, reflex tachycardia, angina,
Metoprolol: Betalock Zok, Mepresor, Metocard.
ischemic arrhythmias.
Nadolol: Corgard.
(3) GIT: Anorexia, nausea.
Pindolol: Vikaldix.
(4) Skin: Sweating; lupus erythematosus like synd.
Propranolol: Beta Prograne, Blockonol, Cardinol,
characterized by arthralgia, myalgia, skin rashes, &
Inderal, Oprinol.
fever.
Timolol: Betalol, Timosol.
Contraindications
(5) Ca++ Channel Blockers
(1) Coronary artery disease.
Nifedipine: Adalat, Cardipine, Nidipine, Nifedicor.
(2) Lupus Erythematosus.
Nicardipine: Nicapress R.
Dosage
Amlodipine: Amlocard, Norvasc, Sofvasc.
40 - 200 mg /d.
Felodipine: Plendil.
Isradipine: Dynacirc.
MINOXIDIL
Diltiazem: Angizem, Calcard, Calzem, Cardiazem,
Mechanism of Action Deltazem, Dilzem, DTZ, Herbesser, Lacerol, Tiazem.
Same as diazoxide. Verapamil: Calan, Isocardin, Zavera.
Clinical Uses (6) ACE Inhibitors
(1) Severe hypertension. Candesartan: Advant, Canaxit, Canditensin, Treatan.
(2) Severe hypertension coupled with renal functional Eprosartan: Eveten.
impairment. Irbesartan: Aprovel, Coaprovel.
(3) Topically used as a stimulant of hair growth for Losartan: Bepsar, Cosartan, Eziday, Co-Eziday*,
correction of baldness. Losartan.
Adverse Effects Valsartan: Diovan, Varlan.
(1) CNS: Headache. Captopril: Acetropil, Capoten, Capozide*, Capril,
(2) CVS: Tachycardia, palpitations, angina, pericardial Katopril, Ropril, Vasotone.
effusion, tamponade.
M. Shamim’s PHARMACOLOGY 88

Enalapril: Cardace, Co-Renitec*, Cortec, Ranitec, (iii) Nitroglycerine 2% ointment ( 3-6 hrs).
Stadelant.
Fosinopril: Monopril. (iv) Nitroglycerine  Slow release buccal
Lisinopril: Lace, Novotec, Zestril. preparation ( 3-6 hrs).
Perindopril: Coversyl, Dopril. (v) Isosorbide dinitrate  Oral (4-6 hrs).
Quinapril: Accupril. (c) Long Acting
Ramipril: Hiace, Tritace. (i) Pentaerythritol tetranitrate  Oral (6-8
Trandolapril: Gopten. hrs).
(7) Vasodilators (ii) Erythrityl tetranitrate (6-8 hrs).
Na Nitroprusside: Nipride. (iii) Nitroglycerine  Oral sustained- action
(6-8 hrs).
(iv) Isosorbide mononitrate  Oral (6-10 hrs) .
Unit II (v) Nitroglycerine  Slow release trans-
cutaneous preparation (8-10 hrs).
(B) Miscellaneous Vasodilators
Anti - Anginal Drugs Nicorandil.

BETA ADRENOCEPTOR BLOCKERS

ANGINA PECTORIS Propranolol, Atenolol, Metoprolol, Nadolol, Pindolol.

CALCIUM CHANNEL BLOCKERS

It is the strangling chest pain often radiating to the left
(A) Dihydropyridines
shoulder & arm that occurs when coronary blood flow is
Nifedipine, Nicardipine, Nisoldipine, Amlodipine,
inadequate to supply the oxygen required by the heart.
Felodipine, Isradipine.
Types
(B) Miscellaneous
(1) Classic (Atherosclerotic) Angina
Diltiazem, Verapamil, Bepridil.
Caused by atheromatous obstruction of the large
coronary vessels.
(2) Variant (Angiospastic or Prinzmetal's) Angina NEWER ANTIANGINAL DRUGS
Caused by transient spasm of localized portions of Ranolazine, Trimetazidine, Ivabradine.
large coronary vessels.
NITRATES & NITRITES
DRUG CLASSIFICATION
MECHANISM OF ACTION
CORONARY VASODILATORS Nitroglycerine is denitrated into nitric oxide  NO reacts
(A) Nitrites & Nitrates with sulfhydryl-containing receptors associated with
(1) According to Chemical Nature guanyl cyclase  Guanyl cyclase is activated  Inc. cGMP
(a) Nitrites level  Smooth muscle relaxation.
(i) Inorganic nitrites: Sodium nitrite.
(ii) Organic nitrites: Amylnitrite, Ethyl- PHARMACOLOGICAL EFFECTS
nitrite. (A) Cardiovascular System
(b) Nitrates Relaxation occur in all segments of vascular system:
Glyceryl trinitrate (Nitroglycerine), Erythrityl (1) Arterioles & precapillary sphincters are dilated
tetranitrate, Pentaerythritol tetranitrate, less, due to reflex responses.
Isosorbide dinitrate, Isosorbide mononitrate. (2) Inc. venous capacitance due to dec. venous tone 
(2) According to Duration of Action Dec. ventricular preload  Dec. cardiac output.
(a) Short Acting (3) Arterial dilation  Dec. mean systemic arterial
(i) Amyl nitrite  Inhalant (duration 3-5 min ). pressure  Dec. after load of the heart  Dec.
(ii) Nitroglycerine  Sublingual (10-30 min). Cardiac oxygen requirement.
(iii) Isosorbide dinitrate  Sublingual (10-60 (4) Venous dilation  Dec. preload  Dec. myocardial
min). wall tension  Dec. myocardial oxygen requirement.
(b) Intermediate Acting (5) Dec. left ventricular end-diastolic volume reduces
(i) Isosorbide dinitrate  Sublingual tissue pressure around subendocardial vessels 
( 11/2 - 2 hr ). Inc. coronary blood flow to this area.
(ii) Isosorbide dinitrate  Chewable (2-3 hrs). (6) Selective dilation of large epicardial & collateral
coronary arteries occurs.
11: Cardiovascular System Drugs 89

(7) Vasodilation of cerebral vessels Inc. intracranial UNDESIRABLE EFFECTS IN ANGINA

pressure & headache. (A) Inc. end-diastolic volume, due to dec. heart rate.
(8) Cutaneous vasodilation  Flushing. (B) Inc. ejection time, also due to dec. heart rate.
(B) Other Smooth Muscle Organs These results in inc. myocardial oxygen requirement.
Relaxation of smooth muscles occur in the bronchi, GIT
including biliary system, & genitourinary system. USES IN ANGINA
These effects has little clinical value b/c of short (1) Used only in classic angina.
duration of drugs' action. (2) Used concomitantly with nitrates to balance its
(C) Blood undesirable effects
Nitrite ion reacts with hemoglobin to produce
methemoglobin which result in pseudocyanosis &
tissue hypoxia. CALCIUM CHANNEL BLOCKERS

CLINICAL USES MECHANISM OF ACTION

(1) Classic angina pectoris. Bind to receptors on voltage-gated calcium channels  This
(2) Variant angina pectoris. results in blocking of Ca++ channels  This results in
(3) Paroxysmal nocturnal dyspnea. inhibition of Ca++ influx into cardiac & smooth muscle cells.
(4) Cyanide poisoning.
PHARMACOLOGICAL EFFECTS
ADVERSE EFFECTS (A) Vascular Smooth Muscle
(1) CNS: Throbbing headache, dizziness, weakness, Relaxation occur, more in the arterioles than in the veins;
cerebral ischemia. (1) Dilation of main coronary arteries & coronary
(2) CVS: Orthostatic hypotension, reflex tachycardia. arterioles, & inhibition of coronary artery spasm 
(3) Blood: Hypoxia, pseudocyanosis, methemoglobinemia. Inc. myocardial oxygen delivery in pts. with variant
(4) Skin: Flushing. angina.
(2) Dilation of peripheral arterioles decreases total
CONTRAINDICATIONS peripheral vascular resistance  Dec. BP (esp. with
(1) Elevated intracranial pressure. nifedipine)  Dec. myocardial oxygen requirement.
(2) Severe anemia. (B) Cardiac Muscle
Dec. oxygen requirement in pts. with angina, due to;
DOSAGE (1) Dec. impulse generation in SA node.
(1) Nitroglycerine (SL)  0.15-1.2 mg. (2) Dec. conduction in AV node.
(2) Nitroglycerine (SRBP)  6.5-13 mg/4 hrs. (3) Dec. cardiac contractility.
(3) Isosorbide dinitrate (SL)  2.5-10 mg/2 hr. (4) Dec. cardiac output.
(4) Isosorbide dinitrate (oral)  10-60 mg/4-6 hrs. Note: Verapamil & diltiazem, have greater cardiac
(5) Pentaerythritol tetranitrate (oral)  40 mg/6-8 hrs. effects.
Why Given Sublingually? (C) Other Smooth Muscles
These drugs are inactivated by the hepatic nitrate reductase, Relaxation occurs in bronchiolar, gastrointestinal &
so sublingual route is preferred for achieving a therapeutic uterine smooth muscles, but these are less sensitive
blood level rapidly. than vascular smooth muscle.
(D) Other Effects
(1) Interfere with stimulus-couple secretion in glands
BETA - ADRENOCEPTOR BLOCKERS & nerve endings.
(2) Verapamil has slight local anesthetic action (due to
BENEFICIAL EFFECTS IN ANGINA less effective blockade of sodium channels).
(A) Thru its -blocking effect, it decreases sympathetic (3) Verapamil inhibits insulin release.
stimulation of heart, resulting in;
(1) Dec. heart rate. CLINICAL USES
(2) Dec. contractility. (1) Classic angina pectoris.
(3) Dec. cardiac output. (2) Variant angina pectoris.
(4) Dec. arterial pressure. (3) Hypertension.
These effects dec. myocardial oxygen requirement at (4) Supraventricular tachyarrhythmias.
rest & during exercise. (5) Hypertrophic cardiomyopathy.
(B) Dec. heart rate causes an inc. diastolic perfusion time (6) Migraine.
that inc. the myocardial perfusion. (7) Raynaud's phenomenon.
(8) Atherosclerosis.
M. Shamim’s PHARMACOLOGY 90

ADVERSE EFFECTS
(1) CNS: Dizziness. Drug Treatment of CCF
(2) CVS: Cardiac arrest, bradycardia, AV-block, congestive
cardiac failure, hypotension, peripheral edema.
(3) GIT: Nausea, constipation. CONGESTIVE CARDIAC FAILURE (CCF)
(4) Skin: Flushing.
(5) Verapamil inc. serum level of digitalis during the first
It refers to failure of the heart to pump enough blood to
week of therapy, & thus can cause digitalis toxicity.
meet the needs of the tissues, following myocardial damage.
Causes
CONTRAINDICATIONS
(1) Diseases of myocardium, mainly ischemic.
(1) Severe hypotension. (2) Excessive workload due to arterial hypertension.
(2) Cardiogenic shock. (3) Valvular disease.
(3) Sick sinus syndrome. (4) Arteriovenous shunt.
(4) Digitalized patients. Clinical Features
(1) Tachycardia.
MISCELLANEOUS VASODILATORS (2) Dec. exercise tolerance.
(3) Shortness of breath.
(4) Peripheral & pulmonary edema.
DIPYRIDAMOLE
(5) Cardiomegaly.
Pharmacological Effects
(1) Inhibits uptake of adenosine ( a coronary vasodilator)
into erythrocytes & other tissues, to inc. its plasma DRUG CLASSIFICATION
level.
(2) Dec. coronary vascular resistance, & inc. coronary (A) Drugs Having Positive Inotropic Effects
blood flow. (1) Cardiac Glycosides (Digitalis)
(3) Inhibits platelet aggregation, so used to prevent Digoxin, Digitoxin, Deslanoside, Lanatoside C.
formation of thromboemboli in pts with prosthetic (2) Bipyridines
cardiac valves. Inamrinone, Milrinone.
(3) 1 - Adrenoceptor Agonists
PAPAVERINE Dobutamine.
Pharmacological Effects (B) Drugs Without Positive Inotropic Effects
(1) It is a potent inhibitor of phosphodiesterase enzyme. (1) Angiotensin Blockers
(2) It relaxes smooth muscle of large blood vessels, & (a) Angiotensin Converting Enzyme Inhibitors
decreases total peripheral vascular resistance thru an Benzapril, Captopril, Enalapril, Fosinopril,
effect on arterioles. Lisinopril, Moexipril, Perindopril, Quinapril,
(3) If given IV, it produces a quinidine-like effect that Ramipril, Trandolapril.
results in sudden death. (b) Angiotensin Receptor Blockers
Candesartan, Eprosartan, Irbesartan, Losartan,
GENERIC & TRADE NAMES Olmesartan, Telmisartan, Valsartan.
(2) Direct Vasodilators
Hydralazine, Nitroprusside, Isosorbide dinitrate,
(1) Nitrates & Nitrites Nesiritide, Bosentan.
Isosorbide dinitrate: Carsodil, Isobid, Isoday, Isoket,
(3) - Adrenoceptor Blocker
Isordil, Sorbid.
Prazosin.
Glyceryl trinitrate: Angised, Deponit, Glytrin,
Nitrocine, Nitromint, Nitronal, Sustac. (4) -Adrenoceptor Blockers
Bisoprolol, Carvedilol, Metoprolol.
Isosorbide mononitrate: Corlet, Elantan, Ismo-20,
Monis, Monosor, Vasocord. (5) Diuretics
(2) - Adrenoceptor Blockers
See Unit I. DIGITALIS
(3) Ca++ Channel Blockers
See Unit I. PHARMACOLOGICAL EFFECTS
(A) Cardiac Effects
(1) Mechanical Effects
Unit III (a) Digitalis increases myocardial contractility,
both by increasing velocity of cardiac muscle
11: Cardiovascular System Drugs 91

contraction & by increasing the max. force (b) Abnormal cardiac automaticity is inhibited by
that is developed. hyperkalemia, thus moderately inc.
(b) Cardiac output is inc., with dec. in cardiac extracellular K+ decreases toxic effects of
filling pressure, heart size, & venous & digitalis.
capillary pressure. (2) Ca++ facilitates toxic actions of digitalis by accele-
Mechanism rating the overloading of intracellular Ca++ stores.
Digitalis inhibits Na+ - K+ -ATPase resulting in (3) Mg++ effect is opposite to that of Ca++.
intracellular accumulation of Na+ (& loss of intra-
cellular K+)  Influx of Ca++ secondary to CLINICAL USES
activation of memb. Na+ - Ca++ carrier  Inc. (1) Congestive cardiac failure.
amount of free intracellular Ca++  Ability of (2) Atrial flutter.
sarcoplasmic reticulum to bind Ca++ is dec. leading (3) Atrial fibrillation.
to more intracellular Ca++ available  Inc. intensity (4) Paroxysmal atrial tachycardia.
of interaction of actin & myosin filaments. (5) AV-nodal tachycardia.
(2) Electrical Activity
(a) Inc. refractory period of AV node. ADVERSE EFFECTS
(b) Dec. conduction velocity thru AV node. (1) CNS
(c) Inc. vagal tone of heart (indirect effect). Headache, fatigue, malaise, neuralgias, disorientation,
(3) Heart Rate hallucination, delirium, visual disturbances, convulsions.
Digitalis has negative chronotropic effect, due to (2) CVS
direct slowing of SA node as well as due to Premature ventricular beats, ventricular tachycardia,
indirect stimulation of vagal tone. ventricular fibrillation, AV block, sinus arrhythmias, SA
(4) Myocardial Oxygen Consumption block, paroxysmal & nonparoxysmal atrial tachycardia.
(a) Inc. contractility causes an inc. myocardial O2 (3) GIT
consumption. Anorexia, nausea, vomiting, diarrhea.
(b) Dec. ventricular volume due to inc. muscle (4) Endo
tone & cardiac output, decreases myocardial Gynecomastia, galactorrhea.
O2 consumption. Treatment
(c) Net consumption depends upon which of the (1) Discontinuation of digitalis & K- depleting diuretics.
above two factor is dominant. (2) KCI is given, if hypokalemia is present.
(B) Extracardiac Effects (3) Phenytoin is given, for ventricular & atrial arrhythmias.
These are due to inhibition of Na+ - K+ -ATPase & an (4) Lidocaine & procainamide, for ventricular
inc. in intracellular Ca++. tachyarrhythmias.
(1) Central Nervous System (5) Propranolol, to treat ventricular & supraventricular
Inc. spontaneous activity of neurons, due to tachycardia.
depolarization. (6) Atropine, to control sinus bradycardia & AV block.
(2) Cardiovascular System (7) Digitalis immune fab ( a digitalis antibody).
(a) Dec. peripheral vascular resistance &
venomotor tone in congestive cardiac failure; CONTRAINDICATIONS
however, in normal persons, digitalis produces (1) Cardiac tamponade.
venous & arterial constriction). (2) Constrictive pericarditis.
(b) Inc. systolic BP, due to inc. stroke volume. (3) Idiopathic hypertrophic subaortic stenosis.
(c) Dec. diastolic BP, due to improved circulation (4) Wolff- Parkinson - White pts, with atrial fibrillation.
& dec. reflex vasoconstriction. (5) Ventricular fibrillation.
(3) Gastrointestinal Tract (6) Ventricular tachycardia.
Inc. spontaneous activity of smooth muscle of GIT.
(4) Renal DIGITALIZATION
Diuresis occur due to improved myocardial If there is no urgent need for a desired effect, an oral
contractility & dec. sympathetic activity, which "digitalizing dose" is first administered &, then the
results in inc. renal blood flow promoting excretion "maintenance dose" is adjusted on the basis of clinical
of salt & water. & laboratory assessment. This is called digitalization.
(C) Interactions With K+, Ca++ , & Mg++
(1) K+ & digitalis interacts in 2 ways;
(a) They inhibit each other's binding to Na+ - K+ (1) Digoxin
ATPase; therefore, hyperkalemia decreases Digitalizing dose is 0.5 to 0.75 mg every 8 hours for 3
enzyme-inhibiting actions of digitalis, whereas doses, while the maintenance daily dose is 0.125 to
hypokalemia facilitates these actions. 0.5 mg.
M. Shamim’s PHARMACOLOGY 92

(2) Digitoxin (3) Combination of both.

Digitalizing dose is 0.2 to 0.4 mg every 12 hours for 3 Factors Precipitating Arrhythmias
doses, while the maintenance daily dose is 0.05 - 0.2 mg. (1) Hypoxia, & ischemia.
(2) Acidosis or alkalosis.
(3) Electrolyte abnormalities.
BIPYRIDINES
(4) Excessive catecholamine exposure.
(5) Autonomic influences.
Mechanism of Action (6) Drug toxicity (eg digitalis).
It inhibits phosphodiesterase enzyme  Inc. cAMP conc. (7) Overstretching of cardiac fibres.
 Inc. Ca++ influx. (8) Presence of scarred or diseased cardiac tissue.
Pharmacological Effects
(1) A positive inotropic effect.
DRUG CLASSIFICATION
(2) A vasodilating effect, which reduces both pulmonary &
systemic vascular resistance.
Clinical Uses (1) Class 'I' Agents ( Na-Channel Blockers )
Congestive cardiac failure. (A) Group 'I A'
Adverse Effects Increases the duration of action potential; eg,
(1) CVS: Ventricular tachycardia in pts. with atrial flutter Quinidine, Procainamide, Disopyramide,
or fibrillation. Amiodarone.
(2) GIT: Nausea, vomiting. (B) Group 'I B'
(3) Blood: Thrombocytopenia. Decreases the duration of action potential; eg,
Lidocaine, Tocainide, Mexiletine, Moricizine,
(C) Group 'I C'
GENERIC & TRADE NAMES eg Flecainide, Encainide, Propafenone, Moricizine.
(II) Class 'II' Agents ( blockers )
(1) Digitalis Propranolol, Esmolol, Atenolol, Sotalol, Amiodarone.
Digoxin: Digox, Digoxin, Doxin. (III) Class 'III' Agents
(3) 1 Agonists Includes drugs that prolong effective refractory period
Dobutamine: Dobuject, Dobutamine, Dobutrex. by mech. other than or in addition to Na- channel
(4) ACE Inhibitors blocking eg,
See Unit I. Bretylium, Amiodarone, Sotalol, Dofetilide, Ibutilide.
(5) Vasodilators (IV) Class 'IV' Agents (Ca Channel Blockers)
See Unit I. Verapamil, Diltiazem, Amiodarone.
(6)  &  Blockers (V) Miscellaneous Antiarrhythmics
See Chapter 2, Unit III. Adenosine, Magnesium, Potassium.
(7) Diuretics
See Chapter 12. QUINIDINE

Unit IV MECHANISM OF ACTION

It blocks activated as well as inactivated sodium channels.

Drug Treatment of PHARMACOLOGICAL EFFECTS

(A) Cardiac Effects
Cardiac Arrhythmias At high conc., it has direct effect on most cells of heart;
while at lower conc., indirect (anticholinergic) effects
may significantly contribute to effects on heart.
(1) Dec. pacemaker rate, esp. that of ectopic
CARDIAC ARRHYTHMIAS pacemaker.
(2) Dec. conduction velocity, & inc. effective
It refers to abnormalities in rate, regularity, or site of origin refractory period in atrial, ventricular & purkinje
of cardiac impulse, or a disturbance in conduction of fibres.
impulse such that the normal sequence of activation of atria (3) Dec. excitability, esp. in depolarized tissue.
& ventricles is altered. (4) In low doses AV conduction is inc. due to anti-
Causes cholinergic effect, & pts. with atrial flutter or
(1) Faulty impulse initiation. fibrillation may experience an inc. in ventricular
(2) Faulty impulse conduction. rate.
11: Cardiovascular System Drugs 93

(5) Lengthens action potential duration which along (6) Arrhythmias due to digitalis toxicity.
with inc. effective refractory period reduces the
maximum reentry frequency.
PROCAINAMIDE
(6) ECG changes
(a) Prolongation of QRS complex.
(b) Prolongation of Q-T interval. Mechanism of Action
(c) Prolongation of P-R interval. Same as that of quinidine.
(d) Alterations in T waves ( due to delayed Pharmacological Effects
repolarization). (A) Cardiac Effects
(B) Extracardiac Effects Nearly similar to quinidine;
(1) Quinidine has  - adrenoceptor blocking properties (1) Suppresses abnormal ectopic pacemaker activity, &
which causes vasodilation & a reflex inc. in SA lengthens the duration of action potential &
nodal rate. refractory period in the atria & ventricles.
(2) It also has antimalarial, antipyretic & oxytocic (2) Slows conduction in atrium, AV node & ventricles.
properties. (3) Unlike quinidine, it has less prominent
antimuscarinic action.
CLINICAL USES (4) Ganglionic blocking properties results in more
(1) Premature atrial contractions. potent negative inotropic effects than quinidine.
(2) Paroxysmal atrial fibrillation & flutter. (5) Induces severe CCF in pts. with preexisting
(3) Intra-atrial & atrioventricular nodal reentrant ventricular dysfunction.
arrhythmias. (B) Extracardiac Effects
(4) Wolff-Parkinson-White tachycardia. Reduces peripheral vascular resistance, & cause
(5) Premature ventricular contractions. hypotension due to ganglionic blocking effects.
(6) Ventricular tachycardias. Clinical Uses
(1) Atrial & ventricular arrhythmias.
(2) Ventricular arrhythmias associated with acute
ADVERSE EFFECTS
myocardial infraction.
(1) CNS
Adverse Effects
Cinchonism occur characterized by;
(1) CNS: Mental confusion, psychosis.
Tinnitus, hearing loss, headache, diplopia, photophobia,
(2) Eye: Precipitation of acute glaucoma.
altered color perception, confusion, psychosis, vomiting,
(3) CVS: Ventricular arrhythmias, ventricular fibrillation,
diarrhea.
cardiac depression, hypotension, pericarditis.
(2) CVS
(4) Resp. tract: Pleuritis, parenchymal pulmonary disease.
(a) Quinidine syncope characterized by recurrent light
(5) GIT: Anorexia, nausea, vomiting, diarrhea.
headedness, & episodes of fainting.
(6) Liver: Hepatitis.
(b) AV block, ventricular tachyarrhythmias, depression
(7) Renal: Urinary retention.
of myocardial contractility.
(8) Blood: Agranulocytosis.
(c) Precipitate digitalis toxicity as it inc. plasma
(9) Skin: Lupus erythematosus-like syndrome consisting
digitalis level.
of arthralgia & arthritis, rashes.
(d) Angioneurotic edema, hypotension.
(10) Body temp: Fever.
(3) GIT
Contraindications
Anorexia, nausea, vomiting, diarrhea.
(1) AV block.
(4) Skin
(2) Systemic lupus erythematosus.
Rashes.
Dosage
(5) Blood
Up to 50 mg/ kg daily in divided doses every 3 to 6 hours.
Thrombocytopenia.
(6) Liver
Hepatitis. DISOPYRAMIDE
(7) Metabolic
Fever. Mechanism of Action
Similar to quinidine.
CONTRAINDICATIONS
(1) Complete AV block with an AV nodal or idioventricular Pharmacological Effects
pacemaker. Similar to quinidine, but it has even more marked anti-
(2) History of embolism. muscarinic effects.
(3) Old standing atrial fibrillation. Clinical Uses
(4) Subacute bacterial endocarditis. Ventricular arrhythmias.
(5) Heart failure. Adverse Effects
M. Shamim’s PHARMACOLOGY 94

(1) Eye: Blurred vision, worsening of pre-existing It blocks the activated & inactivated Na+ channels, but
glaucoma. shorten the action potential duration.
(2) CVS: CCF, hypotension, depressed myocardial Pharmacological Effects
contractility, conduction disturbances. (1) It is a potent suppressor of abnormal cardiac activity.
(3) GIT: Dry mouth, constipation. (2) It prolonged diastole, due to shorten action potential
(4) Renal: Urinary retention in pts. with prostatic duration.
hypertrophy. (3) It has little effect on atria.
Contraindications (4) It shortens effective refractory period of Purkinje fibres.
(1) 2nd or 3rd degree AV block. (5) It is an amide local anesthetic.
(2) Cardiogenic shock. Clinical Uses
(3) Severe uncompensated cardiac failure. (1) Ventricular arrhythmias during
Dosage (a) Open cardiac surgery
300-800 mg daily in divided doses. (b) Digitalis toxicity
(c) Acute myocardial infarction
(2) For local anesthesia
AMIODARONE
Adverse Effects
(1) CNS: Paresthesias, tremor, nausea of central origin,
Mechanism of Action lightheadedness, hearing disturbances, slurred speech,
(1) It is an effective blocker of Na+ channels, but only the convulsions, respiratory arrest.
channels in the inactivated state. (2) CVS: Circulatory collapse, SA nodal standstill, hypo-
(2) It is a weak Ca++ channel blocker. tension.
(3) It is also a non-competitive inhibitor of  - &  - Dosage
adrenoceptors. IV loading dose of 150 - 200 mg in 15 min. followed by
Pharmacological Effects maintenance infusion of 2 - 4 mg/min.
(1) Inc. action potential duration, & effective refractory
period in atrial & ventricular muscles.
PHENYTOIN
(2) Inc. P-R, QRS, & Q-T intervals.
(3) Dec. sinus rate, & AV conduction.
(4) Causes both systemic & coronary vasodilation. Antiarrhythmic Effect
(5) Also has an antianginal effect. (1) Effects are very similar to lidocaine.
Clinical Uses (2) It depresses spontaneous automaticity in atrial &
(1) Premature ventricular contractions. ventricular tissues without altering intraventricular
(2) Ventricular tachycardia. conduction.
(3) Supraventricular arrhythmias. (3) Inc. conduction thru damaged purkinje fibers.
(4) Arrhythmias in pts. with Wolff- Parkinson-White (4) It is especially useful for ventricular arrhythmias
syndrome. associated with digitalis toxicity or acute myocardial
Adverse Effects infarction.
(1) CNS: Paresthesias, tremor, ataxia, headache, dizziness, Note: For more detail, see Chapter 5, Unit III.
peripheral neuropathy.
(2) Eye: Yellowish brown micro-crystalline deposits on FLECAINIDE
cornea.
(3) CVS: Bradycardia, AV block, paradoxical ventricular
arrhythmias. Mechanism of Action
(4) Resp. tract: Pulmonary fibrosis & inflammation. Na+ channel blocker.
(5) GIT: Anorexia, nausea, vomiting, constipation. Pharmacological Effects
(6) Liver: Hepatocellular necrosis. (1) Dec. automaticity of ectopic pacemaker.
(7) Blood: Inc. in serum levels of digitalis, diltiazem, (2) Dec. conduction & excitability, & inc. refractory period
quinidine, procainamide. (more in the depolarized tissue).
(8) Endo: Hypo-or Hyperthyroidism. Clinical Uses
(9) Skin: Photodermatitis. (1) Premature ventricular contractions.
(2) Ventricular tachycardia.
Dosage Adverse Effects
200 - 400 mg/d. (1) CNS: Dizziness, blurred vision, nervousness.
(2) CVS: Aggravate arrhythmias or induce new ones,
SA nodal depression, AV block in pts. with conduction
LIDOCAINE disturbances.
(3) GIT: Anorexia, nausea, vomiting.
Mechanism of Action (4) Repro: Impotence.
11: Cardiovascular System Drugs 95

PROPRANOLOL Unit V

Antiarrhythmic Effects
Effects are primarily due to  - adrenoceptor blockade but Self-Assessment (T/F)
also result from a direct memb. effect;
(1) Depresses SA nodal firing. ( See answers on page no. 241)
(2) Dec. automaticity in purkinje fibres. (90) Regarding methyldopa & clonidine, following are
(3) A substantial inc. in effective refractory period of AV correct
node. (A) Both stimulates pre-synaptic central alpha-2
Antiarrhythmic Uses receptors.
(1) Atrial flutter & fibrillation. (B) Both causes rebound hypertension on sudden
(2) Paroxysmal supraventricular tachycardia. withdrawal.
(3) Ventricular arrhythmias, due to; (C) Orthostatic hypotension is a common adverse
(a) Enhanced adrenergic stimulation. effect.
(b) Digitalis toxicity. (D) Both causes sedation.
(E) Both increases renal vascular resistance.
BRETYLIUM (91) Captopril & enalapril do all of the following
(A) Competitively inhibit angiotensin at its receptor.
Mechanism of Action (B) Inhibit angiotensin converting enzyme peptidyl-
(1) It is an adrenergic neuronal blocking agent. It dipeptidase.
accumulates in postganglionic adrenergic nerve (C) Dec. angiotensin II conc. in blood.
terminals, where it initially stimulates norepinephrine (D) Reflex sympathetic activation.
release but then inhibits the release of norepinephrine (E) Acute renal failure.
in response to neuronal stimulation. (92) Following are correct, regarding direct acting
(2) It also has direct electrophysiologic effects on heart. vasodilators
Pharmacological Effects (A) Diazoxide is a venodilator.
Cardiac Effects (B) Na nitroprusside is used intravenously in
(1) Inc. ventricular action potential duration & effective hypertensive emergencies.
refractory period, more pronounced in ischemic cells. (C) Hydralazine is an arteriolar dilator.
(2) Also inc. action potential duration & effective (D) Minoxidil is used topically for correction of
refractory period of atrial muscle & AV node. baldness.
(3) Some positive inotropic effect, due to initial release of (E) Hydralazine reduces diastolic BP more than
norepinephrine. systolic BP.
Clinical Uses
(93) Postural hypotension is a common adverse effect of
Life-threatening ventricular arrhythmias refractory to other
(A) Na nitroprusside.
therapy.
(B) Propranolol.
Adverse Effects
(C) Phenoxybenzamine.
(1) CVS: Hypotension esp. orthostatic.
(D) Methyldopa.
(2) GIT: Nausea, vomiting.
(E) Reserpine.
(94) Nitroglycerine, either directly or thru reflexes,
GENERIC & TRADE NAMES results in
(A) Tachycardia.
(1) Na+ Channel Blockers (B) Inc. venous capacitance.
Quinidine: Quinidine bisulphate. (C) Dec. afterload.
Procainamide: Pronestyl. (D) Dec. myocardial wall tension.
Disopyramide: Norpace. (E) Inc. cardiac output.
Amiodarone: Cordarone, Sedacoron. (95) Antianginal effect of propranolol is attributed to
Lidocaine: Anacaine, Xylocaine, Xyles. (A) Dec. heart rate.
(2) Beta Blockers (B) Dec. arterial pressure.
See Chapter 2, Unit III. (C) Inc. end-diastolic ventricular volume.
(3) Class III Agents (D) Inc. in ejection time.
Bretylium: Bretylol. (E) Dec. contractility.
(4) Ca++ Channel Blockers
See Unit I. (96) Nitroglycerin in moderate doses may produce
(A) Cerebral vasodilation.
M. Shamim’s PHARMACOLOGY 96

(B) Reflex tachycardia. (E) Dec. excitability.

(C) Methemoglobinemia. (104) Recognized adverse effects of quinidine include
(D) Flushing. (A) Cinchonism.
(E) Sympathetic discharge. (B) Constipation.
(97) Regarding Ca channel blockers, following are (C) Thrombocytopenic purpura.
correct (D) Displacement of digoxin from its binding site
(A) They inhibit influx of Ca++ into cardiac & with possible digoxin toxicity.
smooth muscle cells. (E) Angioneurotic edema.
(B) They dilate main coronary arteries & coronary
arterioles.
(C) Nifedipine has greater effect on heart.
(D) Used clinically in classic as well as in variant
angina pectoris.
(E) Constipation may occur.
(98) Primary mechanism of action of digitalis involves
(A) An inc. of action potential amplitude.
(B) An inc. in ATP synthesis.
(C) A modification of actin molecule.
(D) An inc. in intracellular Ca++ levels.
(E) A block of Na+-Ca++ exchange.
(99) Important effects of digitalis on heart include
(A) Inc. force of contraction.
(B) Dec. AV conduction velocity.
(C) Inc. heart rate.
(D) Prolonged refractory period of AV node.
(E) Inc. ectopic automaticity.
(100) All of the following are therapeutically useful in
treatment of congestive cardiac failure
(A) A vasodilator such as hydralazine.
(B) A cardiac glycoside such as digoxin.
(C) A beta-agonist such as norepinephrine.
(D) A diuretic such as hydrochlorothiazide.
(E) A beta-blocker such as propranolol.
(101) All of the following are useful in treatment if
digitalis overdose
(A) Quinidine.
(B) Digoxin immune FAB fragment.
(C) Dietary potassium supplements for pts. being
treated concomitantly with diuretics.
(D) Lidocaine.
(E) Phenytoin.
(102) All of the following pairs correctly match a drug with
its action
(A) Quinidine  Blocks Na+ channels.
(B) Bretylium  Blocks K+ channels.
(C) Verapamil  Blocks Ca++ channels.
(D) Propranolol  Blocks -adrenoceptors.
(E) Procainamide  Blocks K+ channels.
(103) Cardiac effects of quinidine includes
(A) Dec. pacemaker rate esp. of ectopic pacemaker.
(B) Dec. conduction velocity in atrial, ventricular, &
purkinje fibres.
(C) Dec. refractory period in atrial, ventricular, &
purkinje fibres.
(D) Shortening of action potential duration.
M. Shamim’s PHARMACOLOGY 97

12 RENAL DRUGS

(a) Aldosterone Antagonists

Unit I Spironolactone, Eplerenone.
(b) Direct Acting
Triamterene, Amiloride.
Diuretics (2) ADH Antagonists
Conivaptan, Lithium salts, Demeclocycline.
(E) Miscellaneous Diuretics
(1) Alkalizers
DRUG CLASSIFICATION Citrates, Acetates & Bicarbonates of Sodium &
Potassium.
DIURETICS (2) Plasma Expanders
Drugs inducing a state of increase urine flow are called Dextran, Albumin.
diuretics. These agents are ion transport inhibitors that
dec. Na+ reabsorption at different sites in nephron. As a OSMOTIC DIURETICS
result, Na+ & other ions eg C1- enter urine in greater
amounts than normal, along with water, which is carried
passively to maintain osmotic equilibrium. MANNITOL
Mechanism of Action
CLASSIFICATION OF DIURETICS (1) Mannitol & other osmotic diuretics are filtered at
(A) Drugs Acting on Proximal Tubule glomerulus  Reabsorbed poorly, due to their large
(1) Osmotic Diuretics molecular size  Dec. reabsorption of water in proximal
Mannitol, Urea, Isosorbide. tubule & descending limb of loop of Henle (due
(2) Carbonic Anhydrase Inhibitors to their osmotical presence) Large volume of urine.
Acetazolamide, Brinzolamide, Dorzolamide, (2) Mannitol also cause an inc. in renal medullary blood
Methazolamide, Dichlorphenamide. flow via a prostaglandin-mediated mechanism.
(3) Acidifying Salts Clinical Uses
Ammonium chloride. (1) To inc. water excretion in preference to Na+ excretion,
(4) Xanthine Diuretics eg when renal hemodynamics are compromized.
Aminophylline, Tea, Coffee, Soda.
(2) To maintain urine volume & to prevent anuria, that
(B) Drugs Acting on Ascending Limb of Henle’s
Loop may result from large pigment loads to kidneys (eg,
(1) Loop ( High - Ceiling ) Diuretics hemolysis or rhabdomyolysis).
Furosemide, Bumetanide, Ethacrynic acid, (3) To dec. intracranial pressure in neurologic conditions.
Torsemide, Muzolimine, Piretanide. (4) To dec. intraocular pressure before ophthalmologic
(2) Mercurial Diuretics procedures.
Mercaptomerin. Adverse Effects
(C) Drugs Acting on Distal Tubule (1) CNS: Headache.
(1) Thiazide Diuretics (2) CVS: Complicate congestive cardiac failure.
Bendroflumethiazide, Benzthiazide, Chlorothiazide, (3) Resp. tract: Florid pulmonary edema.
Hydrochlorothiazide, Hydroflumethiazide, Methy- (4) GIT: Nausea , vomiting.
clothiazide, Polythiazide, Trichlormethiazide. (5) Water & electrolytes: ECF expansion & hyponatremia,
(2) Sulfonamide Diuretics
severe dehydration, hypernatremia.
Qualitatively similar to thiazides: eg,
Dosage
Chlorthalidone, Indapamide, Metolazone,
50 - 200 g / day, IV.
Quinethazone, Xipamide, Clopamide, Mefruside.
(D) Drugs Acting on Collecting Tubule
(1) K+- Sparing Diuretics CARBONIC ANHYDRASE INHIBITORS
M. Shamim’s PHARMACOLOGY 98

MECHANISM OF ACTION (2) Furosemide inc. renal blood flow & causes
They inhibit carbonic anhydrase, predominantly at redistribution of blood flow within renal cortex.
proximal convoluted tubule  Dec. bicarbonate (HCO3-) (3) Furosemide & bumetanide weakly inhibit carbonic
anhydrase.
reabsorption in proximal tubule  Inc. loss in urine
( bicarbonate diuresis ).
Note: HCO3- depletion leads to inc. NaCl reabsorption by CLINICAL USES
(1) Acute pulmonary edema.
remaining tubule segments  Hyperchloremic metabolic
(2) Edema associated with congestive cardiac failure, renal
acidosis.
failure, & hepatic cirrhosis.
(3) Diabetic nephropathy.
CLINICAL USES
(4) Hypercalcemia.
(1) Glaucoma (b/c aqueous humor formation is dec). (5) Hyperkalemia.
(2) For urinary alkalinization, eg to inc. excretion of uric (6) Acute renal failure.
acid , cystine, barbiturates or aspirin. (7) Anion (eg, bromide, fluoride, iodide) overdosage.
(3) Metabolic alkalosis; (8) Inc. intracranial pressure.
(a) Due to excessive use of diuretics in pts with
severe cardiac failure. ADVERSE EFFECTS
(b) In pts with respiratory acidosis.
(1) ENT: Ototoxicity.
(4) Acute mountain sickness.
(2) Hypersensitivity reactions: Skin rash, eosinophilia,
(5) Petit mal epilepsy.
interstitial nephritis.
(6) Hypokalemic periodic paralysis.
(3) Water, electrolytes, & acid-base balance:
(7) Severe hyperphosphatemia.
Hypokalemic metabolic alkalosis, hypomagnesemia,
severe dehydration, hyponatremia, hypercalcemia (due
ADVERSE EFFECTS to vol. depletion).
(1) CNS: Drowsiness, paresthesias. (4) Joints: Precipitate attacks of gout (due to
(2) Renal: Calculus (due to phosphaturia & hypercalciuria). hyperuricemia).
(3) Hypersensitivity reactions: Fever, rashes, bone (5) Muscles: Severe pain & tenderness in pts with renal
marrow suppression, interstitial nephritis. failure.
(4) Electrolytes & acid-base balance: Renal potassium (6) Blood: Transient granulocytopenia & thrombocytopenia.
wasting, hyperchloremic metabolic acidosis.
Precautions CONTRAINDICATIONS
(1) Gout.
(1) Renal failure with anuria.
(2) Diabetes.
(2) Hepatic coma.
(3) Pregnancy.
(3) Hypokalemia.
(4) Hypotension.
CONTRAINDICATIONS
(5) Hypersensitivity to sulfonamides.
(1) Hepatic cirrhosis.
(2) Chronic closed-angle glaucoma. DOSAGE
(3) Renal hyperchloremic acidosis.
Furosemide
(4) Adrenal insufficiency.
20-80 mg/day orally, or 20-50 mg 1M or IV.
(5) Na+ or K+ depletion.

DOSAGE THIAZIDE DIURETICS

Acetazolamide
250 mg , 1-4 times daily, orally. MECHANISM OF ACTION
(1) They inhibit NaCl reabsorption from luminal side of
LOOP (HIGH - CEILING) DIURETICS epithelial cells in distal convoluted tubule &, also to a
small extent in late proximal tubule  Inc. conc. of NaCl
MECHANISM OF ACTION in tubular fluid Inc. urine volume.
(2) They also inc. Ca+2 reabsorption in distal convoluted
(1) They inhibit Na+/ K+/ 2Cl- co-transport system in lumi-
tubule, probably resulting from a lowering of cell Na+.
nal memb. of thick ascending limb of Henle's loop  (3) They also cause direct relaxation of arteriolar smooth
(a) Dec. reabsorption of NaCl. muscle, accounting for continued hypotensive effect.
(b) Dec. the normal lumen-positive potential that Note: Initial hypotensive effect is due to dec. blood vol.
derives from K+ recycling Inc. excretion of
Mg+2 & Ca+2 . CLINICAL USES
(1) Hypertension.
12: Renal Drugs 99

(2) Congestive cardiac failure. (a) In male: Gynecomastia, impotence, benign

(3) Nephrolithiasis due to idiopathic hypercalciuria. prostatic hypertrophy.
(4) Nephrogenic diabetes insipidus. (b) In female: Menstrual irregularities.
(5) Diabetic nephropathy. (4) Electrolytes & Acid - Base Balance
(6) Nephrosis. Hyperkalemia, hyperchloremic metabolic acidosis.
Contraindications
ADVERSE EFFECTS (1) Chronic renal insufficiency.
(1) CNS (2) Liver disease.
Weakness, fatigability, paresthesias. (3) Hyperkalemia.
(2) Hypersensitivity Reactions Dosage
Photosensitivity, generalized dermatitis, hemolytic 25 mg 1 - 4 time daily, orally.
anemia, thrombocytopenia, acute necrotizing pancrea-
titis, interstitial nephritis. TRIAMTERENE & AMILORIDE
(3) Electrolytes & Acid - Base Balance Mechanism of Action
Hypokalemia, metabolic alkalosis, hyponatremia, They directly interfere with Na+ entry thru sodium-selective
hypercalcemia. ion channels, that is coupled with K+ secretion, in apical
(4) Metabolism memb. of collecting tubules Inc. urinary Na+ & volume.
Hyperglycemia, hyperuricemia, hyperlipidemia. Clinical Uses
(1) As an adjuvant to other diuretics to dec K+ loss.
CONTRAINDICATIONS (2) Hypertension.
(1) Hepatic cirrhosis. (3) Edema due to secondary aldosteronism, eg from;
(2) Borderline renal failure. (a) Congestive cardiac failure.
(3) Hypersensitivity to thiazide or sulfonamides. (b) Hepatic cirrhosis.
(c) Nephrotic syndrome.
DOSAGE Adverse Effects
(1) Bendroflumethiazide 2.5-10 mg OD, orally. (1) CNS
(2) Hydrochlorthiazide  25-100 mg OD, orally. Dizziness.
(2) GIT
Nausea, vomiting.
POTASSIUM - SPARING DIURETICS (3) Electrolyte, & Acid - Base Balance
Hyperkalemia, hyperchloremic metabolic acidosis.
SPIRONOLACTONE (4) Metabolism
Mechanism of Action Triamterene  Azotemia, hyperuricemia.
(1) It binds to cytoplasmic aldosterone receptors & (5) Muscles
prevents translocation of receptor complex to nucleus Leg cramps.
in target cell  This results in failure to produce (6) Renal
mediator proteins that normally stimulate Na+ - K+ Triamterene Acute renal failure, calculus.
exchange sites of collecting tubule  Dec. Na+ Contraindications
reabsorption, & dec. K+ & H+ secretion, in collecting (1) Liver disease.
(2) Gout.
tubules & duct  Inc. urinary Na+ & volume.
(3) Hyperkalemia
(2) It also dec. intracellular formation of active metabolites
Dosage
of aldosterone by inhibition of 5  - reductase activity.
(1) Triamterene
Clinical Uses
100 mg 1-3 times daily, orally.
(1) Primary hyperaldosteronism, eg, Conn's synd, ectopic
(2) Amiloride
ACTH production.
5 mg OD, orally.
(2) Secondary aldosteronism, resulting from;
(a) Congestive cardiac failure.
(b) Hepatic cirrhosis. ADH ANTAGONISTS
(c) Nephrotic syndrome.
(3) As an adjuvant to other diuretics to dec. K+ loss. Mechanism of Action
Adverse Effects They inhibit effects of ADH at collecting tubule 
(1) CNS
Dec. water reabsorption  Inc. urine volume.
Lethargy, mental confusion, headache.
Clinical Uses
(2) GIT
(1) Syndrome of inappropriate ADH secretion (SIADH).
Nausea, diarrhea.
(2) Other conditions causing inc. ADH, eg dec. effective
(3) Endo & Repro
circulatory blood volume.
M. Shamim’s PHARMACOLOGY 100

Adverse Effects (2) Sodium cellulose phosphate (binds Ca+2 in gut, & dec.
(1) CNS urinary Ca+2 excretion).
Tremulousness, mental obtundation. (3) Allopurinol (reversed hyperuricemia).
(2) CVS (4) Potassium citrate (alkalinizes urine).
Cardiotoxicity.
(3) Renal DRUGS USED TO ALLEVIATE ABNORMAL
Nephrogenic diabetes insipidus, renal failure.
MICTURITION
(4) Endo
Thyroid dysfunction.
(5) Blood Drug Classification
Leukocytosis. (A) Incontinence Preventors
(1) Antimuscarinics, eg
Oxybutynin, Propantheline.
GENERIC & TRADE NAMES (2) Tricyclic antidepressants, eg
Imipramine, Amitriptyline, Nortriptyline.
(A) Osmotic Diuretics (3) Smooth muscle relaxants, eg
Mannitol: Mannitol, Osmotol. Flavoxate.
(B) Carbonic Anhydrase Inhibitors (4) Estrogens
Acetazolamide: Acemox, Diamox. (B) Micturition Promoters
Brinzolamide: Azopt. (1) Alpha-adrenoceptor antagonists, eg
Dorzolamide: Trusopt, Co-dorzal*. Prazosin, Doxazosin, Indoramin.
(C) Loop Diuretics (2) Parasympathomimetics, eg
Furosemide: Frusinox, Lasix, Losamide, Lasoride*. Bethanechol, Carbachol, Distigmine.
(D) Thiazide & Similar Diuretics
Hydrochlorothiazide: Diuza, Urozide.
Indapamide: Natrilix. Unit III
(E) K+ - Sparing Diuretics
Spironolactone: Aldactazide*, Aldactone, Spiromide*.
Triamterene: Dyazide*.
Amiloride: Conserve*, Moduretic*.
Drug Induced Renal
Diseases
Unit II
DRUG CAUSING TUBULAR DISEASES
Other Renal Drugs
(A) Toxic Tubular Necrosis
Caused By
(1) Aminoglycosides esp. if combine with cephalo-
ANTI-DIURETICS sporins or furosemide.
(2) Cephalosporins.
These are drugs that inhibit water loss from body. (3) Paracetamol overdosage.
Drug Classification (4) Amphotericin
(1) Antidiuretic hormone (ADH). (5) Cisplatin
(2) Drugs that release ADH, eg (6) Iodine contrast media
Morphine, Nicotine, Yohimbine, Ether, Cyclopropane. (B) Acute Ischemic Tubular Necrosis
(3) Drugs that produce constriction of afferent renal Caused By
arterioles, eg (1) Antihypertensives
Epinephrine. (2) Opiates
(4) Thiazides (act as antidiuretic in nephrogenic diabetes (3) Drugs inducing volume depletion, eg
insipidus). Diuretics, & Drugs causing severe diarrhea or
vomiting.
(4) NSAIDs
DRUGS FOR NEPHROLITHIASIS

DRUGS CAUSING TUBULO-INTERSTITIAL

Drug Classification DISEASES
(1) Thiazides (dec. excretion of Ca+2 & oxalate in urine).
12: Renal Drugs 101

(A) Acute Tubulo-Interstitial Nephritis (1) Drugs to be Avoided

Caused By Codeine, Dihydrocodeine, Morphine, Dextropropoxy-
(1) Antibiotics, eg phene, Pethidine.
Penicillins, Sulfonamides, Cephalothin, Rifampin. (2) Safe Alternatives
(2) Analgesics, eg Methadone, Naloxone.
NSAIDs, Phenylbutazone.
(3) Others, eg NON-OPIOID ANALGESICS
Allopurinol, Azathioprine, Cimetidine, Furosemide. (1) Drugs to be Avoided
(B) Chronic Interstitial Nephritis NSAIDs.
Caused By (2) Safe Alternative
Analgesics, eg Acetaminophen (Paracetamol).
Aspirin, Phenacetin, Indomethacin, Naproxen, & other
NSAIDs. CNS DRUGS
(A) Sedative-Hypnotics
DRUGS CAUSING GLOMERULAR DISEASES Start with small doses.
(B) Anticonvulsants
(1) Used with Caution
Glomerulonephritis
Phenobarbital, Benzodiazepines.
Caused By
(2) Safe Alternatives
(1) Penicillamine
Phenytoin, Na valproate, Carbamazepine,
(2) Gold
Ethosuximide.
(3) Captopril
(C) Antipsychotics
(4) Troxidone
Start with small doses.
(D) Anti-Parkinsonism Drugs
(1) Drugs to be Avoided
Unit IV Amantadine.
(2) Safe Alternatives

Drug Selection in Renal Bromocriptine, Benzhexol, Levodopa.

(E) Antimanic Drugs
Disease (1) Drugs to be Avoided
Lithium.
(2) Other Alternatives
Antipsychotics, starting with small doses.
GENERAL RULES
CARDIOVASCULAR DRUGS
(1) No drug should be given unless specifically indicated. (1) Drugs to be Avoided
(2) Least toxic alternative must be chosen. Bethanidine, Guanethidine, Procainamide.
(3) Dosage (2) Drugs Used with Reduced Dosage
(a) Drugs that are wholly or largely excreted by Atenolol, Propranolol & other -blockers, Captopril,
kidneys or, drugs that produce active renally- Enalapril, Lisinopril, Nifedipine, Nicardipine, Prazosin,
Methyldopa, Hydralazine.
eliminated metabolites  Give a normal or slightly
reduced initial dose, & lower the maintenance (3) Drugs Used with Inc. Dosage-Interval
dose or lengthen the dose interval. Disopyramide, Na nitroprusside.
(b) Drugs that are wholly or largely metabolized to (4) Safe Alternatives
Diazoxide, Digoxin, Digitoxin, Lidocaine, Quinidine.
inactive products  Give normal doses.
(c) Drugs that are partly eliminated by kidneys &
DIURETICS
partly metabolized Give a normal initial dose, &
modify maintenance dose or dose interval in the (1) Drugs to be Avoided
light of pts' renal function. Spironolactone, Amiloride, Triamterene, Ethacrynic
(4) Pts must be observed regularly for signs of adverse acid, Acetazolamide, Thiazides.
effects, & the drug stopped or dose reduced if these (2) Safe Alternatives
develop. Furosemide, Bumetanide, Metolazone.

GIT DRUGS
DRUG SELECTION (1) Drugs to be Avoided
Sodium bicarbonate, Mg salts, Metoclopramide,
OPIOID ANALGESICS Carbenoxolone.
M. Shamim’s PHARMACOLOGY 102

(2) Drugs Used with Reduced Dosage (B) Chlorthalidone  Hyperuricemia.

Cimetidine, Famotidine, Nizatidine, Ranitidine. (C) Spironolactone  Gynecomastia.
(3) Safe Alternatives (D) Acetazolamide  Metabolic acidosis.
Omeprazole, Cyclizine. (E) Triamterene  Azotemia.

ANTI-DIABETICS (109) Loop diuretics are useful in the treatment of

(A) Congestive cardiac failure.
(1) Drugs to be Avoided (B) Acute pulmonary edema.
Acetohexamide, Chlorpropamide, Glibenclamide.
(C) Ascites from cirrhosis.
(2) Drugs Used with Reduced Dosage (D) Hypocalcemia.
Gliclazide, Glipizide, Insulin.
(E) Acute renal failure.
(3) Safe Alternatives
Tolbutamide, Gliquidone.

ANTI-MICROBIALS
(1) Drugs to be Avoided
Chloramphenicol, Cinoxacin, Ethambutol, Neomycin,
Tetracyclines, (except doxycycline & minocycline),
Nitrofurantoin, Nalidixic acid.
(2) Drugs Used with Reduced Dosage
Aminoglycosides, Cephalosporins, Penicillins,
Co-trimoxazole, Trimethoprim, Enoxacin, Norfloxacin,
Isoniazid.
(3) Safe Alternative
Erythromycin.

Unit V

Self Assessment (T/F)

(See answers on page no. 241)
(105) Following diuretics can produce hypokalemia by
continued use
(A) Spironolactone.
(B) Acetazolamide.
(C) Amiloride.
(D) Hydrochlorothiazide.
(E) Furosemide.
(106) Following diuretics markedly increases the
excretion of Ca++ from body
(A) Acetazolamide.
(B) Chlorothiazide.
(C) Furosemide.
(D) Spironolactone.
(E) Ethacrynic acid.
(107) Hydrochlorothiazide can produce
(A) Hyperkalemia.
(B) Hyperuricemia.
(C) Hypertension.
(D) Metabolic acidosis.
(E) Hyperglycemia.
(108) All of the following correctly pairs the diuretic drug
with one of its adverse effects
(A) Furosemide  Ototoxicity.
M. Shamim’s PHARMACOLOGY 103

13 DRUGS AFFECTING
RESPIRATORY SYSTEM
Mediators of Mast Cells' Granules
Unit I (a) Histamine.
(b) Tryptase & other neutral proteases.
(c) Leukotrienes C4 & D4.
Anti - Asthmatics (d) Prostaglandin D2.
(e) Eosinophilic chemotactic factor.
(f) Neutrophil chemotactic factor.
INTRODUCTION
DRUG CLASSIFICATION
ASTHMA
It is a disease characterized by; BRONCHODILATORS
(1) Inc. responsiveness of trachea & bronchi to various (1) Sympathomimetics
stimuli. (a)  &  Non - Selective
(2) Widespread narrowing of airways that changes in Epinephrine, Ephedrine.
severity either spontaneously or as a result of therapy. (b) 1 &  2 Non - Selective
Types
Isoproterenol.
(1) Early onset (atopic or allergic) asthma.
(c) 2 Selective
(2) Late onset (non-atopic) asthma.
Clinical Features Albuterol (Salbutamol), Levalbuterol, Bitolterol,
Recurrent episodic bouts of ; Metaproterenol, Terbutaline, Ritodrine, Procaterol,
(1) Coughing. Isoetharine, Formoterol, Pirbuterol, Salmeterol.
(2) Breathlessness. (2) Antimuscarinics
(3) Chest tightness. Ipratropium Br, Tiotropium.
(4) Wheezing. (3) Methylxanthine Drugs
Pathological Features Theophylline, Aminophylline (theophylline +
Narrowing of airways due to ; ethylenediamine), Theobromine, Caffeine, Oxtriphylline
(1) Contraction of airway smooth muscle. Dyphylline, Pentoxiphylline, Acephylline.
(2) Mucosal thickening from edema & cellular infiltration.
(3) Inspissation in airway lumen of abnormally thick, MAST CELL STABILIZERS
viscid plugs of mucus. Cromolyn sodium (Disodium cromoglycate), Nedocromil Na,
Trigger Factors Ketotifen.
(1) Allergens (antigens) eg, pollen, mites in house dust,
animate dander etc. They causes allergic asthma. CORTICOSTEROIDS
(2) Non-antigenic stimuli eg, exercise, cold air, distilled Beclomethasone, Budesonide, Dexamethasone, Flunisolide,
water, tobacco smoke, emotional stress, rapid respira- Fluticasone, Hydrocortisone, Methylprednisolone,
tory maneuvers. Mometasone, Prednisone, Triamcinolone.
Pathogenesis
Classic allergic asthma is mediated by reexposure of LEUKOTRIENE PATHWAY INHIBITORS
sensitized IgE antibodies, bound to mast cells in airway (1) 5-Lipooxygenase Inhibitor
mucosa, to an antigen  Antigen-antibody reaction takes Zileuton,
place on mast cells' surface  This triggers both the (2) LTD4-Receptor Antagonists
release of mediators stored in mast cells' granules &, Zafirlukast, Montelukast.
synthesis & release of other mediators  These mediators
diffuse thru-out the airway wall &, causes narrowing thru MISCELLANEOUS DRUGS
muscle contraction, edema, cellular infiltration & a change (1) Anti-IgE Monoclonal Antibodies
in mucus secretion. Omalizumab.
M. Shamim’s PHARMACOLOGY 104

(2) K+ Channel Openers (2) Chronic asthma.

Cromakalim. (3) Pulmonary edema associated with cardiac failure.
(3) Ca++ Channel Blockers (4) Bronchospasm associated with bronchitis &
Nifedipine, Verapamil. emphysema.
Adverse Effects
BRONCHODILATORS (1) CNS
Headache, anxiety, seizures, insomnia.
(2) CVS
METHYLXANTHINE DRUGS Cardiac arrhythmias, tachycardia.
Mechanism of Action (3) GIT
(1) Inhibit enzyme phosphodiesterase (that hydrolyzes Anorexia, nausea, vomiting, abdominal discomfort.
cyclic nucleotides)  Inc. level of intracellular cAMP  Dosage
Smooth muscle relaxation, & cardiac stimulation. (1) 5 mg theophylline (or 6 mg aminophylline) per kg of
(2) Inhibit cell surface receptors for adenosine (that causes body weight, IV, over 30 minutes.
contraction of airway smooth muscle & inc. histamine (2) 3-4 mg /kg of theophylline, every 6 hours, orally.
release from cells present in lung). (3) 0.5 gm rectal suppositories.
Pharmacological Effects
(A) Central Nervous System OTHER BRONCHODILATORS
(1) At Low & Moderate Doses (A) Sympathomimetics
(a) Mild cortical arousal , with inc. alertness. See chapter 2, unit II.
(b) Deferral of fatigue. (B) Antimuscarinics
(2) At High Doses See chapter 3, unit III.
(a) Medullary stimulation.
(b) Convulsions.
MAST CELL STABILIZERS
(c) Nervousness.
(d) Tremor.
(B) Cardiovascular System CROMOLYN NA, & NEDOCROMIL
(1) Heart Mechanism of Action
(a) Positive chronotropic effect (inc. heart rate). (1) Prevent transmembrane Ca+2 influx provoked by
(b) Positive inotropic effect (inc. contractility). IgE antibody-antigen interaction on mast cell surface 
Note: At low conc., these effects results from inc. This stabilizes mast cell memb.  This prevents
catecholamine release that is caused by inhibition release of histamine & leukotrienes from sensitized
of presynaptic adenosine receptors; while, at mast cells.
higher conc. results from Ca+2 influx due to inc. (2) May inhibit phosphodiesterase  Inc. intracellular
in cAMP level. cAMP.
(2) Blood Vessels, BP, & Blood Flow (3) May alter neural pathways that influence airway
(a) Dec. blood viscosity. smooth muscle tone.
(b) Inc. blood flow. Clinical Uses
(c) At higher doses, relax vascular smooth muscle (1) Prophylaxis of ;
except in cerebral blood vessels, where they (a) Exercise - induced bronchoconstriction.
cause contraction. (b) Aspirin - induced bronchoconstriction.
(C) Bronchial Smooth Muscle (c) Bronchospasm provoked by industrial agents eg,
Bronchodilation, due to; wood dusts, toluene diisocyanate.
(1) Direct relaxation effect. (2) Perennial asthma.
(2) Inhibition of antigen- induced release of histamine (3) Extrinsic (allergic) asthma in young pts.
from lung tissue. (4) Intrinsic asthma in old pts.
(D) Gastrointestinal Tract (5) To prevent seasonal inc. in bronchial reactivity in pts
(1) Inc. gastric acid secretion. with allergic asthma.
(2) Inc. digestive enzyme secretion. (6) Allergic rhinitis.
(E) Kidney Adverse Effects
Weak diuretic effect, due to; (1) Resp. tract: Throat irritation, cough, chest tightness,
(1) Inc. glomerular filtration. wheezing, pulmonary eosinophilic infiltration.
(2) Dec. tubular Na+ reabsorption. (2) GIT: Dry mouth, gastroenteritis.
(F) Skeletal Muscle (3) Skin: Dermatitis.
Improve contractility & reverse fatigue of diaphragm in (4) Muscle: Myositis.
chronic obstructive pulmonary disease (COPD). (5) Hypersensitivity reactions: Anaphylaxis.
Clinical Uses Dosage
(1) Acute asthma.
13: Drugs Affecting Respiratory System 105

Cromolyn Mechanism of Action in Asthma

2 - 4 mg inhaled (thru metered - dose inhaler), QID. Inhibit Ca+2 influx in bronchial smooth muscle cells & other
cells involved in asthma  Prevent contraction of airway
CORTICOSTEROIDS smooth muscle, & secretion of mucus & other mediators.
Clinical Uses in Asthma
Bronchoconstriction induced by;
Mechanism of Action in Asthma (1) Exercise.
(1) Inhibit or modify inflammatory response in airways, eg (2) Hyperventilation.
inhibit release of arachidonic acid from cell memb. & (3) Inhalation of aerosolized histamine, methacholine, or
thereby inhibit first step in production of eicosanoid antigen.
products from arachidonic acid (that are responsible Note: For detail description see Chapter 11, Unit II.
for airway function abnormalities in asthmatic pts).
(2) Potentiate the effects of  - adrenoceptor agonists.
GENERIC & TRADE NAMES
Clinical Uses in Asthma
(1) Mild to moderate asthma.
(2) Asthma that do not improve adequately with broncho- (A) Bronchodilators
dilators or that worsens despite maintenance broncho- (1) Sympathomimetics
dilator therapy. See Chapter 2, Unit II
(3) Severe acute asthma (with  2 agonists & aminophylline). (2) Antimuscarinics
Adverse Effects See Chapter 3, Unit III.
See Chapter 17, Unit IV. (3) Methylxanthine Drugs
Dosage in Asthma Acephylline: Acefyl, Broncophylline, Etaphylline.
(1) Prednisone Aminophylline: Amphyll, Asmol*, Asmoline,
30 - 60 mg/day, orally. Phylocontin.
(2) Methylprednisolone Caffeine: Asmol*, Panadol extra, Trigesic....
1 mg/kg every 6 hours, IV. Pentoxifylline: Agapurin.
(3) Beclomethasone, Triamcinolone, Budesonide, & Theophylline: Asthalin, Asmasal, Quibron-T/SR,
Flunisolide Theo-Dur, Theograd, Theophylline.
2 puffs QID, or 4 puff BD. (B) Other Antiasthmatics
Note: For more detail, see Chapter 17, Unit IV. (1) Mast Cell Stabilizers
Ketotifen: Asfen, Asthanil, Asthotifen, Ketofen,
Mactifen, Totifen, Zatofen.
LEUKOTRIENE PATHWAY INHIBITORS (2) Corticosteroids
See Chapter 17, Unit IV.
Mechanism of Action (3) Ca Channel Blockers
(1) Montelukast & zafirlukast are leukotriene receptor See Chapter 11, Unit II.
antagonists, that blocks the action of leukotriene D4 on (4) LTD4 Antagonists
the cysteinyl leukotriene receptor CysLT1 in the lungs Zafirlukast: Freair, Zafir, Zukast.
& bronchial tubes by binding to it. This reduces the Montelukast: Aerotel, Bronast, Lucast, Montiget.
bronchoconstriction otherwise caused by the leukotriene,
& results in less inflammation.
(2) Zileuton blocks leukotriene synthesis by inhibiting 5- Unit II
lipoxygenase, an enzyme of the eicosanoid synthesis
pathway.
Respiratory Stimulants
Clinical Uses
(1) Maintenance treatment of asthma. (Analeptics)
(2) To relieve symptoms of seasonal allergies.
Adverse Effects
(1) CNS: Sleep disorders. DRUGS CLASSIFICATION
(2) GIT: Gastrointestinal disturbances.
(3) Blood: Increased bleeding tendency. ANALEPTICS
(4) Hypersensitivity reactions. It refers to drugs that stimulate respiratory centre in
medulla, & are used for emergency treatment of respiratory
MISCELLANEOUS DRUGS failure.

CLASSIFICATION
CA+2 CHANNEL BLOCKERS
M. Shamim’s PHARMACOLOGY 106

(A) Direct Stimulants of Respiratory Center INTRODUCTION

(1) Brainstem Stimulants
Nikethamide, Doxapram, Ethamivan, Leptazol.
(2) Cerebral Stimulants COUGH
Caffeine, Ephedrine, Amphetamine, Atropine, It is a protective reflex with sudden noisy expulsion of air
Scopolamine. from airways, that serves the purpose of expelling sputum
(3) Competitive Opioid Antagonists & other irritant materials from upper part of airways.
Nalorphine, Levallorphan, Naloxone. Types
(4) Gases (1) Productive (Useful) Cough
Carbon dioxide (CO2). It effectively expels secretions, exudates, transudates, or
(B) Reflex Stimulants of Respiratory Centre extraneous material from respiratory tract.
(1) Stimulants of Chemoreceptors (2) Unproductive (Useless) Cough
CO2, Nikethamide, Lobeline. It is due to local irritation, eg smokers cough.
(2) Respiratory Mucosal Irritants
Aromatic spirit of Ammonia or Alcohol. DRUG CLASSIFICATION

NIKETHAMIDE DRUGS FOR PRODUCTIVE COUGH

(1) Expectorants
Mechanism of Action (a) Sedative Expectorants
(1) Directly stimulate medullary respiratory centre by (i) Alkaline Expectorants
increasing its sensitivity to CO2. Potassium citrate & acetate.
(2) Reflexly stimulate medullary respiratory centre thru (ii) Nauseant Expectorants
Tincture ipecacuanha, Ammonium
stimulation of chemoreceptors of carotid & aortic
chloride & carbonate.
bodies.
Clinical Uses (iii) Saline Expectorants
Sodium & Potassium iodide.
(1) Acute respiratory failure, eg from acute exacerbations
of chronic lung diseases. (b) Stimulant (Aromatic) Expectorants
Creosote, Guaiacol, Terpene hydrate, Guai-
(2) Overdosage of central depressants.
phenesin.
Adverse Effects
(1) CNS: Restlessness, twitching (at first around mouth). (2) Mucolytics
Acetylcysteine, Bromohexine, Carbocysteine,
(2) CVS: Cardiac arrhythmias.
Methylcysteine, Proteolytic enzymes (eg, Pancreatic
(3) GIT: Vomiting.
dornase & trypsin), Ambroxol.
(4) Skin: Itching, flushing.
Contraindications
(1) Ischemic heart disease. DRUGS FOR UNPRODUCTIVE COUGH
(2) Status asthmaticus. (1) Peripheral Antitussives
(3) Severe hypertension. (a) Demulcents
(4) Thyrotoxicosis. Liquorice lozenges.
Dosage (b) Steam Inhalation
1 - 5 ml of 25% sol. , IM or IV. With tincture benzoin co. or menthol.
(c) Drugs with Local Anesthetic Activity
Benzonatate.
GENERIC & TRADE NAMES (2) Central Antitussives
(a) Opioid Antitussives
Nikethamide: Nikethamid. (i) Nonaddicting Drugs
Naloxone: Naloxone. Codeine phosphate, Dihydrocodeinone,
Pholcodine.

(ii) Addicting Drugs

Morphine, Methadone, Heroin, Dihydro-
morphinone.
Unit III (b) Nonopioid Antitussives
Dextromethorphan, Narcotine, Chlorphedianol,
Carbetapentane, Oxeladin, Benzonatate.
Anti - Tussives
DRUGS FOR PRODUCTIVE COUGH
13: Drugs Affecting Respiratory System 107

EXPECTORANTS They suppress cough reflex by decreasing the input of

It refers to drugs that facilitate removal of respiratory stimuli from cough receptors in respiratory passages.
secretions by coughing. (1) Demulcents
Mechanism of Action They glutinously & soothingly coat pharynx.
(A) Sedative Expectorants (2) Steam Inhalation
They soothe inflamed respiratory mucosa by stimulating Steam inhalation with tincture benzoin co. or menthol
protective mucus secretions from secretory cells of promotes secretion of protective mucus.
respiratory airways  Inc. fluidity of sputum, that (3) Drugs with Local Anesthetic Activity
helps in its expectoration by cough. Benzonatate reduce cough by depressing pulmonary
(1) Alkaline Expectorants stretch receptors. It also has a central cough suppres-
Inc. alkaline reserve of blood, excess base being sant effect.
excreted thru bronchial glands; Clinical Uses
(a) Mildly stimulate bronchial glands to secrete (1) Demulcents
protective mucus. Cough due to sore - throat & pharyngitis.
(b) Dissolve mucus or sputum, by rendering it (2) Steam Inhalation
thinner or less sticky. Cough due to tracheo - bronchitis.
(2) Nauseant Expectorants
Stimulate sensory nerve ending in stomach & CENTRAL ANTI-TUSSIVES
duodenum  Reflex stimulation of copious Mechanism of Action
bronchial secretions. They suppresses cough by a direct depressant effect on
(3) Saline Expectorants medullary cough centre.
Directly stimulate bronchial secretory cells & Clinical Uses
liquefy tenacious sputum. Un-productive cough.
(B) Stimulant Expectorant Adverse Effects
(1) Stimulate healing & repair of chronically inflamed See chapter 8.
respiratory mucosa. Dosage
(2) Dec. amount of sputum, & remove its objectionable (1) Pholcodine: 10-20 mg , orally, TDS or QID.
odor & taste. (2) Codeine: 15-30 mg , orally, at bed time.
(3) Dextromethorphan: 15-30 mg , orally, TDS.
MUCOLYTICS
It refers to drugs that liquefy viscid bronchial secretions, GENERIC & TRADE NAMES
& so enhances therapeutic efficacy of expectorants.
Mechanism of Action
Acetyl - , Carbo - , & Methylcysteine (A) Expectorants
Split sulfhydryl groups that opens disulfide bonds in Ammonium Chloride: Amchol*, Amcodrin*,
mucus, & reduces its viscosity. Amcoride*, Ammodryl*, Ammonium Cl, Bronex*,
Bromohexine Bronochol*, Hydryllin*, Pulmonol*.........
Reduces viscosity of bronchial secretions by depoly- Ammonium Carbonate: Pacific’s Mixture*.
merization of mucopolysaccharides in ground substance Guaiphenesin: Azmolin*, Bilfensein*, Triaminic
of bronchial secretions. chest*, Triaminic E*, Ventolin*.
Clinical Uses (B) Mucolytics
(1) Acute & chronic bronchitis. Acetylcysteine: Mucolator, Rinofluimucil.
(2) Respiratory conditions associated with viscid mucus. Ambroxol: Fluibron, Mucosolvon.
Adverse Effects (C) Central Antitussives
(1) CNS: Headache, tinnitus. Pholcodine: Avanol*, Brovenol*, Davenol*, Liskoz*,
(2) GIT: GI disturbances. Phensedyl-P*, Pholcodine, Sancos*, Tixylix*, Tricof*.
(3) Skin: Urticaria. Dextromethorphan: Actified DM*, Babynol*,
Dosage Benatus*, Combinol - D*, Dexodine*, Dextro-
(1) Bromohexine: 8-16 mg , orally, TDS. methorphan, Hydrillin DM, Rondec, Triaminic cough,
(2) Ambroxol: 30 mg , orally, TDS. Tussivil.
(3) Acetylcysteine: 1 sachet (200 mg), orally, TDS. Noscapine: Noscabine*, Triplon - N*, Tripofed*.

DRUGS FOR UNPRODUCTIVE COUGH Unit IV

PERIPHERAL ANTI-TUSSIVES
Mechanism of Action Self - Assessment (T/F)
M. Shamim’s PHARMACOLOGY 108

(See answers on page no. 241)

(110) Regarding theophylline, following are correct
(A) It stimulates cell surface receptors for adenosine.
(B) It causes inc. intracellular level of cAMP.
(C) It inhibits gastric acid & digestive enzyme
secretions.
(D) It is useful in acute & chronic asthma.
(E) It may cause headache & tremors.
(111) Major action of cromolyn sodium is
(A) Smooth muscle relaxation in bronchi.
(B) Stimulation of cortisol release by adrenals.
(C) Blockade of Ca++ channels in lymphocytes.
(D) Blockade of mediator release from mast cells.
(E) Blockade of cAMP synthesis in basophils.
(112) Regarding analeptics, following are correct
(A) Nikethamide causes reflex, as well as direct
stimulation of respiratory centre.
(B) Amphetamine is a brainstem stimulant.
(C) Nikethamide is useful for treating respiratory
failure in acute asthma.
(D) Nikethamide may cause cardiac dysrhythmias.
(E) Doxapram stimulates respiratory centre in
medulla.
(113) Central anti-tussives includes
(A) Pholcodine.
(B) Benzonatate.
(C) Dextromethorphan.
(D) Ammonium chloride.
(E) Bromohexine.
M. Shamim’s PHARMACOLOGY 109

14 GASTROINTESTINAL DRUGS

(b) Non-Systemic Antacids

Unit I (i) Magnesium Salts
Mg-oxide, Mg-hydroxide, Mg-carbonate, Mg-
trisilicate.
Anti - Peptic Ulcer Drugs (ii) Calcium Salts
Ca - carbonate.
(iii) Aluminium Salts
Al - hydroxide, Al - phosphate, Dihydroxy-
INTRODUCTION aluminium aminoacetate, Basic Al-
carbonate.
PEPTIC ULCER (c) Physical Antacids
It refers to an excoriation of GIT mucosa in or adjacent to (i) Drugs Forming Colloidal Sol.
an acid-bearing area. Gastric mucin, Al - hydroxide gel, Mg-
Sites trisilicate.
(1) Stomach & proximal duodenum. (ii) Anion Exchange Resins
(2) Esophagus (with reflux esophagitis).
(3) Jejunum (in Zollinger- Ellison syndrome or after GASTRIC ANTI - SECRETORY DRUGS
gastrectomy). (1) Proton Pump Inhibitors
(4) Meckel's diverticulum (that contains ectopic gastric Omeprazole, Esomeprazole, Lansoprazole, Pantoprazole,
mucosa). Rapeprazole.
Etiology (2) H2 - Receptor Antagonists
(1) Imbalance b/w acid-pepsin secretion & normal Cimetidine, Famotidine, Nizatidine, Ranitidine.
defences of gastroduodenal mucosa; (3) Anti - Muscarinics
(a) Inc. gastric acid & pepsin secretion. Pirenzepine, Propantheline, Methscopolamine.
(b) Dec. mucosal resistance to acid, due to ;
(i) Dec. production of gastroduodenal mucus. MUCOSAL PROTECTIVE AGENTS
(ii) Dec. secretion of bicarbonate by epithelial (1) Sucralfate (Al - sucrose sulfate).
cells. (2) Colloidal Bismuth compounds, eg;
(2) Bacterium Helicobacter pylori Bismuth subsalicylate, Bismuth dinitrate, Bismuth
(3) Hereditary subcitrate.
Precipitating Factors (3) Carbenoxolone.
(1) Aspirin (4) Prostaglandins analogues, eg;
(2) NSAIDs Misoprostol.
(3) Mental stress
(4) Smoking
(5) Alcohol ANTACIDS

DRUG CLASSIFICATION MECHANISM OF ACTION

Antacids are weak bases that neutralizes gastric acidity by
reacting with gastric HCl to form a salt & water.
ANTACIDS
(A) Sodium Bicarbonate
(1) Dietary Antacids NaHCO3 + HCl  NaCl + CO2 + H2O.
Milk, Fats, Oils.
(2) Chemical Antacids (B) Magnesium Oxide
(a) Systemic Antacid MgO + 2HCl  MgCl2 + H2O. (Note: MgCl2 reacts with
Sodium bicarbonate ( NaHCO3). NaHCO3 of intestinal secretions to form carbonate, &
chloride is released & reabsorbed).
M. Shamim’s PHARMACOLOGY 110

Box 14.1 PROPERTIES OF AN IDEAL ANTACID Diarrhea.

(2) Electrolyte Balance
1) Immediate & prolonged neutralization of acid Hypermagnesemia (in pts with renal insufficiency).
without increasing pH above 4. (C) Calcium Carbonate
2) Action should be confined to GIT. (1) GIT
3) No constipating or laxative effects. Constipation, acid rebound.
4) No effects on acid - base balance. (2) Kidney
5) Free from adverse effects.
Nephrolithiasis.
6) Palatable to pts.
(3) Electrolyte Balance
Hypercalcemia.
(C) Magnesium Trisilicate (4) Milk - Alkali Syndrome
(1) Mg - Trisilicate + 2HCl  MgCl2 + Silicon dioxide. Occur with concomitant heavy milk drinking (often
(2) Silicon dioxide has also a demulcent action, & also advised in peptic ulcer), & is characterized by;
adsorbs gastric HCl. (a) Headache, weakness.
(D) Calcium Carbonate (b) Anorexia, nausea, vomiting, abdominal pain,
constipation.
CaCO3 + 2HCl  CaCl2 + CO2 + H2O.
(c) Thirst, polyuria, temporary or permanent renal
Note: In small intestine CaCl2 is precipitated as damage.
carbonate, phosphate & insoluble soap. (D) Aluminium Hydroxide
(E) Aluminium Hydroxide (1) GIT
(1) Al (OH)3 + 3HCl  AlCl3 + 3H2O. Constipation.
Note: AlCl3 reacts with intestinal secretions to (2) Electrolyte Balance
produce insoluble salts esp. phosphate, & chloride Hypophosphatemia.
is released & reabsorbed. (3) Drugs Adsorption
(2) Al - compounds also acts via a direct cytoprotec- Reduces bioavailability of some drugs, eg
tive action, or by binding HCl & pepsin. tetracyclines, atropine.

CLINICAL USES CONTRAINDICATIONS

(A) Sodium Bicarbonate (A) Sodium Bicarbonate
(1) As antacid for; (1) Renal insufficiency.
(a) Gastric hyperacidity. (2) Cardiac failure.
(b) Peptic ulcer. (3) Hypertension.
(2) As base for systemic acidosis. (4) Peripheral & pulmonary edema.
(3) As urine alkalinizer. (5) Toxemia of pregnancy.
(B) Magnesium Compounds & Aluminium (B) Magnesium & Calcium Compounds
Hydroxide Renal insufficiency.
Usually available in combinations (to balance their
purgative & constipative effects); GASTRIC ANTI - SECRETORY DRUGS
(1) Gastric hyperacidity.
(2) Peptic ulcer.
(3) Dyspepsia. H2 - RECEPTOR ANTAGONISTS
(4) Hiatus hernia. Mechanism of Action
(5) Acute & chronic recurrent gastritis. (1) Competitively block histamine at H2-receptors on
(C) Calcium Compounds gastric parietal cells  Dec. HCl secretion.
(1) Gastric hyperacidity. (2) Competitively block histamine at H2-receptors on
(2) Peptic ulcer
vascular smooth muscle cells  Block histamine
induced vasodilation.
ADVERSE EFFECTS Pharmacological Effects
(A) Sodium Bicarbonate (1) Gastrointestinal Tract
(1) GIT (a) Inhibits gastric acid secretion stimulated by
Gastric distension & discomfort, peptic ulcer histamine, gastrin, insulin, caffeine, muscarinic
perforation or hemorrhage, acid rebound. drugs, & vagal stimulation.
Note: These effects are due to CO2. (b) Dec. basal, food-stimulated, & nocturnal secretion
(2) Water & Acid - Base Balance of gastric acid.
Metabolic alkalosis, fluid retention. (c) Dec. volume & H+ conc. of gastric juice.
(B) Magnesium Compounds (2) Liver
(1) GIT
14: Gastrointestinal Drugs 111

Cimetidine & ranitidine (to a lesser extent) inhibit PIRENZEPINE

cytochromic P-450 mixed function oxidase system  Mechanism of Action
Slows hepatic microsomal metabolism of some drug, Blocks selectively gastric M1-muscarinic cholinoceptors 
eg warfarin, theophylline, diazepam, phenytoin, Inhibits gastric secretions.
lignocaine, propranolol. Clinical Uses
Note: Famotidine & nizatidine have no effect on (1) Gastric ulcer.
hepatic drug metabolism. (2) Duodenal ulcer.
(3) Endocrine Adverse Effects
Cimetidine (& only rarely ranitidine & famotidine) inc. (1) CNS: Headache.
serum prolactin level, & alter estrogen metabolism (2) Eye: Difficulty in visual accommodation.
in males  Reversible gynecomastia & sexual (3) GIT: Dry mouth, constipation, diarrhea.
dysfunction. Dosage
Clinical Uses 25 - 50 mg BD orally before meals, for 4 - 6 weeks.
(1) Duodenal ulcer.
(2) Benign gastric ulcer. PROTON PUMP INHIBITORS (PPI)
(3) Stomal ulcer. Mechanism of Action
(4) Reflux esophagitis. Irreversibly inhibit gastric parietal cell proton pump
(5) Prophylaxis of GI bleeding due to gastric erosions, eg
(H+/K+ ATPase)  Inhibit exchange of proton (H+) in cell
from burns, fulminant hepatic failure, renal failure,
cytoplasm & K+ in canalicular lumen  No H+ is secreted
trauma.
in canaliculi to combine with Cl- &, so, no HCl forms.
(6) Before anesthesia for emergency surgery & before
Clinical Uses
labor to lessen the risk of aspirating gastric acid.
(1) Erosive reflux esophagitis.
(7) Zollinger - Ellison syndrome.
(2) Benign peptic ulcers unresponsive to conventional
(8) Systemic mastocytosis, & multiple endocrine adenomas.
treatment.
Adverse Effects
(3) Zollinger - Ellison syndrome.
(1) CNS
(4) Systemic mastocytosis & multiple endocrine
Confusional states, headache, somnolence, halluci-
neoplasias.
nations, delirium, brainstem dysfunction, peripheral
neuropathy. Box 14.2 ERADICATION THERAPY
(2) CVS
Bradycardia, cardiac conduction defects. 1) It is used for H pylori associated peptic ulcer.
(3) GIT 2) The goal is to heal the ulcer & eradicate the
Diarrhea, constipation. organism.
(4) Liver 3) First 2 antibiotics & a proton pump inhibitor are given
Transient & reversible change in liver function tests for 10-14 days;
(LFTs). a) PPI twice daily + clarithromycin 500 mg BD +
amoxicillin 1 g BD
(5) Endo
b) PPI twice daily + clarithromycin 500 mg BD +
(a) In male: Gynecomastia, impotence. metronidazole 500 mg BD (in patients allergic to
(b) In female: Galactorrhea. penicillin)
(See also pharmacological effects above). 4) Then PPI alone for further 4-6 weeks.
(6) Blood
Reversible blood dyscrasias.
Adverse Effects
Precautions (1) CNS: Headache.
(1) Malignancy.
(2) GIT: Nausea, diarrhea, constipation.
(2) Renal insufficiency.
(3) Skin: Rashes.
(3) Pregnancy & lactation.
Contraindications
Dosage
(1) Pregnancy & lactation.
(1) Cimetidine (2) Malignancy.
(a) Oral: 400 - 600 mg BD, or 800 mg at bed - time.
(3) Renal insufficiency (Lansoprazole).
(b) IM: 200 mg; may be repeated at 4 - 8 hourly
Dosage
intervals.
(1) Omeprazole
(c) IV: 400 mg diluted in 100 ml 5% Dextrose, given
20 - 40 mg OD, orally or IV, for 4 - 8 weeks.
over 30 minutes; upto a max of 2400 mg daily.
(2) Lansoprazole
(2) Ranitidine & Nizatidine 30 mg OD, orally, for 4 - 8 weeks.
150 mg BD orally, or 300 mg at bed - time.
(3) Rabeprazole
(3) Famotidine 20 mg OD, orally, for 4 - 8 weeks.
20 mg BD orally, or 40 mg at bed - time.
M. Shamim’s PHARMACOLOGY 112

MUCOSAL PROTECTIVE AGENTS (2) Dec. H+ diffusion from lumen into mucosa.
(3) Dec. rate of shedding of gastric mucosal cells.
Clinical Uses
SUCRALFATE (1) Gastric ulcer.
Mechanism of Action (2) Duodenal ulcer.
(1) In acid environment of stomach, Al+3 moiety dissociates Adverse of Effects
& negatively charged sucrose-sulfate binds electro- Results from its aldosterone - like activity.
statically to positively charged protein molecules that (1) CVS: Hypertension, heart failure.
transude from necrotic ulcer base  Result is a (2) Water & electrolyte balance: Fluid retention. edema,
viscuous paste that adheres selectively to ulcer base, hypokalemia.
where it act as a barrier to acid, pepsin, & bile.
(2) Binds to & inactivates pepsin & bile salts. MISOPROSTOL
(3) Stimulate endogenous prostaglandin synthesis. Mechanism of Action
(4) Prevent damaging back-diffusion of H+ from lumen to (1) Inhibit gastric secretion thru inhibition of histamine -
mucosa. stimulated cAMP production.
Clinical Uses (2) Stimulate mucus & bicarbonate secretion.
(1) Benign gastric ulcer. (3) Prevent luminal H+ from diffusing into mucosa, eg in
(2) Duodenal ulcer. response to aspirin, ethanol & bile salts.
(3) Chronic gastritis. (4) Inc. rate of mucosal cell replication.
Adverse Effects (5) Maintain adequate mucosal blood flow  Remove H+ &
(1) GIT: Benign gastric ulcer ensures a supply of O2 & nutrients.
(2) Drug absorption: Al content interfere with absorption Clinical Uses
of other drugs, eg tetracyclines, phenytoin, cimetidine, (1) Duodenal ulcer.
digoxin. (2) Gastric ulcer.
(3) Treatment & prophylaxis of NSAID - induced peptic
COLLOIDAL BISMUTH COMPOUNDS ulceration.
Mechanism of Action Adverse Effects
(1) Selectively bind to an ulcer & coat it, to protect from (1) GIT: Diarrhea, abdominal pain.
acid & pepsin. (2) Endo & Repro: Dysmenorrhea, spotting.
(2) Inhibit pepsin activity . (3) Pregnancy: Abortion.
(3) Stimulate mucus production.
(4) Stimulate endogenous prostaglandin synthesis.
(5) Have some antimicrobial activity against Helicobacter GENERIC & TRADE NAMES
pylori.
Clinical Uses (A) Antacids
(1) Duodenal ulcer. Sodium Bicarbonate: Citro-soda*, Eno*, Gaviscon*,
(2) Gastric ulcer. Gripe water.
Adverse Effects Magnesium Hydroxide: Phillips milk of Magnesia.
GIT: Darkens tongue, teeth, & stool. Magnesium Trisilicate: Amtri.
Aluminium Hydroxide: Actal.
CARBENOXOLONE Al - Hydroxide & Mg - Hydroxide: Geogil, Magalcid,
Mechanism of Action Magnacid.
(1) Inc. production & viscosity of gastric & intestinal Al – Hydroxide, Mg – Hydroxide & Simethicone:
mucus. Alucid, Gelusil, Mylanta 2, Simeco.
Al – Hydroxide, Mg – Hydroxide & Oxethazaine:
Box 14.3 Dicaine, Mucaine.
Al – Hydroxide, Mg – Hydroxide, Simethicone &
DRUGS CONTRAINDICATED IN PEPTIC ULCER Dicyclomine: Colenticon.
Al - Hydroxide & Mg - Carbonate: Algicon.
1) Salicylates Al – Phosphate & Simethicone: Aluphagel.
2) NSAIDs (B) Gastric Antisecretory Drugs
3) Adrenal steroids & ACTH
Omeprazole: Encid, Losec, Omezol, Ramezol, Risek,
4) Phenylbutazone
5) Reserpine Teph 20.
6) Tolazoline Esomeprazole: Esodin, Esopra, Nexum.
7) Alcohol Lansoprazole: Agopton, Gerd, Lanzac, Lazol, Zoton.
8) Xanthine beverages (coffee, tea) Pantoprazole: Gastrocid, Pantozol, Pezole.
9) Tobacco Rabeprazole: Rabz, Repar.
14: Gastrointestinal Drugs 113

Cimetidine: Cimet, Cimetamat, Citamet, Normacid, Dronabinol, Nabilone.

Semidine, Tagamet, Ulceloc, Ulcemet, Ulcerex.
Famotidine: Fadiphene, Famdine, Famopsin, Famot, CENTRAL & PERIPHERAL ANTIEMETICS
H2F, Pepcidine, Peptiban, Zepcin. (1) D2 - Receptor Antagonists
Nizatidine: Axid, Ulcid. (a) Substituted Benzamides
Ranitidine: Apsar, Hitac, H2 Rec, Ranax, Ranidine, Metoclopramide, Trimethobenzamide.
Ranitid, Ranitin, Zantac. (b) Phenothiazines
Pirenzepine: Gastrozepin. Chlorpromazine, Prochlorperazine, Promethazine
(C) Mucosal Protective Agents Thiethylperazine.
Sucralfate: Alusulin, Macralfate, Sucfate, Sulcrate, (2) Serotonin 5HT3 - Receptor Antagonists
Ulcerat, Ulsanic.
Ondansetron, Granisetron, Dolasetron, Palonosetron.
Bismuth Subsalicylate: Bismol.
(3) Antimuscarinics
Misoprostol: Cytotec.
Scopolamine, Atropine.
(4) H1 - Receptor Antagonists
Unit II Cyclizine, Cinnarizine Meclizine, Dimenhydrinate,
Diphenhydramine.

Anti - Emetics PERIPHERAL ANTIEMETICS

(1) Demulcents
Gum acacia, Gum tragacanth.
(2) Adsorbents
INTRODUCTION Aluminium hydroxide, Kaolin.
(3) Gastric Mucosal Anesthetics
VOMITING (EMESIS) Chloretone (Chlorbutanol), Dilute hydrocyanic
acid.
It is a protective reflex mechanism for eliminating irritant or
harmful substances from upper GIT.
Control of Vomiting METOCLOPRAMIDE
Vomiting is controlled by 'vomiting centre' located in
reticular formation of medulla, that co-ordinates act of MECHANISM OF ACTION
emesis on receiving stimuli from;
(1) Central
(1) Chemoreceptor trigger zone (CTZ).
Block dopamine D2 - receptors in CTZ.
(2) Vestibular system.
(3) Periphery, eg in distension or irritation of gut, (2) Peripheral
myocardial infarction, biliary or renal calculus. Enhances action of acetylcholine at muscarinic nerve
(4) Cortical centres. endings in gut  This causes;
Causes of Vomiting (a) Inc. tone of lower esophageal sphincter.
(1) Pregnancy. (b) Relaxation of pyloric antrum & duodenal cap.
(2) Motion sickness. (c) Inc. peristalsis & emptying of upper gut.
(3) GI obstruction.
(4) Peptic ulcer. CLINICAL USES
(5) Drug toxicity. (1) Nausea & vomiting associated with;
(6) Myocardial infarction. (a) GI disorders.
(7) Renal failure. (b) Postsurgical conditions.
(8) Hepatitis. (c) Cytotoxic drugs.
(d) Radiotherapy.
(2) To empty stomach (ie, prokinetic use);
DRUG CLASSIFICATION
(a) Before emergency anesthesia.
(b) In labor.
CENTRAL ANTIEMETICS (c) In diabetic gastroparesis (delayed gastric emptying).
(1) Dopamine D2 - Receptor Antagonist (d) After vagotomy.
Droperidol, Haloperidol. (e) In gastroesophageal reflux.
(2) Sedative - Hypnotics
Barbiturates, Benzodiazepines. ADVERSE EFFECTS
(3) Neurokinin Receptor Antagonists (1) CNS: Restlessness, torticollis, facial spasms, trismus,
Aprepitant. oculogyric crisis, tardive dyskinesia.
(4) Cannabinoids (2) GIT: Diarrhea.
M. Shamim’s PHARMACOLOGY 114

(3) Endocrine: Gynecomastia, lactation (due to inc. Tropisetron: Navoban.

prolactin secretion). (C) Antimuscarinics
Precautions See chapter 3.
(1) Pregnancy & lactation. (D) H1 - Receptor Antagonists
(2) Renal or hepatic impairment. Cyclizine: Marzine, Migril*.
Cinnarizine: Cerebrin, Stugeron.
CONTRAINDICATIONS Dimenhydrinate: Devinate, Dimenic, Gravinate.
(1) Recent gastrointestinal surgery. Meclizine: Navidoxine, Sevidoxine.
(2) Prolactin - dependent breast carcinoma. Promethazine: Miprozine, O - Zine, Phenergan,
(3) Pheochromocytoma. Promazine, Semozin.

DOSAGE
10 mg TDS orally, IM or IV. Unit III

DRUG TREATMENT OF SPECIFIC VOMITING

Anti-Diarrheals
(A) Motion Sickness [Constipatives]
(1) Cinnarizine.
(2) Cyclizine.
(3) Dimenhydrinate. INTRODUCTION
(4) Scopolamine.
(5) Promethazine. DIARRHEA
(B) Vomiting due to Cytotoxic Drugs It refers to inc. frequency & liquidity of feces.
(1) Dexamethasone. Causes (Types) of Diarrhea
(2) Lorazepam. (1) Travellers' diarrhea
(3) Metoclopramide. (2) Infective Diarrheas
(4) Ondansetron. (a) Amebic dysentery.
(C) Vomiting in Pregnancy (b) Giardiasis.
(1) Promethazine. (c) Typhoid fever.
(2) Thiethylperazine. (d) Cholera.
(3) Vit B6 (Pyridoxine). (e) Bacillary dysentery.
(4) Vit B6 plus Meclizine. (f) Food poisoning.
(D) Vertigo (3) Malabsorption Diarrheas
(1) Scopolamine. (a) Celiac disease.
(2) Phenothiazines, eg Prochlorperazine or (b) Tropical sprue.
Thiethylperazine. (c) Whipple's disease.
(3) Cyclizine. (d) Lactose intolerance.
(4) Betahistine (a histamine analogue). (e) Stagnant loop syndrome.
(5) Cinnarizine. (4) Bowel Inflammations
(a) Ulcerative colitis.
(b) Crohn's disease.
GENERIC & TRADE NAMES
(5) Drug - Induced Diarrheas
(a) Antimicrobials, eg penicillins, cephalosporins,
(A) D2 - Receptor Antagonists clindamycin, lincomycin.
Haloperidol: Haldol, Serenace. (b) Mg - containing antacids.
Metoclopramide: Digestine, Fimet, Gastrolon, (c) Iron salts.
Maxolon, Metoclon, Metomide, Plasil, Regelan. (d) NSAIDs, eg indomethacin, mefenamic acid,
Domperidone: Costi, Motilium, Pelton, Peridone. flurbiprofen.
Chlorpromazine: Largactil, Sedectil.
Prochlorperazine: Dometil, Stabil, Stemetil. DRUG TREATMENT OF DIARRHEA
Promethazine: Avomine, Phenergan, Phenerzine,
Thiethylperazine: Torecan.
Acepromazine: Acozine. FLUID & ELECTROLYTE TREATMENT
(B) 5 - HT3 - Receptor Antagonists Oral rehydration therapy (ORT) with glucose-
Ondansetron: Ondison, Setron, Zofran. electrolyte solution (eg ORS).
Granisetron: Gytril.
14: Gastrointestinal Drugs 115

SPECIFIC TREATMENT OF CAUSE

Unit IV
(1) Anti - bacterials, eg
Trimethoprim or ciprofloxacin for typhoid fever, food
poisoning & bacillary dysentery.
(2) Amebicides, eg Laxatives
Metronidazole for amebic dysentery.
(3) Bile salt-binding resins, eg [Anti-Constipatives, Purgatives, Cathartics,
Cholestyramine or colestipol for diarrhea cause by Evacuants, Aperient]
excess fecal bile acids.
(4) Octreotide (a somatostatin analog) for diarrhea caused INTRODUCTION
by carcinoid tumor, VIPoma, vagotomy, dumping
syndrome, short bowel syndrome or AIDS.
(5) Withdrawal of food causing malabsorption. CONSTIPATION
(6) Withdrawal of drugs causing diarrhea. It refers to infrequent or difficult evacuation of hard feces.
Causes of Constipation
ANTI - DIARRHEALS (1) Inadequate diet & lifestyle, eg
Lack of fibre & exercise.
(1) Gastrointestinal Protectives & Adsorbents
(2) Drugs, eg;
Bismuth subsalicylate, Attapulgite, Kaolin, Pectin.
(a) Opioid analgesics.
(2) Astringents
(b) Anti-inflammatory agents.
Vegetable drugs that release tannic acid, eg;
(c) Ca - & Al - containing antacids.
Kino, Krameria, Cathechu.
(d) Anti - depressants.
(3) Anti - Motility Drugs
(e) Diuretics.
(a) Antimuscarinics
(f) Antimuscarinics, eg atropine.
Atropine, Mepenzolate, Propantheline,
(3) Psychiatric & neurological disorders, eg;
Dicyclomine.
(a) Ignoring call to stool.
(b) Opioid Derivatives
(b) Physical disability.
Codeine, Diphenoxylate, Loperamide.
(4) Organic diseases of anus, rectum, & colon.
(5) Secondary intestinal motility disorders, eg;
GENERIC & TRADE NAMES (a) Hypothyroidism.
(b) Disease of colonic muscle or nervous plexuses, eg
(A) Oral Rehydration Salt (ORS) scleroderma.
Arosal F, Neolyte, Babylyte ORS, Orasal-F, Peditral,
Pedialyte. DRUG CLASSIFICATION
(B) Adsorbents
Bismuth subsalicylate: Bismol.
BULK LAXATIVES
Attapulgite: Detox, Entox - P, Jetox, Kaltin AP*,
Kaopectal, Neo-Intestopan, Novotox, Semotox. (1) Hydrophilic Colloids
Kaolin & Pectin: Diarhol, Kaltin, Kaolin pectin, Agar, Psyllium seeds & husks (Ispaghula husk),
Kaomagma, Kaostop, Kaptin, Streptomagma. Methylcellulose, Polycarbophil, Bran, Sterculia.
(C) Antimuscarinics (2) Osmotic Laxatives
See chapter 3. (a) Saline Cathartics
(D) Opioid Derivatives Magnesium citrate, Mg hydroxide, Mg oxide (milk
Diphenoxylate: Lomotil*, Motilex*, Reostop*, of magnesia), Sodium citrate, Na sulfate, K - Na -
Rexotil*. tartarate.
Loperamide: Diastop, Imodium, Loperamide 2, Lopra, (b) Non-absorbable Sugar
Tabromide. Sorbitol, Lactulose.
(c) Balanced polyethylene glycol

STIMULANT (IRRITANT) LAXATIVES

(1) Mild Stimulants
Figs & prunes, Castor oil.
(2) Moderate Stimulants
(a) Anthraquinone group, eg
Senna, Danthrone, Cascara, Rhubarb, Aloes.
(b) Phenolphthalein.
(c) Bisacodyl.
(d) Serotonin 5HT4 receptor agonists, eg
M. Shamim’s PHARMACOLOGY 116

Tegaserod. (1) Softens feces by lowering the surface tension of

(3) Severe Stimulants fluids in bowel which allows more water to remain in
(a) Resinous laxatives, eg feces.
Resins of jalap, colocynth, podophyllum. (2) Also stimulates bowel.
(b) Croton oil. Liquid Paraffin
It is indigestible, & acts by softening & lubrication of feces.
STOOL SOFTENERS (EMOLLIENTS)
(1) Surface Active Agents ENEMAS
(a) Docusate sodium (Dioctyl Na sulfosuccinate). Produce defecation by softening feces & distending bowel.
(b) Poloxamers eg, Poloxalkol.
(2) Mineral Oils
CLINICAL USES OF LAXATIVES
Liquid Paraffin.

MISCELLANEOUS (1) Constipation.

(1) Suppositories (2) To remove ingested poison (saline laxatives are
Bisacodyl, Glycerin. preferred).
(2) Enemas (3) To evacuate GIT,
Sodium phosphate. (a) Before surgery.
(b) Before radiological examination of GIT.
(c) Before abdominal ultrasound.
MECHANISM OF ACTION OF LAXATIVES (4) Before & after anti - helmintics (saline laxatives are
preferred).
HYDROPHILIC COLLOIDS (5) To prevent straining in pts with,
They form gel by imbibing water within large intestine  Inc. (a) Hernia.
(b) Cardiovascular disease.
volume & dec. viscosity intestinal contents  Intestinal
(6) Hepatic encephalopathy (lactulose).
distension that stimulates peristaltic activity  Large, soft,
(7) To soften stool in fistula - in - ano.
solid stool.

OSMOTIC LAXATIVES ADVERSE EFFECTS OF LAXATIVES

These are poorly absorbed from GIT  Hold water in
intestinal lumen by osmotic force & cause distension Liquid Paraffin
Evacuation. (1) Resp. Tract
Lipid pneumonia (if gain access to lungs).
STIMULANT LAXATIVES (2) GIT
Castor Oil Pruritus ani, anal polyp, typical foreign body reaction
It is hydrolyzed in small intestine to glycerol & ricinoleic in intestinal mucosa (& also in mesenteric lymph
acid  Ricinoleic acid stimulates peristalsis & reduces nodes, liver, & spleen).
fluid absorption. (3) Wound Healing
Anthraquinone Laxatives Delayed wound healing after anorectal surgery.
They contain amodin alkaloids that are liberated & (4) Drug Absorption
absorbed from small intestine  Excreted in colon, Interferes with absorption of fat - soluble vitamins,
where it stimulates peristalsis (probably thru calcium, & phosphate.
Auerbach's plexus). Anthraquinone Laxatives
Bisacodyl & Phenolphthalein (1) GIT
They promote evacuation by stimulating sensory Colicky pain, melanotic pigmentation of colonic
endings in colon via direct action from lumen. mucosa.
Serotonin 5HT4 Receptor Agonists (2) Urinary Tract
They stimulate 5HT4 receptors on presynaptic terminal of Discolored urine to yellowish-brown ( if acidic), or
submucosal intrinsic primary afferent nerves, enhancing the reddish-violet (if alkaline).
release of their neurotransmitters that stimulate second-order (3) Lactation
enteric neurons to promote peristaltic reflex. Affect infant suckling
Phenolphthalein
STOOL SOFTENERS (1) Urinary Tract
Surface Active Agents Discolored urine to red (if alkaline).
(2) Skin
Rashes.
14: Gastrointestinal Drugs 117

CONTRAINDICATIONS OF LAXATIVES DRUG TREATMENT OF IRRITABLE BOWEL

SYNDROME (IBS)
(1) Intestinal obstruction.
(2) Abdominal pain of unknown etiology. IBS is an idiopathic chronic, relapsing disorder characterized
(3) Acute surgical abdomen. by abdominal discomfort (pain, bloating, distension or
(4) Pregnancy. cramps) in association with alterations in bowel habits
(diarrhea, constipation or both).
Drug Classification
GENERIC & TRADE NAMES
(1) Anti-diarrheals
In patients with predominant diarrhea.
Ispaghula husk: Fiberad, Fybogel, Ispalax. (2) Osmotic laxatives & fiber supplements
Lactulose: Constilac, Duphalac, Laevolac. In patients with predominant constipation.
Castor oil: Castor oil. (3) Anti-spasmodics
Bisacodyl: Bicolax, Bisacon, Dulcolax. Dicyclomine & Hyoscyamine.
Liquid Paraffin: Cremaffin*, Paraffin liquid. (4) Serotonin 5HT3 Receptor Antagonists
Phenolphthalein: Irzafin, Phenothin. Alosetron.
Tegaserod: Tegmac, Uniserod. (5) Serotonin 5HT4 receptor Agonists
Glycerine: Glycerine suppositories, Microenema*. Tegaserod.
Sodium phosphate: Instant enema*, Kleen enema*, Radi
enema*.
DRUG TREATMENT OF INFLAMMATORY BOWEL
DISEASE (IBD)
Unit V
It denotes 2 distinct disorders: ulcerative colitis & Crohn’s
disease.
Miscellaneous GIT Drugs Drug Classification
(1) Aminosalicylates
(a) Azo compounds eg, Sulfasalazine, Balsalazine,
Olsalazine.
PROKINETICS (b) Mesalamine compounds eg, Pentasa, Asacol.
(2) Glucocorticoids
These are drugs that selectively stimulate gut motor function. (a) Oral prednisone, prednisolone or budesonide.
(1) Drugs that increase lower esophageal sphincter pressure (b) Hydrocortisone enemas or suppositories.
Useful for GERD. (3) Purine Analogs
(2) Drugs that improve gastric emptying Useful for Azathioprine, 6-Mercaptopurine.
gastroparesis & postsurgical gastric emptying delay. (4) Methotrexate
(5) Anti-tumor Necrosis Factor
(3) Drugs that stimulate small intestine Useful for
Infliximab.
postoperative ileus or chronic intestinal pseudo-
obstruction.
(4) Drugs that increase colonic transit Useful for EMETICS
constipation.
Drug Classification Drug Classification
(1) Cholinomimetic Drugs (A) Central Emetics
(a) Bethanechol for GERD & gastroparesis. Apomorphine.
(b) Neostigmine for chronic intestinal pseudo- (B) Peripheral Emetics
obstruction (Ogilvie’s syndrome). (1) Rapidly Acting
(2) D2 Receptor Antagonists (a) Salts of heavy metals, eg
Metoclopramide & Domperidone for GERD, Copper sulfate, Zinc sulfate.
gastroparesis, postsurgical delayed gastric emptying, (b) Hypertonic salt solutions.
nonulcer dyspepsia. (c) Mustard in warm water.
(3) Macrolides (2) Slowly Acting
Erythromycin in gastroparesis. (a) Vegetable irritants, eg
(4) Chloride Channel Activator Tincture lpecacuanha, Tincture senega.
Lubiprostone for chronic constipation. (c) Ammonium carbonate.
M. Shamim’s PHARMACOLOGY 118

Clinical Uses CARMINATIVES

In cases of poisoning, to prevent further absorption of
poison.
Contraindications It refers to drugs that causes expulsion of gases from
(1) Unconscious pts. stomach by eructation.
(2) Corrosive poisoning. Drug Classification
(3) Petroleum poisoning. (1) Chloroform
(4) Pregnancy. (2) Ether.
(3) Volatile oils, eg
Oils of peppermint, Camphor, Anise, Caraway,
SIALOGOGUES Cinnamon.
(4) Carbonated waters, eg
It refers to drugs that increase salivary gland secretions. Cola beverages.
Drug Classification
(1) Parasympathomimetics SPASMOLYTICS ( ANTI- SPASMODICS)
Nicotine, Lobeline, Pilocarpine.
(2) Direct Salivary Stimulants
Potassium, Iodine, & Mercury salts. It refers to drugs that relieve smooth muscle spasm (eg, of
(3) Reflex Sialogogues GIT, genito urinary tract, biliary tract), & are used in the
(a) Stomachics (see below). treatment of colics.
(b) Emetics, eg Ammonium carbonate, Tincture Drug Classification
ipecacuanha. (1) Antimuscarinics
Atropine, Scopolamine, Methscopolamine, Ciclonium,
Dicyclomine, Pipenzolate, Propantheline, Anisotropine.
ANTI - SIALOGOGUES (2) Direct Spasmolytics
Volatile oils, Khellin, Papaverine, Aminophylline,
It refers to drugs that inhibit salivary gland secretions. Nitrites, Mebeverine, Tiropramide, Drotaverine,
Drug Classification Pramiverine, Fenoverine.
(1) Parasympatholytics, eg Atropine, Scopolamine,
Methscopolamine.
(2) Ganglion blockers. Unit VI
(3) Demulcents.
(4) Astringents.
Self-Assessment (T/F)
STOMACHICS
[See answers on page no. 241]
It refers to drugs that improve appetite, & reflexly inc. (114) All of the following drugs are correctly matched to
salivary & gastric secretions. their actions
Drug Classification (A) Cimetidine  Blocks H2 histamine receptors.
(1) Locally Acting (B) Misoprostol  Inhibits adenyl cyclase.
(a) Bitters (C) Omeprazole  Activates adenyl cyclase.
(i) Simple Bitters: Quassia, Calumba, Gentians. (D) Sucralfate  Protects ulcerated mucosa.
(ii) Aromatic Bitters: Bitter orange peel. (E) Pirenzepine  Selectively blocks muscarinic
(iii) Astringent Bitters: Cosparia, Cascarilla. receptors in stomach.
(iv) Alkaloidal Bitters: Quinine, Strychnine.
(b) Spices (115) Bulk-forming laxative includes
Pepper. (A) Castor oil.
(2) Centrally Acting (B) Psyllium.
Pizotifen, Cyproheptadine, Buclizine, Metopine. (C) Colloidal bismuth.
(3) Others (D) Sucralfate.
(a) Flavors, eg volatile oils. (E) Phenolphthalein.
(b) Ethyl alcohol beverages (upto 7 %). (116) Use of a Al- containing antacid is most likely to
cause
(A) Constipation.
(B) Diarrhea.
(C) Hypertension.
(D) Headache.
14: Gastrointestinal Drugs 119

(E) Nausea.
(117) Regarding anti-peptic ulcer drugs, all of the
following statements are correct
(A) Omeprazole blocks muscarinic receptors of
parietal cell.
(B) Pirenzepine is similar to atropine in its action.
(C) Famotidine blocks the action of gastrin on
parietal cells.
(D) Carbenoxolone increases the amount & quality
of mucus.
(E) Chronic use of omeprazole may results in
gastric tumor.
(118) Anti- emetics include
(A) Apomorphine.
(B) Ammonium carbonate.
(C) Cyclizine.
(D) Chlorpromazine.
(E) Aluminium hydroxide.
M. Shamim’s PHARMACOLOGY 120

15 HEPATO-PANCREATICO-
BILIARY DRUGS
Mannitol 20%.
Unit I (3) Nutrition
Glucose, Fluid & Electrolyte therapy.
(4) For Infection
Liver & Drugs Broad-spectrum antibiotics, eg Cefotaxime.
(5) To Prevent GI Bleeding
Cimetidine, Ranitidine.
(C) Prophylaxis of Viral Hepatitis
HEPATIC DRUGS (1) For Hepatitis A
Immune globulin (IG).
CHOLERETICS (2) For Hepatitis B
It refers to drugs that stimulate hepatic cells to secrete bile, Hepatitis B immune globulin (HBIG), Hepatitis B
resulting in inc. volume & solid constituents of bile. vaccine (inactivated surface antigen).
Drug Classification
(1) Primary Bile Acids DRUG INDUCED HEPATIC DAMAGE
Cholic acid, Chenodeoxycholic acid.
(2) Secondary Bile Acids
Deoxycholic acid, Lithocolic acid. TYPE A (AUGMENTED)
(3) Bile Acid Conjugates Hepatic injury occurs as the dose of some drugs is
Sodium glycocholate, Sodium taurocholate, Sodium raised.
choleate. (1) Centrizonal Necrosis
Clinical Uses Caused by Paracetamol & Carbon tetrachloride.
(1) To help digestion. (2) Hepatocellular Necrosis
(2) To promote vit K absorption in obstructive jaundice. Caused by Salicylates.
(3) To relieve flatulence, dyspepsia, & constipation. (3) Fatty Liver
Caused by Tetracyclines.
HYDROCHOLERETICS (4) Hepatitis
It refers to drugs that act on hepatocytes, & increases Caused by Alcohol & Amiodarone.
bile volume (but not its solid constituents). (5) Interference with Bilirubin Metabolism &
Drugs Classification Excretion
(1) Oxidized bile acids, eg dehydrocholic acid. Caused by;
(2) Salicylates. Androgens, Anabolic steroids, Estrogens, Progestins,
(3) Benzoates. Rifampin, Fusidic acid, Cholecystographic media.
Clinical Uses
To flush diseased biliary passage. TYPE B (BIZARRE)
Contraindications Hepatic injury is due to unusual properties of pt
Acute hepatitis interacting with drug, & is unrelated to dose.
(1) Acute Hepatocellular Necrosis
DRUG TREATMENT OF VIRAL HEPATITIS Caused by;
(A) Treatment of Acute Hepatitis (a) General anesthetics, eg Halothane, Methoxyflurane.
(1) A light diet supplemented by fruit drinks & glucose (b) Anticonvulsants, eg Carbamazepine, Phenytoin, Na
(about 2000 -3000 Kcal daily). valproate, Phenobarbital.
(2) Drugs should be avoided. (c) Antidepressants, eg MAO inhibitors.
(B) Treatment of Fulminant Hepatic Failure (d) NSAIDs, eg Indomethacin, Ibuprofen.
(1) For Encephalopathy (e) Antimicrobials, eg Sulfonamides, Nitrofurantoin.
Neomycin, Lactulose, Enemas. (f) Anti - hypertensives, eg Methyldopa, Hydralazine.
(2) For Cerebral Edema (2) Cholestatic Hepatitis
15: Hepatopancreaticobiliary Drugs 121

Caused by; Isoniazid, Erythromycin, Rifampin, Tetracyclines &

(a) Phenothiazines, esp. Chlorpromazine. Ketoconazole should be avoided or used in reduced
(b) Antidiabetics, eg Chlorpropamide, Tolbutamide, doses.
Glibenclamide. (F) Endocrine Drugs
(c) Carbimazole, Erythromycin, & Gold. Androgens, Anabolic steroids, Oral contraceptives,
Metformin, Chlorpropamide & Tolbutamide should be
TYPE C (CONTINUED USE) avoided.
Hepatic injury is due to prolonged use of drugs. (G) Respiratory System Drugs
(1) Chronic Active Hepatitis Theophylline should be used in reduced doses.
Caused by;
Methyldopa, Isoniazid, Dantrolene, Nitrofurantoin. GENERIC & TRADE NAMES
(2) Hepatic Cirrhosis
Caused by Alcohol & Methotrexate.
(A) Choleretics
TYPE D (DELAYED EFFECTS) Sodium Choleate: Panchol*.
(B) Hydrocholeretics
Benign Hepatic Tumors
Dehydrocholic acid: Bilsan*.
Caused by anabolic steroids & oral contraceptives, when
(C) Hepatitis Vaccines
used for more than 5 years.
Hepatitis A vaccine: Avaxim, Havrix.
Hepatitis B vaccine: Engerix -B, Heprovac B.
DRUGS SELECTION IN PATIENTS WITH HEPATIC
DISEASE
Unit II
GENERAL PRINCIPLES

Biliary & Pancreatic Drugs

(1) Drugs should only be used, when clearly indicated.
(2) Smaller than usual doses should be given initially.
(3) Frequency of administration should be determined from
effects.
(4) Monitor liver function tests regularly. CHOLAGOGUES
DRUG SELECTION
(A) CNS Drugs It refers to drugs that stimulate flow of bile from gall-
(1) Sedative - Hypnotics bladder to duodenum.
Lorazepam, Oxazepam, & Temazepam are Drug Classification
preferred. (A) Drugs that Relax Sphincter of Oddi
(2) Antiepileptics Mg- sulfate.
Should be used in lowest effective doses. (B) Drugs that Causes Gallbladder Contraction
(3) Antidepressants Cholecystokinin, Parasympathomimetics, Pituitrin.
Tricyclics may be used, but avoid MAO inhibitors.
(B) Analgesics GALLSTONE DISSOLUTANTS
(1) Opioid Analgesics
Should be avoided.
It refers to drugs that dissolves small gall-stones.
(2) Non - Opioid Analgesics
Drug Classification
Paracetamol is used in lowest dose.
(1) Primary Bile Acid
(C) CVS Drugs
Chenodiol (Chenodeoxycholic acid), Ursodiol
(1) Beta - Blockers
(Ursodeoxycholic acid).
Propranolol & Labetalol should be used in reduced
(2) Others
initial doses.
(a) Methyl tert-butyl ether.
(2) Ca+2 Channel Blockers
(b) Monoctanoin.
Nicardipine, Nifedipine & Verapamil should be
used in reduced initial doses.
(3) Diuretics PANCREATIC ENZYMES
Potassium - sparing diuretics are preferred.
(D) GIT Drugs Drug Classification
Antacids should be avoided. (1) Pancreatin .
(E) Antimicrobials (2) Pancrelipase.
Clinical Uses
M. Shamim’s PHARMACOLOGY 122

Pancreatic exocrine insufficiency.

DRUG TREATMENT OF VARICEAL HEMORRHAGE

Drug Classification
(1) Somatostatin & octreotide.
(2) Vasopressin & terlipressin.
(3) Beta-receptor blockers.

GENERIC & TRADE NAMES

Ursodiol: Urosofalk.
Pancreatin: Pepzym, Plasil with enzyme, Wobenzym N.
Somatostatin: Somatosan.
Octreotide: Sandostatin.

Unit III

Self - Assessment (T/F)

[See answers on page no. 241]
(119) Choleretics include
(A) Chenodeoxycholic acid.
(B) Deoxycholic acid.
(C) Sodium taurocholate.
(D) Dehydrocholic acid.
(E) Salicylates.
(120) Drugs that cause hepatic damage includes
(A) Halothane.
(B) Carbamazepine.
(C) Paracetamol.
(D) Isoniazid.
(E) Quinidine.
M. Shamim’s PHARMACOLOGY 123

16 AUTACOIDS & ITS

ANTAGONISTS
(2) Activation of H2 receptors causes inc. intracellular
Unit I cAMP.
(3) Activation of H3 & H4 receptors causes dec. histamine

Histamine & its Antagonists

release from histaminergic neurons & blood cells,
mediated by dec. Ca ++ influx.

Box 16.1 HISTAMINE RECEPTORS

Receptor Location Agonists Antagonists
INTRODUCTION
H1 Smooth muscle, Histaprodifen Mepyramine,
endothelium, Loratadine
SYNTHESIS brain
Histamine is formed by decarboxylation of L-histidine, H2 Gastric mucosa, Amthamine Ranitidine,
catalyzed by histidine decarboxylase. cardiac muscle, Tiotidine
mast cells, brain

STORAGE SITES H3 Presynaptic R--Methyl- Thioperamide,

Brain, Myenteric histamine, Iodophenpro-
Histamine is stored in bound form in granules of ; plexus, other Imetit, pit
(1) Mast cells & basophils, in lungs & skin. neurons Immepip
(2) Atypical mast cells in gastrointestinal mucosa. H4 Eosinophils, Clobenpropit, Thioperamide
(3) Neurons in tuberomamillary nucleus of posterior neutrophils, CD4 Imetit,
hypothalamus. T cells Clozapine

RELEASING FACTORS PHARMACOLOGICAL EFFECTS

(1) Allergy & anaphylaxis. (A) Cardiovascular System
(2) Destruction of storage cells as a result of cold, (1) Heart
bacterial toxins, bee sting venoms, trauma, etc. (a) Inc. pacemaker rate ( +ve chronotropism).
(3) Dissolution of cytoplasmic granules as a result of (b) Inc. contractility (+ve inotropism).
actions of radiation or surfactants. (2) Blood Vessels & BP
(4) Drugs, eg tubocurarine, morphine, dextran, or (a) Vasodilation of arterioles & precapillary
radiographic contrast media. sphincters  Dec. BP.
(b) Vasodilation & inc. permeability of vessels of
INACTIVATION PATHWAYS microcirculation esp. postcapillary vessels 
(1) Conversion to methylhistamine by imidazole N- Edema.
methyltransferase  Oxidation to methylimidazole- Triple Response
acetic acid by diamine oxidase. Results from intradermal inj. of histamine:
(2) Direct conversion to imidazoleacetic acid by diamine (i) Reddening at the site of inj., due to
oxidase. dilation of small vessels.
(ii) Edematous wheal at the site of inj., due
to inc. microvasculature permeability.
HISTAMINE
(iii) Red irregular flare surrounding the wheal.
(B) Extravascular Smooth Muscle
MECHANISM OF ACTION (1) GIT smooth muscle  Contraction.
Histamine binds to its specific cell surface receptors ( see (2) Bronchiolar smooth muscle  Contraction.
box 16.1), that is associated with various G proteins similar (3) Pregnant uterus  Contraction  Abortion.
to adrenoceptors (see chapter 2). (C) Nerve Endings
(1) Activation of H1 receptors causes inc. phospho- Stimulation of sensory nerve endings, esp. those
inositol hydrolysis & inc. intracellular Ca ++. mediating pain & itching.
(D) Secretory Tissues
M. Shamim’s PHARMACOLOGY 124

Inc. gastric acid secretion, & also pepsin & intrinsic H1- RECEPTOR ANTAGONISTS
factor (to a lesser extent). Also potentiates gastric acid Mechanism of Action
secretion induced by gastrin & acetylcholine. Block action of histamine by reversible competitive
(2) Inc. small & large intestinal secretions. antagonism at H1- receptors.
(3) Inc. pancreatic & bronchiolar secretions.
Pharmacological Effects
(4) Inc. lacrimation & salivation.
(A) Effects Caused by H1- Receptor Blockade
CLINICAL USES Smooth Muscles
(1) Microvascular smooth muscle  Dec. histamine-
(1) As a provocative test of bronchial hyperreactivity.
(2) As a diagnostic agent in testing for gastric acid secret- induced permeability  Dec. edema.
ing ability. (Now pentagastrin is used for this purpose). (2) GIT smooth muscle  Reverses histamine-
(3) For diagnosis of pheochromocytoma (now obsolete). induced contraction.
(3) Bronchiolar smooth muscle  Reverses histamine-
ADVERSE EFFECTS induced bronchoconstriction.
(1) CNS: Headache. (B) Effects Not Caused by H1- Receptor Blockade
(2) CVS: Flushing, tachycardia, hypotension, wheals. These probably results from similarity of drug's
(3) Resp. Tract: Bronchoconstriction, dyspnea. general structure to drugs that have effects at musca-
(4) GIT: Diarrhea. rinic cholinoceptors, - adrenoceptors, serotonin &
local anesthetic receptor sites.
CONTRAINDICATIONS (1) Central Nervous System
(1) Asthma. (a) Sedation
(2) Peptic ulcer. (i) Marked sedation  Dimenhydrinate,
(3) GIT bleeding. Diphenhydramine, Doxylamine, Prome-
thazine.
(ii) Moderate sedation  Carbinoxamine,
HISTAMINE ANTAGONISTS (ANTI-HISTAMINICS) Ethylenediamines, Cyproheptadine.
(iii) Slight sedation  Piperazine derivatives,
DRUG CLASSIFICATION Alkylamines.
(A) H1-Receptor Antagonists (iv) Little or no sedation  Piperidines,
(1) Ethanolamines Loratadine.
Carbinoxamine, Dimenhydrinate, Doxylamine, (b) Antinausea & antiemetic effects.
Diphenhydramine. (c) Anti- Parkinsonism effects.
(2) Ethylenediamines (d) Serotonin blocking effects (Cyproheptadine).
Antazoline, Pyrilamine (Mepyramine), (2) Autonomic Nervous System
Tripelennamine. (a) Atropine-like effects (Ethanolamines,
(3) Piperazine Derivatives Ethylenediamines).
Buclizine, Cyclizine, Hydroxyzine, Meclizine. (b) -adrenoceptor blocking effects
(4) Alkylamines (phenothiazines).
Bromopheniramine, Chlorpheniramine. (3) Local Anesthesia
(5) Phenothiazine Derivatives Diphenhydramine & Phenothiazine produces local
Promethazine. anesthetic effect by blocking Na- channels in
(6) Piperidines excitable membranes.
Astemizole, Terfenadine, Fexofenadine. Clinical Uses
(7) Miscellaneous (1) Allergic reactions, eg
Cyproheptadine, Loratadine, Desloratadine, (a) Allergic rhinitis (Hay fever).
Cetirizine, Azelastine, Clemastine, Emedastine, (b) Urticaria.
Epinastine, Ketotifen, Levocabastine, Olopatadine, (c) Allergic conjunctivitis.
Phenindamine. (d) Allergic drug reactions.
(B) H2 - Receptor Antagonists (e) Anaphylaxis.
Cimetidine, Ranitidine, Famotidine, Nizatidine. (2) Prophylaxis of motion sickness & vestibular
(For detail, See Chapter 14 Unit I). disturbances.
(C) H3 - Receptor Antagonists (3) Nausea & vomiting of pregnancy.
Adverse Effects
Thioperamide, Iodophenpropit.
(1) CNS
(D) H4 - Receptor Antagonists Sedation, nervousness, lassitude.
Thioperamide. (2) Eye
Blurred vision.
16: Autacoids & its Antagonists 125

(3) ENT Astemizole: Mayasen.

Tinnitus. Fexofenadine: Fenadex, Fexet, Fexet D*.
(4) CVS Cyproheptadine: Periactin, Tres -orix forte*.
Orthostatic hypotension, arrhythmias (Astemizole). Loratadine: Alor, Claridine, Histadine, Softin.
(5) GIT Desloratadine: Aloret, Destina.
GI distress. Cetrizine: Cipzin, Rigix.
(6) Urinary Tract Azelastin: Azosin, Rhinolast.
Urinary retention. Clemastine: Tandegyl.
(7) Allergic Reactions Emedastine: Emadine.
(8) Acute Poisoning Ketotifen: Asfen, Asthanil, Ketofen.
Results from overdosage esp. in children, manifested by; (B) H2 - Receptor Antagonists
Hallucinations, excitement, ataxia, convulsions. See chapter 14, Unit I.

GENERIC & TRADE NAMES

Unit II
(A) H1- Receptor Antagonists
Carbinoxamine: Davenol*, Rondec*.
Dimenhydrinate: Devinate, Dimenic, Gravinate.
Serotonin & its Antagonists
Diphenhydramine: Acefyl*, Benatus*, Benadryl*,
Brondyl*, Chlorohist*.
Antazoline: Cural -A, Spersallerg. SEROTONIN ( 5 - HYDROXY - TRYPTAMINE)
Pyrilamine: Decon -A*, Tussivil*.
Buclizine: Longifene. Synthesis
Cyclizine: Marzine, Migril*. Serotonin (5 - HT) is an indole - ethylamine formed from
Hydroxyzine: Roxyzine. amino acid tryptophan by hydroxylation of indole ring
Meclizine: Navidoxine, Sevidoxine. followed by decarboxylation of amino acid.
Chlorpheniramine: Allergon, Allerphene, Coldrex*, Mechanism of Action
Histamol, Piriton, Tempramine*. Actions of 5 - HT is mediated thru a variety of cell memb.
Promethazine: Diprozine, Phenergan, Tixylix.

Box 16.2 SEROTONIN RECEPTOR SUBTYPES

Receptors Location 2nd Messenger Effects Agonists Antagonists
5- HT1A Raphe nuclei, hippocampus  cAMP, Buspirone
 K+ conductance
5- HT1B Substantia nigra, globus  cAMP, 5- Hydroxy-3
pallidus, basal ganglia tetrahydro-pyridyl-4-
azaindole, Eletriptan
5- HT1Da,b Brain  cAMP, Sumatriptan,
Eletriptan
5- HT1E Cortex, putamen  cAMP,
5- HT1F Cortex, hippocampus  cAMP, Eletriptan
5- HT1P Enteric nervous system Slow EPSP 5-Hydroxyindalpine Renzapride
5- HT2A Platelets, smooth muscle,  IP3 - methyl-5-HT Ketanserin,
cerebral cortex Ritanserin
5- HT2B Stomach fundus  IP3 - methyl-5-HT
5- HT2C Choroid, hippocampus,  IP3 - methyl-5-HT Mesulergine
substantia nigra
5- HT3 Area postrema, sensory & Receptor is a Na+/K+ 2-methyl-5-HT Tropisetron,
enteric nerve ion channel Ondansetron,
Granisetron
5- HT4 CNS & myenteric neurons, cAMP 5-methoxytryptamine,
smooth muscle Metoclopramide,
Renzapride,
Cisapride, Tegaserod
5- HT5A,B Brain  cAMP
5- HT6,7 Brain cAMP Clozapine (7)
M. Shamim’s PHARMACOLOGY 126

receptors, that include both G protein - coupled receptors SEROTONIN RECEPTOR ANTAGONISTS
(similar to adrenoceptors) & a ligand - gated ion channels.
(See box 16.2).
Pharmacological Effects Examples
(A) Central Nervous System Cyproheptadine, Ketanserin, Ritanserin, Ondansetron,
Act as a neurotransmitter in pathways originating from Granisetron, Tropisetron, Clozapine.
neurons in raphe or midline regions of pons & upper Clinical Uses
brainstem. (A) Cyproheptadine
(1) In most areas, causes strong inhibitory effect. (1) Treatment of smooth muscle manifestations of
(2) In some cells, causes slow excitement. carcinoid tumor.
(3) Concerned with regulation of sleep, temperature, (2) Postgastrectomy dumping syndrome.
appetite, & neuroendocrine control. (3) Cold - induced urticaria.
(B) Peripheral Nervous System (4) As appetite stimulant.
(1) Stimulation of pain & itch sensory nerve endings. (B) Ketanserin
(2) Activation of chemosensitive endings located in (1) Hypertension.
coronary vascular bed  Chemoreceptor reflex  (2) Vasospastic conditions.
Bradycardia & hypotension. (C) Ondansetron & Tropisetron
(C) Cardiovascular System Prophylaxis of nausea & vomiting associated with
(1) Heart cancer chemotherapy.
(a) Direct positive chronotropic & inotropic effects.
(b) Reflex bradycardia (described above). GENERIC & TRADE NAMES
(2) Blood Vessels
(a) Vasoconstriction, more marked in pulmonary
& renal vessels. (A) Serotonin Analogues
(b) Vasodilation in skeletal muscle & cardiac Buspirone: Buspar, Novatil.
vessels. Eletriptan: Alle.
Sumatriptan: Sumapan.
(c) Venoconstriction & inc. capillary filling 
Zolmitriptan: Zomig, Zominat.
Flush.
Tegaserod: Uniserod.
(3) Blood Pressure
Triphasic blood pressure response; (B) Serotonin Antagonists
(a) Initially, dec. in heart rate, cardiac output, & Cyproheptadine: Periactin, Tres-orix forte*.
Ondansetron: Setron, Zofran.
BP (due to chemoreceptor reflex).
Granisetron: Kytril.
(b) Followed by, inc. BP (due to vasoconstriction).
Tropisetron: Navoban.
(c) Finally, again, dec BP (due to vasodilation in
Clozapine: Clozaril.
skeletal muscles).
(D) Blood
Aggregation of platelets.
(E) Gastrointestinal Tract Unit III
(1) Contraction of GIT smooth muscle  Inc. tone &
peristalsis.
(2) Little effect on secretions, generally inhibitory. Eicosanoids
(F) Respiration
(1) Bronchoconstriction.
(2) Hyperventilation (due to chemoreceptor reflex). PROSTAGLANDINS & THROMBOXANE
Clinical Uses
Serotonin has no clinical application as a drug.
Serotonin Agonists SYNTHESIS
(1) Buspirone (1) Synthesis begin with PGG2 formation from arachidonic
As non-benzodiazepine anxiolytic. acid, catalyzed by cyclooxygenase  Peroxidase
(2) Triptans, eg Almotriptan, Eletriptan, Frovatriptan, converts PGG2 into PGH2.
Naratriptan, Rizatriptan, Sumatriptan & (2) Depending on the tissues, PGH2 is converted into;
Zolmitriptan
(a) PGD2 (by PGD synthetase).
(a) Acute migraine
(b) Cluster headache (b) PGE2 (by PGE synthetase)  PGF2 (by PGE 9 -
(3) Tegaserod ketoreductase).
Irritable bowel syndrome with constipation. (c) PGI2 (by PGI synthetase).
(d) TXA2 (by TX synthetase).
16: Autacoids & its Antagonists 127

METABOLISM (3) Raynaud's phenomenon.

Prostaglandins are rapidly catabolized in the body by; (4) Peripheral atherosclerosis.
(1) 15 - Hydroxydehydrogenase pathway. (5) Impotence or erectile dysfunction (Intra-cavernosal
(2) Cytochrome P450 system. inj. therapy).
(6) Prophylaxis of NSAID - induced gastric ulcer.
MECHANISM OF ACTION (B) PGE2
Prostaglandins bind to specific cell surface receptor that (1) For 1st - & 2nd - trimester abortion (given as
are G protein - linked  Activation of adenyl cyclase or vaginal suppositories).
phosphatidylinositol metabolism  cAMP or  IP3. (2) To initiate & stimulate labor.
(3) Hypertension.
(4) Raynaud's phenomenon.
PHARMACOLOGICAL EFFECTS
(5) Peripheral atherosclerosis.
(A) Smooth Muscle (6) As bronchodilator (given in aerosol form).
(1) Vascular (C) PGF2
(a) PGE2 & PGI2 causes relaxation of arteriolar
(1) For 1st - & 2nd - trimester abortion (given intra -
smooth muscle (vasodilation). amniotically or intra - muscularly).
(b) TXA2 & PGF2 causes smooth muscle (2) To initiate & stimulate labor.
contraction esp. of veins (vasoconstriction). (D) PGI2
(2) Gastrointestinal Tract (1) Primary & secondary pulmonary hypertension.
(a) PGE2 & PGF2 causes contraction of (2) Raynaud's phenomenon.
longitudinal muscle. (3) Peripheral atherosclerosis.
(b) PGE2 also causes relaxation of circular muscle. (4) As anti - thrombosis.
(c) PGI2 & PGF2 causes contraction of circular (5) To prevent cell - mediated organ transplant
muscle. rejection.
(3) Respiratory Tract
(a) PGE1, PGE2, & PGI2 causes bronchodilation. GENERIC & TRADE NAMES
(b) TXA2 & PGF2 causes bronchoconstriction.
(B) Platelets (A) PGE1 Analogues
(1) PGE1 & PGI2 inhibit aggregation.
Alprostadil: Caverject, Prostavasin.
(2) TXA2 facilitates aggregation. (B) PGE2 Analogues
(C) Central Nervous System Dinoprostone: Prostin E2, Prepidil.
PGE1 & PGE2 increases body temperature. (C) PGF2 Analogues
(D) Peripheral Nervous System Dinoprost: Prostin F2 alpha, Preglan.
PGE inhibit norepinephrine release from sympathetic
presynaptic nerve endings.
(E) Neuroendocrine
Unit IV
PGE promote release of growth hormone, prolactin,
thyroid - stimulating hormone, adrenocorticotropic
hormone, follicle - stimulating hormone, & luteinizing
hormone. Self - Assessment (T/F)
(F) Reproductive System
(1) Female (See answers on page no. 241)
PGE2 & PGF2 promote uterine contractions  (121) Regarding histamine, following are correct
(a) Abortion. (A) It has positive inotropic & positive chronotropic
(b) Facilitation of labor. effects.
(c) Dysmenorrhea during menstruation. (B) It causes triple response, when injected in skin.
(2) Male (C) Thru H1 receptor stimulation, it causes smooth
Men with a low seminal prostaglandin conc. are muscle relaxation.
relatively infertile. (D) Combination of histamine with H2 receptors
causes stimulation of gastric acid secretion.
CLINICAL USES (E) Used for diagnosis of pheochromocytoma.
(A) PGE1
(122) Histamine H1 receptor blockers are useful in the
(1) To maintain patency of ductus arteriosus in
treatment of
neonates with congenital cardiac diseases, until
(A) Urticaria.
surgery can be performed.
(B) Seasonal rhinitis.
(2) Hypertension.
M. Shamim’s PHARMACOLOGY 128

(C) Drug reactions.

(D) Bronchial asthma.
(E) Peptic ulcer.
(123) Cyproheptadine is useful in the treatment of
(A) Carcinoid tumors.
(B) Postgastrectomy dumping syndrome.
(C) Hepatitis.
(D) Migraine.
(E) Pruritic dermatosis.
M. Shamim’s PHARMACOLOGY 129

17 ENDOCRINE DRUGS

Unit I THYROTROPIN- RELEASING HORMONE (TRH)

Pharmacological Effects

Hypothalamic & Pituitary

Stimulates pituitary production of thyrotropin.
Clinical Uses
Hormones (1) To diagnose hyperthyroidism.
(2) To diagnose hypothyroidism.

GONADOTROPIN- RELEASING HORMONE (GNRH)

HYPOTHALAMIC HORMONES & ANTAGONISTS Pharmacological Effects
Stimulates pituitary production of FSH & LH.
Clinical Uses
HORMONES AFFECTING GROWTH HORMONE
(1) To diagnose & treat hypogonadotropic hypogonadism in
RELEASE
both males & females.
(A) Growth Hormone-Releasing Hormone (GHRH) (2) To induce biochemical castration;
Pharmacological Effects (a) In adults with prostatic cancer, uterine fibroids,
Stimulates pituitary production of growth hormone endometriosis, & polycystic ovary syndrome.
(GH). (b) In children with precocious puberty.
Clinical Uses
(1) Diagnostically, to evaluate the cause of GH GNRH RECEPTOR ANTAGONISTS
deficiency.
Examples
(2) Therapeutically, in GH deficiency where pituitary
Ganirelix, Cetrorelix.
somatotrophs are responsive to GHRH.
Pharmacological Effects
(B) Somatostatin (GH-Inhibiting Hormone) &
Inhibits pituitary production of FSH & LH in a dose-
Octreotide
dependent manner.
Pharmacological Effects
Clinical Uses
(1) Inhibit growth hormone release.
For preventing LH surge during controlled ovarian
(2) Also inhibit release of glucagon, insulin, & gastrin.
hyperstimulation.
Clinical Uses
Octreotide (a somatostatin analogue) is used in;
(1) Acromegaly.
(2) Carcinoid syndrome. ANTERIOR PITUITARY HORMONES &
(3) Gastrinoma. ANTAGONISTS
(4) Glucagonoma.
(5) Nesidioblastosis. GROWTH HORMONE (GH, SOMATOTROPIN)
(6) Watery diarrhea, hypokalemia & achlorhydria
Pharmacological Effects
(WDHA) syndrome.
(1) Anabolic
(7) Diabetic diarrhea.
GH produces growth of bone & soft tissues, mediated
Note: Octreotide, an analog of somatostatin, is 45 times
indirectly by somatomedins which is produced in liver).
more potent than somatostatin in inhibiting GH release.
(2) Metabolic
(a) Initially: Insulin-like effect with inc. tissue uptake
CORTICOTROPIN-RELEASING HORMONE (CRH)
of both glucose & amino acids, & dec. lipolysis.
Pharmacological Effects (b) Within a few hours: Peripheral insulin-
Stimulates ACTH secretion from anterior pituitary. antagonistic effects with impaired glucose uptake,
Clinical Uses & inc. lipolysis.
Diagnostically, to distinguish Cushing's disease from Clinical Uses
ectopic ACTH secretion. (1) Growth failure in pediatric patients associated with;
M. Shamim’s PHARMACOLOGY 130

(a) Growth hormone deficiency. DOPAMINE AGONISTS (PROLACTIN

(b) Chronic renal failure. ANTAGONISTS)
(c) Prader-Willi syndrome. Examples
(d) Turner's syndrome. Bromocriptine, Cabergoline, Pergolide, Quinagolide.
(e) Idiopathic short stature. Pharmacological Effects
(2) Growth hormone deficiency in adults. Suppress prolactin release in patients with
(3) Wasting in patients with AIDS. hyperprolactinemia.
(4) Short bowel syndrome. Clinical Uses
(1) Hyperprolactinemia.
ADRENOCORTICOTROPIN (CORTICOTROPIN, (2) To suppress physiologic lactation.
ACTH)
Pharmacological Effects POSTERIOR PITUITARY HORMONES &
(1) Stimulates adrenal cortex to produce glucocorticoids, ANTAGONISTS
mineralocorticoids, & androgens.
(2) Stimulates adrenal hypertrophy, & hyperplasia.
(3) Inc. skin pigmentation. OXYTOCIN
Clinical Uses Pharmacological Effects
(1) To diagnose adrenal insufficiency. (1) Alters transmemb. ionic currents in myometrial smooth
(2) To distinguish late-onset congenital adrenal muscle cells to produce sustained uterine contraction.
hyperplasia from ovarian hyperandrogenism. (2) Causes contraction of myoepithelial cells surrounding
(3) In chronic conditions, as an anti-inflammatory or mammary alveoli  Milk ejection.
immunosuppressive agent. (3) Weak antidiuretic & pressor activity.
Clinical Uses
THYROID-STIMULATING HORMONE (TSH, (1) To diagnose intrauterine growth retardation.
THYROTROPIN) (2) To induce labor & augment dysfunctional labor in,
Pharmacological Effects (a) Maternal diabetes.
It stimulates production of thyroid hormones by follicles (b) Preeclampsia.
of thyroid gland. (c) Rh problems.
Clinical Uses (d) Uterine inertia.
To diagnose hypothyroidism & recurrence of thyroid (e) Incomplete abortion.
carcinoma. (3) To control postpartum hemorrhage (PPH).
(4) Impaired milk ejection.
FOLLICLE- STIMULATING HORMONE (FSH), &
LUTEINIZING HORMONE (LH) OXYTOCIN ANTAGONISTS
Pharmacological Effects Examples
(1) FSH stimulate gametogenesis & follicular development Atosiban.
in women, & spermatogenesis in men. Pharmacological Effects
(2) Both LH & FSH are needed for proper ovarian An antagonist of oxytocin receptors.
steroidogenesis. Clinical Uses
(3) FSH stimulates sertoli cells in testes to produce Preterm labor.
androgen-binding protein.
Clinical Uses VASOPRESSIN (ANTIDIURETIC HORMONE, ADH)
Human menopausal gonadotropins (hMG), a mixture of Pharmacological Effects
partially catabolized human FSH & LH, are used in; (1) Stimulate V1 receptors on vascular smooth muscle cells
(1) Pituitary or hypothalamic hypogonadism with inferti-  Vasoconstriction.
lity. (2) Stimulate V2 receptors on renal tubule cells 
(2) Women with anovulatory conditions eg, primary
Antidiuresis thru inc. water permeability & water
amenorrhea, secondary amenorrhea, polycystic ovary
reabsor- ption in collecting tubules.
syndrome, & anovulatory cycles.
(3) Male infertility. (3) Stimulate extrarenal V2 - like receptors  Release of
coagulation factor VIIIc & von Willebrand factor.
PROLACTIN Clinical Uses
(1) Pituitary diabetes insipidus.
Pharmacological Effects
(1) Stimulates milk production. (2) Esophageal variceal bleeding.
(2) Induces mitogenesis in lymphocytes. (3) Colonic diverticular bleeding.
Clinical Uses
No preparation is available for clinical use. VASOPRESSIN ANTAGONISTS
17: Endocrine Drugs 131

Examples (3) To prevent cretinism in hypothyroid infants.

Conivaptan, Tolvaptan. (4) To treat infertility in hypothyroid women.
Pharmacological Effects
Antagonists of V1 & V2 vasopressin receptors. ADVERSE EFFECTS
Clinical Uses (A) In Children
Hyponatremia. Restlessness, insomnia, & accelerated bone maturation
& growth.
GENERIC & TRADE NAMES (B) In Adults
Nervousness, heat intolerance, palpitation, tachycardia,
unexplained weight loss.
(A) Hypothalamic Hormones & Antagonists
Octreotide: Sandostatin.
Goserelin (Gn RH analogue): Zoladex. ANTI - THYROID DRUGS
Ganirelix: Orgalutran.
(B) Anterior Pituitary Hormones & Antagonists DRUG CLASSIFICATION
Somatropin (GH analogue): Eutropin, Genotropin, (A) Drugs Interfering with Synthesis of Thyroid
Hht, Humatrope, Norditropin. Hormones
Somatostatin: Ikestatina. (1) Thioamides
ACTH: Acthar gel. Propylthiouracil, Methimazole, Carbimazole,
Menotropins (hMG): Humegon, Pergonal. Thiouracil, Thiourea.
Bromocriptine: Bromicon, Brotin, Parlodel. (2) Anion Inhibitors
(C) Posterior Pituitary Hormones & Antagonists Perchlorate, Pertechnetate, Thiocyanate.
Oxytocin: Syntocinon. (B) Drugs Preventing Release of Thyroid
Hormones
(1) Iodides
Unit II Potassium iodide, Sodium iodide.
(2) Iodinated Contrast Media

Thyroid & Antithyroid

Diatrizoate, Iohexol.
(C) Drugs Producing Thyroid Gland Destruction

Drugs Radioactive iodine (I131).

(D) Adjunctive Drugs
(1)  - Blockers, eg Propranolol.
(2) Adrenergic neuron blockers, eg Guanethidine,
THYROID HORMONES & ANALOGUES Reserpine.
(3) Diltiazem.
(4) Aspirin or NSAIDs.
CLASSIFICATION (5) Corticosteroids.
(A) Endogenous
Thyroxine (T4), Triiodothyronine (T3). THIOAMIDES
(B) Animal Origin Mechanism of Action
Desiccated thyroid. (1) Inhibit thyroid peroxidase  Block iodine organification
(C) Synthetic
(ie, iodination of tyrosine)  Prevent synthesis of T4 &
Levothyroxine, Liothyronine, Liotrix.
T3.
PHARMACOLOGICAL EFFECTS (2) Propylthiouracil & (to a much lesser extent) methima-
(1) Regulate growth & development in children. zole inhibit peripheral deiodination of T4 & T3.
(2) Exert a calorigenic effect by increasing basal metabolic Clinical Uses
rate. (1) Hyperthyroidism (thyrotoxicosis).
(3) Accelerate carbohydrate utilization, & enhance lipolytic (2) Thyroid storm (thyrotoxic crisis).
reactions. (3) Preoperative preparation in toxic multinodular goitre.
(4) Inhibit pituitary secretion of thyrotropin by negative (4) Thyrotoxicosis during pregnancy (propylthiouracil).
feedback. Note: Methimazole is avoided b/c of the risk of fetal
(5) Stimulate cardiovascular system. scalp defects.
(5) Neonatal Graves' disease (propylthiouracil).
CLINICAL USES Adverse Effects
(1) Hypothyroidism. (1) CVS: Vasculitis.
(2) Myxedema coma. (2) Liver: Cholestatic jaundice, hepatitis.
(3) Blood: Hypoprothrombinemia, agranulocytosis.
M. Shamim’s PHARMACOLOGY 132

(4) Lymph nodes: Lymphadenopathy. (1) Pregnancy.

(5) Serous memb: Polyserositis. (2) Lactation.
(6) Joints: Arthralgia.
(7) Body temp: Fever.
GENERIC & TRADE NAMES
(8) Skin: Maculopapular pruritic rash, urticarial rash,
lupus - like reaction.
(A) Thyroid Hormones & Analogues
ANION INHIBITORS Thyroxine: Thyroxine.
Mechanism of Action (B) Anti - Thyroid Drugs
Block uptake of iodide by thyroid gland thru competitive Propylthiouracil: Procarbizol.
inhibition of iodide transport mechanism. Carbimazole: Carbizole, Mercazole, Neomercazole.
Clinical Uses Iodine: Lugol's Iodine.
No therapeutic use b/c of their toxicity, eg aplastic anemia
(perchlorate); however, can be used for diagnostic purposes.
Unit III
IODIDES
Mechanism of Action
(1) Inhibit hormone release thru inhibition of thyro- Anti - Diabetic Drugs
globulin proteolysis.
(2) Inhibit organification.
(3) Dec. vascularity, size, & fragility of hyperplastic INTRODUCTION
thyroid gland.
Clinical Uses
(1) Thyroid storm. DIABETES MELLITUS
(2) Iodine deficiency goitre. It is a clinical syndrome characterized by hyperglycemia
(3) Preoperative preparation for thyroidectomy. due to absolute or relative deficiency of insulin.
Adverse Effects Types
Iodism (1) Type I (Insulin Dependent Diabetes Mellitus)
(1) Eye: Conjunctivitis. (a) Occur commonly in juveniles, & occasionally in
(2) ENT: Rhinorrhea. non-obese adults.
(3) Blood: Bleeding disorders. (b) Associated with ketoacidosis in untreated state.
(4) GIT: Swollen salivary glands, metallic taste. (c) Circulating insulin is virtually absent & pancreatic
(5) Mucus memb: Ulcerations. B cells fail to respond to all insulinogenic stimuli.
(6) Skin: Acneiform rash. (2) Type II (Non-Insulin Dependent Diabetes
(7) Allergic reactions: Drug fever, anaphylaxis. Mellitus)
(a) Occur predominantly in obese adults, &
IODINATED CONTRAST MEDIA occasionally in adolescents.
Mechanism of Action (b) Circulating endogenous insulin is sufficient to
(1) Inhibit conversion of T4 to T3 in liver, kidneys, pituitary prevent ketoacidosis.
gland, & brain. (c) There is tissue insensitivity to insulin, & an
(2) Inhibit thyroid hormone release due to release of iodine. accompanying deficiency of pancreatic B cell's
Clinical Uses response to glucose.
(1) As adjunct in thyroid storm. Clinical Features
(2) As alternatives, when thioamides or iodides are (1) Polyuria, thirst, & polydipsia (due to osmotic diuresis).
contraindicated. (2) Fatigue (due to hyperglycemia).
(3) Vulvitis & balanitis (due to glycosuria).
(4) Hypotension & hypothermia (due to ketoacidosis).
RADIOACTIVE IODINE (I131)
(5) Wasting & weight loss (due to inc. catabolism).
Mechanism of Action Drugs Causing Diabetes Mellitus
It is rapidly incorporated into colloid of thyroid follicles  (1) Corticosteroids.
Emit beta rays that destroy thyroid parenchyma. (2) Thiazide diuretics.
Clinical Uses (3) Phenytoin.
(1) Hyperthyroidism esp. in pts over 30 years of age.
(2) Toxic uninodular goitre.
Adverse Effects CLASSIFICATION OF ANTI - DIABETIC DRUGS
(1) Delayed hypothyroidism.
(2) Delayed onset in control of hyperthyroidism. INSULIN PREPARATIONS
Contraindications
17: Endocrine Drugs 133

(1) Rapid Acting Insulins Insulin binds to extracellular - subunit of insulin receptors
(a) Standard on target cells  This stimulates tyrosine kinase activity in 
Insulin lispro, Human insulin inhaled. - subunit of insulin receptors (that spans the cell memb) 
(b) Purified This results in,
Insulin aspart, Insulin glulisine. (1) Self - phosphorylation of  - subunit  Inc. aggregation
(2) Short Acting Insulins of  heterodimers, & stabilization of activated state
(a) Standard of receptor tyrosine kinase.
Regular insulin (crystalline Zn insulin), (2) Phosphorylation of other intracellular proteins 
Regular iletin I insulin. Translocation of glucose transporter proteins from
(b) Purified sequestered sites within the cells to exposed locations
Regular, Regular humulin, Regular iletin II,
on cell surface  Inc. transport of glucose into cells.
Velosulin, Humulin BR.
(See Box 17.1).
(3) Intermediate Acting Insulins
Finally, insulin - receptor complex is internalized  This
(a) Standard
may contributes to further insulin action, or terminate
Isophane NPH (neutral protamine Hagedorn), Lente,
the action of insulin by removing insulin & its receptor
Lente iletin I, NPH iletin I.
into scavenger lysosomes.
(b) Purified
Lente humulin, Lente iletin II, NPH humulin, NPH
Box 17.1 GLUCOSE TRANSPORTERS
iletin II, NPH.
(4) Long Acting Insulins Transporter Location Function
(a) Standard GLUT 1 All tissues esp Basal uptake of
Ultralente, Ultralente iletin I. RBCs, brain glucose, transport
(b) Purified across BBB
Ultra lente, Ultralente humulin. GLUT 2 B cells of Regulation of insulin
(5) Premixed Insulins pancreas, liver, release
Consists of 70% NPH, & 30% Regular; kidney, gut
(a) Novolin 70/30.
GLUT 3 Brain, kidney, Uptake of glucose
(b) Humulin 70/30. placenta, other
tissues
ORAL HYPOGLYCEMIC AGENTS
GLUT 4 Muscle, adipose Uptake of glucose
(1) Insulin Secretogogues tissue
(a) Sulfonylureas
GLUT 5 Gut, kidney Intestinal absorption
(i) First Generation
of fructose
Tolbutamide, Chlorpropamide, Tolazamide,
Acetohexamide.
(ii) Second Generation PHARMACOLOGICAL EFFECTS
Glyburide (Glibenclamide), Glipizide, (A) Liver
Glimepiride, Gliclazide. (1) Reversal of Catabolic Features of Insulin
(b) Meglitinides Deficiency
Repaglinide. (a) Inhibits glycogenolysis.
(c) D-Phenylalanine Derivatives (b) Inhibits conversion of fatty acids & amino
Nateglinide. acids to keto acids.
(2) Biguanides (c) Inhibits gluconeogenesis.
Phenformin, Buformin, Metformin. (2) Anabolic Actions
(3) Thiazolidinedione Derivatives (a) Promotes glucose storage as glycogen.
Ciglitazone, Pioglitazone, Englitazone, Rosiglitazone. (b) Increases triglyceride & VLDL synthesis.
(4) Alpha-Glucosidase Inhibitors (B) Muscle
Acarbose, Miglitol. (1) Inc. protein synthesis.
(5) Miscellaneous (2) Inc. glycogen synthesis.
Pramlintide, Exenatide, Sitagliptin. (C) Adipose Tissue
Inc. triglyceride storage.

INSULIN PREPARATIONS
CLINICAL USES
(1) Insulin - dependent diabetes mellitus (IDDM).
MECHANISM OF ACTION (2) Non - insulin - dependent diabetes mellitus (NIDDM).
M. Shamim’s PHARMACOLOGY 134

ADVERSE EFFECTS (B) Oral Hypoglycemics

(1) Hypoglycemia. Chlorpropamide: Diabenese, Diabtus.
(2) Insulin allergy. Glyburide: Benil, Daonil, Diabeta, Diamide, Euglocon,
(3) Immune insulin resistance. Glabinol, Glaonil, Gliben, Glicon, Semi - Glicon.
(4) Lipodystrophy at injection site. Glipizide: Glibenese, Glipase, Minidiab.
Glimepiride: Amaryl, Diatrol, Geopride, Getformin,
Getryl, Glyset.
SULFONYLUREAS Gliclazide: Diabetron, Diaglic, Diamicron, Diclazide,
Glicozid, Gluconorm, Zaclazide.
Mechanism Of Action Repaglinide: Novonorm, Repaglin.
(1) Stimulate insulin secretion from pancreatic  - cells. Metformin: Dianorm, Getformin, Glimet, Glucometl,
(2) Dec. serum glucagon levels. Tabrophage.
(3) Potentiates the action of insulin on its target tissues. Pioglitazone: Diazone, Gliden, Zolid.
Clinical Uses Rosiglitazone: Rosita, Rozi.
Non - insulin - dependent diabetes mellitus. Acarbose: Glucobay.
Adverse Effects
(1) Metabolism: Hypoglycemia.
(2) GIT: Nausea, vomiting. Unit IV
(3) Endo: Inappropriate ADH secretion.
(4) Blood: Leukopenia, agranulocytosis, thrombocytopenia,
pancytopenia, hemolytic anemia. Adrenocorticosteroids &
(5) Skin: Rashes, flushing, photosensitivity.
Contraindications Analogues
(1) Hepatic impairment.
(2) Renal insufficiency.
DRUG CLASSIFICATION
BIGUANIDES
(A) Glucocorticoids
Mechanism Of Action (1) Short- to Medium- Acting
(1) Direct stimulation of glycolysis in peripheral tissues, Hydrocortisone (cortisol), Cortisone, Prednisone,
with inc. glucose removal from blood. Prednisolone, Fluocortolone, Methylprednisolone,
(2) Dec. hepatic gluconeogenesis. Meprednisone.
(3) Slowing of glucose absorption from GIT. (2) Intermediating - Acting
(4) Dec. plasma glucagon levels. Triamcinolone, Paramethasone, Fluprednisolone.
(5) Inc. insulin binding to insulin receptors. (3) Long - Acting
Clinical Uses Betamethasone, Dexamethasone.
(1) Pts with refractory obesity whose hyperglycemia is due (B) Mineralocorticoids
to ineffective insulin action. Aldosterone, Fludrocortisone, Deoxycorticosterone
(2) Non - insulin - dependent diabetes mellitus (in acetate.
combination with sulfonylureas). Note: Hydrocortisone & Cortisone have also some
Adverse Effects mineralocorticoid activity.
GIT: Anorexia, nausea, vomiting, abdominal discomfort,
diarrhea.
Contraindications MECHANISM OF ACTION
(1) Renal disease.
(2) Alcoholism. Corticosteroids diffuse or transported thru cell memb., &
(3) Hepatic disease. bind to cytoplasmic steroid receptors  Steroid - receptor
(4) Chronic cardiopulmonary dysfunction. complex is then transported into nucleus, where it interacts
with corticosteroid response elements (CREs) on various
GENERIC & TRADE NAMES genes & other regulatory proteins  This stimulates or
inhibits the expression of CREs & regulatory proteins (eg
enzymes), that control rate - limiting reactions in various
(A) Insulin Preparations metabolic pathways.
Actrapid, Humalog, Humulin Ultralente, Humulin-70
30-mix, Humulin-N, Humulin-R, Insulatard, Insulin Inj,
Lantus, Mixtard 30-hm, Novopen, Novormx 30, PHARMACOLOGICAL EFFECTS
Zansulin 70/30, Zansulin N.P.H., Zansulin Regular.
17: Endocrine Drugs 135

(A) Glucocorticoids Inflammatory bowel disease, non-tropical sprue,

(1) Central Nervous System subacute hepatic necrosis.
Behavioral disturbances, euphoria. (6) Hematologic disorders, eg
(2) Neuroendocrine Acquired hemolytic anemia, autoimmune hemolytic
(a) Inhibit pituitary release of ACTH, &  - anemia, leukemia, idiopathic thrombocytopenic
lipotropin. purpura, multiple myeloma.
(b) Dec. secretion of TSH, & FSH. (7) Infections, eg
(3) Cardiovascular System Acute respiratory distress syndrome, sepsis,
Maintenance of cardiovascular function by systemic inflammatory response sydrome.
potentiating norepinephrine. (8) Inflammatory conditions of joints & bones, eg
(4) Gastrointestinal Tract Arthritis, bursitis, tenosynovitis.
Large dose stimulate excessive acid - pepsin (9) Neurologic disorders, eg
secretion in stomach. Cerebral edema, multiple sclerosis.
(5) Blood (10) Pulmonary diseases, eg
Inc. RBCs & platelets count. Aspiration pneumonia, sarcoidosis.
(6) Metabolism (11) Renal disorders, eg
(a) Stimulate gluconeogenesis in fasted state, & Nephrotic syndrome.
in diabetics. (12) Skin diseases, eg
(b) Inc. glycogen deposition in liver. Atopic dermatitis, dermatoses, seborrheic dermatitis.
(c) Inc. lipolysis. (13) Thyroid diseases, eg
(7) Anti - Inflammatory & Immunosuppressive Malignant exophthalmos, sub - acute thyroiditis.
Effects (14) In organ transplantation, for prevention & treatment
(a) Dec. neutrophil migration. of rejection.
(b) Dec. circulating lymphocytes, monocytes,
eosinophils, & basophils (which are moved to ADVERSE EFFECTS
lymphoid tissues).
(c) Inhibit functions of leukocytes, & tissue
macrophages. (A) Iatrogenic Cushing's Syndrome
(d) Stabilizes lysosomal membrane. Occurs when 100 mg cortisol (or equivalent synthetic
(e) Dec. prostaglandin & leukotriene synthesis. steroid) is given daily for more than 2 weeks.
(f) Dec. capillary permeability. (1) CNS: Insomnia, inc. appetite.
(B) Mineralocorticoids (2) Face: Altered by rounding, puffiness, & plethora.
(1) Inc. reabsorption of Na+ by distal renal tubules, (3) Musculo - Skeletal: Muscle wasting, osteoporosis,
loosely coupled with secretion of K+ & H+. aseptic necrosis of hip.
(2) Inc. reabsorption of Na+ in sweat & salivary (4) Skin: Inc. growth of fine hair over thighs & trunk,
glands, & GI mucosa. acne, & thinning of skin with stria & bruising.
(5) Fat deposition: Redistributed from extremities to
trunk & face.
CLINICAL USES (6) Metabolic: Hyperglycemia, diabetes.
(7) Body weight: Weight Gain.
(A) Adrenal Disorders (8) Wound Healing: Impaired.
(1) Addison's disease (Cortisol + Fludrocortisone). (B) Other
(2) During & after adrenalectomy. (1) CNS: Psychosis, dizziness.
(3) To diagnose Cushing's syndrome (dexamethasone (2) Eye: Posterior subcapsular cataract, glaucoma.
suppression test). (3) CVS: Hypertension, congestive cardiac failure.
(B) Nonadrenal Disorders (4) GIT: Peptic ulcer, nausea.
(1) Prophylaxis of respiratory distress syndrome in (5) Water, electrolytes, & acid - base balance:
premature infants (betamethasone to mother). Hypernatremia, edema, hypokalemia, hypochlo-
(2) Allergic reactions, eg remic alkalosis.
Asthma, angioneurotic edema, drug reactions, (6) Endo: Adrenal suppression.
rhinitis, serum sickness, urticaria. (7) Growth: Growth retardation in children.
(3) Collagen - vascular disorders, eg
Lupus erythematosus, polymyositis, rheumatoid CONTRAINDICATIONS
arthritis, Giant cell arteritis.
(4) Eye diseases, eg
Acute uveitis, allergic conjunctivitis, choroiditis, (1) Peptic ulcer.
optic neuritis. (2) Heart disease or hypertension with congestive cardiac
(5) Gastrointestinal diseases, eg failure.
M. Shamim’s PHARMACOLOGY 136

(3) Infections.
(4) Psychosis. Gonadal Hormones &
(5)
(6)
Diabetes mellitus.
Osteoporosis.
Antagonists
(7) Glaucoma.
(8) Herpes simplex infection.
FEMALE GONADAL HORMONES
DOSAGE
ESTROGENS
(1) Betamethasone Classification
0.5 - 5 mg/d, orally; reduce for maintenance to min. (A) Natural Steroidal
effective dose. Estradiol, Estrone, Estriol.
(2) Dexamethasone (B) Synthetic Steroidal
(a) In chronic conditions  20 mg IM ; repeated as Ethinyl estradiol, Mestranol, Quinestrol.
necessary. (C) Synthetic Nonsteroidal
(b) 5 - 20 mg by intra - articular & soft tissue inj. ; Diethylstilbestrol, Chlorotrianisene, Methallenestril,
may be repeated at intervals of 1 - 3 weeks. Dienestrol, Benzestrol, Hexestrol, Methestrol.
(3) Hydrocortisone Mechanism of Action
100 - 500 mg by slow IV inj. Estrogen enter its target cell by diffusion  Transported to
nucleus, where it binds to estrogen receptors  Estrogen -
Box 17.2 CORTICOSTEROID ANTAGONISTS receptor complex forms a homodimer that binds to estrogen
response element on gene & interacts with specific cellular
1) Synthesis Inhibitors & Glucocorticoid Antagonists
a) Metyrapone proteins Activate transcription & regulate the formation
b) Aminoglutethimide of specific mRNA  Induction of protein synthesis in cell.
c) Ketoconazole Pharmacological Effects
d) Mifepristone (1) Female Sex Organs
e) Mitotane (a) Stimulate development of vagina, uterus, & uterine
f) Trilostane tubes.
2) Mineralocorticoid Antagonists (b) Stimulate stromal development & ductal growth in
a) Spironolactone
breast.
b) Eplerenone
c) Drospirenone (c) Stimulate development of secondary sex
characteristics, eg growth of axillary & pubic hairs,
broadening of pelvis, & redistribution of body fat so
GENERIC & TRADE NAMES as to produce typical female body contours.
(2) Skeletal System
Glucocorticoids (a) Accelerate growth phase & closing of epiphyses of
Hydrocortisone: Cortisol, Daktacort, Fusac H*, Hydrosone, long bones at puberty.
Hysone, Neo-cort*, Solu-cortef, Daktacort*. (b) Decrease rate of bone resorption.
Prednisolone: Blephapred, Deltacortil, Fortipred, (3) Pigmentation
Mildopred, Mydosone, Pred forte, Prednicol, Biopred*. Inc. pigmentation in nipples, areolas, & genital regions.
Fluocortolone: Ultralanum. (4) Blood
Methylprednisolone: Depo-medrol, Solu-medrol. (a) Inc. blood levels of transcortin, thyroxine-
Triamcinolone: Kenacomb*, Kenacort, Kenacort-A, binding globulin, sex hormone-binding globulin,
Kenalog, Kenoidal*, Ledercort, Tricort. transferrin.
Betamethasone: Anglosone, Betacin N*, Betaderm, (b) Inc. blood levels of factor II, VII, IX, & X, &
Betanate, Betnesol, Betnesol - N*, Probeta, Probeta - N*. dec. antithrombin III level  Inc. coagulability.
Dexamethasone: Baycuten, Decadron, Decadron - N*, (c) Inc. plasminogen levels.
Dexa N, Dexone, Dosachlor*, Fortecortin, Fradex*, Phesone. (d) Dec. platelet adhesiveness.
(e) Inc. HDL & triglyceride levels.
(f) Dec. LDL & cholesterol levels.
Clinical Uses
(1) As replacement therapy in,
(a) Primary hypogonadism, eg Turner's syndrome &
Unit V panhypopituitarism in girls.
(b) Postmenopausal synd. (hot flushes, osteoporosis).
(2) Intractable dysmenorrhea.
17: Endocrine Drugs 137

(3) Hirsutism & amenorrhea, due to excessive secretion of (c) Depressant & hypnotic effects on brain.
androgens by ovary. (4) Renal
(4) To stop excessive uterine bleeding due to endometrial (a) Competes with aldosterone at renal tubule  Dec.
hyperplasia. Na+ reabsorption  Inc. aldosterone secretion.
(5) As oral contraceptive (see below). (b) Inc. urinary nitrogen excretion.
Adverse Effects (5) Blood
(1) CNS: Migraine headache. Dec. plasma level of many amino acids.
(2) CVS: Hypertension. Clinical Uses
(3) GIT: Nausea. (1) As replacement therapy in,
(4) Biliary Tract: Cholestasis, gallbladder disease. (a) Primary hypogonadism.
(5) Repro: Postmenopausal bleeding, breast tenderness, (b) Postmenopausal syndrome.
hyperpigmentation. (2) As oral contraceptive (see below).
(6) Cancer: Inc. risk of breast & endometrial cancer. (3) Dysmenorrhea, endometriosis, hirsutism, & bleeding
Contraindications disorders when estrogens are contraindicated.
(1) Carcinoma of endometrium. (4) Precocious puberty.
(2) Carcinoma of breast. (5) As a test of estrogen secretion.
(3) Undiagnosed genital bleeding. Adverse Effects
(4) Liver disease. (1) CNS: Depression.
(5) Thromboembolic disorder. (2) CVS: Hypertension, myocardial infarction.
(3) Blood: Low HDL levels.
PROGESTINS (4) Resp. tract: Pulmonary embolus.
Classification (5) Body fluid: Edema.
(1) Natural (6) Body weight: Weight gain.
Progesterone. (7) Lymphatics: Thrombophlebitis.
(2) Synthetic
(a) 21-Carbon Compounds ORAL CONTRACEPTIVES
Hydroxyprogesterone, Medroxyprogesterone, It refers to hormonal preparations that decreases fertility &
Megestrol. prevent the occurrence of pregnancy, when taken orally.
(b) 17-Ethinyl Testosterone Derivatives Drug Classification
Dimethisterone. (A) Combination Pills
(c) 19-Nortestosterone Derivatives (1) Monophasic Combination Pills
Desogestrel, Norgestimate, Norethynodrel, It involves same dose of estrogen & progestin
Lynestrenol, Norethindrone, Ethynodiol, Norgestrel. thru - out the menstrual cycle, eg;
Mechanism of Action (a) Ethinyl estradiol + Norethindrone, Desogestrel,
Progestins enter cell & bind to progestin receptors that are Norgestrel, Ethynodiol, or Norgestimate.
distributed b/w nucleus & cytoplasmic domains  (b) Mestranol + Norethindrone, Norethynodrel, or
Progestin - receptor complex binds to a response element on Ethynodiol.
gene & interacts with specific cellular proteins  This (2) Biphasic Combination Pills
stimulates or inhibits expression of response element & It involves 2 different doses of estrogen & progestin,
cellular proteins. given in 2 divided phases of menstrual cycle, eg;
Pharmacological Effects Ethinyl estradiol + Norethindrone.
(1) Female Sex Organs (3) Triphasic Combination Pills
(a) Causes maturation & secretory changes in It involves 3 different doses of estrogen & progestin,
endometrium following ovulation. given in 3 divided phases of menstrual cycle, eg;
(b) Causes alveolo-lobular development of secretory Ethinyl estradiol + Norgestrel, Norethindrone, or
apparatus in breast. Norgestimate.
(2) Metabolism (B) Single Pills
(a) Stimulates lipoprotein lipase activity, & favors fat (1) Daily Progestin Pills
deposition. Norethindrone, Norgestrel.
(b) Inc. basal insulin level, & insulin response to (2) Postcoital Pills
glucose. Conjugated estrogens, Ethinyl estradiol,
(c) Promote glycogen storage in liver. Diethylstilbestrol, Norgestrel.
(d) Promote ketogenesis.
(3) Central Nervous System Mechanism of Action
(a) Alters temperature - regulation centre in hypotha- (A) Combination Pills
lamus  Inc. body temperature. Suppress mid-cycle surge of LH & FSH  Suppress
(b) Inc. respiratory centre response to CO2. ovulation, & ovarian follicle growth.
M. Shamim’s PHARMACOLOGY 138

(B) Progestin Pills (2) GIT: Nausea.

Thickens the consistency of cervical mucus, which is a (3) Repro: Mastalgia, break - thru bleeding, failure of
barrier to sperm. withdrawal bleeding.
Pharmacological Effects (4) Body fluids: Edema.
(A) Ovary (5) Blood: Changes in serum proteins (see above), inc.
(1) Depress ovarian functions, with minimal follicular ESR.
development. (B) Moderate Adverse Effects
(2) Dec. ovarian size. (1) Repro: Break-thru bleeding, vaginal infections,
(B) Uterus amenorrhea after discontinuance, galactorrhea.
(1) Stromal deciduation towards the end of cycle. (2) Urinary tract: Ureteral dilation, bacteriuria.
(2) Glandular atrophy. (3) Skin: Inc. pigmentation, acne, hirsutism.
(3) Hypertrophy & polyp formation in cervix. (4) Body weight: Weight gain.
(4) Thick, & less copious cervical mucus. (C) Severe Adverse Effects
(C) Breast (1) CNS: Depression.
(1) Slight enlargement. (2) CVS: Venous thromboembolic disease, myocardial
(2) Suppress lactation. infarction, cerebrovascular accident.
(D) Other (3) GIT: Ischemic bowel disease secondary to
(1) CNS thrombosis of celiac & mesenteric vessels.
(a) Estrogen increases excitability in brain. (4) Hepato-biliary tree: Cholestatic jaundice,
(b) Progestins decreases excitability in brain, & cholecystitis, cholangitis, hepatic adenoma.
also has thermogenic effects. Contraindications
(2) CVS (1) Thrombophlebitis.
Inc. heart rate & BP  Inc. cardiac output. (2) Thromboembolic phenomena.
(3) Endocrine (3) Cerebrovascular accidents.
(a) Inhibit pituitary gonadotropin secretion. (4) Vaginal bleeding of unknown cause.
(b) Inc. plasma cortisol level, due to inc. plasma (5) Breast tumor or other estrogen-dependent neoplasms.
conc. of corticosteroid - binding globulin. (6) Adolescents in whom epiphyseal closure has not yet
(c) Inc. aldosterone secretion, due to inc. plasma been completed.
renin activity. Precautions
(d) Inc. plasma thyroxine level, due to inc. (1) Liver disease.
thyroxine - binding globulin. (2) Asthma.
(4) Liver (3) Eczema.
(a) Inc. synthesis of various 2 - globulins, & (4) Migraine.
fibrinogen. (5) Diabetes.
(6) Hypertension.
(b) Dec. haptoglobin synthesis.
(7) Optic neuritis.
(c) Inc. cholic acid, & dec. chenodeoxycholic acid (8) Retrobulbar neuritis.
in bile  Cholelithiasis. (9) Convulsive disorders.
(d) Dec. bile flow. (10) Congestive cardiac failure.
(5) Blood
(a) Inc. factor VII, VIII, IX, & X  Serious
ESTROGEN & PROGESTERONE INHIBITORS &
thromboembolic phenomena.
ANTAGONISTS
(b) Inc. serum iron & total iron - binding capacity.
(c) Folic acid deficiency anemias.
(6) Metabolism Drug Classification
(1) Antiestrogens
(a) Slightly dec. triglycerides & HDL.
(a) Receptor antagonists
(b) Dec. rate of carbohydrate absorption from GIT, (i) Full antagonists, eg Fulvestrant.
& inc. basal insulin level. (ii) Selective estrogen receptor modulator
(7) Skin (SERMs), eg Tamoxifen,Toremifene,
(a) Inc. skin pigmentation (chloasma). Raloxifene, Clomiphene.
(b) Inc. or dec. in sebum secretion & acne. (b) Aromatase inhibitors
Clinical Uses Anastrozole, Letrozole, Exemestane, Fadrozole.
(1) Oral contraception. (c) GnRH agonists
(2) Endometriosis. Nafarelin, Buserelin.
Adverse Effects (d) Danazol
(A) Mild Adverse Effects (2) Antiprogestins
(1) CNS: Headache, worsening of migraine. Mifepristone.
17: Endocrine Drugs 139

TAMOXIFEN Pharmacological Effects

Mechanism of Action (A) Male Sex Organs
(1) Tamoxifen competitively binds to estrogen receptors on Development of secondary sex characteristics;
tumors & other tissue targets, producing a nuclear (1) Penis.
complex that decreases DNA synthesis & inhibits (2) Scrotum.
estrogen effects. (3) Prostate.
(2) It is a nonsteroidal agent with potent antiestrogenic (4) Seminal vesicles.
properties which compete with estrogen for binding (B) Skin
sites in breast & other tissues. (1) Appearance of pubic, axillary & beard hair, &
(3) It causes cells to remain in the G0 & G1 phases of the frontal baldness.
cell cycle. (2) More active sebaceous glands, with thicker &
Clinical Uses oilier skin Acne.
(1) Breast cancer treatment, both early & advanced ER+ (3) Darkening of skin.
(estrogen receptor positive) breast cancer in pre- & post- (4) Inc. skin circulation.
menopausal women. (C) Larynx
(2) Prevention of breast cancer in women at high risk of Enlargment, with thickening of vocal cords Low-
developing the disease. pitched voice.
(3) Infertility in women with anovulatory disorders. (D) Musculo - Seketal System
(4) Gynecomastia. (1) Stimulate skeletal growth, with epiphyseal closure
(5) Bipolar disorder (by blocking protein kinase C, an acceleration.
enzyme that regulates neuron activity in the brain). (2) Inc. musculature.
(6) Control of gene expression (as a research tool). (E) Blood
Adverse Effects Stimulate erythrocyte production.
(1) Blood: Triglyceridemia, increased risk of (F) Protein Metabolism
thromboembolism Inc. protein synthesis & dec. protein breakdown 
(2) Liver: Fatty liver, otherwise known as steatorrheic Dec. nitrogen excretion in urine.
hepatosis or steatosis hepatis. Clinical Uses
(3) Repro: Reduction of libido. (1) Androgen replacement therapy in hypogonadal men.
(4) Cancer: Inc. risk of endometrial & uterine cancer. (2) Gynecologic disorders in women;
Dosage (a) To reduce breast engorgement during postpartum
10-20 mg BD. period (usually with estrogens).
(b) To eliminate endometrial bleeding in postmeno-
MALE GONADAL HORMONES & ANTAGONISTS pausal period (with estrogens).
(c) Breast tumors in premenopausal women.
(3) As protein anabolic agent, eg
ANDROGENS After trauma, surgery, or prolonged immobilizations, &
Classification in pts with debilitating diseases.
(A) Natural (4) Refractory anemias.
Testosterone, Dihydrotestosterone, Androstenedione, (5) Osteoporosis.
Dehydroepiandrosterone. (6) To stimulate growth in prepubertal boys.
(B) Synthetic (7) As anabolic steroid (androgen abuse).
(1) With Equal Androgenic & Anabolic Activity (8) Aging.
Testosterone cypionate, Testosterone enanthate, Adverse Effects
Testosterone propionate, Methyltestosterone. (A) In Women & Prepubertal Children
(2) With More Anabolic Activity (1) Repro: Depression of menses, clitoral enlargement,
Fluoxymesterone, Methandrostenolone, Oxy- endometrial bleeding.
metholone, Ethylestrenol, Oxandrolone, (2) Skin: Hirsutism, acne.
Nandrolone phenpropionate, Nandrolone decanoate, (3) Larynx: Deepening of voice.
Stanozolol, Dromostanolone propionate. (4) Blood: Alter serum lipids  Inc. susceptibility to
Mechanism of Action atherosclerotic disease.
Similar to progestins & corticosteroids. (B) In Infants
(1) In muscle & liver, testosterone itself is the active (1) Profound effects on maturation of CNS centres
compound. governing sexual development.
(2) In reproductive tissues & skin, testosterone is first (2) Masculinization of external genitalia of female
converted to 5 - dihydrotestosterone (DHT). Synthetic infant, if given to mother during pregnancy.
androgens that cannot be converted to DHT have less (C) Other Adverse Effects
effect on reproductive system.
M. Shamim’s PHARMACOLOGY 140

(1) Hepato-biliary tree: Hepatic dysfunction, Nandrolone: Abolon, Durabolin.

cholestatic jaundice, hepatocellular carcinoma. Stanozolol: Anasynth.
(2) Fluid & electrolyte balance: Sodium retention, (F) Antiandrogens
edema. Flutamide: Eulexin, Flutacan, Fluten.
(3) Males: Prostatic hyperplasia. Cyproterone: Androcur, Climen, Diane 35.
Contraindications Finasteride: Genesis, Proscar.
(1) Pregnancy. Bicalutamide: Casodex.
(2) Carcinoma of prostate.
(3) Carcinoma of breast in males.
(4) Infants & young children. Unit VI

ANTIANDROGENS
Self - Assessment (T/F)
Drug Classification
(See answers on page no. 241)
(1) Receptor antagonists, eg Flutamide.
(2) 5--reductase inhibitors, eg Cyproterone, Finasteride, (124) Effects of glucocorticoids include all of the
Bicalutamide, Nilutamide, Spironolactone. following
(3) Synthesis inhibitor, eg Ketoconazole. (A) Inc. RBC count.
(4) Others, eg GnRH agonists, combined oral (B) Suppresses leukocyte migration.
contraceptives. (C) Stabilizes lysosomal membrane.
(D) Inc. gluconeogenesis.
(E) Dec. lipolysis.
GENERIC & TRADE NAMES
(125) Adverse effects of corticosteroids include all of the
following
(A) Estrogens (A) Hypoglycemia.
Estradiol: Femoston, Kliogest, Progyluton, Progynon (B) Osteoporosis.
depot, Progynova. (C) Psychosis.
Estriol: Ovestin. (D) Peptic ulcer.
(B) Progestins (E) Salt retention.
Progesterone: Cyclogest, Progesterone.
Hydroxyprogesterone: Gravibinan, Hydroxy- (126) All of the following agents are useful as oral or
progesterone, Proluton Depot. implantable contraceptives except
Medroxyprogesterone: Ciclotal, Depo-provera, (A) Ethinyl estradiol.
Medrosterona, Roxyprog Depo. (B) Mestranol.
Lynestrenol: Orgametril. (C) Clomiphene.
Norgestrel: Emkit, Mirena, Ovral, Postinor. (D) Norethindrone.
(C) Oral Contraceptives (E) Norgestrel.
Ethinyl estradiol + Norgestrel: Ovral. (127) All of the following are recognized effects of oral
Ethinyl estradiol + Levonorgestrel: Famila 28, contraceptives
Nordette, Nova, Novodol, Ovlodiol, Redate. (A) Inc. risk of myocardial infarction.
Ethinyl estradiol + Norethisterone: Geogynon, (B) Nausea.
Gyneric, Gynorit. (C) Edema.
Ethinyl estradiol + Desogestrel: Marvelon, Meliane. (D) Inc. risk of endometrial cancer.
(D) Antiestrogens (E) Dec. risk of ovarian cancer.
Tamoxifen: Nolvadex, Tamofen, Tamooex, Tamoplex, (128) All of the following are recognized effects of natural
Tamox, Tamoxifen, Lachema, Tamoxin, Temocab, androgens or androgenic steroids
Tumen, Zitazonium. (A) Growth of facial hair.
Raloxifene: Denser, Evista, Raloxi, Relofin, Revera. (B) Inc. muscle bulk.
Clomiphene: Bemot, Clocit, Clofer, Clomid, Clomitab, (C) Inc. milk production in nursing women.
Clomocite, Hope, Lexofene, Umeed. (D) Induction of growth spurt in prepubertal boys.
Anastrozole: Arimidex. (E) Inc. alkaline phosphatase & SGOT level in blood.
Letrozole: Femara.
Danazol: Danocrine, Danzol. (129) In order to achieve rapid control of severe
(E) Androgens ketoacidosis in a hospitalized 13 year old boy, the
Testosterone: Androxon, Sustanon 250, Testosterone, appropriate antidiabetic agent to use is
Testoviron, Vigrol forte*. (A) Crystalline zinc insulin.
Ethylestrenol: Orabolin. (B) Isophane (NPH) insulin.
17: Endocrine Drugs 141

(C) Protamine zinc or ultralente insulin.

(D) Tolbutamide.
(E) Glyburide.
(130) All of the following act by stimulating insulin release
from pancreatic beta - cells
(A) Tolbutamide.
(B) Tolazamide.
(C) Chlorpropamide.
(D) Glipizide.
(E) Phenformin.
(131) Effects of insulin include all of the following
(A) Inc. glucose transport into cells.
(B) Induction of lipoprotein lipase.
(C) Dec. gluconeogenesis.
(D) Stimulation of glycogenolysis.
(E) Inc. protein synthesis.
(132) Possible complications of insulin therapy include
(A) Dilutional hyponatremia.
(B) Hypoglycemia.
(C) Pancreatitis.
(D) Inc. bleeding tendency.
(E) Lipodystrophy at injections site.
(133) Important drugs used in the treatment of
thyrotoxicosis include
(A) Propylthiouracil.
(B) Potassium iodide.
(C) Thyroglobulin.
(D) Radioactive iodine.
(E) Methimazole.
(134) Following are recognized adverse effects of
propylthiouracil
(A) Agranulocytosis.
(B) Lymphadenopathy.
(C) Hyperglycemia.
(D) Hypokalemia.
(E) Cholestatic jaundice.
M. Shamim’s PHARMACOLOGY 142

18 CHEMOTHERAPY OF
BACTERIAL INFECTIONS
eg Chloramphenicol, Tetracyclines, Aminoglycosides,
Unit I Erythromycin, Lincomycin.
(4) Thru inhibition of nucleic acid synthesis
eg Sulfonamides , Trimethoprim, Pyrimethamine,
Introduction Rifampin, Quinolines, Novobiocin.

USE OF ANTIMICROBIALS
(1) Choice of Antimicrobials
CHEMOTHERAPY
(a) It follows automatically from the clinical diagnosis.
(b) It should be based, wherever possible, on
It refers to drug treatment of parasitic infections in which bacteriological identification & sensitivity test.
the parasites ( bacteria, viruses, protozoa, fungi, worms) are (2) Administration of Antimicrobials
destroyed or removed without injuring the host. (a) Oral: It is convenient & less unpleasant but the
food retards absorption & peak plasma conc. are
ANTIMICROBIAL AGENTS therefore lower. So, in general, antimicrobials
These are agents that kills microorganisms or suppresses should be taken, b/w meals or at least one hour
their multiplication or growth. before a meal.
Classification of Antimicrobials (b) Parenteral: It is used for serious infection. IV
(1) Antibacterial agents. route is generally preferred.
(2) Antiviral agents. (3) Combinations of Antimicrobials
(3) Antiprotozoal agents. 2 or more antimicrobials can be used concomitantly:
(4) Antifungal agents. (a) To obtain potentiation.
(5) Antihelmintic agents. (b) To delay development of drug resistance.
Antibiotics (c) To broaden the spectrum of antibacterial activity.
These are soluble compounds that are derived from certain Disadvantages of Combined Therapy
microorganisms & that inhibit the growth of other (a) A false sense of security, discouraging efforts
microorganisms. towards accurate diagnosis.
Bacteriostatic Drugs (b) Broader suppression of normal flora with inc. risk
These are drugs that temporarily inhibits the growth of a of opportunistic infection with resistant organisms.
microorganism. When the drug is removed, organism will (c) Inc. incidence & variety of adverse effects.
resume growth & infection or disease may recur.
Typical bacteriostatics: Tetracyclines, sulfonamides. PROBLEMS WITH ANTIMICROBIALS
Bactericidal Drugs (1) Microbial Resistance to Drugs
These are drugs that attaches to its receptor on micro- Mechanism of Resistance
organisms, & causes their death. (a) Via producing enzymes that destroy active drug, eg
Typical bactericidals: Penicillins, cephalosporins, staphylococcal resistance to penicillin G.
aminoglycosides. (b) Via altering memb. permeability to drug, eg
streptococcal resistance to aminoglycosides.
MECHANISM OF ACTION OF ANTIMICROBIALS (c) Via developing an altered structural target for
(1) Thru inhibition of cell wall synthesis drug, eg resistance to aminoglycosides.
eg Penicillins , Cephalosporins, Cycloserine, (d) Via developing an altered metabolic pathway that
Vancomycin, Bacitracin, Ristocetin. bypasses the reaction inhibited by drug, eg
(2) Thru inhibition of cell memb. function resistance to sulfonamide.
eg Amphotericin B, Nystatin, Imidazoles, Colistin, (e) Via developing an altered enzyme that can still
Polymyxins. perform its metabolic function but is much less
(3) Thru inhibition of protein synthesis affected by the drug, eg resistance to sulfonamide.
Origin of Drug Resistance
18: Chemotherapy of Bacterial Infections 143

(a) Nongenetic Origin

(i) Microorganisms that are metabolically inactive Penicillins
(nonmultiplying) may be resistant to drugs;
however, their offspring are fully susceptible.
(ii) Microorganism may lose the specific target DRUG CLASSIFICATION
structure for a drug for several generations &
thus be resistant.
(b) Genetic Origin (A) According to Nature
(i) Chromosomal resistance: This develops as a (1) Natural Penicillins
result of spontaneous mutation in a locus on Penicillin G or Benzyl penicillin.
bacterial chromosome that controls suscep- (2) Semisynthetic Penicillins
tibility to a given antimicrobial. A change in (a) Long Acting Penicillins
the structural receptors for the drug occur Procaine penicillin, benzathine penicillin G.
which causes resistance. (b) Orally Effective Penicillins
(ii) Extrachromosomal resistance: Plasmids are Phenoxymethyl penicillin (Penicillin V),
extrachromosomal circular DNA molecules. Phenbenicillin, Propicillin.
Plasmid genes for antimicrobial resistance (c) Penicillinase - Resistant (Antistaphylococcal)
control the formation of enzymes capable of Penicillins
destroying antimicrobial drugs. (i) Methicillin.
Cross Resistance (ii) Nafcillin.
Microorganism resistant to a certain drug may also be (iii) Isoxazolyl penicillins: Oxacillin,
resistant to other drugs that share a mechanism of Cloxacillin, Dicloxacillin, Flucloxacillin.
action or attachment, this is called cross-resistance. (d) Broadspectrum Penicillins (Aminopenicillins)
(2) Opportunistic Infection Ampicillin, Amoxycillin, Bacampicillin,
When any antimicrobial drug is used, there is Pivampicillin, Cyclacillin, Hetacillin,
suppression of part of the normal flora of pt, which Amoxycillin plus Clavulanic acid, Ampicillin
varies according to drug. Often, this causes no ill plus Cloxacillin, Amdinocillin/Mecillinam.
effects, but sometimes a drug-resistant organism, freed (e) Anti - Pseudomonal Penicillins
from competition, proliferates to an extent that can be (i) Carboxypenicillins: Carbenicillin, Carbe-
fatal. This is opportunistic infection. nicillin indanyl Na, Ticarcillin.
eg, antibiotic-associated colitis with drugs esp. (ii) Ureidopenicillins: Azlocillin, Mezlocillin,
lincomycin, clindamycin, amoxycillin, ampicillin & Piperacillin.
cephalosporins. (B) On the Basis of Penicillinase Sensitivity
(3) Adverse Effects of Antimicrobials (1) Penicillinase Sensitive
(a) Allergic-type effects occur commonly. (a) Acid Labile
(b) Direct organ toxicity also occur. Penicillin G, Procaine Penicillin, Benzathine
(4) Drug Interactions with Antimicrobials Penicillin G, Carbenicillin, Ticarcillin,
(a) On absorption: Tetracycline chelates iron & Ca, Azlocillin, Mezlocillin, Piperacillin,
& absorption of all from the gut is dec. Amdinocillin/Mecillinam.
(b) On metabolism: Rifampin induces hepatic drug (b) Acid Stable
metabolizing enzymes & may cause an oral Penicillin V, Phenbenicillin, Propicillin,
contraceptive to fail; metronidazole, cefamandole & Ampicillin, Amoxycillin, Bacampicillin,
latamoxef inhibit alcohol metabolism to cause a Pivampicillin, Amoxycillin plus Clavulanic
disulfiram-like reaction. acid, Ampicillin plus Cloxacillin, Carbenicillin
(c) On elimination: Probenecid competes with indanyl.
penicillin for renal tubular anion transport (2) Penicillinase Resistant
mechanism, causing penicillin to be retained. (a) Acid Labile
(d) On organs: Gentamicin & furosemide in high dose Methicillin, Nafcillin.
create inc. risk of ototoxicity. (b) Acid Stable
(5) Treatment Failure Oxacillin, Cloxacillin, Dicloxacillin,
(a) It may be due to drug resistance. Flucloxacillin.
(b) Where the organism is sensitive to the drug used,
failure is due to the way the drug is used or due to
some factor peculiar to the pts.
MECHANISM OF ACTION

Unit II
M. Shamim’s PHARMACOLOGY 144

Penicillins inhibit bacterial cell wall synthesis by binding to (3) Acute urinary tract inf. (caused by gram negative
specific PBP (penicillin binding protein) receptors on bacteria).
bacteria  This results in; (4) Salmonella inf., eg typhoid & paratyphoid fever.
(1) Inhibition of cell wall synthesis by blocking trans- (5) Mixed bacterial inf. of respiratory tract, eg sinusitis,
peptidation of peptidoglycan by interfering with the otitis, bronchitis.
enzymes transpeptidase & endopeptidase. (6) In inf. where penicillin G is the drug of choice but
(2) Activation of autolytic enzymes in cell wall resulting oral therapy is preferred.
in lesions that causes bacterial death. (E) Antipseudomonal Penicillins
Infection caused by gram-negative bacteria esp.
pseudomonas aeruginosa, indole-positive proteus &
RESISTANCE
enterobacter (eg bacteremia, pneumonia, burn inf.,
urinary tract inf.)
(1) Certain bacteria (eg many staphylococcus aureus, some (F) Penicillinase-Resistant Penicillins
H. influenzae, gonococci) produce beta-lactamases Beta-lactamase producing staphylococcal inf., eg
(penicillinases) which opens up beta-lactam ring & bacteremia, cellulitis, osteomyelitis, pneumonia,
hydrolyzes it to penicilloic acid, a harmless form. carbuncles, enteritis, wound inf.
(2) Certain bacteria lack specific receptors.
(3) In some bacteria autolytic enzyme in cell wall is not
ADVERSE EFFECTS
activated, eg streptococci.
(4) Certain organisms lack cell wall, eg mycoplasma.
(1) GIT
Nausea, vomiting, diarrhea, & enteritis occur with oral
CLINICAL USES
therapy (due to luxuriant overgrowth of staphylococci,
pseudomonas, proteus or yeasts).
(A) Penicillin G (2) Liver
(1) Pneumococcal infections, eg pneumonia, meningitis, Hepatitis.
suppurative arthritis, mastoiditis, endocarditis, (3) Bone Marrow
pericarditis, osteomyelitis. Bone marrow depression, agranulocytosis.
(2) Group 'A' streptococcal infections, eg pharyngitis, (4) Blood
scarlet fever, impetigo, puerperal sepsis, rheumatic Impairment of platelet aggregation, hypokalemia &
fever. elevated serum transaminase with carbenicillin.
(3) Meningococcal infections, eg nasopharyngitis, (5) Allergic Reactions
meningococcemia, Waterhouse-Friderichsen synd., (a) Anaphylaxis: Severe hypotension & shock, or
arthritis, endocarditis, meningitis. laryngeal edema, or diffuse pruritus, urticaria &
(4) Non-beta lactamase producing staphylococcal & flushing.
gonococcal infections. (b) Serum sickness reactions: Urticaria, fever, joint
(5) Treponema pallidum inf., eg syphilis. swelling, angioneurotic edema, intense pruritus, &
(6) Bacillus anthracis inf., eg anthrax. respiratory embarrassment.
(7) Clostridial inf., eg tetanus, gas gangrene. (c) Skin lesions: Skin rashes, stevens-johnson synd.,
(8) Actinomycosis. morbilliform eruptions, erythematous eruptions,
(9) Listeria infections. urticaria, dermatitis.
(10) Diphtheria. (d) Oral lesions: Glossitis, stomatitis, furred tongue,
(11) Rat bite fever. chellosis.
(12) Bacteroides inf. (except of B. fragilis). (e) Blood dyscrasias: Eosinophilia, hemolytic anemia,
(B) Penicillin V thrombocytopenia.
(1) Pneumococcal infections. (f) Drug fever
(2) Group 'A' streptococcal inf. (g) Interstitial nephritis
(3) Staphylococcal inf. (h) Vasculitis
(4) Meningococcal inf. (6) IV Administration
(5) Gonococcal inf. Causes phlebitis, thrombophlebitis, local pain,
(C) Procaine Penicillin induration or degeneration of accidentally injected
Gonococcal inf., eg gonorrhea, prostatitis, arthritis, nerve.
salpingitis, urethritis, meningitis.
(D) Broadspectrum Penicillins
CONTRAINDICATIONS
(1) Uncomplicated gonorrhea.
(2) H. influenza inf., eg meningitis, osteomyelitis,
epiglottitis, pneumonia, septic arthritis. (1) History of previous hypersensitivity reaction to
penicillins &/or cephalosporins.
18: Chemotherapy of Bacterial Infections 145

(2) Parenteral inj. into or near an artery or nerve. Effective against a wide range of gram-negative bacteria
including Citrobacter, Enterobacter, E coli, Hemophilus,
Klebsiella, Proteus, & Serratia species.
DOSAGE
Adverse Effects
(1) Skin: Injection site reactions, rash, toxic epidermal
Penicillin Units necrolysis.
Activity of penicillin G was originally defined in units. (2) GIT: Nausea, vomiting, diarrhea.
Crystalline Na penicillin G contains approx 1600 (3) Blood: Drug-induced eosinophilia.
unit/mg (1unit = 0.6 g; 1million units = 0.6g). Most
semisynthetic penicillins are prescribed by weights rather
CARBAPENEMS
units.
(1) Penicillin G  0.6 - 5 million units (0.36-3 g) per day;
IM, QID. Examples
(2) Procaine penicillin  4.8 to 10 million units (2.8-6 g), Ertapenem, Imipenem, Meropenem.
OD, IM. Mechanism of Action
(3) Ampicillin  300-500 mg QID; orally, IM or IV. (1) Imipenem acts as an antimicrobial thru inhibiting cell
(4) Cloxacillin  0.25 - 0.5 g orally every 4 - 6 hrs. wall synthesis of various aerobic & anaerobic Gram
(5) Carbenicillin  300 - 500 mg/kg/d; IV. positive as well as Gram negative bacteria, including P
aeruginosa & the Enterococcus species.
(2) It remains very stable in the presence of beta-lactamase
BETA-LACTAMASE INHIBITORS (both penicillinase & cephalosporinase)
Adverse Effects
Examples (1) CNS: Seizures (imipenem).
Clavulanic acid, Sulbactam, Tazobactam. (2) Skin: Injection site reactions, rash.
Mechanism of Action (3) GIT: Nausea, vomiting, diarrhea.
They are -lactamase inhibitors that extends antibacterial Dosage
spectrum of the companion -lactam antibiotics by Imipenem: 0.25-0.5 gm, TDS or QID, intravenously.
irreversibly binding to & inhibiting the enzyme.
Clinical Uses VANCOMYCIN
(1) Combination of clavulanic acid & amoxycillin is used to
treat infections caused by beta-lactamase producing
Mechanism of Action
strains of H. influenza, B. catarrhalis, S. aureus, E. coli,
Similar to penicillins.
Klebsiella & enterobacter.
(2) Combination of sulbactam & ampicillin or cefoperazone Clinical Uses
is used to treat infections caused by beta-lactamase (1) Serious staphylococcal inf.
producing strains of H. influenza, N gonorrheae, S. (2) Endocarditis not responding to other treatment.
aureus, E. coli, salmonella, shigella, & K pneumoniae. (3) Pseudomembranous colitis (caused by clostridium
(3) Combination of tazobactam & piperacillin is also used difficile).
to treat infections caused by beta-lactamase producing Adverse Effects
strains of H. influenza, N gonorrheae, S. aureus, E. coli, (1) Allergic reactions: Skin rashes, anaphylaxis
salmonella, shigella, & K pneumoniae (2) ENT: Deafness.
Adverse Effects (3) Nephrotoxicity
There are no serious adverse effects associated with (4) IV inj: Thrombophlebitis
-lactamase inhibitors . Dosage
0.5 gm, QID.
MONOBACTAMS
GENERIC & TRADE NAMES
Examples
Aztreonam. (1) Natural Penicillins
Mechanism of Action Penicillin G: Polybiotic*, Benzyl penicillin inj.
Aztreonam is similar in action to penicillin. It inhibits (2) Semi - Synthetic Penicillins
mucopeptide synthesis in the bacterial cell wall. Procaine Penicillin: Polybiotic*.
Clinical Uses Penicillin V: Penicillin V.
Cloxacillin: Auropen, Cloxacillin, Cloxazan, Orbenin,
Venal.
M. Shamim’s PHARMACOLOGY 146

Ampicillin: Amicil, Ampicil, Ampcigen, Ampicap, (2) Parenteral drugs: Cefoperazone, Cefotaxime,
Ampiceena, Ampicillin, Amplipen, Anglocillin, Cefixime, Ceftazidime, Ceftizoxime, Ceftriaxone,
Epocillin, Fedrapen, Omnipen, Penbritin, Pencin. Moxalactam.
Amoxycillin: Adamox, Amocillin, Amoxil, (D) Fourth Generation Cephalosporins
Amoxycillin, Amoxygen, Cipamox, Geomoxin, Maxil, More broad-spectrum & more beta-lactamase resistant
Ocemox, Ospamox, Princimox, Wilmox, Zeemox. than third generation cephalosporins, & also have good
Bacampicillin: Penglobe. CSF penetrability.
Carbenicillin: Pyopen. Parenteral drugs: Cefepime.
Piperacillin: Pipril.
Ticarcillin: Timentin.
MECHANISM OF ACTION
Ampicillin Plus Cloxacillin: Amcopen, Ampiclox,
Anclox, Anglocin, Apoclox, Bioclox, Cloxapen, Dicillin,
Dosaclox, Elkobiotic, Jaclox, Linclox, Maxiclox, Similar to penicillins.
Novoclox, Penciclox, Pencit.
Amoxycillin Plus Flucloxacillin: Aflox, Bactoxyl, RESISTANCE
Deflox, Fclox, Flomoxin, Flucomox, Twin, Varaflox,
Biflocin.
Amoxycillin plus Clavulanic acid: Augmentin, (1) Poor penetration of bacteria by the drugs.
Clamentin, Fortecin, Loment, Potentin. (2) Lack of PBP for a specific drug.
Amoxycillin Plus Sulbactum: Moxsul, Sulbamox, (3) Degradation of drug by beta-lactamases (cephalo-
Sulbarex, Sulzone. sporinases).
Piperacillin Plus Tazobactam: Tanzo, Tazocin. (4) Failure of activation of autolytic enzymes in cell wall.
(3) Other Drugs
Aztreonam: Azactam. CLINICAL USES
Imipenem: Tienam.
Meropenem: Meronem.
Vancomycin: Vanacin. (A) First Generation Cephalosporins
(1) Oral Drugs
(a) Urinary tract infections.
(b) Staphylococcal inf., eg skin inf., osteomyelitis,
Unit III
endocarditis.
(c) Minor polymicrobial inf., eg cellulitis, soft
Cephalosporins tissue abscess.
(2) Parenteral Drugs
(a) Surgical prophylaxis during the insertion of
prosthetic devices.
DRUG CLASSIFICATION (b) K. pneumonia inf.
(c) As an alternative in penicillin allergic pts.
(B) Second Generation Cephalosporins
(A) First Generation Cephalosporins (1) Branhamella catarrhalis inf., eg sinusitis, otitis
Narrow-spectrum, beta-lactamase sensitive antibiotics, media.
having poor CSF penetrability. (2) H. influenzae inf., eg sinusitis, otitis media.
(1) Oral drugs: Cefadroxil, Cephalexin, Cephradine. (3) H. influenza meningitis (only cefuroxime is used).
(2) Parenteral drugs: Cefazolin, Cephalothin, (4) Mixed anaerobic inf., eg peritonitis, diverticulitis.
Cephapirin, Cephaloridine. (5) Sepsis.
(B) Second Generation Cephalosporins (C) Third Generation Cephalosporins
Intermediate-spectrum antibiotics, variably stable to (1) Meningitis, caused by pneumococci, meningococci,
beta-lactamase, having unreliable CSF penetrability. H. influenza & enteric gram negative rods (except
(1) Oral drug: Cefaclor. cefoperazone).
(2) Parenteral drugs: Cefamandole, Cefonicid, (2) Sepsis.
Ceforanide, Cefoxitin, Cefuroxime, Cefmetazole, (D) Fourth Generation Cephalosporins
Cefotetan, Cefprozil, Cefpodoxime, Loracarbef. Infections caused by P aeruginosa, S aureus, multiple
(C) Third Generation Cephalosporins drug resistant S pneumonia & Enterobacteriaceae.
Broad-spectrum, beta-lactamase resistant antibiotics,
having good CSF penetrability.
(1) Oral drug: Cefixime, Cefdinir, Cefditoren pivoxil, ADVERSE EFFECTS
Ceftibuten.
(1) GIT
18: Chemotherapy of Bacterial Infections 147

Anorexia, nausea, vomiting, diarrhea. Cefpodoxime: Cefpomed, Cefprox, Evodoxim,

(2) Blood Dyscrasias Nefdoxim, Neudoxin, Posoxime, Prelox, Trusef.
Hemolytic anemia, neutropenia, leukopenia, (3) Third Generation Cephalosporins
thrombocytopenia, hypoprothrombinemia. Cefoperazone: Cefobid, Cefapezone, Hanpezon,
(3) Renal Prontokef.
Nephritis & tubular necrosis with cephaloridine. Cefotaxime: Baxim, Cefax, Cefotam, Cefotax, Cefoxim,
(4) Allergic Reactions Taxime, Wintax.
Anaphylaxis, drug fever, skin rashes, nephritis, Ceftazidime: Cefazid, Cefcom, Fortazim, Fortum,
granulocytopenia, hemolytic anemia. Zatron.
Note: Cross-allergenicity to cephalosporins in Ceftizoxime: Cefizox, Sydocef, Tezox, Zoxcef.
penicillin allergic pts occurs in about 10% cases. Ceftriaxone: Ceftison, Ceftrex, Cefxone, Maxef,
(5) IM Inj Rocephin, Tazecef, Titan, Vexa.
Local irritation causing severe pain. Cefixime: Bestar, Caricef, Cebosh, Cefacef, Cefamax,
(6) IV Inj Cefspan, Maxpan, Refixime, Refspan, Tycef.
Thrombophlebitis. Cefdinir: Cefnir, Dinor.
(7) Superinfection (4) Fourth Generation Cephalosporins
Resistant gram positive organisms esp. staphylococci Cefepime: Cef-4, Cefstar, Endopime, Maxipime,
& enterococci, as well as fungi often proliferate & Neupime, Perin, Pime, Swisspime.
induce superinfection.

CONTRAINDICATIONS Unit IV

(1) Hypersensitivity to cephalosporins or penicillins.

(2) Combination with aminoglycosides & loop diuretics,
Chloramphenicol,
b/c of their potential of causing nephrotoxicity. Macrolides, & Clindamycin
DOSAGE
CHLORAMPHENICOL
(1) Cefadroxil  0.5-1g BD, orally.
(2) Cephalexin  0.25-0.5 g QID, orally. MECHANISM OF ACTION
(3) Cephradine  Same as cephalexin. It binds reversibly to a receptor site on 50 S ribosomal
(4) Cefazolin  1-2 g TDS, IV. subunit  This interferes with incorporation of amino acids
(5) Cefaclor  10-15 mg/kg/d in 3-4 divided doses, orally. into newly formed peptides by blocking the action of
(6) Cefuroxime  0.75-1.5 g, IV every 8-12 hrs. peptidyl transferase  Microbial protein synthesis is
(7) Cefoperazone  25-100 mg/kg/d, IV every 8-12 hrs. inhibited.
(8) Ceftriaxone  15-30 mg/kg/d, IV every 12-24 hrs.
RESISTANCE
GENERIC & TRADE NAMES It results from the production of 'chloramphenicol acetyl-
transferase' that inactivates the drug.
(1) First Generation Cephalosporins CLINICAL USES
Cefadroxil: Camex, Cedrox, Duricef, Evacef, Neucef.
(A) Systemic Uses
Cephalexin: Anglolexin, Cefalex, Ceporex, Kavelex,
(1) Salmonella inf, eg typhoid & paratyphoid fever.
Keflex, Keforal, Oceflox, Oracef, Ospexin, Safexin,
(2) H. influenzae inf, eg meningitis, laryngotracheitis
Solvocef, Zafalexin.
or pneumonia.
Cephradine: Amspor, Biocef, Cefatil, Cefrinex,
(3) Meningococcal inf.
Ceprol, Dynacef, Kaysef, Kefril, Monocef, Polycef,
(4) Anaerobic or mixed inf. in CNS, eg brain abscess,
Sefrin, Valodin, Vefradin, Velosef.
cerebritis, meningitis.
Cephazolin: Cefazolin.
(5) Rickettsial inf.
(2) Second Generation Cephalosporins
(6) Brucellosis.
Cefaclor: Ceclor, Cedrate, Ceclor, Cetaclor, Proclor.
(7) Melioidosis.
Cefamandole: Kafadol.
(8) Sepsis.
Ceforanide: Precef, Rancef.
Cefuroxime: Apotex, Cefroxil, Cefuzin, Maxima, (B) Topical Uses
(1) Superficial conjunctival &/or corneal inf.
Roxime, Zecef, Zinacef.
Cefprozil: Cefzil, Zilpro.
M. Shamim’s PHARMACOLOGY 148

(2) Superficial gram-positive or gram-negative inf of (5) As penicillin alternatives in penicillin allergic pts with
external auditory canal streptococcal or pneumococcal inf.
(6) Legionnaires' disease.
ADVERSE EFFECTS (7) Acne.
(1) CNS Adverse Effects
Headache, mild depression, mental confusion, delirium. (1) GIT: Anorexia, nausea, vomiting, diarrhea.
(2) GIT (2) Allergic reactions: Cholestatic hepatitis, fever,
Nausea, vomiting, diarrhea. eosinophilia, rashes.
(3) Blood Dyscrasias (3) IV inj: Thrombophlebitis.
Bone marrow depression leading to aplastic anemia, (4) Superinfection: Candidiasis
hypoplastic anemia, reticulocytopenia, Dosage
thrombocytopenia, granulocytopenia. 0.25-0.5 gm, QID.
(4) Allergic Reactions Drug Interactions
eg Drug fever, macular rashes, vesicular rashes, It inc. the effects & toxicity of oral anticoagulants,
angioedema, urticaria, anaphylaxis.
carbamazepine, digoxin & theophylline compounds, by
(5) Gray Baby Syndrome
interfering with hepatic metabolism.
It occurs in newborn infants due to chloramphenicol
accumulation b/c of the absence glucuronic acid
conjugation mechanism, & is characterized by; CLINDAMYCIN (& LINCOMYCIN )
Vomiting, flaccidity, hypothermia, gray color, shock,
cyanosis, irregular respiration, & cardiovascular Mechanism of Action
collapse.
Similar to chloramphenicol.
(6) Superinfection
Oropharyngeal candidiasis, vaginal candidiasis & acute Note: Clindamycin is a chlorine - substituted derivative of
staphylococcal enterocolitis can occur. lincomycin.
Clinical Uses
CONTRAINDICATIONS (1) Bacteroides inf, esp. B. fragilis which causes anaerobic
History of previous hypersensitivity to &/or toxicity from abdominal inf.
chloramphenicol. (2) Acne.
(3) Anaerobic intrauterine inf.
DRUG INTERACTIONS (4) Female genital tract inf, eg septic abortion, pelvic
(1) It inhibits metabolism of dicumarol, phenytoin, abscess.
tolbutamide, chlorpropamide & warfarin. Adverse Effects
(2) Antagonize bactericidal action of penicillins & (1) GIT: Pseudomembranous colitis resulting in diarrhea,
aminoglycosides. abdominal pain, fever &, mucus & blood in stools.
(3) Concomitant use of paracetamol inc. its serum level. (2) Liver: Impaired liver function with or without jaundice.
(3) Blood: Neutropenia.
DOSAGE Dosage
(1) Adults: 50 mg/kg/d in divided doses 6 hrly. 0.15-0.3 gm, QID.
(2) Children: Under 2 weeks, half adult dose; over 2 weeks,
same as adult.
GENERIC & TRADE NAMES

MACROLIDES
(1) Chloramphenicol
Biostat*, Chloramphenicol, Chlorofen, Chloromycetin,
Examples Chloromycetin -H*, Dexachlor*, Decachlor, Methachlor,
Erythromycin, Clarithromycin, Azithromycin, Neo-Phenicol, Vasochlor, Vitachlor.
Oleandomycin, Spiramycin, Telithromycin. (2) Macrolides
Mechanism of Action Erythromycin: Ecin, Emycin, Erithrine, Erythromycin,
Similar to chloramphenicol. Erybron*, Eryderm, Erythrocin, Trocin.
Clinical Uses Clarithromycin: Amiclar, Bv-clar, Clarabac, Clarithro,
(1) Corynebacterial inf, eg diphtheria, sepsis, erythrasma. Klaricid, Megaklar, Neo-klar, Tarithrocid.
(2) Chlamydial inf of respiratory tract, eye, genital tract, & Azithromycin: Azibect, Azicin, Azimycin, Azithrocin,
neonates. Azoxin, Azrocin, Rezoxin, Zithrosan, Zomysin.
(3) Mycoplasmal pneumonia. Spiramycin: Rovamycine.
(4) Campylobacter jejuni inf. Telithromycin: Engtel.
(3) Clinda- & Lincomycin
18: Chemotherapy of Bacterial Infections 149

Clindamycin: Clindacin, Dalacin C, Dalacin T. (7) Mixed bacterial inf of respiratory tract esp. sinusitis
Lincomycin: Amlin, Limera, Lincin, Linco, Lincocin, & bronchitis.
Lincomycin, Olinc. (8) Skin inf esp. inflammatory acne.
(9) Leptospirosis.
(10) Urinary tract inf.
Unit V (11) Syndrome of inappropriate ADH secretion
(Demeclocycline).

Tetracyclines ADVERSE EFFECTS

(1) ENT
DRUG CLASSIFICATION Vestibular disturbances, eg dizziness, vertigo, nausea,
vomiting, occur with minocycline.
(A) Short Acting Tetracyclines (2) Teeth & Bones
Tetracyclines given to children, b/c of their chelating
Half lives  6-9 hrs, eg;
properties, bound to Ca deposits on growing bones
Tetracycline, Oxytetracycline, Chlortetracycline.
& teeth with the formation of a tetracycline-Ca
(B) Intermediate Acting Tetracyclines
orthophosphate complex. This causes;
Half lives  14 - 16 hrs, eg;
(a) Yellow & then brown discoloration of teeth.
Demeclocycline, Methacycline.
(b) Enamel dysplasia.
(C) Long Acting Tetracyclines
(c) Inc. sensitivity to carries.
Half lives  17 - 20 hrs, eg; (d) Growth inhibition of bones.
Doxycycline, Minocycline, Tigecycline. (3) GIT
Epigastric pain, nausea, vomiting, diarrhea.
MECHANISM OF ACTION (4) Liver
Impair hepatic function, hepatic necrosis.
(5) Renal Toxicity
Tetracyclines bind reversibly to receptors on 30 S
(6) Allergic Reactions
ribosomal subunit, in a position that blocks binding of
eg, skin rashes, drug fever.
aminoacyl-tRNA to acceptor site on mRNA ribosome
(7) Skin
complex  This prevents addition of new amino acids to
Photosensitization esp. with demeclocycline.
growing peptide chain  This inhibits bacterial protein (8) Local Tissue Toxicity
synthesis. (a) IV inj. causes thrombophlebitis.
(b) IM inj. causes painful local irritation.
RESISTANCE (9) Fanconi Syndrome
It results from ingestion of outdated & degraded
tetracyclines, & characterized by renal tubular
(1) Organisms lack an active transport mechanism across
dysfunction which can lead to renal failure
cell memb., & thus do not concentrate tetracyclines in
(10)Superinfection
their cells.
Vaginal or oral candidiasis, staphylococcal enterocolitis,
(2) Organisms may lack passive permeability to
pseudomembranous colitis & anal pruritus.
tetracyclines.

CONTRAINDICATIONS
CLINICAL USES

(1) Hypersensitivity to tetracyclines.

(1) Rickettsial inf, eg Rocky Mountain spotted fever,
(2) Pregnancy.
Q fever, Brill's disease, Murine & scrub typhus,
(3) Children below 12 years of age.
Rickettsial pox.
(4) Renal insufficiency (except doxycycline).
(2) Chlamydial inf, eg lymphogranuloma venereum,
inclusion conjunctivitis, trachoma, psittacosis.
(3) Mycoplasmal inf. DOSAGE
(4) Intestinal amebiasis.
(5) Bacillary inf, eg brucellosis, tularemia, cholera, some
(1) Short acting tetracyclines  250 mg QID, orally.
shigella & salmonella inf.
(2) Methacycline  300 mg BD, orally.
(6) Venereal inf, eg gonorrhea, syphilis, chancroid,
granuloma inguinale, chlamydial urethritis or cervicitis. (3) Doxycycline  100-200 mg OD, orally or IV.
(4) Minocycline  100 mg BD, orally.
M. Shamim’s PHARMACOLOGY 150

GENERIC & TRADE NAMES (A) Streptomycin

(1) Pulmonary tuberculosis.
(2) Miliary dissemination.
(1) Short Acting Tetracyclines (3) Bacterial meningitis.
Tetracycline: Achromycin, Chemicycline, Dosamycin, (4) Plague.
Furosal*, Pexocycline, Tetrawil, Vagmycin*. (5) Tularemia.
Oxytetracycline: Egocin, Epoxylin, Marvicycline, (6) Subacute bacterial endocarditis (caused by
Oxyn, Oxywil. enterococci or streptococcus viridians).
(2) Long Acting Tetracyclines (7) Brucellosis.
Doxycycline: Apdoxy, Capsidon, Dekomycin, (8) Peritonitis.
Doxymycin, Etidoxine, Megadox, Novodox, (9) Urinary tract inf.
Vibramycin, Vibradoxine, Wellcodox. (10) Respiratory tract inf.
Minocycline: Minocin, Minowil. (B) Neomycin, Paromomycin, Framycetin, &
Kanamycin
(1) Topical
Unit VI (a) Injected into abscess cavity, or in a infected
body cavity eg joints, pleural cavity or, other
tissue spaces.
Aminoglycosides (AG ) (b) Applied on infected skin lesions.
(c) Applied in the nares for suppression of
staphylococci.
(2) Oral
DRUG CLASSIFICATION (a) For preoperative reduction of gut flora before
surgery.
(A) AG Causing Cochlear Nerve Damage (b) In hepatic coma, to dec. the number of bacteria
Amikacin, Netilmycin, Kanamycin in intestine esp. coliforms.
(B) AG Causing Vestibular Nerve Damage (c) Intestinal amebiasis (paromomycin).
Streptomycin, Tobramycin, Gentamycin (C) Gentamycin, Tobramycin, Netilmycin, &
(C) AG Not For Parenteral Use Amikacin
Neomycin, Paromomycin, Framycetin. (1) Parenteral
(D) Others (a) Sepsis & pneumonia, caused by gram-negative
Spectinomycin. bacteria esp. pseudomonas, enterobacter,
serratia, proteus, acinetobacter, & klebsiella.
(b) Endocarditis or sepsis, by enterococci (with
MECHANISM OF ACTION
Penicillin G).
(2) Topical
AGs bind specifically to bacterial 30 S ribosomal subunit  (a) Infected burns, wounds or skin lesions.
This inhibits ribosomal protein synthesis, via; (b) Prophylaxis of intravenous catheter inf.
(1) Interfering with the initiation complex of peptide (3) Intrathecal
formation. Meningitis, by gram negative bacteria.
(2) Inducing misreading of code on mRNA template which (D) Spectinomycin
causes incorporation of incorrect amino acids into Gonorrhea (in pts with allergy or resistance to
peptides. penicillin).
(3) Causing a breakup of polysomes into nonfunctional
monosomes. ADVERSE EFFECTS

RESISTANCE (1) Eye

Scotomas, due to optic nerve dysfunction (with
(1) Alteration in cell surface occur which interfere with the streptomycin).
permeation of aminoglycosides into cell. (2) ENT
(2) Receptors on 30S ribosomal subunit may be altered. (a) Vestibular nerve damage manifested by dizziness,
(3) Microorganisms acquire the ability to produce enzyme vertigo, ataxia, & loss of balance.
that inactivate the drug by adenylation, acetylation or (b) Cochlear nerve damage manifested by hearing loss,
phosphorylation. & tinnitus.
(3) GIT
Anorexia, nausea, vomiting, inc. salivation, stomatitis.
CLINICAL USES
(4) Neuromuscular Junction
18: Chemotherapy of Bacterial Infections 151

Neuromuscular blockade causing progressive flaccid (1) Short Acting Sulfonamides

paralysis & potentially fatal respiratory arrest; occur Sulfisoxazole, Sulfadiazine, Sulfamethoxazole,
esp. when the drug (esp. kanamycin) is given in high Sulfacytine, Sulfadimidine, Sulfamethizole.
dose, or in combination with cruriform drugs. (2) Long Acting Sulfonamides
(5) Urinary Tract Sulfamethoxypyridazine, Sulfametopyrazine,
Acute renal insufficiency, tubular necrosis, proteinuria, Sulfaphenazole, Sulfadoxine.
azotemia, oliguria. (B) Oral Nonabsorbable Agents
Note: Gentamycin is most nephrotoxic. Phthalyl sulfathiazole (Sulfathalidine), Sulfasalazine.
(6) Blood (C) Topical Agents
Eosinophilia, hemolytic anemia, bleeding due to Sulfacetamide, Maphenide, Sulfapyridine, Silver
antagonism of factor V. Sulfadiazine.
(7) Bone Marrow
Bone marrow depression.
MECHANISM OF ACTION
(8) Allergic Reactions
eg skin rashes, pruritus, urticaria, fever.
Sulfonamides inhibit DNA synthesis by preventing
incorporation of para-aminobenzoic acid into folic acid (by
CONTRAINDICATIONS dihydropteroate synthetase thru competitive inhibition)
which, in the reduced form, is necessary in purine biosyn-
(1) Known hypersensitivity. thesis for the transfer of one carbon units.
(2) Myasthenia gravis.
RESISTANCE
DOSAGE
(1) Some microorganism produce a large excess of PABA.
(1) Amikacin  15 mg/kg/d, IM or IV. (2) Others may be relatively impermeable to sulfonamides.
(2) Kanamycin  1gm/d in 2 - 4 divided doses for max. (3) A structural change may occur in folic acid synthesizing
of 6 days , IM. enzyme with a lowered affinity for sulfonamides
(3) Tobramycin  3-5 mg/kg/d in 3-4 divided doses, IM
or IV. CLINICAL USES
(4) Gentamycin  Upto 5 mg/kg/d in 3 divided doses for
7-10 days; orally, IM or IV.
(A) Oral
(1) Acute uncomplicated urinary tract inf.
GENERIC & TRADE NAMES (2) Chlamydia trachomatis inf. of eye, genital tract, &
respiratory tract.
Amikacin: Amika, Amikin, Amkay, Grasil. (3) Bacterial inf., eg nocardiosis, sinusitis, bronchitis,
Kanamycin: Kanabid, Kanacyn, Kanacillin*, Kumycin. pneumonitis, otitis media, bacillary dysentery.
Tobramycin: Abbocin, Bromycin, Nebcin, Nebra, Tobracin , (4) Dermatitis herpetiformis.
Tobradex*, Tobrex. (5) Toxoplasmosis.
Gentamycin: Gentacil, Gentalek, Genicol, Genticyn-B*, (B) Topical
Genticyn, Genticyn HC*. (1) For temporary inhibition of intestinal aerobic flora
Streptomycin: Polybiotic*, Streptomycin. in preparing the bowel for surgery (Phthalylsulfa-
Neomycin: Flogocid, Newcin, Probeta N*, Xyloaid. thiazole).
Framycetin: Fradex*, Framycin, Sofra-tulle. (2) Applied to burn skin esp burn sepsis & wounds
Spectinomycin: Trobicin. (Mafenide, Silver sulfadiazine).
(3) Inclusion conjunctivitis ( Sulfacetamide).
(4) Ulcerative colitis, enteritis & other inflammatory
Unit VII bowel disease (Sulfasalazine).
(C) Intravenous
Reserved for comatose pts esp. with meningitis or pts
Sulfonamides who are unable to take medication by mouth.

ADVERSE EFFECTS
DRUG CLASSIFICATION
(1) GIT
Nausea, vomiting, diarrhea, stomatitis.
(A) Oral Absorbable Agents
M. Shamim’s PHARMACOLOGY 152

(2) Liver TRIMETHOPRIM

Hepatitis, focal or diffuse hepatic necrosis.
(3) Urinary Tract
Acetylated metabolite of sulfonamides may ppt. in MECHANISM OF ACTION
urine esp. at neutral or acid pH causing crystalluria, Trimethoprim inhibits the enzyme 'dihydrofolic acid
hematuria, or even obstruction; nephrosis & allergic reductase', that converts dihydrofolic acid into tetrahydro-
nephritis. folic acid  Synthesis of thymidine is blocked, b/c
(4) Blood tetrahydrofolic acid is required for its synthesis  This
Hemolytic anemia esp in G-6-P-dehydrogenase causes inhibition of purine synthesis  Leading to inhibition
deficiency, aplastic anemia, granulocytopenia, of DNA synthesis.
thrombocytopenia, sulfhemoglobinemia.
Note: Inc. risk of kernicterus in newborn (if the drug is CLINICAL USES
taken near term). (1) Urinary tract inf.
(5) Allergic Reactions (2) Prostatic & vaginal inf.
Drug fever, skin rashes, urticaria, exfoliative dermatitis,
polyarteritis nodosa, stevens-johnson synd, eosinophilia, ADVERSE EFFECTS
photosensitivity.
(1) CNS
Headache, nervousness.
CONTRAINDICATIONS (2) GIT
Nausea, vomiting, abd cramps, glossitis, stomatitis.
(1) Hypersensitivity. (3) Blood
(2) Pregnancy at term. Leukopenia, agranulocytosis, thrombocytopenia,
(3) Lactation. methemoglobinemia, megaloblastic anemia.
(4) Impaired renal function. (4) Allergic Reactions
(5) Impaired hepatic function. Drug fever, skin rashes, vasculitis.

CONTRAINDICATIONS
DOSAGE (1) Hypersensitivity.
(2) Megaloblastic anemia.
(1) Sulfadiazine  Initially 4 g, followed by 1g/4 hrs.
(2) Sulfisoxazole  Initially 4g, followed by 1g/6 hrs. TRIMETHOPRIM PLUS SULFAMETHOXAZOLE
(3) Sulfamethoxypyridazine  Initially 1 g, followed by ( COTRIMOXAZOLE )
0.5 g/day
(4) Sulfasalazine  Initially 4g, followed by 1g/6 hrs.
MECHANISM OF ACTION
(5) Sulfacetamide  Eye drops (10-30 %) & ointment (6%).
Co-trimoxazole has inhibitory effect on the synthesis of
tetrahydrofolic acid at two successive stages;
GENERIC & TRADE NAMES (1) Sulfamethoxazole inhibits incorporation of PABA into
folic acid, by interfering with dihydropteroate
(1)Sulfisoxazole: Pediazole*. synthetase.
(2) Sulfadiazine: Sulphadiazine. (2) Trimethoprim inhibits the next step, ie enzymatic
(3) Sulfamethoxazole: See Unit VIII. reduction of dihydrofolic acid to tetrahydrofolic acid
(4) Sulfadoxine: Fansidar*, Favax*, Maladar*, Malarest*, by dihydrofolic acid reductase.
Malarina*, Malidar*.
(5) Sulfasalazine: Salazodine, Salazine, Sulfasal. CLINICAL USES
(6) Sulfacetamide: Blephamide*, Blephapred, Mydosone*, (1) Respiratory tract inf esp acute exacerbations of chronic
Panocid, Sulphapred, Sulphamed*. bronchitis caused by H. influenzae, & S. pneumoniae.
(7) Silver Sulfadiazine: Dermazin, Flamazin. (2) Complicated urinary tract inf.
(3) Genital tract inf esp of prostate & vagina.
(4) Salmonella inf, eg typhoid & paratyphoid fever.
Unit VIII (5) Symptomatic shigella enteritis.
(6) Serratia sepsis.
(7) Pneumocystis carinii pneumonia (a protozoal inf).
Trimethoprim, & (8) Pharyngeal gonorrhea.
(9) Skin & soft tissue inf, eg boils, carbuncles, abscess,
Co - Trimoxazole burns, wounds.
18: Chemotherapy of Bacterial Infections 153

ADVERSE EFFECTS (1) Inhibition of DNA gyrase prevents the relaxation of

As for sulfonamides & trimethoprim. supercoiled DNA that is required for normal
transcription & replication.
CONTRAINDICATIONS (2) Inhibition of topoisomerase IV interferes with
(1) Neonates separation of replicated chromosomal DNA into the
(2) Pregnancy respective daughter cells during cell division.
(3) Severe renal insufficiency
(4) Severe hepatic insufficiency RESISTANCE
(5) Blood dyscrasias.
(6) Hypersensitivity.
It is due to;
(1) One or more point mutations in the quinolone binding
DOSAGE
region of the target enzyme, or
(1) Oral TMP/SMZ  160 mg/800 mg to 320 mg/1600 mg, (2) Change in the permeability of organism.
twice daily.
(2) IM inj  160 mg/800 mg, thrice daily.
CLINICAL USES

GENERIC & TRADE NAMES

(1) Urinary tract infections (even when caused by multi-
drug-resistant bacteria, eg pseudomonas).
Co- Trimoxazole: Bacitran, Bactrim, Co-trimax, Colitran, (2) Infectious diarrhea (eg, due to shigella, salmonella,
Comax, Cotrim, Mactran, Mazatrim, Mexazol, Nicotrim, toxigenic E coli, campylobacter).
Semozol, Septran, Septrozole, Trimoxin. (3) Infections of soft tissues, bones, & joints.
Trimethoprim: Syraprim. (4) Abdominal & respiratory tract infections.
Trimethoprim + Sulfadimidine: Penetrin. (5) Prophylaxis & treatment of anthrax.
Trimethoprim + Sulfadiazine: Antrima. (6) Sexually transmitted diseases (eg, gonococcal &,
chlamydial infections).
(7) Mycobacterial infections.
Unit IX (8) For eradication of meningococci from carriers.
(9) Prophylaxis of infection in neutropenic pts.

Fluoroquinolones ADVERSE EFFECTS

(1) CNS: Headache, dizziness, insomnia.

DRUG CLASSIFICATION (2) GIT: Nausea, vomiting, diarrhea.
(3) Hepatic: Abnormal liver function tests.
(1) First Generation Fluoroquinolones (4) Skeletal: Damage to growing cartilage.
These are least active against both gram-negative & (5) Skin: Rashes.
gram-positive organisms. (6) Concomitant administration of theophylline lead to
Examples: Norfloxacin. elevated levels of theophylline with the risk of toxic
(2) Second Generation Fluoroquinolones effects, especially seizures.
They have excellent gram-negative activity & moderate (7) Superinfection with streptococci & candida.
to good activity against gram-positive organisms.
Examples: Ciprofloxacin, Enoxacin, Levofloxacin, GENERIC & TRADE NAMES
Lomefloxacin, Ofloxacin, Pefloxacin.
(3) Third Generation Fluoroquinolones
They have improved activity against gram-positive Norfloxacin: Alenbit, Chibroxine, Nolicin, Norfax, Norocin,
organisms esp. S pneumoniae & staphylococci. Noroxin, Uracin, Urisept, Uritec, Utinor.
Examples: Gatifloxacin, Gemifloxacin, Moxifloxacin. Enoxacin: Enoxabid, Enoxa.
Ciprofloxacin: Algocin, Ciplox, Cipacin, Ciprin, Ciprocide,
Ciprox, Ciproxin, Nafcin, Novidat, Proflox, Quinoflox.
MECHANISM OF ACTION Levofloxacin: Cravit, Lavilox, Leflox, Qumic, Xeflox.
Lomefloxacin: Floxlome, Lomedin, Loxoflox.
Fluoroquinolones block bacterial DNA synthesis by Ofloxacin: Albact, Bactacin, Eracin, Fugacin, Korvid,
inhibiting bacterial topoisomerase II (DNA gyrase) & Oflobid, Oflocin, Oflox, Ofloxin, Tariflox, Tarivid.
topoisomerase IV; Pefloxacin: Abaktal, Euphen, Peflacine, Peflox.
Gatifloxacin: Gati, Gatox, Glax, Quintec.
M. Shamim’s PHARMACOLOGY 154

Gemifloxacin: Grat. (3) Urinary tract: Urinary retention.

Moxifloxacin: Avelox, Mofilox, Moxiflox. (4) Blood: Hemolysis in G - 6 - P dehydrogenase
deficiency.
(5) Allergic reactions: Fever, skin rashes, hepatitis.
Unit X Contraindications
Pts. with previous isoniazid associated hepatic injury, or
other severe adverse effects with isoniazid.
Anti-Tuberculous Drugs Dosage
5 mg/kg/d upto to a max of 300 mg, orally.

RIFAMPIN
TUBERCULOSIS Mechanism of Action
It inhibits RNA synthesis in mycobacteria & chlamydiae,
It is a communicable chronic granulomatous disease caused by binding to DNA-dependent RNA polymerase.
by "Mycobacterium tuberculosis". It usually involves the Clinical Uses
lungs, but may affect any organ or tissue in the body. (1) Tuberculosis.
Typically the centres of granulomas undergo caseous (2) Atypical mycobacterial inf.
necrosis to create soft tubercles. (3) Leprosy.
Clinical Features (4) Prophylaxis of H. influenzae type b disease in children.
(1) Malaise, anorexia, & weight loss. Adverse Effects
(2) Low grade remittent fever (appearing late each after- (1) Allergic reactions: Fever, skin rashes.
noon & then subsiding ) with night sweating. (2) Blood: Thrombocytopenia, hemolytic anemia.
(3) Cough with sputum (at first-mucoid & later purulent). (3) Kidney: Nephritis, light chain proteinuria.
(4) Hemoptysis. (4) Immunity: Impaired antibody response.
(5) Pleuritic pain. (5) Hepatotoxicity.
(6) GIT disturbances.
(7) Harmless orange color to urine, sweat, tears, &
DRUGS USED IN TUBERCULOSIS
saliva.
Contraindications
DRUG CLASSIFICATION Hypersensitivity.
(A) First Line Drugs Dosage
Isoniazid, Rifampin, Ethambutol, Streptomycin, 600 mg/d, with isoniazid, ethambutol or other
Pyrazinamide. antituberculous drugs.
(B) Second Line Drugs
Amikacin, Capreomycin, Ciprofloxacin, Clofazimine, ETHAMBUTOL
Cycloserine, Ethionamide, Levofloxacin, Para- Mechanism of Action
aminosalicylic acid, Rifabutin, Rifapentin, Viomycin. It probably inhibits RNA synthesis.
Clinical Uses
ISONIAZID Tuberculosis, in combination with other antituberculous
Mechanism of Action drugs.
It interferes with cellular metabolism esp. synthesis of Adverse Effects
mycolic acid (an important constituent of mycobacterial cell (1) Eye: Optic neuritis, reduction in visual acquity, retinal
wall), thus interfering with the formation of mycobacterial damage.
cell wall. (2) Allergic reactions: Fever, skin rashes.
Clinical Uses Dosage
(1) Treatment of tuberculosis. 15 - 25 mg/kg/day.
(2) Prophylaxis of tuberculosis.
Note: Nine months of chemotherapy with isoniazid plus STREPTOMYCIN
rifampin is the treatment of choice for uncomplicated See Unit VI 'Aminoglycosides'.
pulmonary tuberculosis.
Adverse Effects PYRAZINAMIDE
(1) CNS: Peripheral neuritis, insomnia, restlessness, Mechanism of Action
muscle twitching, convulsions, psychosis. Unknown, but at pH 5.0 it strongly inhibits growth of
Note: Concomitant administration of pyridoxine tubercle bacilli.
prevent these effects.. Adverse Effects
(2) Liver: Abnormal liver function tests, jaundice, (1) Liver: Hepatitis.
multilobular necrosis, hepatitis. (2) Joints: Arthralgia associated with hyperuricemia.
18: Chemotherapy of Bacterial Infections 155

PARA-AMINOSALICYLIC ACID (PAS) (1) Lepromatous leprosy.

Mechanism of Action (2) Tuberculoid leprosy.
PAS compete for the active center of an enzyme involved
in converting PABA to dihydropteroic acid, thereby DRUGS USED IN LEPROSY
inhibiting purine & ultimately DNA synthesis.
Clinical Uses
Tuberculosis, in combination with INH or streptomycin DRUG CLASSIFICATION
(in the past). (1) Sulfones
Adverse Effects Dapsone, Acedapsone, Glucosulfone Na, Sulfoxone Na,
(1) GIT: Anorexia, nausea, diarrhea, epigastric pain, Sulfetrone Na, Thiazolesulfone.
peptic ulcer, GIT bleeding. (2) Antituberculous Drugs
(2) Nephrotoxicity. Rifampin, Ethionamide.
(3) Hepatotoxicity. (3) Miscellaneous Drugs
(4) Endo: Goitre with or without myxedema. Clofazimine, Thiambutosine.
(5) Allergic reactions: Fever, skin rashes, granulocyto-
penia, joint pains, neurologic symptoms. SULFONES
(6) Acid - Base Balance: Metabolic acidosis. Mechanism of Action
Similar to sulfonamides.
GENERIC & TRADE NAMES Clinical Uses
(1) Leprosy.
(2) Pneumocystis pneumonia in AIDS (Dapsone).
(1) Isoniazid (INH): INH, Isoniazid, Isozide, Niazid, Adverse Effects
Nydrazide, Polyzide, Sonorex. (1) GIT disturbances.
(2) Rifampin: Abrifam, Lederrif, Rifac, Rifacin, Rifadin, (2) Blood: Hemolysis esp. in G - 6 - P dehydrogenase
Rifagen, Rifamate, Rifamed, Rifampicin. deficiency, methemoglobinemia.
(3) Ethambutol: Abbutol, Ethambutol, Etibi, Myambutol. (3) Allergic reactions: Fever, skin rashes, pruritus,
(4) Pyrazinamide: Medizinamide, Piramide, Pyrazid, erythema nodosum leprosum.
Pyrazinamide, PZA-Ciba, Zinamid. Dosage
(5) Isoniazid Plus Rifampin: Rifazol junior, Rifamate INH, Begin with 25-50 mg orally per week, inc. by 25 mg weekly
Riso, Rifazid, Rifinah, Rifazid forte. until a full dose of 400 - 600 mg per week is reached.
(6) Ethambutol Plus Isoniazid: Butarex, Myambutol INH.
(7) Isoniazid, Rifampin Plus Ethambutol: Cyrex, Myrin, RIFAMPIN
Rifatol, Risen, Tuberin. See Unit X, 'Antituberculous Drugs'.
(8) Isoniazid, Rifampin Plus Pyrazinamide: Pyratar,
Rifados, Rifatar. CLOFAZIMINE
(9) Isoniazid, Rifampin, Ethambutol Plus Pyrazinamide:
Mechanism of Action
Cyrex P, Myrin P, Rifa 4, Risen P, Tuberlin P.
Unknown, but it may involve DNA binding.
(10) Cycloserine: Tuberserine.
Clinical Uses
(11) Amikacin & Streptomycin: See Unit VI.
(1) Sulfone-resistant leprosy, or intolerance to sulfone.
(12) P-aminosalicylic acid: PAS tab.
(2) Mycobacterium avium - intracellulare inf in pts with
(13) Fluoroquinolones: See Unit IX.
AIDS.
Adverse Effects
(1) Gastrointestinal disturbances.
Unit XI
(2) Skin discoloration ranging from red - brown to nearly
black.
Dosage
Anti-Leprotic Drugs 100 - 300 mg/day, orally.

GENERIC & TRADE NAMES

LEPROSY
Antituberculous drugs: See Unit X.
It is a chronic communicable disease, caused by 'Myco-
bacterium leprae', which produces various granulomatous
lesions in the skin, mucus memb. & peripheral nervous
system.
Principal Types
M. Shamim’s PHARMACOLOGY 156

Clinical Uses
Unit XII
Urinary tract inf.
Adverse Effects
Drug Treatment of UTI (1) CNS: Neuropathies.
(2) GIT: Anorexia, nausea, vomiting.
(3) Blood: Hemolytic anemia is G - 6 - P dehydrogenase
deficiency.
URINARY TRACT INFECTIONS ( UTI ) (4) Allergic reactions: Skin rashes, pulmonary infiltration.
Contraindications
(1) Impaired renal function.
Urinary tract inf is a disorder resulting from invasion & (2) Pregnant women at term.
multiplication of microorganism in some parts of urinary Dosage
tract. 100 mg, QID, orally, with meals or milk.
Types Drug Interactions
(1) Lower Tract Inf (Ascending Inf) It antagonizes the action of nalidixic acid.
Urethritis, cystitis, prostatitis.
(2) Upper Tract Inf (Descending Inf) NALIDIXIC ACID
Acute pyelonephritis.
Mechanism of Action
Causative Organisms
It blocks bacterial DNA synthesis by inhibiting DNA
(1) Escherichia coli.
gyrase.
(2) Proteus spp.
Clinical Uses
(3) Klebsiella pneumoniae.
Urinary tract inf. with coliform organisms.
(4) Pseudomonas aeruginosa.
Adverse Effects
(5) Staphylococcus aureus.
(1) CNS: Seizures.
(6) Enterococci.
(2) Visual disturbances
(7) Micrococci.
(3) GIT disturbances
(4) Metabolism: False - positive test for glucose in urine,
DRUGS USED IN UTI hyperglycemia, glycosuria.
(5) Allergic reactions: Skin rashes, photosensitivity.
DRUG CLASSIFICATION Contraindications
(1) History of convulsive disorders.
(A) Urinary Antiseptics
(2) Porphyria.
These exert antibacterial activity in urinary tract, but
Dosage
have little or no systemic antibacterial effect;
1gm orally, QID, for 1-2 weeks.
(1) Furan derivatives: Nitrofurantoin.
(2) Quinolones: Nalidixic acid, Oxolinic acid,
METHENAMINE MANDELATE & HIPPURATE
Cinoxacin.
(3) Methenamine mandelate Mechanism of Action
(4) Methenamine hippurate Mandelic acid or hippuric acid taken orally is excreted
(5) Acidifying salts: NH4Cl, Ascorbic acid, Mandelic unchanged in urine, where they are bactericidal for some
gram-negative bacteria if the pH can be kept below 5.5.
acid, Methionine, Hippuric acid, Na acid citrate,
Methenamine releases formaldehyde in the urinary tract, if
Pipedemic acid.
the pH of urine is below 5.5, which act as bactericidal b/c
(B) Systemic Drugs
bacteria can not survive in the presence of high conc. of
(1) Fluoroquinolones
formaldehyde.
(2) Sulfonamides.
Clinical Uses
(3) Trimethoprim.
Urinary tract inf.
(4) Co-trimoxazole.
Adverse Effects
(5) Penicillins.
(1) GIT disturbances.
(6) Cephalosporins.
(2) Allergic reaction eg, skin rashes.
(7) Tetracyclines.
(3) Bladder irritation.
(8) Streptomycin.
Contraindications
(9) Cycloserine.
(1) Severe dehydration.
(2) Severe renal failure.
NITROFURANTOIN (3) Metabolic acidosis.
Mechanism of Action Dosage
Unknown, the activity of nitrofurantoin is greatly (1) Methenamine mandelate  1gm, QID, orally.
enhanced at pH 5.5 or below, but dec. by very high conc. (2) Methenamine hippurate  1gm, BD, orally.
of bacteria in urine.
18: Chemotherapy of Bacterial Infections 157

GENERIC & TRADE NAMES (139) All of the following drugs interfere with vit K
availability, leading to hypoprothrombinemia &
bleeding disorders
(1) Nitrofurantoin: Furatin, Furadin, Furasol. (A) Cefoperazone.
(2) Nalidixic acid: Nalacid, Negram, Uriben. (B) Moxalactam.
(3) Oxolinic acid: Utibid. (C) Nafcillin.
(4) Hexamine hippurate: Urodonal. (D) Carbenicillin.
(5) Pipedemic acid: Pimic, Urixin, Urotractin. (E) Cefotaxime.
(6) Ascorbic acid: See Chapter 24.
(140) All of the following statements about
(7) Na acid citrate: Albacit, Alkacitron, Bliss-Alkali,
chloramphenicol are correct
Citralka, Citrol, Hyocit, Pexocitral, Prosalkali, Sioalkali,
(A) It inhibits peptidyl transferase.
Sykol, Ural, Uralka.
(B) When it is given to neonates, their limited
hepatic glucuronyl-transferase activity may
result in cyanosis.
Unit XIII
(C) It is usually bacteriostatic.
(D) Clinical resistance occurs thru change in

Self - Assessment (T/F) structure of bacterial peptidyl-transferase.

(E) Dose should be reduced in pts with hepatic
failure.
(See answers on page no. 241)
(141) Appropriate clinical uses of chloramphenicol
(135) Mechanism of antibacterial action of cephalosporins includes
involves (A) Typhoid fever.
(A) Inhibition of peptide synthesis. (B) Topical application for chlamydial infections of
(B) Interference with synthesis of ergosterol. eye.
(C) Inhibition of transpeptidase enzymes. (C) Meningococcal meningitis in a penicillin allergic
(D) Inhibition of beta-lactamases. person.
(E) Inhibition of DNA gyrase. (D) H influenzae meningitis.
(136) All of the following antibiotics are correctly matched (E) Sepsis.
with an appropriate clinical use (142) Mechanism of antibacterial action of tetracyclines
(A) Penicillin G  Pneumonia caused by Klebsiella involves
pneumoniae. (A) Inhibition of conversion of lanosterol to
(B) Carbenicillin  Urinary tract infection caused by ergosterol.
pseudomonas aeruginosa. (B) Inhibition of DNA-dependent RNA polymerase.
(C) Ampicillin  Bacterial meningitis caused by H. (C) Blockade of binding of aminoacyl-tRNA to
influenzae. bacterial ribosomes.
(D) Penicillin G  Syphilis caused by Treponema (D) Selective inhibition of ribosomal peptidyl-
pallidum transferases.
(E) Cefazolin  Osteomyelitis. (E) Inhibition of transpeptidase, & endopeptidase.
(137) Following drugs are effective in the treatment of an (143) Appropriate clinical uses of tetracyclines includes
infection caused by S aureus (A) Rickettsial infections.
(A) Amoxycillin. (B) Pneumonia caused by Mycoplasma pneumoniae.
(B) Nafcillin. (C) Osteomyelitis due to methicillin resistant
(C) Cefazolin. staphylococci.
(D) Oxacillin. (D) Gonorrhea.
(E) Azlocillin. (E) Inclusion conjunctivitis.
(138) Third generation cephalosporins (144) Following are recognized adverse effects of
(A) Show greater activity than first generation tetracyclines
cephalosporins against G-ve bacilli. (A) Hepatic necrosis.
(B) Include agents that are active against pseudo- (B) Enamel dysplasia in children.
monas aeruginosa. (C) Gray baby syndrome.
(C) Include agents that are effective in treating (D) Superinfection.
meningitis. (E) Dizziness, vertigo.
(D) Are beta-lactamase sensitive. (145) All of the following statements about
(E) Have poor CSF penetrability. aminoglycosides are correct
M. Shamim’s PHARMACOLOGY 158

(A) Antibacterial action involves binding to 50 S (D) It can cause GIT disturbances.
ribosomal subunit & subsequent inhibition of (E) It is effective in pharyngeal diphtheria.
peptidyl-transferase. (151) Primary reason for the use of drug combinations in
(B) Clinical resistance occur thru alteration in cell the treatment of tuberculosis is to
surface, which interfere with drug permeation (A) Prolong the plasma half-life of each drug.
into cell. (B) Lower the incidence of adverse effects.
(C) They are bactericidal. (C) Enhance activity against metabolically inactive
(D) Streptomycin is clinically useful in pulmonary mycobacteria.
tuberculosis & plague. (D) Delay the emergence of resistance.
(E) Neomycin is usually administered intravenously. (E) Provide long-term prophylaxis.
(146) Regarding adverse effects of aminoglycosides, (152) Concerning isoniazid, all of the following statements
following are correct are correct
(A) Gentamycin is the least nephrotoxic (A) It increases phenytoin plasma levels by
aminoglycoside. inhibiting its liver metabolism.
(B) Neuromuscular blockade may be noted with (B) It is not used in children b/c of high risk of
kanamycin. Hepatotoxicity.
(C) Streptomycin may cause scotomas. (C) Pyridoxine protects against peripheral neuritis
(D) Amikacin may cause dizziness & vertigo. caused by isoniazid.
(E) Tobramycin may cause fanconi synd. (D) It interferes with the synthesis of mycolic acid.
(147) All of the following statements about sulfonamides (E) It may cause hemolysis in G-6-P dehydrogenase
are correct deficient pts.
(A) They inhibit bacterial dihydropteroate synthetase. (153) Concerning rifampin, following statements are
(B) Acute hemolysis may occur in pts with G-6-P correct
dehydrogenase deficiency. (A) It colors body secretions orange.
(C) They are antimetabolites of PABA. (B) It disrupts bacterial lipid metabolism as its
(D) Crystalluria is most likely to occur at high major mechanism of action.
urinary pH. (C) Although rare, it can cause serious hepatotoxicity.
(E) Clinical resistance may occur thru production of (D) When used alone, there is a high risk of
a large excess of PABA. emergence of resistant strains of mycobacteria.
(148) Regarding clinical uses of sulfonamides, (E) It can cause optic neuritis.
following are correct (154) Regarding anti-leprotic drugs, following are correct
(A) Sulfadiazine is effective in acute urinary tract (A) Mechanism of action of dapsone probably
infections due to nonresistant E coli. involves inhibition of folic acid synthesis.
(B) Topical sulfacetamide is useful for chlamydial (B) Clofazimine should not be given to pts. who are
inf of eye. intolerant to dapsone or who fail to respond to
(C) Sulfamethoxazole is effective in Rocky Mountain treatment with dapsone.
spotted fever in pts allergic to tetracyclines. (C) Monthly dosage of rifampin delay the emergence
(D) Sulfasalazine is effective in ulcerative colitis. of resistance to dapsone.
(E) Sulfadimidine is useful in burn sepsis. (D) Clofazimine can cause discoloration of urine.
(149) All of the following statements about the (E) Dapsone causes hemolysis in G-6-P-
combination of trimethoprim plus sulfamethoxazole dehydrogenase deficient pts.
are correct (155) Following drugs are effective in treating urinary
(A) It is effective in the treatment of pneumonia due tract infections
to pneumocystis carinii. (A) Nitrofurantoin.
(B) Drugs produce a sequential blockade of folic acid (B) Cinoxacin.
synthesis. (C) Co-trimoxazole.
(C) Fever & pancytopenia can occur. (D) Chloramphenicol.
(D) It is appropriate for the treatment of streptococcal (E) Nalidixic acid.
pharyngitis.
(E) It is effective in prostatitis.
(150) All of the following statement about erythromycin
are correct
(A) It is often used as a penicillin substitute.
(B) It binds to 50 S ribosomal subunit.
(C) Valid clinical uses include respiratory inf. caused
by mycoplasma pneumoniae.
M. Shamim’s PHARMACOLOGY 160

19 CHEMOTHERAPY OF FUNGAL
INFECTIONS
Resistance
Unit I It may results from a dec. in memb. ergosterol or a
modification in its structure so that it combines less well
with the drug.
Antifungal Agents Clinical Uses
(1) Pulmonary, cutaneous, & disseminated forms of
blastomycosis.
(2) Acute pulmonary coccidioidomycosis.
DRUG CLASSIFICATION (3) Pulmonary histoplasmosis.
(4) Cryptococcus neoformans inf.
(A) According to Chemical Nature (5) Candidiasis, including disseminated forms.
(1) Polyenes (6) Fungal meningitis.
Amphotericin B, Nystatin, Natamycin. (7) Corneal ulcers caused by fungi.
(2) Azole Derivatives (8) Naegleria meningo-encephalitis.
(a) Imidazoles (9) Cutaneous & muco-cutaneous lesions of American
Ketoconazole, Clotrimazole, Miconazole. leishmaniasis.
(b) Triazoles (10) Injected into joints infected with coccidioidomycosis
Fluconazole, Itraconazole, Voriconazole. or sporotrichosis.
(3) Echinocandins Adverse Effects
Caspofungin, Micafungin, Anidulafungin. (1) CNS: A variety of neurologic symptoms.
(4) Miscellaneous (2) CVS: Hypotension, cardiac arrest (due to hypokalemia).
Griseofulvin, Flucytosine, Tolnaftate, Haloprogin, (3) Blood: Normochromic normocytic anemia.
Naftifine, Fatty acid (Undecylenic acid & its salts). (4) Liver: Hepatotoxicity.
(B) According to Site of Action (5) Kidney: Impaired renal function causing inc. in K+
(1) Systemic Antifungals for Systemic clearance, & dec. in creatinine clearance.
Infections (6) Allergic reactions: Skin rashes, fever, anaphylaxis.
Amphotericin B, Flucytosine, Ketoconazole, (7) IV inj: Chills, fever, vomiting, headache,
Triazoles, Echinocandins. thrombophlebitis.
(2) Systemic Antifungals for Mucocutaneous Dosage
Infections (1) Given by slow IV infusion over a period of 4-6 hours.
Griseofulvin, Terbinafine. (2) Initial dose is 1-5 mg/d, inc. daily by 5 mg until a final
(3) Topical dose of 0.4-0.7 mg/kg/d is reached.
Nystatin, Natamycin, Tolnaftate, Azoles (3) This is continued for 6-12 weeks with a daily dose not
(clotrimazole, miconazole, econazole, oxiconazole, exceeding 60 mg.
sulconazole, butaconazole, terconazole, &
tioconazole), Undecylenic acid, Haloprogin, NYSTATIN
Butenafine, Terbinafine, Naftifine. Mechanism of Action
Similar to Amphotericin B.
POLYENES Clinical Uses
Candidiasis of skin, mouth, vagina, & intestinal tract.
Adverse Effects
AMPHOTERICIN B GIT disturbances with oral administration.
Mechanism of Action
It binds firmly to fungal cell memb. in the presence of NATAMYCIN
ergosterol  This alters cell memb. thru the formation of Mechanism of Action
amphotericin pores  This results in loss of cellular Similar to Amphotericin B.
macromolecules & ions, producing irreversible damage. Clinical Uses
19: Chemotherapy of Fungal Infections 161

(1) Corneal keratitis caused by Fusarium, Cephalosporium MISCELLANEOUS

or other fungi.
(2) Oral & vaginal candidiasis.
GRISEOFULVIN
Mechanism of Action
AZOLE DERIVATIVES
It interferes with microtubule function, or with nucleic acid
synthesis & polymerization.
KETOCONAZOLE Clinical Uses
Mechanism of Action Severe dermatophytosis involving skin, hair, or nails esp. if
It alters fungal cell memb. permeability by blocking caused by Trichophyton rubrum (eg tinea capitis, pedis,
biosynthesis of fungal lipids esp. ergosterol in cell memb. cruris & corporis).
Clinical Uses Adverse Effects
(1) Oral, vaginal, & muco-cutaneous candidiasis. (1) CNS: Mental confusion, headache.
(2) Blastomycosis. (2) GIT: Nausea, vomiting, diarrhea.
(3) Liver: Hepatotoxicity.
(3) Coccidioidomycosis.
(4) Allergic reactions: Fever, skin rashes, leukopenia,
(4) Histoplasmosis. serum sickness.
(5) Paracoccidioidomycosis. (5) Skin: Photosensitivity.
(6) Dermatophytosis. Dosage
Adverse Effects 0.5 -1 gm daily in divided doses; for 3-6 weeks if only
(1) GIT: Nausea, vomiting. hairs & skin are involved, but for 3-6 months if nails are
(2) Liver: Hepatotoxicity. affected.
(3) Endocrinal abnormalities: Block synthesis of adrenal
steroids & androgens, & can cause gynecomastia. FLUCYTOSINE
(4) Allergic reactions: Skin rashes, urticaria, anaphylaxis. Mechanism of Action
Contraindications It is converted within fungal cells to fluorouracil, a
(1) Liver disease. metabolic antagonist that ultimately leads to inhibition of
(2) Pregnancy. thymidylate synthetase & DNA synthesis.
Dosage Clinical Uses
200 - 400 mg once daily with meals, for at least one week. Inf. caused by candida albicans & cryptococcus
meningitidis.
MICONAZOLE Adverse Effects
(1) Fatal bone marrow depression.
Mechanism of Action
(2) Gastrointestinal disturbances.
Similar to ketoconazole.
(3) Skin rash.
Clinical Uses
(4) Hepatic dysfunction.
(1) Topically in vaginal candidiasis, & dermatophytosis.
(2) Systemically in disseminated candidiasis, coccidioido- TOLNAFTATE
mycosis, paracoccidioidomycosis, cryptococcis, & Topical antifungal drug, used for the treatment of
blastomycosis. dermatophytosis.
(3) Intrathecally in fungal meningitis.
Adverse Effects FATTY ACIDS
(1) GIT: Nausea, vomiting. Fatty acids esp. Undecylenic acid & its salts are used
(2) Blood: Anemia, leukemia, thrombocytosis, topically in tinea pedis & corporis.
hyponatremia.
(3) Allergic reactions GENERIC & TRADE NAMES
(4) Thrombophlebitis
Dosage
(1) Polyenes
(1) Topical 2% cream. Nystatin: Davistin, Myconil, Mystate, Nilstat, Nistoral,
(2) IV inj 30 mg/kg/d. Nystrin, O-Nystat, Tergynan*.
(3) Intrathecal 10 - 20 mg/d. Natamycin: Ophth-natamycin.
(2) Azole Derivatives
CLOTRIMAZOLE Clotrimazole: Baycuten N*, Canestan, Clotrim,
It is used topically in oral & vaginal candidiasis, & in Clotrima, Dermosporin, Gynosporin, Gynosporin-1,
dermatophytosis. Novestin.
M. Shamim’s PHARMACOLOGY 162

Fluconazole: Candican, Diflucan, F-zole, Flucon,

Flucozal, Fluderm, Funganil, Fungix, Hiflucan, Zolanix.
Ketoconazole: Conaz, Funginil, Kenzol, Ketacon,
Konazole, Nizoral.
Miconazole: Candistat, Daktacort*, Daktarin, Dermicon,
Gynostin, Gyno-daktarin, Myconit.
Itraconazole: Itazol, Itracon, Itrazole, Rolac, Sporanox.
Econazole: Econophen, Gyno-Pevaryl*.
Tioconazole: Trosyd.
(3) Miscellaneous
Griseofulvin: Fungivin, Grifin, Griful, Grifulvin,
Griseofulvin, Grivin, Gryso.
Naftifine: Exoderil.
Terbinafine: Antifin, Docinaf, Onyfine, Terbiderm,
Terbin, Terbino, Terbisan, Terbisil, Terbix, Verticil.

Unit II

Self - Assessment (T/F)

(See answers on page no. 241)
(156) Following drugs are used for the treatment of
systemic fungal infections
(A) Amphotericin B.
(B) Flucytosine.
(C) Ketoconazole.
(D) Nystatin.
(E) Clotrimazole.
(157) All of the following statements correctly describe
Ketoconazole
(A) It inhibits conversion of lanosterol to ergosterol.
(B) It may produce gastrointestinal upsets.
(C) It can cause gynecomastia in males.
(D) It is useful as systemic antifungal in pts with
liver disease.
(E) It is effective in candida infections.
(158) Regarding amphotericin B, following are correct
(A) Its mechanism of action involves formation of
amphotericin pores in fungal cell memb.
(B) It is applied topically in oral & vaginal
candidiasis.
(C) It is effective in pulmonary coccidioidomycosis
& pulmonary histoplasmosis.
(D) It may causes hypertension.
(E) It may cause an inc. in K clearance & dec. in
creatinine clearance.
M. Shamim’s PHARMACOLOGY 163

20 CHEMOTHERAPY OF VIRAL
INFECTIONS
Amprenavir, Atazanavir, Fosamprenavir, Indinavir,
Unit I Lopinavir, Ritonavir, Nelfinavir, Saquinavir,
Tipranavir.
(2) Neuraminidase Inhibitors
Antiviral Drugs Zanamivir, Oseltamivir.

AMANTADINE
CLASSIFICATION OF ANTIVIRAL DRUGS
Mechanism of Action
(A) Drugs Inhibiting Adsorption & Penetration of (1) It inhibits penetration of susceptible cells, or uncoating
Susceptible Cells of certain myxoviruses, eg influenza A, rubella & some
(1) Gamma Globulins tumor viruses.
(2) Adamantanamines (2) Being a weak base, amantadine may act by buffering the
Amantadine, Rimantadine, Tromantadine. pH of endosomes (memb. bound vacuoles that surround
(3) Aliphatic Alcohol virus particles as they are taken into cell)  Prevention
Docosanol. of acidification in these vacuoles blocks fusion of virus
(4) Fusion Inhibitors envelope with endosome memb., thereby preventing
Enfuvirtide transfer of viral genetic material into cell cytoplasm.
(B) Drugs Inhibiting Late Protein Synthesis Clinical Uses
Methisazone. (1) For prophylaxis during influenza A virus epidemics.
(C) Drugs Inhibiting Nucleic Acid Synthesis (2) Parkinson's disease (b/c it potentiates the dopami-
(1) Pyrimidine & Purine Analogues nergic function).
(a) Guanosine analog: Acyclovir, Famciclovir, Adverse Effects
Ganciclovir, Penciclovir, Valacyclovir, (1) CNS: Restlessness, depression, irritability, insomnia,
Valganciclovir, Abacavir, Entecavir. agitation, excitement, hallucinations, confusion,
(b) Cytosine analog: Cidofovir, Lamivudine, headache.
Emtricitabine, Zalcitabine. Note: These effects occur b/c the drug causes release
(c) Thymidine analog: Stavudine. of stored catecholamines.
(d) Deoxythymidine analog: Zidovudine. (2) CVS: Congestive cardiac failure, postural hypotension,
(e) Adenosine analog: Adefovir, Tenofovir. peripheral edema.
(f) Deoxyadenosine analog: Didanosine. (3) GIT: Dry mouth, anorexia, nausea, constipation.
(g) Miscellaneous: Idoxuridine, Cytarabine, (4) Renal: Urinary retention.
Trifluridine, Vidarabine. Contraindications
(2) Non-Nucleoside Reverse Transcriptase (1) Pts. with a history of seizures.
Inhibitors (NNRTIs) (2) Congestive cardiac failure.
Delavirdine, Efavirenz, Nevirapine. Dosage
(3) Others 200 mg/day, for 2-3 days before & 6-7 days after influenza
Ribavirin, Foscarnet. A infection.
(D) Drugs Inhibiting Both Nucleic Acid & Protein
Synthesis RIBAVIRIN
Interferon alfa.
(E) Drugs Inhibiting Assembly or Release of Viral
Particles Mechanism of Action
(1) Protease Inhibitors (1) It may interfere with the formation of viral messenger
RNA, & may inhibit viral RNA polymerase.
M. Shamim’s PHARMACOLOGY 164

(2) It may act by interfering with guanidine monophos- Adverse Effects

phate formation & subsequent nucleic acid synthesis. (1) Topical application: Local discomfort, pruritus.
Clinical Uses (2) Oral therapy: Nausea, vomiting, diarrhea, headache.
(1) Herpes simplex infection. (3) IV therapy: Thrombophlebitis, rash, nephrotoxicity,
(2) Influenza A & B. neurologic reactions, hives.
(3) Respiratory syncytial viral infection. Dosage
(1) Topical  5% ointment.
(4) Viral hepatitis.
(2) Oral  200 mg 5 times daily.
(5) Lassa fever.
Adverse Effects (3) IV  15 mg/kg/day.
(1) Rash & conjunctivitis (with aerosol use).
(2) Mutagenic, teratogenic & carcinogenic. GANCICLOVIR
Contraindications
Pts requiring mechanical ventilation b/c small aerosol Mechanism of Action
particles ppt. on the respirator valves & tubing, causing It is first phosphorylated to a deoxyguanosine triphosphate
malfunction that can be lethal. (dGTP) analogue. This competitively inhibits the
incorporation of dGTP by viral DNA polymerase, resulting
VIDARABINE in the termination of elongation of viral DNA.
Clinical Uses
(1) CMV retinitis in immuno-compromized pts.
Mechanism of Action (2) CMV pneumonitis in immunosuppressed pts.
It is phosphorylated in the cell to triphosphate derivative, (3) Prevention of CMV disease in bone marrow & solid
which inhibits viral DNA polymerase (much more organ transplant recipients.
effectively than mammalian DNA polymerase). (4) Acute CMV colitis in HIV/AIDS.
Clinical Uses Adverse Effects
(1) Herpes simplex encephalitis. (1) CNS: Headache, confusion, hallucination, seizures.
(2) Herpes simplex keratoconjunctivitis. (2) GIT: Nausea, vomiting, dyspepsia, diarrhea, abdominal
(3) Neonatal disseminated herpes simplex inf. pain, flatulence, anorexia.
(4) Viremia in chronic active hepatitis. (3) Liver: Raised liver enzymes.
(5) Herpes zoster inf. in immunosuppressed pts. (4) Renal: Increased serum creatinine & blood urea.
Adverse Effects (5) Blood: Granulocytopenia, neutropenia, anemia,
(1) CNS toxicity. thrombocytopenia.
(2) GIT disturbances. (6) Temp: Fever.
(3) Carcinogenic. (7) Skin: Sweating, rash, itch.
Dosage (8) Local: Pain & phlebitis at injection site.
(1) Topically, 3% ointment. Dosage
(2) IV inj, 10-15 mg/kg/d over 12 hours. (1) Acute infections are treated in two phases:
(a) Induction phase, 5 mg/kg, IV, every 12 hours for
ACYCLOVIR 14-21 days.
(b) Maintenance phase, 5 mg/kg, IV every day.
(2) Stable disease is treated with 1000 mg orally three times
Mechanism of Action daily.
It is converted in vivo into triphosphate form which (3) As slow-release formulations for insertion into the
interferes with viral DNA polymerase & inhibits viral DNA vitreous humor of the eye.
replication. It is incorporated into DNA & leads to
premature chain termination.
Clinical Uses ZIDOVUDINE
(1) Primary mucocutaneous herpes simplex inf. in
immunocompromized pts. Mechanism of Action
(2) Herpes genitalis inf. It is incorporated into retrovirus HIV, & causes termination
(3) Herpes simplex encephalitis. of DNA polymerase chain synthesis of viral DNA.
(4) Neonatal herpatic dissemination. Clinical Uses
(5) Prophylactically before bone marrow transplants to Acquired immunodeficiency synd. (AIDS) caused by
protect against severe herpes lesions during post- retrovirus HIV.
transplant immunosuppression. Adverse Effects
(6) After heart transplants to prevent dissemination of (1) CNS: Headache, agitation, insomnia.
herpes from existing lesions. (2) Blood: Severe anemia, granulocytopenia &
(7) Varicella-Zoster virus inf. thrombocytopenia, due to bone marrow depression.
20: Chemotherapy of Viral Infections 165

Dosage (11) Cytarabine: Alexan, Cytocin.

200 mg orally per 4 hours. (12) Interferons: Alphaferoi, Anferon, Ceron-alfa, Ceron-
alpha, Heberon-alpha, Infron-alpha, Intron-A, Roferon-
A, Viteron-A.
METHISAZONE
(13) Lopinavir/Ritonavir: Kaletra.
(14) Oseltamivir: Influ-rid, Oselta, Pronto, Tamiflu.
Mechanism of Action
It inhibits viral replication by interfering with the synthesis
of a 'late' structural protein. Unit II
Clinical Uses
(1) Small pox virus inf.
(2) Vaccinia virus inf. Self - Assessment (T/F)
INTERFERON (See answers on page no. 241)
(159) All of the following statements about the mechanism
Mechanism of Action of action of antiviral drugs is correct
Interferon induces host cell ribosomes to produce cellular (A) Vidarabine inhibits viral DNA polymerase.
enzymes that subsequently block viral reproduction by (B) Inc. activity of host cell phosphodiesterase that
inhibiting transcription of viral mRNA into viral proteins. degrade tRNA is one of the antiviral actions of
Three enzymes are known to be induced: interferons.
(1) Protein kinase: It leads to phosphorylation of (C) Acyclovir is incorporated into viral RNA
elongation factor 2, resulting in inhibition of peptide causing premature chain termination.
chain initiation. (D) Ribavirin interfere with the formation of viral
(2) Oligoisoadenylate synthetase: It leads to activation of messenger RNA.
an RNase & degradation of viral mRNA. (E) Methisazone interfere with the synthesis of a
(3) Phosphodiesterase: It degrades the terminal nucleo- 'late' structural protein.
tides of tRNA, inhibiting peptide elongation. (160) All of the following statements about amantadine are
Clinical Uses correct
(1) Herpes zoster inf. in pts with lymphoma. (A) It is effective in prophylaxis of influenza A inf.
(2) Neoplastic diseases, eg Hairy-cell leukemia. (B) It causes CNS disturbances at high doses.
(3) For reducing cytomegalovirus shedding after renal (C) It is contraindicated in pts. with Parkinsonism.
transplantation. (D) It may cause diarrhea.
(4) For preventing reactivation of herpes after trigeminal (E) It is used topically in herpes genitalis inf.
root section.
(5) Viremia with hepatitis B virus. (161) Each of the following statements about anti-viral
(6) Warts of condylomata acuminata. agents is correct
(7) Rabies. (A) Interferons may prevent dissemination of
(8) Hemorrhagic fever. herpes zoster virus in cancer pts & reduce CMV
Adverse Effects shedding after renal transplantation.
(1) CNS: Fatigue, weakness. (B) Ribavirin is useful in viral hepatitis.
(2) GIT: Gastrointestinal disturbances. (C) Blood dyscrasias may be noted with
(3) Blood: Anemia. azidothymidine.
(D) Amantadine is contraindicated in pts with a
history of seizures.
GENERIC & TRADE NAMES (E) Vidarabine in effective in rabies.

(1) Gamma globulin: Allerglobulin, Gamma-16 vaccine.

(2) Amantadine: PK-Merz, Virofral.
(3) Tromantadine: Viru-Merz.
(4) Ribavirin: Virazole.
(5) Acyclovir: Acylex, Cycloz, Elovir, Lovir, Ophth-
cyclovir, Santovir, Verox, Virucid, Zaclovir, Zovirax.
(6) Famiclovir: Famvir.
(7) Lamivudine: Lamudine, Zeffix.
(8) Zalcitabine: Hivid.
(9) Adefovir: Hepovir, Hepsera.
(10) Idoxuridine: Herpidu.
M. Shamim’s PHARMACOLOGY 166

21 CHEMOTHERAPY OF
PROTOZOAL INFECTIONS
(2) 8 - Aminoquinolines
Unit I Primaquine.
(3) Quinoline Methanol (Cinchona Alkaloids)
Quinine, Quinidine, Mefloquine.
Drug Treatment of Malaria (4) 2,4 - Diaminopyrimidines
Pyrimethamine.
(5) Biguanides
Proguanil.
MALARIA (6) Phenanthrene Methanol
Halofantrine.
It is an infectious febrile disease caused by protozoa of (7) Amyl Alcohol
genus 'Plasmodium', which are transmitted to humans by the Lumefantrine.
bites of infected female mosquitoes of genus 'Anopheles'. (8) 9 - Aminoacridine
Causative Organisms Quinacrine.
Four species of plasmodium are responsible: (9) Sulfonamides
(1) Plasmodium vivax. Sulfadoxine, Sulfadiazine, Sulfalene (Sulfameto-
(2) Plasmodium ovale. pyrazine), Sulfamethoxazole.
(3) Plasmodium malariae. (10)Sulfones
(4) Plasmodium falciparum. Dapsone
Clinical Features (11)Tetracyclines
(1) Attacks of chills, fever, sweating, anemia, & Doxycycline.
splenomegaly, occurring at intervals which depend on (12)Sesquiterpene Lactone
time required for the development of a new generation Artemisinins (Qinghaosu), Artesunate, Artemether.
of parasites in body. (13)Combinations
(2) After recovery from acute attack, disease has a Fansidar (Pyrimethamine + Sulfadoxine), Maloprim
tendency to become chronic, with occasional relapses. (Pyrimethamine + Dapsone), Chlorproguanil +
Types of Malaria Dapsone, Malarone (Atovaquone + Proguanil).
(1) Tertian Malaria (B) According to Site of Action
It is produced by P. vivax & P. ovale with fever every (1) Drugs Acting on Erythrocytic Stage
third day ie at 48 hour intervals. Disease produced by Chloroquine, Amodiaquine, Quinine, Quinacrine,
P. vivax tends to be chronic with frequent relapses, Mefloquine, Halofantrine, Lumefantrine,
while P. ovale infection is milder. Artemisinins.
(2) Quartan Malaria (2) Drugs Acting on Exo-erythrocyte Stage
It is produced by P. malariae with fever every fourth Primaquine, Sulfonamides, Sulfones.
day, ie at 72 hour intervals, & relapses at long intervals. (3) Drugs Acting on Both Stages
(3) Malignant Tertian Malaria Proguanil, Pyrimethamine.
It is produced by P. falciparum with fever every third
day, & more serious infection. It does not relapse so CHLOROQUINE & AMODIAQUINE
frequently.

MECHANISM OF ACTION
DRUG CLASSIFICATION
They block enzymatic synthesis of DNA & RNA in both
mammalian & protozoal cells, & form a complex with DNA
(A) According to Chemical Nature that prevents replication or transcription to RNA. Selective
(1) 4 - Aminoquinolines toxicity for malarial parasites depends on chloroquine
Chloroquine, Amodiaquine. concentrating mech. in parasitized cells.
21: Chemotherapy of Protozoal Infections 167

PHARMACOLOGICAL EFFECTS (A) Antimalarial Action

(A) Antimalarial Action (1) It is an effective blood schizonticide, eliminating
(1) They are effective blood schizonticide, & used to the asexual stages of all 4 parasites.
prevent or terminate attacks of vivax, ovale, (2) It is also gametocidal against P. vivax & P. malariae.
malariae or sensitive falciparum malaria. (B) Others Effects
(2) They are also moderately effective against (1) On cardiac muscle, it has quinidine like effects (but
gametocytes of P. vivax, P. ovale, & P. malariae. less intense).
(B) Cardiovascular System (2) On gravid uterus, it has a slight oxytocic action,
Chloroquine has a low-level quinidine-like effect on esp. during the third trimester of pregnancy.
CVS, which may cause noticeable change in the T wave (3) In skeletal muscle, it has a curare like effect.
of ECG during therapy. (4) It has a minor antipyretic action.
(5) When given IV, it may cause severe hypotension,
CLINICAL USES or hypoglycemia.
(1) Acute malaria attacks.
(2) Chemoprophylaxis of malaria. CLINICAL USES
(3) Amebic liver abscess. (1) Malaria esp. due to P. falciparum.
(4) Giardiasis. (2) Chemoprophylaxis of malaria.
(5) Lupus erythematosus. (3) Babesiosis.
(6) Rheumatoid arthritis.
ADVERSE EFFECTS
ADVERSE EFFECTS (1) Cinchonism
(1) CNS: Mild headache, confusion, psychosis, Symptoms include flushed & sweaty skin, headache,
convulsions, impaired hearing. blurred vision, impaired hearing, tinnitus, dizziness,
(2) Eye: Retinal & reversible corneal damage. nausea, vomiting, abd. pain, & diarrhea.
(3) CVS: Hypotension. Severe cinchonism is associated with papular or
(4) GIT: Anorexia, nausea, vomiting. urticarial skin rashes, deafness, somnolence, blindness,
(5) Blood: Hemolysis in G-6-P dehydrogenase deficiency. & disturbance in cardiac rhythm & conduction.
(6) Skin: Exfoliative dermatitis, urticaria, pruritus (esp. in (2) Blood Dyscrasias
black persons). Hemolytic anemia in G- 6-P dehydrogenase deficiency,
leukopenia, agranulocytosis, thrombocytopenic purpura,
CONTRAINDICATIONS Henoch-Schonlein purpura, hypoprothrombinemia.
(1) Pts. with psoriasis. (3) Blackwater Fever
(2) Porphyria. Characterized by massive intravascular hemolysis;
(3) With drugs known to cause dermatitis. followed by hemoglobinuria, dark urine, azotemia,
(4) Concomitantly with gold or phenylbutazone therapy. intravascular sludging & coagulation, renal failure, &
(5) Liver damage. uremia.
(6) Alcoholism. (4) IV Inj
(7) Blood dyscrasias. Thrombophlebitis, moderate to marked hypotension
(8) Neurologic disorders. which may progress to shock.
(5) IM Inj
DOSAGE Pain & sterile abscesses at the site of inj.
(1) Chloroquine phosphate  1000 mg initially, then 500 mg
CONTRAINDICATIONS
daily, orally.
(1) Subcutaneous or IM inj.
(2) Amodiaquine HCl  600 mg initially, followed by 300
(2) Tinnitus.
mg 6, 24 & 48 hours later, orally.
(3) Optic neuritis.
(4) Myasthenia gravis.
QUININE (5) Hypersensitivity to quinine or quinidine.
(6) Pregnancy.
MECHANISM OF ACTION
(1) It forms a hydrogen-bonded complex with double- DOSAGE
stranded DNA that inhibits protein synthesis by 650 mg TDS for 3 -7 days, orally.
preventing strand separation & therefore DNA
replication & transcription to RNA.
(2) It depresses many enzyme systems.
PRIMAQUINE
PHARMACOLOGICAL EFFECTS
M. Shamim’s PHARMACOLOGY 168

MECHANISM OF ACTION Dosage

Unknown; quinoline- quinone intermediates derived from it 75 mg/day, orally.
are electron carrying redox compounds that can act as
oxidants. These probably cause hemolysis & PROGUANIL
methemoglobinemia.

ANTIMALARIAL ACTIONS Mechanism of Action

It is a prodrug, which is converted into active metabolite
(1) It is active against late hepatic stages of P. vivax &
'cycloguanil'. It acts by inhibiting dihydrofolate reductase.
P. ovale.
(2) It is also highly active against primary exoerythrocytic Antimalarial Actions
stages of P. falciparum. (1) It has a marked effect on primary exoerythrocytic stages
(3) It is gametocidal against all 4 malaria parasites. of P. falciparum & P. vivax.
(2) It is an effective blood schizonticide.
Clinical Uses
CLINICAL USES
For prophylaxis & treatment of falciparum & vivax malarias.
(1) Radical cure of vivax & ovale malarias. Note: It is considered safe in pregnancy.
(2) Chemoprophylaxis of malaria. Adverse Effects
(3) Pneumocystosis (pneumocystis jiroveci inf). (1) GIT: Vomiting, diarrhea, abd. pain.
(2) Blood: Megaloblastic anemia, leukopenia,
ADVERSE EFFECTS granulocytopenia.
(1) CNS: Headache.
(2) GIT: Nausea, epigastric pain, abd. cramps.
(3) Blood: Leukopenia, agranulocytosis, hemolysis in FANSIDAR
G- 6- P dehydrogenase deficiency, methemoglobinemia.
It is a combination of Pyrimethamine & Sulfadoxine (a
CONTRAINDICATIONS sulfonamide).
(1) Pts. with connective tissue disorders. Mechanism of Action
(2) Pregnancy. Similar to 'Cotrimoxazole'. (See chapter '18').
(3) Parenterally (b/c it may induce marked hypotension). Antimalarial Actions
(4) With other potentially hemolytic drugs. (1) It is an effective blood schizonticide against P.
(5) With drugs that depress bone marrow. falciparum.
(2) It also has a marked effect on primary exoerythrocytic
DOSAGE stages of P. falciparum.
26.3 mg daily, orally for 14 days, usually with chloroquine. Clinical Uses
For prophylaxis & treatment of falciparum malaria.
Adverse Effects
PYRIMETHAMINE (1) GIT: Mild upsets.
(2) Blood: Megaloblastic anemia.
Mechanism of Action (3) Skin: Erythema multiforme, Stevens-Johnson Synd.,
Similar to trimethoprim by inhibiting dihydrofolate toxic epidermal necrolysis.
reductase. ( See chapter '18' ). Contraindications
Antimalarial Actions (1) Pts. who have had adverse reactions to either of its
(1) It is an effective blood schizonticide. components.
(2) It is also gametocidal, & active against primary exo- (2) Pregnant or nursing women.
erythrocytic stages of P. falciparum. (3) Children under 2 months of age.
Clinical Uses (4) Impaired renal function.
(1) For prophylaxis of 4 - Aminoquinoline resistant (5) Impaired hepatic function.
falciparum malaria (with sulfonamides or sulfones). (6) G-6-P dehydrogenase deficiency.
(2) Treatment of 4 - Aminoquinoline resistant falciparum (7) Pts. with severe allergic disorders, bronchial asthma or
malaria (with sulfonamides & quinine). poor nutritional status.
(3) Treatment of toxoplasmosis.
(4) Pneumocystosis. MEFLOQUINE
Adverse Effects
(1) GIT: Mild upsets.
(2) Skin: Rashes. Mechanism of Action
(3) Blood: Megaloblastic anemia. Unknown.
Contraindications Antimalarial Actions
Pregnancy.
21: Chemotherapy of Protozoal Infections 169

It has strong schizonticidal activity against all malarial

Unit II
parasites.
Clinical Uses
P. falciparum malaria resistant to chloroquine & Fansidar.
Adverse Effects Drug Treatment of
(1) CNS: Dizziness, headache, confusion, hallucinations,
depression.
Amebiasis
(2) CVS: Sinus bradycardia.
(3) GIT: Nausea, vomiting, diarrhea, abd. pain.
(4) Skin: Rashes, itching. AMEBIASIS

QUINACRINE It is an infectious disease caused by Entameba histolytica.

It may produce ulceration of large intestine, & also abscess
Antimalarial Actions of liver & rarely of other organs.
It is an effective blood schizonticide that suppresses all 4 Clinical Features
types of malarial parasites. (1) An acute stage with frequent passage of motions
Clinical Uses containing blood & mucus, & accompanied by
(1) P. malariae & P. falciparum malarias (the drug is now abdominal pain & tenesmus.
obsolete for malaria). (2) A chronic stage in which symptoms may entirely
(2) Giardiasis. disappear, & diarrhea may even give place to
Adverse Effects constipation.
(1) CNS: Dizziness, headache, restlessness, confusion,
anxiety, euphoria. DRUG CLASSIFICATION
(2) GIT: Vomiting, diarrhea.
(A) Tissue Amebicides
QINGHAOSU (1) Nitroimidazoles: Metronidazole, Tinidazole,
Ornidazole.
(1) It is an effective blood schizonticide against all 4 types (2) Emetines: Emetine HCl, Emetine bismuth iodide,
of malaria. Dehydroemetine HCl.
(2) It is esp. useful in the treatment of falciparum cerebral (3) 4 - Aminoquinolines: Chloroquine.
malaria, including that due to chloroquine resistant (B) Luminal Amebicides
strains. (1) Dichloroacetamides: Diloxanide furoate,
Clefamide, Etofamide, Teclozan.
(2) Halogenated 8-OH quinolines: Iodoquinol
GENERIC & TRADE NAMES (Diiodohydroxyquin), Clioquinol (Iodochloro-
hydroxyquin).
(1) Chloroquine phosphate: Binaquin, Cloquin, Efroquin, (3) Antibiotics: Tetracycline, Paromomycin,
Kciquin, Proquine, Resochin, Wilquin, Chloroquine Erythromycin.
phosphate tab.
(2) Amodiaquine HCl: Amdaquin, Amoquine, Basoquin, DRUGS USED IN DIFFERENT AMEBIC INFECTIONS
Semoquine. (1) Asymptomatic Intestinal Infection
(3) Primaquine: Primaquine. Drug of Choice: Diloxanide furoate.
(4) Quinine: Hydroquine. Alternative Drug: Iodoquinol, Paromomycin.
(5) Mefloquine: Fansimate, Fansimef. (2) Mild to Moderate Intestinal Infection
(6) Halofantrine: Halfan. Dg/Ch: Metronidazole or Tinidazole, Plus Diloxanide
(7) Artemether: Artem, Artemal, Artemex, Artemose, furoate, Iodoquinol or Paromomycin.
Entum, Hitecxin, Malamether. Alt. drugs: Diloxanide furoate, Iodoquinol or
(8) Pyrimethamine: Fansidar*, Fansimef*, Maladar*, Paromomycin, plus Tetracycline or Erythromycin.
Metafin*, Malarina*, Malidar. (3) Severe Intestinal Inf. (Dysentery)
(9) Sulfonamides & Tetracyclines : See Chapter 18. Dg/Ch: Metronidazole or Tinidazole, Plus Diloxanide
furoate, Iodoquinol or Paromomycin.
Alt. drugs: Diloxanide furoate, Iodoquinol or
Paromomycin, plus Tetracycline, Emetine or
Dehydroemetine.
(4) Hepatic Abscess
M. Shamim’s PHARMACOLOGY 170

Dg/Ch: Metronidazole or Tinidazole, Plus Diloxanide CLINICAL USES

furoate, Iodoquinol or Paromomycin. (1) Amebic dysentery.
Alt. drugs: Dehydroemetine or emetine followed by (2) Fasciola hepatica inf.
Chlroquine + Diloxanide furoate, Iodoquinol or (3) Balantidiasis.
Paromomycin. (4) Paragonimus westermani inf.
(5) Ameboma or Extraintestinal Inf.
Dg/Ch: As for hepatic abscess. ADVERSE EFFECTS
Alt. drugs: As for hepatic abscess but excluding (1) CNS: Headache, fatigue, dizziness, paresthesias,
chloroquine. polyneuritis.
(2) CVS: Tachycardia, arrhythmias, precordial pain,
METRONIDAZOLE & TINIDAZOLE congestive cardiac failure with dyspnea & hypotension.
(3) GIT: Nausea, vomiting, diarrhea.
(4) Renal: Proteinuria.
MECHANISM OF ACTION (5) Blood: Hypokalemia, elevated transaminase level.
Within sensitive protozoal cells, the nitro group of (6) Skeletal muscles: Generalized muscular weakness
metronidazole is chemically reduced by ferrodoxin & the associated with tenderness, stiffness, aching, tremors.
reduction product appears to be responsible for killing (7) Skin: Urticaria, eczema, purpura.
organisms by reacting with various intracellular (8) Local: Pain, tenderness, muscular weakness, sterile
macromolecules. abscess in the area of inj.

CLINICAL USES CONTRAINDICATIONS

(1) Amebiasis. (1) Cardiac disease.
(a) Mild to moderate & severe intestinal inf. (2) Renal disease.
(b) Hepatic abscess. (3) Polyneuritis.
(c) Ameboma. (4) Young children.
(2) Urogenital trichomoniasis. (5) Pregnancy.
(3) Giardiasis.
(4) Balantidiasis. DOSAGE
(5) Gardnerella vaginalis.
1 mg/kg/d, SC or IM for 3-5 days; max. daily dose for
(6) Anaerobic infections.
dehydroemetine is 90 mg, & for emetine 65 mg.
(7) Phagedenic leg ulcers (topically).
(8) Acute ulcerative gingivitis (topically).
(9) Cancrum oris (topically). DILOXANIDE FUROATE
(10) Decubitus ulcers (topically).
Mechanism of Action
ADVERSE EFFECTS Probably directly amebicidal, but the exact mech. is
(1) CNS: Headache, insomnia, weakness, paresthesias, unknown.
vertigo, seizures, ataxia, encephalopathy. Clinical Uses
(2) GIT: Nausea, vomiting, diarrhea, dry mouth, metallic All forms of amebiasis.
taste, stomatitis, pseudomembranous colitis. Adverse Effects
(3) Renal: Urethral burning, dark or reddish-brown urine. (1) GIT: Flatulence, nausea, vomiting, diarrhea, esophagitis,
(4) Blood: Leukopenia. dryness of mouth, abd. cramps.
(5) Skin: Rashes. (2) Renal: Proteinuria.
(6) IV Inj: Thrombophlebitis. (3) Skin: Pruritus, urticaria, tingling sensation.
Contraindications
DOSAGE (1) Pregnancy.
400-800 mg 3 times daily, for 5 days. (2) Children under 2 years of age.
Dosage
500 mg 3 times daily with meals, for 10 days.
EMETINE & DEHYDROEMETINE

IODOQUINOL (DIIODOHYDROXYQUIN)
MECHANISM OF ACTION
They irreversibly block the synthesis of protein by
inhibiting movement of ribosome along mRNA. DNA Mechanism of Action
synthesis is secondarily blocked. Unknown; but it is probably due to its iodine content.
Note: They act only against trophozoites. Clinical Uses
(1) Asymptomatic & mild to moderate intestinal amebiasis.
21: Chemotherapy of Protozoal Infections 171

(2) Giardiasis. raised nodule which then ulcerates, & is distributed on

(3) Dientameba fragilis inf. exposed parts of body esp. on face & extremities.
Adverse Effects (3) Mucocutaneous Leishmaniasis
(1) CNS: Headache, peripheral neuropathy. It is caused by leishmania braziliensis, & is
(2) Eye: Optic atrophy, visual loss. characterized by a specific ulcerative granuloma of skin,
(3) GIT: Nausea, vomiting, diarrhea, constipation, gastritis, followed by involvement of mucocutaneous area in
abd. discomfort. some cases.
(4) Endo: Slight enlargement of thyroid gland.
(5) Blood: Agranulocytosis.
DRUG CLASSIFICATION
(6) Skin: Pruritus ani, discoloration of hairs or nails, hair
loss.
(7) Iodine sensitivity: Characterized by furunculosis, chills, (1) For Kala-azar
fever, various skin reactions. (a) Drugs of Choice: Pentavalent antimonials eg
Contraindications sodium stibogluconate.
(1) Pts. with intolerance to iodine. (b) Alternative drug: Meglumine antimonate,
(2) Renal disease. Pentamidine, Amphotericin B, Mitefosine.
(3) Thyroid disease. (2) For Cutaneous Leishmaniasis
Dosage (a) Drugs of choice: Sodium stibogluconate.
650 mg 3 times daily, for 21 days. (b) Alternative drugs: Meglumine antimonate,
Pentamidine, Ketoconazole.
(3) For Mucocutaneous Leishmaniasis
GENERIC & TRADE NAMES (a) Drugs of Choice: Sodium stibogluconate.
(b) Alternative drugs: Meglumine antimonate,
(1) Metronidazole: Abozole, Amibazol, Candizole-M, Pentamidine, Amphotericin B, Mitefosine
Dependal M, Diloxamet, Diloxazole, Entamizole, Flagyl,
Klint, Merizole, Metgyl, Metodine, Metomet,
SODIUM STIBOGLUCONATE
Metronidazole, Resgyl, Trivizol, Zolen, Zolint.
(2) Tinidazole: Fasigyn, Trichogin.
(3) Diloxanide furoate: Amibazole*, Diloxazole*, Zolen*, MECHANISM OF ACTION
Entamizole*. Pentavalent antimonials are first broken in vivo into
(4) Clioquinol: Clioquinol. trivalent compounds. Trivalent antimonials than inhibit the
enzyme phosphofructokinase, which prevent protozoa from
completing anaerobic metabolism of glucose essential for
Unit III their survival.

CLINICAL USES
Drug Treatment of All forms of leishmaniasis.

Leishmaniasis ADVERSE EFFECTS

(1) CNS: Headache.
(2) CVS: Bradycardia, arrhythmias, circulatory collapse.
LEISHMANIASIS (3) Resp. tract: Lobar pneumonia.
(4) GIT: Nausea, vomiting, abd. pain.
(5) Liver: Hepatitis.
It is a human disorder produced by flagellated tissue (6) Blood: Hemolytic anemia.
protozoa of genus leishmania, transmitted to humans by the (7) Musculo - skeletal system: Joint & muscle pain.
bites of sandflies of genera phlebotomus & lutzomyia. (8) Skin: Maculo-papular rash, pruritus.
Types of Leishmaniasis
(1) Visceral Leishmaniasis (Kala-azar) DOSAGE
It is caused by leishmania donovani, & is characterized
Na stibogluconate  10 mg/kg body wt. for 10 days, IM or
by continuous or remittent fever, hepato-splenomegaly,
IV; 3 courses with interval of a week b/w each course.
lymphadenopathy, epistaxis, emaciation, anemia, & dry,
rough, harsh skin with occasional warty eruption &
mucocutaneous lesions. PENTAMIDINE
(2) Cutaneous Leishmaniasis
It is caused by leishmania tropica, which produces MECHANISM OF ACTION
cutaneous lesion called tropical sore. This begins as a
M. Shamim’s PHARMACOLOGY 172

Unknown; parasite may take up more of the drug than It is caused by 'Trypanosoma cruzi'.
mammalian tissue does, & probably function of Clinical Features
mitochondria & respiration of intact parasites are depressed. Anemia, enlarged glands, & irregular fever.

CLINICAL USES DRUG CLASSIFICATION

(1) Kala-azar.
(2) African trypanosomiasis.
(3) Pneumocystosis. (A) For African Trypanosomiasis
(4) Blastomycosis. (1) For Hemolymphatic Stage
(a) Suramin (Dg/Ch).
ADVERSE EFFECTS (b) Pentamidine, Eflornithine (Alt. drug).
(2) For Late Disease with CNS Involvement
(1) CVS: Hypotension.
(a) Trivalent arsenicals (Dg/Ch) eg Melarsoprol.
(2) Endo: Hypoglycemia, hyperglycemia, diabetes mellitus.
(b) Eflornithine (Alt. drug).
(3) Liver: Abnormal liver function tests.
(B) For American Trypanosomiasis
(4) Pancreas: Acute pancreatitis, selective toxicity to B
(1) Nifurtimox (Dg/Ch).
cells of pancreatic islets causing first insulin release &
(2) Benznidazole (Alt. drug).
then insulin deficiency.
(5) Renal: Kidney dysfunction, azotemia.
(6) Blood: Megaloblastic anemia, thrombocytopenia SURAMIN
(leading to purpura).
(7) Electrolytes: Hyperkalemia, Hypocalcemia. MECHANISM OF ACTION
(8) Skin: Toxic epidermal necrolysis.
It is a non - specific inhibitor of many enzymes.
(9) IM inj: Pain, sterile abscess.
(10) IV inj: Severe hypotension, tachycardia, dizziness,
fainting, itching. CLINICAL USES
(1) Hemolymphatic stage of African trypanosomiasis.
CONTRAINDICATIONS (2) Onchoceriasis.
(1) Diabetes mellitus.
(2) Liver disease. ADVERSE EFFECTS
(3) Kidney disease. (1) CNS: Peripheral neuritis.
(4) Megaloblastic anemia. (2) GIT: Nausea, vomiting.
(3) Liver: Jaundice.
DOSAGE (4) Renal: Nephrotoxicity.
(5) Blood: Anemia.
2 - 4 mg/kg/d, IM for upto 15 doses.
(6) Temp: Fever.
(7) Skin: Urticaria, exfoliative dermatitis.
Unit IV
MELARSOPROL

Drug Treatment of Mechanism of Action

Trypanosomiasis (1) It may act by inhibiting trypanothione reductase.
(2) It may act by inhibiting sulfhydryl enzymes.
Clinical Uses
African trypanosomiasis with CNS involvement.
INTRODUCTION Adverse Effects
(1) CNS: Encephalopathy, crippling sensory neuropathy.
(2) CVS: Capillary damage causing inc. permeability,
AFRICAN TRYPANOSOMIASIS dehydration & shock.
African trypanosomiasis or sleeping sickness is a disease (3) Resp. tract: Bronchitis, laryngitis.
caused by 'Trypanosoma brucei', & is transmitted to (4) GIT: Nausea, vomiting, abd. pain.
humans by flies of genus glossina. (5) Bone marrow: Bone marrow depression.
Clinical Features
Rapid pulse, irregular fever, rashes, glandular enlargement,
& after CNS becomes involved, severe headache, insanity, NIFURTIMOX
emaciation, lethargy, coma which may end in death.
Mechanism of Action
AMERICAN TRYPANOSOMIASIS
21: Chemotherapy of Protozoal Infections 173

It induces hydrogen per oxide production in Trypanosoma

cruzi, which may result in its trypanosomicidal action.
Clinical Uses
American trypanosomiasis.

Unit V

Self - Assessment (T/F)

(See answers on page no. 241)
(162) All of the following statements about anti-
malarial drugs are correct
(A) Chloroquine is a blood schizonticide but does
not affect secondary tissue schizonts.
(B) Proguanil is converted to a reactive metabolite
that is effective blood schizonticide.
(C) Primaquine acts primarily on exoerythrocytic
stages of malarial life cycle.
(D) Mefloquine destroys secondary exoerythrocytic
schizonts.
(E) Pyrimethamine destroys both erythrocytic &
exoerythrocytic stages of malarial parasites.
(163) Following antimalarial drugs causes hemolysis in G
- 6 - P - dehydrogenase deficiency
(A) Chloroquine.
(B) Quinine.
(C) Primaquine.
(D) Pyrimethamine.
(E) Proguanil.
(164) All of the following statements about amebicides are
correct
(A) Paromomycin is effective in extraintestinal
amebiasis.
(B) Diloxanide furoate is a luminal amebicide.
(C) Metronidazole has little activity in gut lumen.
(D) Systemic use of iodoquinol may cause thyroid
enlargement & peripheral neuropathy.
(E) Emetine can cause arrhythmias & precordial pain.
(165) Drugs effective in Kala-azar includes
(A) Amphotericin B.
(B) Na Stibogluconate.
(C) Dehydroemetine.
(D) Neostibosan.
(E) Pyrimethamine.
(166) Following drugs are used in late CNS stages of
African sleeping sickness
(A) Melarsoprol.
(B) Suramin.
(C) Nifurtimox.
(D) Tryparsamide.
(E) Pentamidine.
M. Shamim’s PHARMACOLOGY 174

22 CHEMOTHERAPY OF
HELMINTIC INFECTIONS
Fever, cough, profuse perspiration during night,
Unit I vomiting, urticaria, dysentery with blood & mucus in
feces, hepatosplenomegaly, cirrhosis.

Drug Treatment of DRUG CLASSIFICATION

Schistosomiasis
(1) Praziquantal
(Drug of choice against all 3 species).
SCHISTOSOMIASIS (2) Metrifonate
(Alt. drug in S. hematobium inf).
(3) Oxamniquine
It is a trematode or fluke infection of blood, caused by 3 (Alt. drug in S. mansoni inf).
species of family Schistosomitidae ie S. Mansoni, S.
Hematobium, & S. Japonicum, that gain access thru intact
skin when human baths in water infected with cercariae of PRAZIQUANTAL
Schistosomitidae.
Habitat Mechanism of Action
(1) S. Hematobium in the pelvic venous plexus. It inc. cell memb. permeability to Ca ions, resulting in
(2) S. Mansoni in the mesenteric veins of sigmoido-rectal marked contraction followed by paralysis of worm
area, & in the brs. of portal vein. musculature. Vacuolization & disintegration of tegmen
(3) S. Japonicum in veins of large intestine esp. in occurs & parasite death follows.
hemorrhoidal plexuses, & also in gastric & mesenteric Clinical Uses
veins. (1) Schistosomiasis.
Pathogenesis (2) Clonorchiasis.
They lay large number of eggs in circulatory system which (3) Opisthorchiasis.
causes lesion primarily at the sites of habitat, & secondarily (4) Paragonimiasis.
to other areas (eg in lungs, brain, & spinal cord) due to (5) Cysticercosis.
overflow phenomenon. (6) Beef tape worm inf.
(1) Terminal-spined eggs erode blood vessels causing (7) Fish tape worm inf.
hemorrhages. (8) Dwarf tape worm inf.
(2) Deposited eggs act like foreign protein having irritant (9) Pork tape worm inf.
effect, leading to round cell infiltration & connective (10) Rat tape worm inf.
tissue hyperplasia. (11) Hydatid disease
Clinical Features Adverse Effects
(1) S. Hematobium Infection ( Bilharziasis ) (1) CNS: Headache, dizziness, drowsiness, lassitude.
Hematuria, pain in the bladder region, back & on (2) GIT: Nausea, vomiting, abd. pain, loose to mushy
passing urine, frequency of micturition, hepatospleno- stools.
megaly, & dysentery with passage of blood & mucus (3) Musculo-skeletal system: Arthralgia, myalgia.
in feces if rectum is involved. (4) Blood: Eosinophilia.
(2) S. Mansoni Infection (5) Temp: Low grade fever.
Urticaria, pulmonary signs, abd. pain, dysentery, blood (6) Skin: Pruritus, macular & urticarial skin rashes.
& mucus in feces, prolapse of rectum, Contraindication
Ocular cysticercosis.
hepatosplenomegaly, cirrhosis.
Dosage
(3) S. Japonicum Infection
20 mg/kg TDS, for 1 day.
22: Chemotherapy of Helmintic Infections 175

METRIFONATE (b) Alt. drug  Niclosamide.

(4) For Diphyllobothrium Latum (Fish TW)
Infection
Mechanism of Action (a) Drug of choice  Praziquantal.
It is converted into active metabolite 'dichlorvos' which (b) Alt. drug  Niclosamide.
functions as a cholinesterase inhibitor  This results in (5) For Hymenolepis Diminuta (Rat TW) Infection
temporary paralysis of adult worms, leading in their shift (a) Drug of choice  Praziquantal.
from bladder venous plexus to small arterioles of lungs
(b) Alt. drug  Niclosamide.
where they are trapped & encased, & then die.
(6) For Cysticercosis (Pork TW Larval Infection)
Clinical Uses
(a) Drug of choice  Albendazole.
Bilharziasis ( S. hematobium inf ).
(b) Alt. drug  Praziquantal.
Adverse Effects
(1) CNS: Headache, fatigue, weakness, vertigo. (7) For Echinococcus Granulosus Inf. (Hydatid
(2) GIT: Nausea, vomiting, diarrhea, abd. pain. Disease)
(3) Resp. tract: Bronchospasm. (a) Drug of choice  Albendazole.
(4) Skin: Sweating. (b) Alt. drug  Mebendazole.

OXAMNIQUINE NICLOSAMIDE

Mechanism of Action Mechanism of Action

It may act by DNA binding. Scoleces & segments of tapeworm are rapidly killed on
Clinical Uses contact with niclosamide, due to drug's inhibition of
S. mansoni inf. oxidative phosphorylation or due to its ATPase stimulating
Adverse Effects property.
(1) CNS: Headache, dizziness, drowsiness, seizures, Clinical Uses
hallucinations. (1) Beep TW inf.
(2) Resp. tract: Cough, ronchi. (2) Pork TW inf.
(3) GIT: Nausea, vomiting, diarrhea, abd. colic. (3) Dwarf TW inf.
(4) Liver: Liver enzyme abnormalities. (4) Fish TW inf.
(5) Renal: Orange to red discoloration of urine, proteinuria, (5) Rat TW inf.
hematuria. (6) Fasciolopsis buski inf.
(6) Blood: Leukopenia, lymphopenia, eosinophilia. (7) Heterophyes inf.
(7) Temp: Low grade fever. (8) Metagonimus yokogawai inf.
(8) Skin: Urticaria, pruritus. Adverse Effects
(1) CNS: Headache, vertigo.
(2) GIT: Nausea, vomiting, diarrhea, abd. pain.
Unit II (3) Skin: Skin rashes, urticaria, pruritus ani.
Contraindications
Consumption of alcohol.
Drug Treatment of Dosage
2 gm orally.
Tapeworm (Cestode)
OTHER DRUGS
Infestations
Praziquantal
See Unit I.
DRUG CLASSIFICATION Mebendazole & Albendazole
See Unit III.
(1) For Taenia Saginata (Beef TW) Infection
(a) Drug of choice  Praziquantal, Niclosamide. GENERIC & TRADE NAMES
(b) Alternative drugs Mebendazole.
(2) For Taenia Solium (Pork TW) Infection (1) Mebendazole: Deworm, Erizole, Meben, Nemazole,
(a) Drug of choice  Praziquantal. Vermin, Vermol, Vermox, Wormizole, Zeworm,
(b) Alt. drug  Niclosamide. (2) Albendazole: Alben, Albendix, Albenza, Bendazol,
(3) For Hymenolepis Nana (Dwarf TW) Infection Polyworm, Wormgo, Wormocid, Zentel.
(a) Drug of choice  Praziquantal.
M. Shamim’s PHARMACOLOGY 176

(3) Niclosamide: Yomesan. Adverse Effects

(1) CNS: Headache, dizziness, drowsiness, insomnia.
(2) GIT: Nausea, vomiting, diarrhea, abd. cramps.
Unit III (3) Skin: Rashes.
(4) Temp: Fever.
Dosage
Drug Treatment of 20 mg/kg body weight in a single dose, on two successive
days with a max. of 1 gm.
Roundworm (Nematode)
Infestations MEBENDAZOLE

Mechanism of Action
It inhibits microtubule synthesis in nematodes, & impair
DRUG CLASSIFICATION their uptake of glucose. As a result, intestinal parasites are
immobilized or die slowly.
(1) For Ascaris Lumbricoides (Round Worm) Inf. Clinical Uses
(a) Drug of choice  Albendazole, Pyrantal pamoate, (1) Round worm inf.
Mebendazole. (2) Hook worm inf.
(b) Alt. drug Piperazine. (3) Pin worm inf.
(2) For Nector Americanos & Ankylostoma (4) Whip worm inf.
Duodenale (Hook Worm) Inf. (5) Thread worm inf.
(a) Drug of choice  Pyrantal pamoate, Mebendazole. (6) Trichina worm inf.
(b) Alt. drug  Albendazole. (7) Hydatid disease.
(3) For Enterobius Vermicularis (Pin Worm) Inf. (8) Beef tape worm inf.
(a) Drug of choice  Pyrantal pamoate, Mebendazole. (9) Pork tape worm inf.
(b) Alt. drug  Albendazole. (10) Intestinal capillariasis.
(4) For Trichuris Trichura (Whip Worm) Inf. (11) Visceral larva migrans inf.
Adverse Effects
(a) Drug of choice  Mebendazole, Albendazole.
(1) CNS: Headache, dizziness.
(b) Alt. drug  Pyrantal pamoate, Oxantel pamoate.
(2) GIT: Nausea, vomiting, diarrhea, abd. pain.
(5) For Strongyloides Stercoralis (Thread Worm)
Contraindications
Inf.
(1) Hepatic parenchymal disease.
(a) Drug of choice Ivermectin. (2) Pregnancy.
(b) Alt. drug  Thiabendazole, Albendazole. (3) Children under 2 years of age.
(6) For Trichinella Spiralis (Trichina Worm) Inf. Dosage
(a) Drug of choice  Mebendazole, & ACTH or (1) Thread worms  100 mg, dose is repeated after 2 or 3
Corticosteroids (for severe inf). weeks if required.
(b) Alt. drug  Albendazole, & Corticosteroids (for (2) Other worms  100 mg morning & evening, for 3 days.
severe inf).
(7) For Wuchereria Bancrofti Inf. (Filariasis)
(a) Drug of choice Diethylcarbamazine citrate. ALBENDAZOLE
(b) Alt. drug  Ivermectin.
Mechanism of Action
PYRANTAL PAMOATE It blocks glucose uptake by larval & adult stages of
susceptible parasites, depleting their glycogen stores &
dec. formation of ATP. As a result parasites are immobilized
Mechanism of Action & dies.
(1) It causes inhibition of neuromuscular transmission Clinical Uses
resulting in spastic neuromuscular paralysis with (1) Round worm inf.
subsequent expulsion of worm from host's intestinal (2) Hook worm inf.
tract. (3) Pin worm inf.
(2) It also inhibit cholinesterase. (4) Whip worm inf.
Clinical Uses (5) Thread worm inf.
(1) Round worm inf. (6) Hydatid disease.
(2) Hook worm inf. (7) Cutaneous larva migrans inf.
(3) Pin worm inf. Adverse Effects
(4) Whip worm inf. (1) CNS: Headache, dizziness, insomnia.
22: Chemotherapy of Helmintic Infections 177

(2) GIT: Nausea, diarrhea, epigastric distress. (1) Hepatic dysfunction.

(3) Blood: Leukopenia. (2) Renal dysfunction.
(4) Skin: Alopecia. Dosage
Contraindications 25 mg/kg orally after meals with a max. of 1.5 gm.
(1) Pregnancy.
(2) Children under 2 years of age.
DIETHYLCARBAMAZINE CITRATE
(3) Cirrhosis.
Dosage
400 mg in a single dose, orally. Mechanism of Action
It is an inhibitor of arachidonic acid metabolism in filarial
microfilaria. This makes the microfilaria more susceptible to
PIPERAZINE immune attack.
Clinical Uses
Mechanism of Action (1) Lymphatic filariasis caused by infection with
It causes paralysis of ascaris by blocking acetylcholine at Wuchereria bancrofti, Brugia malayi, or Brugia timori.
myoneural junction, which is then expelled live by normal (2) Tropical pulmonary eosinophilia.
peristalsis. (3) Loiasis.
Clinical Uses Adverse Effects
Ascariasis (round worm inf.) (1) CNS: Headache, malaise, weakness, dizziness.
Adverse Effects (2) GIT: Anorexia, nausea, vomiting.
(1) CNS: Headache, exacerbation of seizures. (3) Reactions to dying microfilariae: Fever, malaise,
(2) GIT: Nausea, vomiting, diarrhea, abd. pain. popular rash, headache, gastrointestinal symptoms,
(3) Allergic reactions: Serum sickness like-synd. cough, chest pain, muscle or joint pain, leukocytosis,
Contraindications eosinophilia, proteinuria, retinal hemorrhages,
(1) Impaired renal function. encephalopathy.
(2) Impaired hepatic function. (4) Reactions to dying adult worms: Lymphangitis,
(3) Chronic neurologic disease. wheals, papules.
Dosage
75 mg/kg orally, for 2 successive days.
GENERIC & TRADE NAMES

THIABENDAZOLE (1) Pyrantal pamoate: Anthelmin, Blissworm, Combantrin.

(2) Mebendazole & Albendazole: See Unit II..
Mechanism of Action (3) Piperazine: Engpar, Piperazine elixir, Pipragen,
It may act on parasites by interfering with microtubule Remipar.
aggregation, & thru inhibition of enzyme fumarate reductase. (4) Levamisole: Antiworm, Geomisole, Nilpar.
Clinical Uses (5) ACTH & corticosteroids: See Chapter 17.
(1) Thread worm inf.
(2) Trichina worm inf.
(3) Cutaneous larva migrans inf. Unit IV
(4) Visceral larva migrans inf.
(5) Intestinal capillariasis.
(6) Dracontiasis.
(7) Scabies (topically).
Self - Assessment (T/F)
(8) Tinea nigra palmaris (topically). (See answers on page no. 241)
Adverse Effect
(1) CNS: Headache, dizziness, drowsiness, giddiness, (167) All of the following statements concerning
tinnitus, paresthesias, visual disturbances. niclosamide are correct
(2) CVS: Bradycardia, hypotension. (A) It is effective in many tapeworm infections.
(3) GIT: Anorexia, nausea, vomiting, epigastric pain, abd. (B) It kills parasitic ova.
cramps. (C) Its effects include inhibition or uncoupling of
(4) Liver: Liver function abnormalities. oxidative phosphorylation.
(5) Skin: Pruritus, skin rashes esp. perianal, erythema (D) It can cause pruritus ani.
multiforme, toxic epidermal necrolysis. (E) It is usually administered intravenously.
(7) Blood: Leukopenia. (168) All of the following statements are correct,
(8) Temp: Fever with chills. regarding drug treatment of round worm
(9) Lymphatics: Lymphadenopathy. infestations
Contraindications
M. Shamim’s PHARMACOLOGY 178

(A) Mebendazole inhibits microtubule synthesis in

nematodes.
(B) Pyrantal pamoate inhibits neuromuscular trans-
mission, resulting in spastic neuromuscular
paralysis of parasites.
(C) Albendazole can cause alopecia.
(D) Piperazine is effective in most round worm
infestations.
(E) Albendazole is contraindicated in children under
2 years of age.
(169) All of the following drugs are effective in
schistosomiasis
(A) Praziquantal.
(B) Niridazole.
(C) Stibocaptate.
(D) Mebendazole.
(E) Na Stibogluconate.
M. Shamim’s PHARMACOLOGY 179

23 CANCER CHEMOTHERAPY

(B) Antimetabolites
Unit I (1) Folate Antagonists
Methotrexate, Pemetrexed.
(2) Purine Antagonists
Anti - Cancers 6-Mercaptopurine, 6-Thioguanine, Fludarabine,
Cladribine.
(3) Pyrimidine Antagonists
5-Fluorouracil, Capecitabine, Cytarabine,
CANCER (NEOPLASIA) Gemcitabine.
(C) Plant Alkaloids
It is a disease of uncontrolled cell division, invasion & (1) Vinca Alkaloids
metastasis, & is due to clonal expansion of a single Vinblastine, Vincristine, Vinorelbine.
neoplastic cell (however, there may be additional somatic (2) Epipodophyllotoxins
mutations, leading to heterogeneous cell population). Etoposide, Teniposide.
Characteristics of Cancer (3) Camptothecins
(1) Some lack of differentiation with anaplasia; structure is Topotecan, Irinotecan.
often atypical.. (4) Taxanes
(2) Rate of growth is erratic, & may be slow to rapid; Paclitaxel, Docetaxel.
mitotic figures usually numerous & abnormal. (D) Anticancer Antibiotics
(3) Invasion without encapsulation; usually infiltrative, but (1) Anthracyclines
may be cohesive & expansile. Daunorubicin, Doxorubicin, Idarubicin, Epirubicin.
(4) Metastasis is frequently present. (2) Miscellaneous
Bleomycin, Dactinomycin, Mitomycin,
Mitoxantrone.
DRUG CLASSIFICATION
(E) Hormonal Agents
(1) Antiandrogens
(A) Alkylating Agents Flutamide, Bicalutamide, Cyproterone.
(1) Bis-Chloroethyl Amines (2) Antiestrogen
Cyclophosphamide, Mechlorethamine (Nitrogen Tamoxifen.
mustard), Chlorambucil, Melphalan. (3) Progestins
(2) Nitrosoureas Megestrol acetate.
Carmustine, Lomustine, Semustine. (4) Adrenocorticosteroids
(3) Aziridines Hydrocortisone, Prednisone.
Triethylenemelamine, Thiotepa (Triethylenethio- (5) Gonadotropin-Releasing Hormone Agonists
phosphoramide), Altretamine (Hexamethyl- Leuprolide, Goserelin acetate.
melamine). (6) Aromatase Inhibitors
(4) Alkylsulfonates Aminoglutethimide, Anastrozole, Letrozole,
Busulfan. Exemestane.
(5) Triazenes (F) Miscellaneous Anticancer Drugs
Dacarbazine. Arsenic trioxide, Asparaginase, Bevacizumab,
(6) Plantinum Analogs Cetuximab, Dasatinib, Erlotinib, Gefitinib, Imatinib,
Cisplatin, Carboplatin, Oxaliplatin, Transplatin. Hydroxyurea, Trastuzumab, Retinoic acid derivatives.
(7) Miscellaneous
Procarbazine, Pentamethylmelamine, Ifosfamide,
BIS-CHLOROETHYL AMINES
Temozolomide.

MECHANISM OF ACTION
M. Shamim’s PHARMACOLOGY 180

(1) Kill rapidly proliferating cells as well as non- Mechanism of Action

proliferating cells, as a result of alkylation of RNA, (1) They decompose into alkylating & carbamylating
DNA & essential proteins. intermediates in aqueous environments.
(2) Antitumor activity results from alkylation of DNA, (2) Cause alkylation of DNA & other nucleophiles, &
most favored sites for alkylation being 7-nitrogen & carbamylation of lysine residues on proteins.
6-oxygen of guanine  This results in ; (3) Consequences of DNA alkylation are similar to nitrogen
(a) Cross linking, resulting in inhibition of DNA mustards.
replication. Clinical Uses
(b) Mispairing of bases, resulting in miscoding of (1) Carmustine
gene, & production of defective proteins. (a) Hodgkin's disease.
(c) Depurination of DNA resulting in weakened sugar- (b) Meningeal leukemia.
phosphate backbone of DNA & strand breakage. (c) Tumor of brain.
Note: Enzyme exist which can repair DNA damage caused (d) Acute lymphocytic leukemia.
by alkylation, & they may limit responsiveness of some (e) Non-Hodgkin lymphomas.
tumors. (f) Multiple myeloma.
(2) Lomustine
CLINICAL USES (a) Hodgkin's disease.
(1) Cyclophosphamide (b) Non-Hodgkin lymphomas.
(a) Hodgkin's disease. (c) Carcinoma of cervix.
(b) Burkitt's lymphoma. (d) Carcinoma of stomach & pancreas.
(c) Ovarian & breast carcinoma. (e) Melanoma.
(d) Oat cell lung cancer. Adverse Effects
(e) Neuroblastoma. (1) Acute Toxicity
(f) As immunosuppressive agent. GIT: Nausea, vomiting.
(2) Mechlorethamine (2) Delayed Toxicity
(a) Hodgkin's disease. (a) Blood : Leukopenia, thrombocytopenia.
(b) Mycosis fungoides. (b) Liver: Hepatitis.
(3) Chlorambucil
(a) Chronic lymphocytic leukemia. PLATINUM ANALOGS
(b) Waldenstrom's macroglobulinemia.
(4) Melphalan
Multiple myeloma. MECHANISM OF ACTION
Platinum complexes are formed in cells, which binds DNA
ADVERSE EFFECTS thru formation of intrastrand & interstrand cross-links,
ultimately inhibiting DNA synthesis & function & triggering
(1) Acute Toxicity
GIT: Nausea, vomiting ( with cyclophosphamide & apoptosis, or programmed cell death.
mechlorethamine ).
(2) Delayed Toxicity CLINICAL USES
(a) Renal: Hemorrhagic cystitis with (1) Cisplatin & Carboplatin
cyclophosphamide. Solid tumors eg sarcomas, some carcinomas (eg small
(b) Blood: Moderate depression of peripheral blood cell lung cancer, & ovarian cancer), lymphomas & germ
cell count. cell tumors.
(c) Bone marrow: Depression with leukopenia, (2) Oxaliplatin
thrombocytopenia & bleeding. Metastatic colorecatal cancer; it is typically
(d) Skin: Alopecia. administered in combination with fluorouracil &
leucovorin in a combination known as FOLFOX for the
DOSAGE treatment of colorectal cancer.
(1) Cyclophosphamide  3.5 - 5 mg/kg/d orally, for 10 days.
ADVERSE EFFECTS
(2) Mechlorethamine  0.4 mg/kg IV in single or divided
doses. Cisplatin & Carboplatin
(1) CNS: Neuropathy (nerve damage).
(3) Chlorambucil  0.1 - 0.2 mg/kg/d orally, for 10 days.
(2) GIT: Nausea, vomiting.
(4) Melphalan  0.25 mg/kg/d orally, for 4 days every
(3) Renal: Nephrotoxicity (kidney damage).
4 - 6 weeks.
(4) ENT: Ototoxicity (hearing loss).
(5) Skin: Alopecia (hair loss).
(6) Body fluids: Electrolyte disturbances include
NITROSOUREAS hypomagnesemia, hypokalemia & hypocalcemia.
23: Cancer Chemotherapy 181

Oxaliplatin MECHANISM OF ACTION

(1) CNS: Neuropathy (both an acute reversible sensitivity (1) It is first converted intracellularly into 6-mercaptopurine
to cold & numbness in the hands & feet, & a chronic ribose-phosphate & also into 6-methylmercaptopurine
irreversible foot/leg, hand/arm numbness, often with ribonucleotide  Both block aminotransferase that is
deficits in proprioception), fatigue. responsible for formation of 5-phosphoribosylamine
(2) GIT: Nausea, vomiting, diarrhea. (first step in purine biosynthesis)  Thus purine &
(3) Skin: Alopecia (hair loss). ultimately DNA synthesis in inhibited.
(4) Blood: Neutropenia. (2) 6- mercaptopurine ribose-phosphate also inhibits both
Note: Oxaliplatin has less ototoxicity & nephrotoxicity than adenylosuccinate synthetase (that converts inosinic
cisplatin & carboplatin acid to adenylosuccinic acid), & inosinate
dehydrogenase (that converts inosinic acid to xanthylic
METHOTREXATE acid).

CLINICAL USES
MECHANISM OF ACTION
(1) Acute lymphocytic leukemia.
(1) It is folic acid analog that competitively inhibits
(2) Acute myelocytic & myelomonocytic leukemia.
dihydrofolate reductase, which catalyzes formation of
(3) Chronic myelogenous leukemia.
tetrahydrofolate from dihydrofolate.
(4) Choriocarcinoma.
(2) Tetrahydrofolate is required for biosynthesis of
thymidylate & purines which are essential for DNA
ADVERSE EFFECTS
synthesis; thus methotrexate block DNA synthesis
resulting in inhibition of mitosis. (1) GIT: Anorexia, nausea.
(3) It also inhibits RNA & protein synthesis (b/c (2) Liver: Jaundice, hepatic necrosis, bile stasis.
tetrahydrofolate is required also for synthesis of (3) Blood: Myelosuppression, hyperuricemia.
methionine & glycine) which results in slow entry of (4) Renal: Hyperuricosuria.
cells into DNA synthesis phase.
DOSAGE
CLINICAL USES 2.5 mg / kg /d orally.
(1) Acute lymphocytic leukemia.
(2) Acute myelocytic & myelomonocytic leukemia. FLUOROURACIL
(3) Carcinomas of head & neck.
(4) Carcinoma of cervix.
MECHANISM OF ACTION
(5) Breast carcinoma.
(6) Choriocarcinoma. First it is activated to 5-fluoro-2'-deoxyuridine-5'-
(7) Carcinoma of testis. monophosphate ( FdUMP ) This block thymidylate
(8) Wilm's tumor. synthetase which transfers a methylene group from reduced
(9) Osteogenic sarcoma. folic acid to deoxyuridylate monophosphate to form
(10) Burkitt's lymphoma. thymidylate, essential for DNA synthesis Thus DNA
(11) Mycosis fungoides. synthesis is inhibited.
(12) Psoriasis.
CLINICAL USES
ADVERSE EFFECTS (1) Carcinomas of head & neck.
(1) CNS: Necrotizing leuko-encephalopathy (when given (2) Carcinoma of endometrium.
with radiation therapy). (3) Carcinoma of ovary.
(2) GIT: Ulcerative stomatitis, nausea, vomiting, diarrhea. (4) Carcinoma of breast.
(3) Liver: Hepatic dysfunction, cirrhosis. (5) Carcinoma of prostate.
(4) Renal: Renal failure. (6) Carcinoma of thyroid.
(5) Blood: Myelosuppression with leukopenia, (7) Carcinoma of stomach.
thrombocytopenia. (8) Carcinoma of pancreas.
(6) Skin: Dermatitis. (9) Carcinoma of colon.
(10) Insulinoma.
DOSAGE
2.5 - 5 mg/d orally; 10 mg intrathecally 1-2 times weekly. ADVERSE EFFECTS
(1) CNS: Neurologic toxicity.
(2) GIT: Stomatitis, nausea, diarrhea.
(3) Blood: Leukopenia.
MERCAPTOPURINE (4) Skin: Alopecia.
M. Shamim’s PHARMACOLOGY 182

DOSAGE (7) In biological & biomedical research as a microtubule

15 mg/kg/d IV for 5 days by 24-hour infusion; 15 mg / kg stabilizer.
weekly IV.
ADVERSE EFFECTS
VINCRISTINE (1) CNS: Tingling in the hands or toes, dizziness.
(2) GIT: Nausea, vomiting, anorexia, change in taste,
change in normal bowel habits.
MECHANISM OF ACTION (3) Resp: Cough, shortness of breath, chest pain.
It binds to tubulin dimers, inhibiting assembly of (4) ENT: Sore throat, dysphagia.
microtubule structures. Disruption of the microtubules (5) Temp: Fever, chills.
arrests mitosis in metaphase. (6) Skin: Thinned or brittle hair, changes in nail color, skin
Note: Vinca alkaloids affect all rapidly dividing cell types rash, facial flushing.
including cancer cells, but also intestinal epithelium & bone (7) Joints: Pain in the joints of arms or legs.
marrow. (8) Local: Bruising, pain/redness/swelling at injection site.

CLINICAL USES GENERIC & TRADE NAMES

(1) Non-Hodgkin's lymphoma as part of the chemotherapy
regimen CHOP.
(2) Hodgkin's lymphoma as part of MOPP, COPP, (1) Alkylating Agents
BEACOPP. Cyclophosphamide: Cyclomide, Endoxan, Shandoxan.
(3) Acute lymphoblastic leukemia. Melphalan: Melpha.
(4) Nephroblastoma (Wilms tumor). Busulfan: Busulf.
(5) As immunosuppressant, in thrombotic thrombocyto- Dacarbazine: Dacarbazine, Darbazine.
penic purpura (TTP). Cisplatin: Blastolem, Ceplatin, Cisplasol, Cisplatin,
Cisplatino, Cisplatinum, Platidiam, Lachema, Platimit,
ADVERSE EFFECTS Platinil, Platosin, Unistin.
(1) CNS: Peripheral neuropathy (eg foot drop). Carboplatin: Carboplatin, Carbotinol, Carpsol,
Cycloplatin, Neoplatine, Pharmaplatin.
(2) GIT: Constipation.
Oxaliplatin: Oxaltie.
(3) Body fluids: Hyponatremia.
Procarbazine: Natulan, P-carbazine.
(4) Skin: Alopecia.
Ifosfamide: Holoxan.
(2) Antimetabolites
PACLITAXEL Methotrexate: Cytotrexate, Emthexate, Methotrexat
lachema, Methotrexate, Metotrexato gador, MTX,
MECHANISM OF ACTION Pharmatrexate, Unitrexate.
Thioguanine: Thioguanine.
(1) Paclitaxel binds to the β subunit of tubulin (the
Fludarabine: Fludara.
"building block" of microtubules), & the binding of
paclitaxel locks these building blocks in place. The Fluorouracil: Pharmauracil.
resulting microtubule/paclitaxel complex does not have Capecitabine: Xeloda.
Cytarabine: Alexan, Cytocin.
the ability to disassemble. This adversely affects cell
Gemcitabine: Gemzar.
function because the shortening & lengthening of
microtubules (termed dynamic instability) is necessary (3) Plant Alkaloids
Vinblastine: Velbe, Vinblas.
for their function as a mechanism to transport other
cellular components. Vincristine: Oncovin, Pharmacristine, Vincristina
(2) It also induces programmed cell death (apoptosis) in Gador, Vincritine, Vinracine.
Vinorelbine: Navelbine.
cancer cells by binding to an apoptosis stopping protein
Etoposide: Etoposide, Etopul, Oncoside, Toposide,
called Bcl-2 (B-cell leukemia 2) & thus arresting its
Vepesid.
function.
Paclitaxel: Anzafax, Ebetaxel, Taxol, Unitaxel.
Docetaxel: Donataxel, Taxotere.
CLINICAL USES
(4) Anticancer Antibiotics
(1) Ovarian cancer. Daunorubicin: Donobin.
(2) Breast cancer. Doxorubicin Adriblastina, D-Rubicin, Deldoxin,
(3) Lung cancer. Doxobin, Doxolem, Doxorubicin, Doxorubin, Rubicin.
(4) Head & neck cancer. Idarubicin: Zavedos.
(5) Kaposi's sarcoma. Epirubicin: Epirubicin.
(6) Restenosis (recurrent narrowing of coronary stents). Bleomycin: Bleomycin.
Dactinomycin: Cosmegen.
23: Cancer Chemotherapy 183

(5) Hormonal Agents

See chapter 17, unit V.
(6) Miscellaneous Agents
Imatinib: Glivec.

Unit II

Self - Assessment (T/F)

(See answers on page no 241)
(170) Concerning mechanism of action of anticancer
drugs, all of the following statements are correct
(A) Alkylating agents commonly attack nucleophilic
N-7 position in guanine.
(B) Fluorouracil can cause thymineless death of
cancer cells.
(C) Mercaptopurine is an irreversible inhibitor of
HGPRTase.
(D) Lomustine causes alkylation of DNA that results
in inhibition of DNA replication.
(E) Methotrexate competitively inhibits dihydrofolate
reductase.
(171) Characteristic adverse effects of anticancer drugs
include
(A) Hemorrhagic cystitis with cyclophosphamide.
(B) Myelosuppression with methotrexate.
(C) Hepatic necrosis with mercaptopurine.
(D) Alopecia with nitrogen mustards.
(E) CNS toxicity with lomustine.
M. Shamim’s PHARMACOLOGY 184

24 VITAMINS & MINERALS

(4) Herpes zoster & neuralgias.

VITAMINS (5) Diabetes mellitus.
(6) Severe mental & physical work.
VITAMIN A Adverse effects
Rare; occasionally allergic reactions.
Mechanism of Action
Dosage
(1) Provides prosthetic group for photosensitive pigment
100-300 mg orally, SC or IM.
"rhodopsin" (essential for dark vision).
(2) Concerned with growth & differentiation of epithelia.
(3) Plays a role in synthesis of adrenal steroids. VITAMIN B2 ( RIBOFLAVIN )
Clinical Uses Mechanism of Action
(1) Prophylaxis & treatment of deficiency diseases of vit. A; It forms co-enzymes flavin adenine dinucleotide (FAD) &
(a) Hyperkeratosis. flavin mononucleotide (FMN); which act as hydrogen
(b) Night blindness (Nyctalopia). carriers.
(c) Xerophthalmia, Bitot spots, & keratomalacia. Clinical Uses
(d) Respiratory tract infections. Ariboflavinosis ( consisting of angular stomatitis, cheilosis,
(e) Squamous metaplasia of epithelium of renal pelvis, glossitis, seborrheic dermatitis, & corneal vascularization,
ureters, & urinary bladder. photophobia & lacrimation ).
(f) Urinary calculi. Dosage
(2) Impaired absorption of vit. A, eg in steatorrhea & 2-10 mg/day orally, SC or IM.
biliary tract obstruction.
(3) During infancy, pregnancy, & lactation. NICOTINAMIDE & NICOTINIC ACID
(4) Certain skin diseases, eg keratosis follicularis. Mechanism of Action
Adverse Effects It forms co-enzymes nicotinamide adenine dinucleotide
Hypervitaminosis A (NAD), & nicotinamide adenine dinucleotide phosphate
Chronic ingestion of 25,000 to 500,000 IU daily causes (NADP); which act as hydrogen carriers.
chronic vit. A toxicity or hypervitaminosis A. It is Clinical Uses
manifested by; (1) Pellagra.
(1) Painful tender swellings over bones. (2) Meniere's disease.
(2) Anorexia. Adverse Effects
(3) Hepatosplenomegaly, & lymphadenopathy. Nicotinic acid (which is converted to nicotinamide) causes:
(4) General malaise. (1) CVS: Peripheral vasodilation, unpleasant flushing,
(5) Skin lesions. fainting
(6) Inc. liability of biological membranes & outer layer of (2) Skin: Itching.
skin, to peel off. Dosage
Dosage (1) 100 mg 5 times/day orally.
(1) Men: 5000 IU/day. (2) 20 mg 2-3 times/day IV.
(2) Women: Normally 4000 IU/day; during pregnancy &
lactation 6000 IU/day. VITAMIN B6 ( PYRIDOXINE )
Mechanism of Action
VITAMIN B1 (THIAMIN) It forms co-enzyme 'pyridoxal-5-phosphate', that catabolize a
Mechanism of Action number of reactions in amino acids metabolism.
Thiamin pyrophosphate (TPP) is a co-enzyme for Clinical Uses
"carboxylase", & is required for carbohydrate metabolism. (1) Vomiting of pregnancy.
Clinical Uses (2) In combination with isoniazid to prevent peripheral
(1) Beriberi. neuritis.
(2) Alcoholic neuritis. (3) Agranulocytosis & anemia.
(3) Wernicke- Korsakoff syndrome. (4) Seborrheic dermatitis.
24: Vitamins & Minerals 185

(5) Radiation sickness. (5) Liver cirrhosis.

(6) With oral contraceptives (b/c the latter lowers its Adverse Effects
serum level). Overdose causes;
Dosage (1) CNS: Headache.
25 - 100 mg orally, IM or IV. (2) Eye: Blurred vision.
Dosage
VITAMIN C ( ASCORBIC ACID ) 15 IU/day, orally.
Mechanism of Action
(1) Acts as a powerful reducing or anti -oxidant agent, eg VIT. B12, FOLIC ACID, & VIT. K
it prevent oxidation of epinephrine in adrenal medulla. See Chapter 10, 'Drugs Affecting Blood'.
(2) Partakes in collagen biosynthesis.
(3) Partakes in tyrosine metabolism. GENERIC & TRADE NAMES
(4) Converts folic acid to folinic acid. (1) Vitamin A: Adexolin*, Geloit AD*, Rovigon*,
Clinical Uses Sclerobion*, Seven Seas*.
(1) Prevention & treatment of scurvy. (2) Vitamin B1: Alinamin - F*, Benerva, Berin, Bevidox*,
(2) Urinary acidification.
Thiamine.
(3) Methemoglobinemia (as a reducing agent).
(3) Vitamin B2: Alinamin - F*, Bevidox*, Neurofort*.
(4) Severe infections, dental caries, gum infections, anemia,
& hemorrhagic states. (4) Nicotinic acid: Nicosur, Nicotinic acid.
Adverse Effects (5) Vitamin B6: Navidoxine*, Sclerobion*, Vita 6, Vit B6
High doses cause sleep disturbances. inj.
Dosage (6) Vitamin B12 , Folic acid, & Vitamin K: See Chapter 10.
0.5 -1 gm daily, orally. (7) Vitamin B1, B6, & B12: Cyanorin Forte, Cytamen Comp,
Dilconeurine, Elkoneurin, Neurobedoxine*, Neurobion,
VITAMIN D3 ( CHOLECALCIFEROL ) Neurofort*, Neurovit, Novobion, Nuramine Forte,
Mechanism of Action Tabrovit, Thiavit, Triovit, Trividox, Uneskobion,
Cholecalciferol is converted in liver to 25-hydroxychole- Vioneurine Forte, Vitrobion.
calciferol, & then in kidney to 1,25-dihydroxycholecalciferol (5) Vitamin C: Ascorbon, Ascorlet, Ascorvit, Atcocee -
under the influence of parathyroid hormone  1,25- 500, CaC 1000*, C-Cor, Cebon, Cecon, Cecovit,
dihydroxycholecalciferol causes; Celimo, Citrovit - C, Efferalgen*, Energy - C*,
(1) Inc. Ca ++ & PO4- absorption from GIT & renal tubules. Redoxan, Semo - C, Vitacimin.
(2) Inc. maturation & calcification of epiphyseal cartilages. (6) Vitamin D: Adexolin*, Calcee D*, Calcico*,
Clinical Uses Calcidron*, Calci-Ostelin*, Calcium P*, Calcivit*,
(1) Prophylaxis & treatment of rickets & osteomalacia. Caltrate*, Calvid*, De-calc*, Gelvit AD*, Ostocalcium*,
(2) Hypoparathyroidism. Seven Seas*.
(3) Lupus vulgaris & tuberculosis of lymph nodes. (7) Vitamin E: Bliss E, Ephynal, Evion, Rovigon*,
Adverse Effects Sclerobion*, Seven Seas*, Vit E.
Hypervitaminosis D (8) Multivitamins without minerals: ABDEC, ACE -
Occurs due to excessive intake of vit. D, manifested by; BEX, Camovit L, Hexavit, Multibionta, Polyvit,
(1) CNS: Headache. Theraplex, Vi-Daylin, Vidaylin F..............
(2) GIT: Abdominal pain, vomiting, diarrhea. (9) Multivitamins with minerals: Becadexamin, Centrum,
(3) Kidney: Impairment of renal function. Dayalets, Genatosan, Nutrisan, Optilets-M, Panvitan-M,
(4) Others: Weakness, wt. loss. Polyvit-M, Stresstabs 600, Theragran-M, Unicap M,
Dosage Vi-Daylin M..........................
(1) 3000 - 4000 units/day.
(2) 600,000 units as a single dose IM. MINERALS

VITAMIN E
CALCIUM
Mechanism of Action
Mechanism of Action
It is antioxidant, that prevents oxidation of essential cellular
(1) Constituent of bone & teeth.
constituents or prevents formation of toxic oxidation
(2) Regulates nerve & muscle function.
products.
Clinical Uses
Clinical Uses
(1) Rickets.
(1) Habitual abortion & sterility.
(2) Osteomalacia.
(2) Muscular dystrophies.
(3) Tetanus.
(3) Coronary & peripheral vascular diseases.
Adverse Effects
(4) Certain types of anemia.
M. Shamim’s PHARMACOLOGY 186

(1) CNS: Irritability.

(2) GIT: Nausea, vomiting, diarrhea.
Contraindications
Renal calculi.
Dosage
(1) For tetanus: 10-20 ml 10% sol. at rate of 2 ml/min IV.
(2) For rickets & osteomalacia: 500 -1000 mg/day.
Generic & Trade Names
CaC 1000*, Calcee*, Calcee - D*, Calcico*, Calcidron*,
Calci-ostelin*, Calcium P*, Calcium Sandoz, Calcivit*,
Caltrate*, Calvid*, De Calc*, Energy C*, Ossopan 800*,
Ostocalcium*, Qalsan, Vitacal 1000 + C*, Upsa - C*.

IRON
See Chapter 10, 'Drugs Affecting Blood'.
M. Shamim’s PHARMACOLOGY 187

25 DRUG INTERACTIONS

(g) Alter Gut Flora

DRUG INTERACTIONS Antimicrobials may potentiate oral anti-coagulant
by dec. bacterial synthesis of vit K in large gut.
It refers to alteration in pharmacological effects of a drug, (2) After Parenteral Administration
due to concomitant administration of another drug. (a) Concomitant SC or IM injection of a drug with
Types epinephrine decreases its absorption (b/c
(1) Pharmacokinetic Drug Interactions epinephrine causes local vasoconstriction).
It is the alteration in plasma level for a given dose of a (b) Concomitant SC or IM injection of a drug with
drug. methacholine, increases its absorption (b/c of
(2) Pharmacodynamic Drug Interactions methacholine's local vasodilating effect).
It is the alteration in pharmacological effects at a given
plasma level of a drug. INTERACTIONS AFFECTING DRUG
DISTRIBUTION
(1) Competition for Plasma Protein Binding
PHARMACOKINETIC DRUG INTERACTIONS
Drugs compete for plasma protein binding sites  Inc.
free conc. & effect of displaced drug, eg;
INTERACTIONS AFFECTING DRUG ABSORPTION Phenylbutazone potentiates anticoagulant actions
(1) After Oral Administration of warfarin.
(a) Drug Binding (2) Displacement from Tissue Binding Sites
Cholestyramine binds drugs in GIT, decreasing It inc. blood conc. & effect of displaced drug, eg of
their absorption, eg of acetaminophen, digitalis digoxin by concurrent quinidine therapy.
glycosides, thiazides, thyroid hormones.
(b) Drug Adsorption INTERACTIONS AFFECTING METABOLISM
Certain drugs with large surface areas, eg (1) Induction or Inhibition of Microsomal
antacids, adsorbs drugs in GIT & dec. their Enzymes
absorption eg, of digoxin, iron, ketoconazole, (a) Induction
quinolones, salicylates, tetracyclines. It results in accelerated metabolism of drugs.
(c) Alter GI Motility Example of inducers: Barbiturates,
(i) Antimuscarinics decreases GI motility  Inc. carbamazepine, glutethimide, phenytoin, primidone,
bioavailability of poor soluble drugs, & dec. rifampin.
bioavailability of drugs degraded in gut eg Example of drugs whose metabolism is
levodopa. increased: Ca+2 channel blockers, corticosteroids,
(ii) Metoclopramide inc. gastric emptying  Dec. cyclosporine, doxycycline, estrogens,
absorption of drug that is absorbed in stomach, phenothiazines, quinidine, theophylline.
eg cimetidine. (b) Inhibition
(d) Absorption Blockade It results in decreased metabolism of drugs.
(i) Phenytoin & oral contraceptives inhibit folic Example of inhibitors: Allopurinol,
acid hydrolysis, & so its absorption. chloramphenicol, cimetidine, ciprofloxacin,
(ii) Colchicine causes vit B12 malabsorption. clarithromycin, diltiazem, enoxacin, erythromycin,
(e) Dietary Influence fluconazole, isoniazid, ketoconazole, metronidazole,
(i) Presence of food in stomach decreases miconazole, omeprazole, phenylbutazone,
absorption of some drugs. verapamil.
(ii) Fatty meal increases absorption of lipid- Example of drugs whose metabolism is
soluble drugs, eg griseofulvin. decreased: Oral anticoagulants, azathioprine,
(f) Alter Gastric pH mercaptopurine, carbamazepine, cyclosporine,
Weak acids, eg salicylates, are not absorbed phenytoin, sulfonylurea, benzodiazepines, lidocaine,
well when gastric pH is inc. with antacids. quinidine, theophylline.
M. Shamim’s PHARMACOLOGY 188

(2) Inhibition of Nonmicrosomal Enzymes PHARMACODYNAMIC DRUG INTERACTIONS

(a) MAO inhibitors dec. metabolism of various drugs,
eg barbiturates, benzodiazepines, serotonin,
norepinephrine. (1) Drug interactions can occur at the level of drug
(b) Xanthine oxidase inhibitors eg allopurinol receptors, eg;
results in accumulation of 6-mercaptupurine. H2 - receptor antagonist cimetidine blocks action of
histamine - like agonists, eg betazole.
INTERACTIONS AFFECTING DRUG EXCRETION (2) Drugs can dec. the effects of other drugs by acting via
(1) Competition for Transport System in different cellular mechanisms, eg;
Proximal Tubule Acetylcholine & norepinephrine have opposing effects
It results in dec. urinary elimination of competing drugs, on heart rate.
eg; (3) Drugs can inc. the effects of other drugs although
(a) Probenecid blocks excretion of penicillin, they act via different cellular mechanisms, eg;
indomethacin, cefazolin, & methotrexate. Ethanol increases CNS depression caused by opioids,
(b) Aspirin blocks excretion of methotrexate. or sedative - hypnotics.
(2) Changes in Urinary pH (4) Effect of one drug can be influenced by changes in
(a) Drugs that alkalinize urine, eg acetazolamide or intracellular or extracellular environment that are caused
NaHCO3, increases excretion of weak acids. by another drug, eg;
(b) Drugs that acidify urine, eg ammonium chloride, Diuretic-induced hypokalemia increases digitalis-
increases elimination of weak bases. induced cardiac toxicity.
(5) Chemical inactivation can occur systemically to reduce
a drug's action, eg;
Protamine binds heparin, thereby neutralizing it.
M. Shamim’s PHARMACOLOGY 189

26 ANTIDOTES

Antidotes: It refers to drugs that prevent absorption, inactivate, or antagonize the actions of poisons.

ANTIDOTE POISONING MECHANISM OF ACTION

Acetylcysteine Paracetamol, Chloroform, Carbon Replenish depleted glutathione stores

tetrachloride
Acids Alkalies Buffer
Alkalies Acids Buffer
Atropine Cholinesterase inhibitors eg, Blocks muscarinic cholinoceptors
Organophosphorus insecticides
Benztropine Drug - causing movement disorders Blocks muscarinic cholinoceptors
Benzyl-penicillin Amatoxin (Amanita phalloides) Displaces toxin from plasma albumin, &
enhances urinary excretion
Bicarbonate, sodium Membrane-depressant cardiotoxic drugs Provides a rapid increase in extracellular sodium
(tricyclic antidepressants, quinidine) that helps overcome sodium channel blockade.
Calcium edetate Lead Chelates lead ions
Calcium gluconate Hydrofluoric acid, Fluorides Binds or precipitates fluoride ions
Desferoxamine Iron Iron Chelates ferrous ions
Dicobalt edetate Cyanide & derivatives eg, Acrylonitrile Chelates to form non-toxic cobalti - &
cobalto – cyanides
Digoxin-specific Antibody Digitalis glycosides Binds free glycoside in plasma, & complex
fragments (FAB) excreted in urine
Dimercaprol (BAL) Arsenic, Copper, Gold, Lead, Inorganic Chelates metal ions
mercury
Esmolol Theophylline, caffeine, metaproterenol Short acting -blocker reverses 1-induced
tachycardia & 2-induced vasodilation
Ethanol Ethylene glycol, Methanol Competitively inhibits alcohol & acetaldehyde
dehydrogenases, preventing formation of toxic
metabolites
Flumazenil Benzodiazepines Competes for benzodiazepine receptors
Fomepizole Ethylene glycol, Methanol More convenient & easier to use than ethanol
Glucagon  - adrenoceptor antagonists Bypasses blockade of  - adrenoceptor;
stimulates cAMP formation with positive cardiac
inotropic effect
Isoprenaline  - adrenoceptor antagonists Competes for  - adrenoceptors

Methionine Paracetamol Replenish depleted glutathione stores

Naloxone Opioids Competes for opioid receptors
Neostigmine Antimuscarinic drugs, Tubocurarine Inhibits acetylcholinesterase, causing
acetylcholine to accumulate at cholinergic
receptor sites
M. Shamim’s PHARMACOLOGY 190

Oxygen Carbon monoxide (CO) Competitively displaces CO from binding sites

on hemoglobin
Penicillamine Copper, Gold, Lead, Zinc, Elemental Chelates metal ions
mercury (vapor)
Phenoxybenzamine Hypertensive drugs eg,  - adrenoceptor Competes for  - adrenoceptors (long - acting)
agonists, with MAOI, clonidine,
ergotamine
Phentolamine As above Competes for  - adrenoceptors (short- acting)
Phytonadione (vitamin Coumarin (warfarin) & Indandione Replenishes vitamin K
K1) anticoagulants
Physostigmine Antimuscarinic drugs Inhibits acetylcholinesterase, causing
acetylcholine to accumulate at cholinergic
receptor sites
Pralidoxime Cholinesterase inhibitors, eg Competitively reactivates cholinesterase
Organophosphorus insecticides ase
Propranolol  - adrenoceptor agonists, Ephedrine, Competes for  – adrenoceptors
Theophylline, Thyroxine
Protamine Heparin Binds ionically to neutralize
Prussian blue (ferric Thallium (in rodenticides) Exchanges for thallium
ferrocyanide)
Unithiol Lead, Elemental & organic mercury Chelates metal ions
M. Shamim’s PHARMACOLOGY 191

27 COMPARATIVE
PHARMACOLOGY

PHYSOSTIGMINE NEOSTIGMINE
(1) Nature (1) Nature
Natural alkaloid. Synthetic drug.
(2) Chemistry (2) Chemistry
(a) Carbamic acid ester of alcohol with tertiary (a) Also carbamic acid ester of alcohol but with
ammonium group. quaternary ammonium group.
(b) Yellow crystalline compound. (b) White crystalline compound.
(3) Mechanism of Action (3) Mechanism of Action
Reversible inhibitor of cholinesterase. Same.
(4) Pharmacological Effects (4) Pharmacological Effects
No direct effect on nicotinic receptors. Has direct nicotinic agonist effect at neuromuscular
junction.
(5) Pharmacokinetics (5) Pharmacokinetics
Well absorbed from GIT. Not well absorbed from GIT.
(6) Clinical Uses (6) Clinical Uses
(a) Used as antidote in atropine, phenothiazine & (a) No such use.
tricyclic antidepressant intoxication.
(b) Used in glaucoma. (b) No such use.
(c) No such use. (c) Used as antidote in paralysis induced by non-
depolarizing neuromuscular blockers.
(d) No such use. (d) Used in treatment of myasthenia gravis,
paralytic ileus & atony of urinary bladder.
(7) Adverse Effects (7) Adverse Effects
Produces CNS toxicity b/c it is capable of penetration Does not cross blood brain barrier, so no CNS toxicity.
of lipid barrier.
M. Shamim’s PHARMACOLOGY 192

TUBOCURARINE SUXAMETHONIUM
(1) Chemistry (1) Chemistry
(a) Quaternary alkaloid obtained from curare. (a) Synthetic quaternary amine compound.
(b) It is a rigid bulky molecule known as Pachycurare. (b) It has a molecule which is slender & flexible
known as Leptocurare.
(2) Pharmacokinetics (2) Pharmacokinetics
Metabolism is negligible, is excreted unchanged in Rapidly metabolized by pseudocholinesterase.
urine.
(3) Mechanism of Action (3) Mechanism of Action
(a) It has both affinity for receptor, but no intrinsic (a) It has both affinity for receptor as well as intrinsic
activity. activity.
(b) Competitively block nicotinic receptors at muscle (b) React with nicotinic receptors at muscle endplate
endplate. leading to depolarization (Phase I), but with
prolonged exposure flaccid paralysis occur due to
reduction in receptor sensitivity (Phase II).
(4) Pharmacological Effects (4) Pharmacological Effects
(a) No fasciculations are seen prior to paralysis. (a) Fasciculations are seen esp. over chest & abdomen
prior to onset of paralysis.
(b) Block autonomic ganglia. (b) Stimulates autonomic ganglia.
(c) No such effect. (c) Stimulates cardiac muscarinic receptors.
(d) Causes moderate inc. in histamine release. (d) Causes slight inc. in histamine release.
(e) No such effect. (e) Causes hyperkalemia.
(f) No such effect. (f) Causes inc. in intraocular pressure.
(g) No such effect. (g) Causes inc. in intragastric pressure.
(5) Effect on Paralysis (5) Effect on Paralysis
(a) Tubocurarine Administration (a) Tubocurarine Administration
Additive. Antagonistic in phase I, but augment phase II.
(b) Suxamethonium Administration (b) Suxamethonium Administration
Antagonistic. Additive in phase I, but augment phase II.
(c) Effect of Cholinesterase Inhibitors (c) Effect of Cholinesterase Inhibitors
Antagonistic. Augment phase I, but antagonizes phase II.
(d) Response to Tetanic Stimulation (d) Response to Tetanic Stimulation
Unsustained. Sustained in phase I, but unsustained in phase II.
(e) Posttetanic Facilitation (e) Posttetanic Facilitation
Present. Absent in phase I, but present in phase II.
(f) Effect of Procaine & Propanidid (f) Effect of Procaine & Propanidid
No effect. Prolong paralysis, b/c they are also metabolized by
pseudocholinesterase.
(g) Effect of Hypothermia (g) Effect of Hypothermia
Additive. Antagonistic.
(h) Effect of Diazepam (h) Effect of Diazepam
Antagonistic. Additive.
(i) No effect. (i) Streptomycin, neomycin, local anesthetics, &
quinidine has additive effects.
(j) Myasthenia Gravis (j) Myasthenia Gravis
Causes initial strengthening of muscle tone. Augments.
27: Comparative Pharmacology 193

MORPHINE CODEINE
(1) Chemistry (1) Chemistry
Member of phenanthrene series of opium alkaloids. Also a member of phenanthrene series of opium
alkaloids.
(2) Mechanism of Action (2) Mechanism of Action
By mimicking actions of opiopeptins, it stimulates Same.
opioidreceptors causing inhibition of release of
excitatory neurotransmitters.
(3) Pharmacological Effects (3) Pharmacological Effects
(a) CNS (a) CNS
(i) Potent analgesic. (i) Analgesic potency is 1/12th that of morphine.
(ii) Causes euphoria, & sedation. (ii) Less euphoriant, & sedative than morphine.
(iii) Causes respiratory depression. (iii) Less resp. depression that morphine.
(iv) Causes cough suppression. (iv) More potent cough suppressant.
(v) Causes miosis, truncal rigidity, & emesis. (v) Same.
(b) GIT (b) GIT
Causes constipation, & dec. gastric acid secretion. Same, but only mild effect.
(c) Biliary Tract (c) Biliary Tract
Constriction of biliary smooth muscle, & sphincter Same.
of oddi.
(d) Genitourinary Tract (d) Genitourinary Tract
(i) Dec. renal plasma flow. (i) Same.
(ii) Inc. ureteral, bladder, & urethral sphincter (ii) Same.
tone.
(e) Uterus (e) Uterus
Prolong labor by reducing uterine tone. Causes less reduction of uterine tone.
(f) Neuroendocrine (f) Neuroendocrine
(i) Stimulate ADH, prolactin, & somatotropin (i) Same.
release.
(ii) Inhibit luteinizing hormone release. (ii) Same.
(4) Clinical Uses (4) Clinical Uses
(a) Relief of mild to severe visceral & somatic pains. (a) Relief of only milder pain.
(b) For relief of dyspnea in pulmonary edema. (b) No such use.
(c) Cough. (c) Cough, & it is prefer over morphine.
(d) Diarrhea, & it is prefer over codeine. (d) Diarrhea.
(e) As premedicant drugs before anesthesia & surgery. (e) No such use.
(5) Adverse Effects (5) Adverse Effects
(a) CNS: Inc. intracranial pressure, behavioral (a) CNS: Same but less effect on intracranial
restlessness, tremor, hyperactivity. pressure.
(b) CVS: Postural hypotension esp. in hypovolemia. (b) CVS: Same but less intense.
(c) GIT: Nausea, vomiting, constipation. (c) GIT: Less effect than morphine.
(d) Renal: Urinary retention. (d) Renal: Same.
(e) Skin: Urticaria, itching. (e) Skin: Less so.
(f) Great addiction liability. (f) Addiction liability is less.
(g) Severe withdrawal symptoms. (g) Less severe withdrawal symptoms.
M. Shamim’s PHARMACOLOGY 194

CHLORPROMAZINE MEPROBAMATE
(1) Chemistry (1) Chemistry
Aliphatic phenothiazine. Propyl alcohol derivative (propanediol carbamate).
(2) Drug Category (2) Drug Category
Anti - psychotic drug or major tranquilizers. Anti - anxiety drug or minor tranquilizers.
(3) Pharmacological Effects (3) Pharmacological Effects
(a) CNS (a) CNS
(i) Produces neuroleptic effects consisting of (i) No such effect but it is useful in pt. suffering
emotional quieting & reduced physical from anxiety, worry & tension.
movement.
(ii) Produces extrapyramidal effects & parkin- (ii) No such effects.
sonism.
(iii) No such effect. (iii) Has anticonvulsant property.
(iv) Does not impair consciousness. (iv) Produces hypnosis.
(v) No such effect. (v) Central muscle relaxant effect thru
inhibitionof interneurons in polysynaptic
reflex pathways.
(vi) Has antiemetic effect due to direct depression (vi) No such effect.
of medullary vomiting centre.
(b) Anesthetic Property (b) Anesthetic Property
Has local anesthetic effect. No such effect.
(c) ANS (c) ANS
(i) Has alpha-adrenergic blocking activity (i) No such effect.
causing hypotension.
(ii) Has anticholinergic effect. (ii) No such effect.
(iii) Has ganglionic blocking activity. (iii) No such effect.
(d) CVS (d) CVS
(i) Has quinidine like antiarrhythmic effect. (i) No such effect.
(ii) Causes hypotension. (ii) No such effect.
(e) Endo (e) Endo
(i) Inhibit ADH secretion. (i) No such effect.
(ii) Stimulate release of lactogenic hormone (ii) No such effect.
causing lactation, galactorrhea, &
gynecomastia.
(f) Temp (f) Temp
Normally produces hypothermia, but in hot No such effect.
climate causes hyperthermia.
(g) Autacoids (g) Autacoids
Has antihistamine & anti-tryptamine effects. No such effect.
(4) Clinical Uses (4) Clinical Uses
Used in psychotic disorders, in treatment of nausea & Used in anxiety, insomnia, & skeletal muscle spasms.
vomiting, & as antipruritics.
(5) Adverse Effects (5) Adverse Effects
(a) CNS: Parkinsonism, acute dystonic reactions, (a) CNS: Drowsiness, ataxia.
tardive dyskinesia, lethargy, drowsiness.
(b) CVS: Orthostatic hypotension, reflex tachycardia. (b) CVS: No effect.
(c) Allergic reactions: Cholestatic jaundice, (c) Allergic reactions: Urticaria, skin rashes,
dermatitis, photosensitivity. pruritus.
(d) Blood: Agranulocytosis, eosinophilia. (d) Blood: Thrombocytopenia, leukopenia.
27: Comparative Pharmacology 195

COCAINE PROCAINE
(1) Chemistry (1) Chemistry
Ester of benzoic acid. Ester of diethylaminoethanol & para-aminobenzoic
acid.
(2) Mechanism of Action (2) Mechanism of Action
Block Na channels, causing inc. threshold for Same mechanism.
excitation slow impulse conduction, declining of rate
of rise of action potential, dec. action potential
amplitude, & finally abolished ability to generate
action potential.
(3) Pharmacological Effects (3) Pharmacological Effects
(a) Peripheral Nerves (a) Peripheral Nerves
Causes differential nerve block. Also causes differential nerve block.
(b) Neuromuscular Junction (b) Neuromuscular Junction
Slows or block impulse transmission. Same effect.
(c) CNS (c) CNS
Initially produces euphoria & some times Same effect.
dysphoria, followed by post-stimulatory
depression.
(d) CVS (d) CVS
(i) Depress abnormal cardiac pacemaker activity, (i) Same effect.
excitability, & conduction.
(ii) Causes tachycardia, & vasoconstriction. (ii) Depresses myocardial contractility & causes
arteriolar dilatation.
(e) Eye (e) Eye
Causes mydriasis. No effect.
(f) ANS (f) ANS
Blocks uptake of catecholamines at adrenergic Prevent release of acetylcholine from motor nerve
nerve terminals. endings.
(g) No such effect. (g) Antagonizes action of sulfonamides thru its
hydrolysis to para-aminobenzoic acid.
(h) Can be used topically. (h) It lacks topical activity.
(i) It has double the potency of procaine. (i) It has potency half that of cocaine.
(j) Has intermediate duration of action. (j) Has short duration of action.
(4) Pharmacokinetics (4) Pharmacokinetics
Degraded by pseudo-cholinesterases. Degraded by pseudo-cholinesterases.
(5) Clinical Uses (5) Clinical Uses
For topical anesthesia of nose, pharynx, & For nerve block, infiltration, & spinal anesthesia.
tracheobronchial tree.
(6) Adverse Effects (6) Adverse Effects
(a) CNS: Euphoria, sleepiness, lightheadedness, (a) CNS: Same effects.
nystagmus, shivering, visual & auditory
disturbances, convulsions, depression.
(b) CVS: No significant effect. (b) CVS: Hypotension, collapse.
(c) Temp: Hyperpyrexia. (c) Temp: No effect.
(d) Allergic reactions (d) Allergic reactions
M. Shamim’s PHARMACOLOGY 196

GUANETHIDINE RESERPINE
(1) Occurrence (1) Occurrence
Synthetic compound. Natural alkaloid derived from Rauwolfia compound.
(2) Pharmacokinetics (2) Pharmacokinetics
(a) Absorption from GIT is low & variable (3% to (a) Well absorbed from GIT.
30%).
(b) Given orally. (b) Given orally or parenterally.
(c) Metabolized by hepatic enzymes. (c) Metabolism involves hydrolysis of ester linkage,
& demethylation.
(3) Mechanism of Action (3) Mechanism of Action
It is taken up & stored in adrenergic nerve It blocks ability of adrenergic transmitter vesicles to
terminals, where it acts ( presynaptically ) to inhibit take up & store biogenic amines 2 This results in
release of norepinephrine, thus reducing response to depletion of norepinephrine, dopamine &
sympathetic nerve activation. serotonin in both central & peripheral neurons.
(4) Pharmacological Effects (4) Pharmacological Effects
(a) Initially, it displaces & releases enough unchanged (a) No initial hypertension & cardiac stimulation.
norepinephrine to cause mild, transient
hypertension & cardiac stimulation.
(b) Hypotension & bradycardia follows. (b) Hypotension & bradycardia occur as initial effects.
(c) Depresses vasoconstrictor reflexes, so postural (c) Only partially inhibits cardiovascular reflexes, so
hypotension is marked. less postural hypotension.
(d) No such effect. (d) Has direct vasodilating effect on vascular smooth
muscle when administered intra-arterially.
(e) Has a direct inhibitory effect on skeletal muscle (e) No such effect.
contraction.
(f) Inc. sensitivity of tissues to catecholamines (f) Not so.
(g) No central actions, as it does not cross blood brain (g) It exerts central actions that produce sedation.
barrier.
(5) Clinical Uses (5) Clinical Uses
Moderate to severe hypertension. Moderate hypertension.
(6) Adverse Effects (6) Adverse Effects
(a) CNS: No effects. (a) CNS: Sedation, lassitude, nightmares, depression,
extrapyramidal signs.
(b) CVS: Postural & exercise-induced hypotension, (b) CVS: Hypotension, bradycardia, nasal
hypertensive crises in pheochromocytoma. congestion.
(c) GIT: Diarrhea. (c) GIT: Diarrhea, abd. cramps, inc. gastric acid
secretion.
(d) Skeletal muscles: Ache & weakness. (d) Skeletal muscles: No effect.
(e) Repro: No effect. (e) Repro: Delayed or retrograde ejaculation.
(f) Tolerance occurs. (f) No tolerance.
27: Comparative Pharmacology 197

DIGOXIN DIGITOXIN
(1) Chemistry (1) Chemistry
A cardiac glycoside, obtained from dried leaves of A cardiac glycoside, obtained from dried leaves of
Digitalis lanata & from seeds of strophanthus gratus. Digitalis purpurea & Digitalis lanata, & from seeds of
strophanthus gratus.

(2) Pharmacokinetics (2) Pharmacokinetics

(a) Variable intestinal absorption (40% - 70%). (a) Well absorbed from GIT (90% - 100%).
(b) Less than 30% bound to plasma proteins. (b) About 97% bound to plasma albumin.
(c) Plasma half life is 36 hrs. (c) Plasma half life is 5-7 days.
(d) Principal metabolic route is kidney. (d) Principal metabolic route is liver.
(e) Has moderate lipid solubility. (e) Has high lipid solubility.
(f) Volume of distribution is 6.3 L / Kg. (f) Volume of distribution is 0.6 L / Kg.
(g) Therapeutic plasma conc. is 0.5-2 ng /ml. (g) Therapeutic plasma conc. is 10-25 ng /ml.
(h) Toxic plasma conc. is greater than 2 ng /ml. (h) Toxic plasma conc. is greater than 35 ng /ml.
(i) Rapid digitalizing dose is 0.5-0.75 mg every 8 hrs, (i) Rapid digitalizing dose is 0.2-0.4 mg every 12 hrs,
for 3 doses. for 3 doses.
(j) Daily maintenance dose is 0.125-0.5 mg. (j) Daily maintenance dose is 0.05-0.2 mg.
(k) Time to peak effect is 3-6 hrs. (k) Time to peak effect is 6-12 hrs.
(3) Pharmacological Effects (3) Pharmacological Effects
(a) Cardiac Effects (a) Cardiac Effects
(i) Inc. myocardial contractility. (i) Same effect.
(ii) Prolong refractory period & dec. conduction (ii) Same effects.
velocity of AV-node.
(iii) Dec. atrial & ventricular refractory periods. (iii) Same effects.
(iv) Inc. abnormal automaticity in ventricles & (iv) Same effects.
Purkinje system.
(v) Bradycardia in pts with CCF. (v) Same effects.
(vi) Prolong P-R interval. (vi) Same effect.
(vii)ST depression, & T wave inversion. (vii)Same effects.
(b) Extracardiac Effects (b) Extracardiac Effects
(i) In CCF, reduces peripheral vascular resistance (i) Same effects.
& venomotor tone.
(ii) Systolic BP inc., but diastolic BP falls. (ii) Same effects.
(4) Clinical Uses (4) Clinical Uses
(a) Congestive cardiac failure. (a) Same use.
(b) Atrial flutter & fibrillation, paroxysmal (b) Same uses.
supraventricular tachycardia.
(5) Adverse Effects (5) Adverse Effects
(a) CNS: Headache, fatigue, neuralgia, delirium, (a) CNS: Same effects.
visual impairment.
(b) CVS: Premature ventricular beats, ventricular (b) CVS: Same effects.
tachycardia & fibrillation, AV block, SA block,
sinus arrhythmia, atrial tachycardia.
(c) GIT: Anorexia, nausea, vomiting. (c) GIT: Same effects.
M. Shamim’s PHARMACOLOGY 198

ACTH CORTICOSTEROIDS
(1) Chemistry (1) Chemistry
(a) Human ACTH is a polypeptide hormone (a) Steroid compounds, composed of a cyclopentano-
consisting of 39 amino acids. perhydrophenanthrene ring.
(b) Synthetic preparations are available. (b) Same.
(2) Pharmacokinetics (2) Pharmacokinetics
(a) Being a polypeptide, it is not administered orally. (a) Readily absorbed from GIT.
(b) Given only parenterally. (b) Can be given parenterally.
(3) Mechanism of Action (3) Mechanism of Action
Stimulate specific protein receptor sites on adrenal Traverses target cell memb. & binds to nuclear
cortical cell memb. 2 cAMP system is activated & receptor forming a complex which then binds to
synthesis of corticosteroids is initiated. chromatin 2 mRNA formation is stimulated which
stimulates synthesis of various enzymes.
(4) Pharmacological Effects (4) Pharmacological Effects
(a) Stimulates growth of adrenal cortex, & secretion (a) Inhibit ACTH secretion by feed-back inhibition,
of corticosteroids (mainly glucocorticoids). leading to inhibition & atrophy of adrenal cortex.
(b) Administration of exogenous ACTH inhibits (b) Administration of exogenous corticosteroids
release of endogenous pituitary ACTH, but has inhibits release of both endogenous ACTH &
stimulatory effect on adrenal cortex. corticosteroids.
(c) Has some melanotropic activity. (c) No such effect.
(d) Carbohydrate Metabolism (d) Carbohydrate Metabolism
Effects (same) are mediated thru glucocorticoids Inc. gluconeogenesis, dec. peripheral carbohydrate
release. utilization, & promote glycogen storage in liver.
(e) Protein Metabolism (e) Protein Metabolism
Effect (same) are mediated thru glucocorticoids Inhibit protein synthesis, & inc. protein
release. catabolism.
(f) Fat Metabolism (f) Fat Metabolism
Effects (same) are mediated thru glucocorticoids Inc. lipolysis, & cause characteristic fat deposition
release. in neck & supraclavicular area (buffalo hump) &
in face (moon face) & trunk.
(g) Water & Electrolyte Metabolism (g) Water & Electrolyte Metabolism
Effects (same) are mediated thru corticosteroids Causes sodium retention, & inc. potassium
release. excretion.
(h) Inflammation (h) Inflammation
Effects (same) are mediated thru glucocorticoids Has anti-inflammatory & antiallergic effects
release. resulting from inhibition of PG & leukotriene
synthesis.
(5) Clinical Uses (5) Clinical Uses
For diagnosis of Addison’s disease, & secondary As replacement therapy in adrenal insufficiency, & in
adrenal insufficiency. management of rheumatoid arthritis & other
inflammatory disorders.
(6) Adverse Effects (6) Adverse Effects
(a) Suppression of pituitary function. (a) Suppression of pituitary-adrenal function.
(b) Inc. susceptibility to infection. (b) Same.
(c) Peptic ulceration. (c) Same.
(d) Less myopathy. (d) Myopathy characterized by proximal arm & leg
weakness.
(e) Less osteoporosis. (e) More osteoporosis.
(f) Hyperglycemia. (f) Hyperglycemia.
(g) Psychological disturbances. (g) Same.
(h) Allergic reactions (h) Not so.
27: Comparative Pharmacology 199

HALOTHANE ETHER
(1) Chemistry (1) Chemistry
(a) Colorless volatile liquid with chloroform like odor. (a) Colorless volatile liquid with a pungent irritant
odor.
(b) Non-inflammable, & non-explosive. (b) Inflammable & explosive.
(c) Boiling point is 50oC. (c) Boiling point is 35oC.
(2) Mechanism of Action (2) Mechanism of Action
Inc. threshold of cells to firing, resulting in dec. Same mechanism.
activity & also reduce rate of rise of action
potential by blocking Na channels.
(3) Pharmacological Effects (3) Pharmacological Effects
(a) CNS (a) CNS
(i) Potent general anesthetic with rapid induction, (i) Potent general anesthetic with slow induction,
& rapid recovery. & delayed recovery.
(ii) Dilate cerebral blood vessels resulting in inc. (ii) Same effect.
blood flow & CSF pressure.
(iii) Causes shivering during recovery. (iii) No such effect.
(b) CVS (b) CVS
(i) Dec. arterial BP. (i) BP maintained b/c of sympathetic activation.
(ii) Depressed myocardial contractility. (ii) Myocardial contractility remains near normal.
(iii) Bradycardia. (iii) Tachycardia.
(iv) Dilation of cutaneous blood vessels causing (iv) Same effect.
flushing.
(v) Interferes with norepinephrine action, & thus (v) No such effect.
antagonizes sympathetic response to arterial
hypotension.
(vi) Inc. automaticity of heart. (vi) No such effect.
(c) Respiratory System (c) Respiratory System
(i) Rapid & shallow respiration. (i) Also rapid & shallow respiration.
(ii) Causes a reduction in ventilatory response to (ii) Ventilatory response to CO2, although
CO2. reduced, is maintained spontaneously by
reflex excitation at peripheral sites.
(iii) Produces bronchiolar dilatation. (iii) Same effect.
(d) Renal (d) Renal
(i) Dec. renal blood flow & glomerular filtration (i) Same effect.
rate.
(ii) No such effect. (ii) Dec. urinary output as it is a strong stimulant
of ADH.
(e) Hepatic (e) Hepatic
Causes halothane hepatitis. Liver functions are only minimally depressed.
(f) Skeletal Muscle (f) Skeletal Muscle
Causes relaxation by both central & peripheral Same effect, but it is more effective relaxant than
mechanisms. halothane.
(g) Uterus (g) Uterus
Relaxes uterine smooth muscle. Same effect.
(4) Clinical Uses (4) Clinical Uses
For general anesthesia. For general anesthesia.
(5) Adverse Effects (5) Adverse Effects
Hepatotoxicity, respiratory depression. Inc. salivary secretion, vomiting, laryngospasm
M. Shamim’s PHARMACOLOGY 200

OPIOID (NARCOTIC) ANALGESICS NONOPIOID (NON-NARCOTIC) ANALGESICS

(1) Site of Analgesic Action (1) Site of Analgesic Action
Both cortical, & subcortical (thalamus). Subcortical on thalamus.
(2) Type of Pain Relieved (2) Type of Pain Relieved
Adequate doses can relieve any type of pain (except Low intensity pain eg, headache, neuralgia, myalgia,
itching). arthralgia, dysmenorrhea.
(3) Relief of Pain Accompanied By (3) Relief of Pain Accompanied By
Euphoria, stupor, or drowsiness. No euphoria, or drowsiness.
(4) Addiction (4) Addiction
Addictive. Non-addictive.
(5) Inflammatory Reaction (5) Inflammatory Reaction
No effect. Has peripheral anti-inflammatory effects which may
contribute to relief of pain (except aniline derivatives).

CODEINE ASPIRIN
(1) Chemistry (1) Chemistry
Phenanthrene derivative of opium alkaloid. Acetylsalicylic acid, a synthetic substance.
(2) Pharmacological Effects (2) Pharmacological Effects
(a) Powerful analgesic. (a) Weak analgesic.
(b) Not so. (b) Anti-inflammatory.
(c) Not so. (c) Anti-pyretic.
(d) Has hypnotic effects, & causes drowsiness, (d) No such effects.
clouding of thoughts, euphoria, reduced mental
activity & inc. in reaction time.
(e) No such effect. (e) Inhibits biosynthesis of prostaglandins.
(f) No such effect. (f) Inhibits hyaluronidase activity.
(g) Respiratory depressant thru depression of (g) Respiratory stimulant, acting directly by
medullary respiratory centre. increasing amount of CO2 peripherally.
(h) Causes vasodilation, & postural hypotension. (h) No significant effect.
(i) No such effect (i) Inc. clotting & prothrombin time.
(j) Stimulates chemoreceptor trigger zone, causing (j) Also stimulates chemoreceptor trigger zone.
nausea & vomiting.
(k) No such effect (k) Inc. gastric acid secretion.
(l) Produces miosis by stimulating Edinger-Westphal (l) No such effect.
nucleus.
(m) Potent cough suppressant. (m) Not so.
(3) Clinical Uses (3) Clinical Uses
(a) Relieving visceral & somatic pains. (a) Relieving mild & superficial pain eg, headache.
(b) No such use. (b) Relieving pain of dysmenorrhea.
(c) No such use. (c) Used in rheumatoid arthritis & acute rheumatic
fever.
(d) Useful in diarrhea due to spasmogenic activity. (d) No such use.
(e) For suppressing cough. (e) No such use.
(f) No such use. (f) Used in gout due to its uricosuric effect.
(4) Adverse Effects (4) Adverse Effects
(a) No such effect. (a) Gastric ulceration & hemorrhage.
(b) High doses cause respiratory acidosis, & (b) High doses cause respiratory alkalosis.
respiratory failure.
(c) Tolerance & addiction with chronic use. (c) No such effects.
(d) Retention of urine. (d) No such effect.
(e) Causes respiratory failure, biliary colic, (e) Causes salicylism characterized by headache,
constipation, prolonged labor, pruritus, sweating, confusion, drowsiness, tinnitus, difficulty in
& pin point pupil. hearing, thirst & diarrhea.
27: Comparative Pharmacology 201

QUINIDINE DIGITALIS
(1) Chemistry (1) Chemistry
An alkaloid isolated from cinchona bark. Obtained from dried leaves of foxglove, Digitalis
purpurea & from seeds of Strophanthus gratus.
(2) Pharmacokinetics (2) Pharmacokinetics
Well absorbed from GIT, & is usually given orally. Absorption from GIT varies (70%-100%) & is given
orally or parenterally.
(3) Pharmacological Effects (3) Pharmacological Effects
(a) Cardiac Effects (a) Cardiac Effects
(i) Depresses myocardial contractility by direct (i) Inc. myocardial contractility by inhibiting
myocardial depression & indirect Na+ - K+ - ATPase, & making more Ca++
anticholinergic effects. available intracellularly.
(ii) Prolong refractory period in AV-node, & dec. (ii) Prolong refractory period of AV-node, & dec.
conduction velocity in AV-node. conduction velocity thru AV-node.
(iii) Dec. refractory period in Purkinje fibres. (iii) Dec. ventricular refractory period.
(iv) Dec. automaticity in ventricles. (iv) Inc. automaticity in ventricles.
(v) Dec. heart rate. (v) Bradycardia in pts with CCF.
(vi) Inc. PR interval. (vi) Same.
(vii)Inc. Q-T interval. (vii)Dec. Q-T interval, with S-T depression.
(b) Extracardiac Effects (b) Extracardiac Effects
(i) Dec. peripheral vascular resistance due to (i) In CCF, a reduction in peripheral vascular
a - receptor blockade. resistance & venomotor tone occurs.
(ii) Not so, but instead hypotension occur. (ii) Systolic BP may inc. due to inc. stroke
volume.
(iii) Not so. (iii) Diastolic BP may fall due to improved
circulation & dec. reflex vasoconstriction.
(iv) Has antimalarial, antipyretic, & oxytocic pro- (iv) No such properties.
perties.
(4) Clinical Uses (4) Clinical Uses
(a) Atrial flutter & fibrillation, & paroxysmal (a) Same.
supra-ventricular tachycardia.
(b) No such use. (b) Congestive cardiac failure.
(c) Ventricular arrhythmias. (c) No such use.
(5) Adverse Effects (5) Adverse Effects
(a) CNS: Cinchonism characterized by tinnitus, (a) CNS: Headache, fatigue, neuralgias, delirium,
hearing loss, headache, diplopia, photophobia, visual impairment.
confusion, psychosis.
(b) CVS: Ventricular tachyarrhythmias, AV block, (b) CVS: Premature ventricular beats, ventricular
myocardial depression, quinidine syncope, inc. tachycardia & fibrillation, AV block, SA block,
digitalis toxicity, hypotension. sinus arrhythmia, atrial tachycardia.
(c) GIT: Anorexia, nausea, vomiting, diarrhea. (c) GIT: Anorexia, nausea, vomiting.
(d) Blood: Thrombocytopenia. (d) Blood: No effect
M. Shamim’s PHARMACOLOGY 202

ATROPINE HYOSCINE (SCOPOLAMINE)

(1) Occurrence (1) Occurrence
An alkaloid obtained from Atropa belladona. Also an alkaloid obtained from Hyoscyamus niger.
(2) Chemistry (2) Chemistry
An ester composed of tropic acid & organic base Also an ester composed of tropic acid & organic base
tropine. scopine.
(3) Mechanism of Action (3) Mechanism of Action
Competes reversibly with acetylcholine at muscarinic Same.
receptors.
(4) Pharmacological Effects (4) Pharmacological Effects
(a) Has more potent antimuscarinic effect on heart, (a) Less potent.
bronchial muscles, & intestines.
(b) Less potent in producing mydriasis, & cycloplegia. (b) More potent.
(c) Less potent in decreasing bronchial, salivary, & (c) More potent.
sweat gland secretions.
(d) Has mild stimulant effect on medullary centres, & (d) Has more marked sedative effects, producing
a slower longer lasting sedative effect. drowsiness & amnesia.
(e) Has longer duration of action. (e) Has shorter duration of action.
(f) Reduces tremor of Parkinson’s disease. (f) Same.
(5) Clinical Uses (5) Clinical Uses
Not so. Excellent for motion sickness.
(6) Adverse Effects (6) Adverse Effects
CNS stimulant effect produces restlessness, insomnia, CNS depressant effect produces sedation, drowsiness,
& excitement. euphoria, amnesia, fatigue, & dreamless sleep.
27: Comparative Pharmacology 203

EPINEPHRINE NOREPINEPHRINE
(1) Chemistry (1) Chemistry
Methylated norepinephrine. Hydroxylated dopamine.
(2) Mechanism of Action (2) Mechanism of Action
Stimulate both alpha & beta receptors. Stimulate alpha & beta-1 receptors.
(3) Pharmacological Effects (3) Pharmacological Effects
(a) Heart (a) Heart
(i) Tachycardia. (i) Reflex bradycardia due to vagal stimulation as
BP rises.
(ii) Inc. force of contraction. (ii) Same.
(iii) Greatly inc. excitability & conductivity. (iii) Less inc. in excitability & conductivity.
(iv) Inc. cardiac output. (iv) Dec. cardiac output or insignificant change.
(b) Blood Vessels (b) Blood Vessels
(i) Skeletal muscle blood vessels are dilated. (i) Constricted.
(ii) Skin & mucous memb. blood vessels are (ii) Same.
constricted.
(iii) Coronary vessels are dilated. (iii) Same.
(iv) Total peripheral resistance is decreased. (iv) Increased.
(c) Blood Pressure (c) Blood Pressure
(i) Systolic BP rises. (i) Same.
(ii) Diastolic BP falls. (ii) Rises.
(d) Smooth Muscle (d) Smooth Muscle
(i) Bronchial smooth muscles relaxed. (i) No effect.
(ii) Intestinal smooth muscles relaxed. (ii) Same.
(iii) Uterine smooth muscle may be inhibited or (iii) Uterine smooth muscle is stimulated only.
stimulated, depending on menstrual phase or
state of gestation.
(e) Metabolic Effects (e) Metabolic Effects
(i) Inc. glucose & lactate production, via liver & (i) No such effects.
muscle glycogenolysis.
(ii) Inhibit insulin secretion causing (ii) Also inhibit insulin secretion & causes
hyperglycemia. hyperglycemia.
(iii) Causes lipolysis resulting in inc. in free fatty (iii) Also causes lipolysis resulting in inc. in free
acids. fatty acids.
(4) Clinical Uses (4) Clinical Uses
Used to treat bronchospasm, hypersensitivity reactions, Used for treating hypotension during anesthesia when
anaphylaxis; to prolong the duration of infiltrative tissue perfusion is good.
anesthesia; to restore cardiac activity in cardiac arrest;
& to facilitate aqueous drainage in chronic open-angle
glaucoma.
M. Shamim’s PHARMACOLOGY 204

ERGOTAMINE ERGOMETRINE
(1) Chemistry (1) Chemistry
(a) Lysergic acid derivative. (a) Also lysergic acid derivative.
(b) Amino acid alkaloid. (b) Amine alkaloid.
(c) Sparingly soluble in water, & readily soluble in (c) Soluble in water & chloroform, but insoluble in
organic solvents. alcohol.
(2) Pharmacokinetics (2) Pharmacokinetics
Poorly & irregularly absorbed from GIT. Completely absorbed from GIT.
(3) Pharmacological Effects (3) Pharmacological Effects
(a) Onset of action is delayed even after parenteral inj. (a) Onset of action is rapid.
(b) Prolong duration of action. (b) Short duration of action.
(c) Competitively block alpha adrenergic receptors. (c) No such effect.
(d) Causes direct vasoconstriction of blood vessels (d) Cause slight vasoconstriction.
leading to elevation of BP.
(e) Has active oxytocic action, but of delayed onset. (e) Also has active oxytocic action, with rapid onset
& short duration.
(f) Stimulates cardioinhibitory centre, & (f) No such effect.
chemoreceptor trigger zone.
(g) Depresses vasomotor centre, psychomotor activity, (g) No such effect.
& respiratory centre.
(4) Clinical Uses (4) Clinical Uses
Migraine. In obstetrics for the treatment & prevention of
postpartum hemorrhage, & for helping involution of
uterus.
(5) Adverse Effects (5) Adverse Effects
May produce gangrene of finger & toes, & also May causes rupture of uterus.
convulsions.
27: Comparative Pharmacology 205

MORPHINE MEPERIDINE ( PETHIDINE )

(1) Chemistry (1) Chemistry
Phenanthrene derivative of opium alkaloid. Phenylpiperidine derivative, a synthetic substance.
(2) Pharmacological Effects (2) Pharmacological Effects
(a) Powerful analgesic. (a) Weak analgesic.
(b) Potent sedative. (b) Weak sedative.
(c) Devoid of any local action. (c) Produces mild local anesthesia.
(d) Produces severe depression of respiratory centre. (d) Produces slight depression of respiratory centre.
(e) Produces miosis due to stimulation of Edinger - (e) Produces mydriasis due to weak atropine-like
Westphal nucleus. activity.
(f) Block intestinal propulsive peristalsis, & stomach (f) No such effect.
motility.
(g) Potent cough suppressant. (g) No such effect.
(3) Clinical Uses (3) Clinical Uses
(a) Relieving both visceral & somatic pains. (a) Relief of (only) visceral pains.
(b) Used as anti-tussive. (b) No such use.
(c) Useful in diarrhea. (c) No such use.
(4) Adverse Effects (4) Adverse Effects
(a) More addiction liability. (a) Less addiction liability.
(b) More severe withdrawal effects. (b) Less withdrawal effects.
(c) More respiratory depression. (c) Less respiratory depression.
M. Shamim’s PHARMACOLOGY 206

HEPARIN WARFARIN
(1) Occurrence (1) Occurrence
(a) Naturally found in association with histamine in (a) Naturally found in spoiled sweet clover.
mast cells.
(b) Commercially obtained from lungs of domestic (b) Also prepared synthetically.
animals.
(2) Chemistry (2) Chemistry
Mucopolysaccharide composed of sulfated D- Bis-hydroxycoumarin.
glucosamine & D-glucoronic acid.
(3) Pharmacokinetics (3) Pharmacokinetics
(a) Not effective orally, & so must be given (a) Well absorbed orally.
parenterally.
(b) Not so. (b) 99% bound to plasma proteins.
(c) Metabolize in liver by heparinase. (c) Also metabolize in liver, & undergo enterohepatic
circulation.
(4) Pharmacological Effects (4) Pharmacological Effects
(a) Prolong clotting time both in vivo & in vitro. (a) Prolong clotting time only in vivo.
(b) Prevents fibrin formation in coagulation process (b) No such effect.
by increasing activity of antithrombin III.
(c) No such effect. (c) Interfere with vit. K dependent synthesis of active
coagulation factors II, VII, IX & X.
(d) Produces a clearing effect on postprandial turbid (d) No such effect.
lipemic plasma, by causing release of lipoprotein
lipase.
(e) Dec. aldosterone secretion & inc. conc. of free (e) No such effect.
thyroxin.
(f) Slows wound healing, & also depresses cell (f) No such effect.
mediated immunity.
(g) Onset of action is immediate after intravenous inj., (g) Onset of action is delayed, taking 1 - 2 days.
& 30 - 60 min. after intramuscular inj.
(h) Duration of action is short (2-4 hrs after IV inj). (h) Duration of action is long (4 - 7 days).
(5) Adverse Effects (5) Adverse Effects
(a) GIT: No effect. (a) GIT: Anorexia, nausea, vomiting, diarrhea.
(b) Blood: Hemorrhages from any site, transient (b) Blood: Hemorrhages from any site.
thrombocytopenia.
(c) Skin: No effect. (c) Skin: Urticaria, purpura, painful erythematous
patch, purple-toe syndrome.
(d) Allergic reactions. (d) Not so.
(e) Transient alopecia. (e) Same.
(6) Antidotes (6) Antidotes
Protamine sulfate, fresh blood transfusion, Vitamin K1 (phytonadione), fresh blood transfusion.
hexadimethrine (polybrene), toluidine blue.
(7) Contraindications (7) Contraindications
Hypersensitivity, bacterial endocarditis, TB, recent Same.
head trauma, recent major surgery.
M. Shamim’s PHARMACOLOGY 208

28 PRACTICAL PHARMACOLOGY

(c) 1000 mg = 100 cg = 10 Decigram = 1 Gram

Unit I (gm).
(d) 1000 gm = 100 Decagram = 10 Hectogram
= 1 Kilogram (Kg) = 0.001 Metric Ton.
Pharmacy (B) Capacity (Vol) Measurements
(1) British (Imperial) System
(a) 1 Minim = 1 drop = 0.0166 Fluid dram.
(b) 1 Fluid dram = 0.125 Fluid ounce = 60 minims.
DEFINITIONS (c) 1 Fluid ounce = 0.25 Gill = 0.0625 Pint = 480
minims.
Pharmacy (d) 1 Pint = 0.5 Quart = 0.125 Gallon = 16 Fluid
It refers to the branch of health sciences that deals with ounces.
preparation, dispensing, & proper utilization of drugs. (e) 1 Gallon = 8 pint = 128 Fluid ounce.
Materia Medica (2) Metric System
It refers to the branch of health sciences that deals with (a) 103 Microliter (l) = 1 Milliliter (ml).
drugs, their sources, preparations, & uses. (b) 10 ml = 1 Centiliter (cl).
Pharmacopoeia (c) 1000 ml = 100 cl = 10 Deciliter = 1 liter (L).
It is an authorative treatise on drugs & their preparations; a (d) 1000 L = 100 Decaliter = 10 Hectoliter
book containing a list of products used in medicine, with = 1 Kiloliter (Kl) = 0.001 Megaliter.
descriptions, chemical tests for determining identity & (C) Domestic Measures
purity, & formulas for certain mixtures of these substances. (1) l Teaspoonful = 5 ml.
Examples (2) l Desert spoonful = 10 ml.
(1) British Pharmacopoeia (BP). (3) l Table spoonful = 15 ml.
(2) United States pharmacopoeia (USP). (4) l Teacupful = 5 fluid oz.
(D) Conversion of Measures
MEASUREMENT SYSTEMS (1) Weight Conversion
(a) l gram = 15 grains (Apothecaries).
(b) l kilogram = 2.68 pound (Apothecaries).
(A) Weight Measurement (c) l pound (Avoirdupois) = 453.59 grams.
(1) British (Imperial) System (d) l ounce (Avoirdupois) = 28.35 grams.
(a) Avoirdupois Weight (2) Volume Conversion
(i) 1 Grain (gr) = 0.0366 Dram. (a) 1 Minim = 0.06 milliliter.
(ii) 1 Dram = 0.0625 Ounce (oz) = 27.34 gr. (b) 1 Fluid dram = 3.70 milliliters.
(iii) 1 Ounce = 0.0625 Pound (lb) = 16 Dram (c) 1 Fluid ounce = 29.57 milliliters.
= 437.5 gr. (d) 1 milliliter = 16.231 minims.
(iv) 1 Pound = 16 oz = 256 Dram = 7000 gr.
(b) Apothecaries' Weight
(i) 1 Grain (gr) = 0.05 Scruple. LOTION
(ii) 1 Scruple = 0.333 Dram = 20 gr.
(ii) 1 Dram = 0.125 Ounce (oz) = 60 gr. Definition
(iii) 1 Ounce = 0.0833 Pound (lb) = 8 Dram It is a liquid suspension or dispersion (ie an aqueous sol. of
= 24 Scruple = 480 gr. an active drug) with alcohol or glycerine, for external
(iv) 1 Pound = 12 oz = 96 Dram = 288 Scruple application to the body.
= 5760 gr. Calamine Lotion
(2) Metric System (1) BP Formula
(a) 103 Microgram (g) = 1 Milligram (mg). (a) Calamine (Z n carbonate) = 150 gm.
(b) 10 mg = 1 Centigram (cg). (b) Zn oxide = 50 gm.
28: Practical Pharmacology 209

(c) Bentonite = 30 gm. (1) Wool fat = 50 gm.

(d) Sodium citrate = 5 gm. (2) Hard paraffin = 50 gm.
(e) Liquid phenol = 5 ml. (3) Alcohol = 50 gm.
(f) Glycerine = 50 ml. (4) Soft paraffin = 850 gm.
(g) Distilled water added upto 100 ml. Sulphur Ointment
(2) Uses (A) BP Formula
(a) As mild astringent. (1) Sulphur = 100 gm.
(b) To allay itching & burning. (2) Soft paraffin = 900 gm.
(c) As antiseptic. (B) Uses
Viva Questions (1) Scabies.
(1) Astringent ? (2) Acne.
These are substances which when applied to wet skin (3) Psoriasis.
precipitates & coagulates the proteins of exudates, eg (4) Chronic eczema.
silver nitrate, zinc oxide, & alcohol. Zinc Oxide Ointment
(2) Purpose of adding alcohol or glycerine to (A) BP Formula
lotion ? (1) ZnO = 150 gm.
(a) Alcohol, to accentuate the cooling effect of lotion. (2) Soft paraffin = 850 gm.
(b) Glycerine, to maintain the surface to which lotion is (B) Uses
applied in a moist condition. As astringent & antiseptic in dry eczema, acne, &
dermatitis.
Viva Questions
LINIMENT
(1) Functions of base ?
(a) To produce stable ointment.
Definition (b) To lubricate the skin.
It is an oily liquid or semiliquid preparation in the form of (c) To reduce water evaporation from skin, thus to keep
emulsion, intended for application to skin with friction. it moist.
Official Liniments (d) To protect skin from external moisture.
(1) Liniment of turpentine. (e) To disperse the active ingredient.
(2) Liniment of camphor. (2) pH of an ointment ?
Liniment of Turpentine Should be neutral.
(A) BP Formula (3) Creams ?
(1) Soft soap = 75 gm. These are semi-solid emulsions, either oil in water ( eg
(2) Camphor = 50 gm. vanishing cream) or water in oil (eg cold cream),
(3) Turpentine oil = 650 ml. intended for topical application.
(4) Water = 225 ml. (4) Scabies ?
(B) Uses It is an itching skin infection caused by a mite called
(1) As counter-irritant for myalgia, neuralgia, sprains, sarcoptes scabiei.
pleurisy, pneumonia, & bronchitis.
(2) As rubefacient.
Viva Questions SOLUTION
(1) Counter-irritants ?
These are substances which when applied to the skin Definition
cause stimulation, followed by paralysis of sensory It is a liquid preparation containing one or more soluble
nerve endings ( eg turpentine, camphor, menthol, chemical substances usually dissolved in water.
mustard, capsicum ). Types
(2) Rubefacients ? (1) Simple solution: A solution prepared by dissolving
These are substances that cause redness of skin by solute in a suitable solvent eg, Ca(OH)2.
local vasodilation. (2) Compound solution: A solution prepared by reacting
two or more solutes in a suitable solvent eg, Lugol's
OINTMENT iodine sol.
% of Solution
Certain part of solute is dissolved in such a quantity of
Definition solvent that produces 100 parts of solution, eg 1% sol.
It is a semi-solid preparation for topical applications, that means 1 gm of solute dissolved in 100 ml of water.
usually contain a medicinal substance. Lugol's Iodine
Base or Vehicle: It is a substance in which active ingredient (A) BP Formula
is dispersed, eg paraffin, wax, fat. (1) Iodine = 50 gm.
BP Formula of Simple Ointment (2) KI = 100 gm.
M. Shamim’s PHARMACOLOGY 210

(3) Water = 1000 ml. POWDERS

(B) Uses
(1) Iodine deficiency goiter.
(2) Thyrotoxicosis (pre-operatively to make it Definition
euthyroid). These are solid medicines in finely divided form.
Viva Questions Types
(1) Solute ? (1) Simple powders: Contain one active ingredient eg,
Substance which is dispersed in a continuous phase. calomel powder.
(2) Solvent ? (2) Compound powders: Contain more than one active
Medium in which dispersion takes place. ingredients eg, powder containing hyoscine hydro-
bromide & pilocarpine nitrate.
(3) Systemic powders: For internal use in the form of
EMULSION tablets or capsules eg, antacids, antiemetics, purgatives,
vitamins, antibiotics.
Definition (4) Topical powders: For external use eg, dusting powders,
It is a preparation of two immiscible liquids one of which is snuff, tooth powders.
dispersed as fine globules (dispersed phase liquid) thru-out Viva Questions
the other (continuous phase liquid). (1) Dry lubricants ?
Types A type of dusting powder that reduces friction b/w
(1) Oil in water: Oil is dispersed phase & water is two opposing skin surfaces eg, talc (hydrated Mg
continuous phase. silicate).
(2) Water in oil: Water is dispersed phase & oil is (2) Drying agents ?
continuous phase. A type of dusting powder that absorb water & are used
Emulsifying Agents in moist skin lesions eg, starch, zinc oxide.
These are substances which lower surface tension of one
of the liquid which is thus divided into fine globules. MIXTURE
Classification
(A) Agents Producing Oil in Water Emulsion
(1) Polymeric carbohydrates: Gum acacia, sodium Definition
alginate, methyl cellulose, Irish mosh. It is a combination of different drugs as a fluid, resulting
(2) Proteins: Gelatin, lecithin, soluble casein. from mixing a fluid with other fluids or with solids, or a
(3) Alkalies: Potassium hydroxide. suspension of a solid in a liquid.
(4) Soaps: Soaps of long chain fatty acids eg, stearic Carminative Mixture
acid. (A) BP Formula
(5) Cationic substances: Amines of quaternary (1) NaHCO3 = 0.6 gm
ammonium compounds eg, cetrimide. (2) Spirit aromatic ammonia = 0.6 ml
(6) Finely divided solids: Bentonite, kaolin. (3) Spirit chloroform = 0.3 ml
(B) Agents Producing Water in Oil Emulsion (4) Tinc. cardamon compound = 2 ml
(1) Polyvalent soaps: Soaps of Ca, Mg, & Zn. (5) Aqua added upto 30 ml
(2) Waxes: Bees wax, wool alcohol. (B) Uses
(3) Finely divided solids: Zinc oxide, talc. (1) As antiflatulent.
Cod Liver Oil Emulsion (2) In indigestion.
(A) BP Formula
Oil : Water : Gum = 4 : 2 : 1
SUSPENSION
(B) Uses
Vit. A & D deficiency diseases eg, osteomalacia, rickets,
night blindness. Definition
Viva Questions It is a preparation of finely divided drug intended to be
(1) Properties of oil in water emulsion ? suspended in some suitable liquid vehicle (eg water) before
(a) White in color. it is used, or already suspended in such a vehicle (eg gum,
(b) Non-greasy. kaolin).
(c) Conducts electricity. Example
(2) Properties of water in oil emulsion ? Alumina & magnesia oral suspension.
(a) Takes on color of oil.
(b) Greasy.
(c) Poor conductor. PRESCRIPTION
28: Practical Pharmacology 211

Definition (2) Ethyl chloride act on human skin ?

It is a physician's written order to a pharmacist to dispense Yes, b/c it is keratolytic.
certain drugs in a particular form, including directions for (3) Local anesthetics given with epinephrine at
its use. base of finger or ear lobes ?
Constituents No, b/c epinephrine causes vasoconstriction that can
(1) Superscription: Consists of the symbol R ( recipe = lead to local ischemic necrosis.
take). (4) Sequence of loss of sensations ?
(2) Inscription: Body of prescription consisting the name Touch  Pain  Temperature.
& quantity of the drugs ordered. (5) Symptoms & signs of cocaine addiction ?
(3) Subscription: Directions to the dispenser. (a) CNS: Euphoria, tremors, hyperexcitability,
(4) Directions to the patient. convulsions.
(5) Pt's name & age are written at the top. (b) Eye: Dilated pupils.
(6) Signature: Dr's initial is in the end. (c) Cocaine bugs.
Abbreviations (d) Cocaine chills.
(1) HS (Hora somni) = At bed time.
(2) QS (Quantum sufficient) = A sufficient quantity.
EXPERIMENT TO STUDY ANALEPTICS ON CNS OF
(3) Rx (Recipe) = Take.
FROG
(4) SOS (Si opus sit) = If necessary.
(5) Mist (Mistura) = Mixture.
(6) ac (Anti cibus) = Before meal. Observations
(7) pc (Post cibus) = After meal. (A) Frog A
(8) CM (Cras mane) = Tomorrow morning. Inj. 0.25 ml of strychnine sol. intraperitoneally;
(9) CN (Cras nocte) = Tomorrow night. (1) Prodromal phase: Rapid respiration, twitching,
(10) OD (Omni die) = Once daily. restlessness.
(11) BID or BD (Bis in die) = Twice daily. (2) Convulsion phase: Tonic, reflexed, & symmetrical
(12) TID or TDS (Ter in die) = Thrice daily. convulsions.
(13) QID (Quarter in die) = Four times a day. (3) Effect of after pithing: Convulsions persist.
(14) Stat (Statum) = Immediately. (B) Frog B
Inj. 0.5 ml of picrotoxin sol. intraperitoneally;
(1) Prodromal phase: Rapid respiration, twitching,
Unit II restlessness.
(2) Convulsion phase: Clonic, non-reflexed, &
asymmetrical convulsions.
Pharmacodynamics (3) Effect of after pithing: Convulsions are abolished.
Inference
Strychnine is spinal stimulant, whereas picrotoxin is higher
centre (medullary) stimulant.
EXPERIMENT OF FROG'S LEG TO DIFFERENTIATE Viva Questions
B/W SURFACE & INFILTRATION ANESTHETICS (1) Clonic convulsion ?
Contractions are intermittent ie muscle alternately
Observations contracts & relaxes, eg in epilepsy & eclampsia.
(1) Check normal reflexes of frog by dipping both of its (2) Tonic (tetanic) convulsions ?
legs in hot water at 60oC  +ve withdrawal response Muscle contraction is sustained, eg in strychnine
in both legs. poisoning & tetanus.
(2) Dip right leg in lignocaine sol. & left leg in procaine for (3) Mechanism of action of picrotoxin ?
5 minutes, & then dip both legs in hot water at 60oC Antagonizes GABA (an inhibitory neurotransmitter) 
 No response in right leg, & +ve withdrawal Increased motor activity.
response in left leg. (4) Mechanism of action of strychnine ?
(3) Inject 0.25 ml of procaine in left leg, & then dip both Reduces the inhibitory influence exerted by Renshaw
legs in hot water at 60oC  No response in both legs. cells in spinal cord  Increased motor activity.
Inference (5) Level of pithing ?
Lignocaine is a surface anesthetic, whereas procaine is an B/w C1 & C2 of frog.
infiltration anesthetic. (6) Treatment of convulsions ?
Viva Questions (a) Diazepam IV.
(1) Surface anesthetics act on human leg ? (b) Clonazepam IV.
No, b/c they are unable to penetrate keratin layer present (c) Pentothal IV.
on human skin.
M. Shamim’s PHARMACOLOGY 212

EXPERIMENT TO STUDY ACTIONS OF DRUGS ON (b) Peristalsis is the movement of intestine in the form
A PIECE OF INTESTINE OF RABBIT of a constrictive ring that moves analward.

Observations EXPERIMENT TO STUDY DRUG'S EFFECTS ON

(A) Identification of Stimulants RABBIT'S EYE
(1) On stimulation by unknown drug, anti-histamine is
put in the tissue tube  If the graph is reversed, Observations
then the unknown drug is histamine; if the graph is (A) Mydriatics
not reversed, then the unknown drug is cholinergic (1) Ephedrine & Epinephrine
(acetylcholine) or BaCl2. (a) Pupil  Dilatation.
(2) Second antagonist atropine is used  If graph is (b) Light reflex  Remain +ve.
reversed, then unknown drug is cholinergic; if the (c) Conjunctival reflex  Remain +ve.
graph is not reversed, the unknown drug is BaCl2. (d) Color of conjunctiva  Pale.
Note: BaCl2 kills the tissue in stimulation. (2) Atropine
(B) Identification of Depressant (a) Pupil  Dilatation.
On depression with an unknown drug, pilocarpine/ (b) Light reflex  Become -ve.
acetylcholine is put into the test tube  (c) Conjunctival reflex  Remain +ve.
(1) An immediate rise in amplitude means that sites for (d) Color of conjunctiva  Pink.
cholinergic drugs are empty (ie unknown drug is (3) Cocaine
not anticholinergic), & so, the unknown drug is an (a) Pupil  Dilatation.
adrenergic drug, ie ephedrine. (b) Light reflex  Remain +ve.
(2) No immediate rise in amplitude means that sites for (c) Conjunctival reflex  Become -ve.
cholinergic drugs are occupied, then unknown drug (d) Color of conjunctiva  Pink.
is anticholinergic, ie atropine. (B) Miotics
Viva Questions Pilocarpine & Physostigmine
(1) Classification of GIT stimulant ? (a) Pupil  Constriction.
(a) Parasympathomimetics, eg acetylcholine, pilocar- (b) Light reflex  Remain +ve.
pine, muscarine. (c) Conjunctival reflex  Remain +ve.
(b) Sympatholytics, eg propranolol. (d) Color of conjunctiva  Pink.
(c) Direct stimulants, eg histamine, BaCl2. Viva Questions
(2) Classification of GIT depressants ? (1) Mechanism of action of cocaine ?
(1) Parasympatholytics, eg atropine, scopolamine. It stimulates sympathetic nerve endings.
(2) Sympathomimetics, eg epinephrine, ephedrine. (2) Morphine causes miosis or mydriasis ?
(3) Direct depressants, eg papaverine, chloral hydrate. Miosis by central action.
(3) Composition of Tyrode solution ? (3) Pupils during 2nd & 4th stages of general
(a) Tyrode A anesthesia?
(i) NaCl = 160 gm. (a) Pupils dilated with intact reflexes during 2nd stage.
(ii) KCl = 4 gm. (b) Pupils dilated with abolished reflexes during 4th
(iii) CaCl2 = 4 gm. stage.
(iv) MgCl2 = 2 gm. (4) Why atropine's action is short in rabbit's eye ?
(v) Water = upto 1000 ml. Because, rabbits eye produces enzyme atropinase that
(b) Tyrode B destroys atropine.
(i) NaHCO3 = 20 gm. (5) Light reflex ?
(ii) Dextrose = 20 gm. If light is thrown on eye(s), then pupil(s) constrict.
(iii) Na2HPO4 = 0.05 gm. (6) Consensual light reflex ?
If light is thrown on one eye, pupil of other eye
(iv) Water = upto 1000 ml.
constricts.
(c) Final solution
(7) Corneal reflex ?
Tyrode A 50 ml + Tyrode B 50 ml + 900 ml water.
If cornea is touched or irritated, eyelids are closed.
(4) Significance of Tyrode Sol?
(8) Conjunctival reflex ?
Tissue is kept alive & in working condition by
If conjunctiva is touched or irritated, eyelids are closed.
providing proper ionic atmospheric, O2 , & temp. of
37oC.
(5) Define tone & peristalsis?
(a) Tone is the tension present in resting muscle.
M. Shamim’s PHARMACOLOGY 213

29 TRUE / FALSE TYPE MCQs

(1) Nalorphine T= (B) Osteoporosis & spontaneous fractures.

T= (A) Dilate pupil in patients with morphine toxicity. F= (C) Hypotensive episodes.
T= (B) Is almost inert at therapeutic doses in the absence T= (D) Reduced glucose tolerance & worsening of
of opioid agonists. diabetes mellitus.
T= (C) Shows no tolerance. T= (E) Suppression of ACTH secretion.
F= (D) Depresses respiration in patients with acute
opioid overdosage. (8) Thiazides can cause
F= (E) Also shows partial agonist activity. F= (A) Hypoglycemia.
T= (B) Hypokalemia.
(2) Therapeutic causes of gynecomastia include F= (C) Hypouricemia.
F= (A) Androgens. F= (D) Hypocalcemia.
T= (B) Estrogens. T= (E) Hypophosphatemia.
T= (C) Cimetidine.
T= (D) Digoxin. (9) Chronic use of estrogen causes
F= (E) Griseofulvin . F= (A) Increased incidence of MI.
F= (B) Increased incidence of ovarian tumors.
(3) Barbiturates T= (C) Increased incidence of cancer of breast.
T= (A) Depress the respiratory centre. T= (D) Increased incidence of venous thrombosis.
F= (B) Inhibits the activity of certain liver enzyme. T= (E) Increased incidence of cholelithiasis.
T= (C) Are usually metabolized in liver.
T= (D) Have anti-convulsant properties. (10) Following drugs are contraindicated in 3rd
F= (E) Are rapidly excreted in acidic urine. trimester
T= (A) Tetracycline.
(4) Chloramphenicol F= (B) Ampicillin.
F= (A) Does not penetrate the blood brain barrier. F= (C) Erythromycin.
F= (B) Must be administered parenterally. F= (D) Cephalosporin.
F= (C) Can be safely used in premature infants. T= (E) Sulfonamides.
T= (D) Can cause depression of bone marrow.
F= (E) Can cause discoloration of developing teeth when (11) Atropine
given to children. F= (A) Promotes salivation.
T= (B) Increases resting heart rate.
(5) Tetracycline F= (C) Induces bronchiolar constriction.
F= (A) Is bactericidal. T= (D) Administration results in constipation.
F= (B) Causes aplastic anemia in toxic doses. T= (E) Causes loss of accommodation.
F= (C) In over-dosage causes depression of bone marrow.
T= (D) Excreted in bile. (12) Methyldopa causes following side effects
T= (E) Excreted in urine. F= (A) Visual disturbances.
F= (B) Weight gain.
(6) Recognized features of acute paracetamol T= (C) Fever.
poisoning include T= (D) Hemolytic anemia.
F= (A) Hyperventilation. F= (E) Urinary retention.
F= (B) Early onset of coma.
T= (C) Hypoglycemia. (13) Drugs having short plasma half life
T= (D) Prolongation of prothrombin time. F= (A) Have low therepeutic index.
T= (E) Nephrotoxicity. F= (B) Are extensively bound to plasma proteins.
T= (C) Reach steady state concentration (Css) quickly.
(7) Adverse effects following prolonged F= (D) Have low volume of distribution.
administration of corticosteroids include F= (E) Are usually weak bases.
F= (A) Dehydration & weight loss.
M. Shamim’s PHARMACOLOGY 214

(14) Morphine use is better avoided in patients with F= (A) Has antimicrobial activity only aganist M.
F= (A) Myocardial infarction. tuberculosis.
T= (B) Head injury. T= (B) Induces hepatic microsomal enzymes.
T= (C) Cor pulmonale. F= (C) Acts by inhibiting microbial cell wall synthesis.
F= (D) Diabetes mellitus. F= (D) Resistance has not been observed in
T= (E) Acute biliary colic. mycobacteria.
T= (E) Attains clinically effective concentration in CSF
(15) Diazepam following oral administration.
T= (A) Is anxiolytic.
T= (B) Is hypnotic. (23) Compared to morphine pethidine is
F= (C) Does not cause dependence. T= (A) Mydriatic.
T= (D) Is anti-epileptic. T= (B) Less potent analgesic.
T= (E) May causes paradoxically increased anxiety. F= (C) More potent antitussive.
F= (D) Not liable to produce dependence.
(16) Atropine is given before anesthesia T= (E) Less constipating.
F= (A) For good induction.
F= (B) For rapid recovery. (24) Most of the H1 histamine receptor blockers
F= (C) For full muscle relaxation. produce
T= (D) To decrease respiratory secretion. T= (A) Dry mouth.
F = (E) To decrease incidence of cardiac arrest. T= (B) Drowsiness.
F= (C) Decrease in gastric acid secretion.
(17) Dopamine
T= (D) Relief in bronchial asthma.
T= (A) Is given in infusion form.
T= (E) Symptomatic relief in allergic conditions.
T= (B) Has inotropic effect an heart.
T= (C) Is given in cardiogenic shock. (25) Nitroglycerine
F= (D) Causes constriction of renal vessels. F= (A) Produces mainly venodilatation.
T= (E) Overdosage results in excessive F= (B) Decreases heart rate.
sympathomimetic effects. T= (C) Decreases venous return.
T= (D) Undergoes extensive first pass metabolizm.
(18) Propranolol can be give safely in
T= (E) Decreases oxygen requirement of heart.
F= (A) Asthma.
F= (B) CCF. (26) Clinically useful actions of diazepam include
F= (C) Heart block. F= (A) Analgesic.
T= (D) Exertional angina. T= (B) Hypnotic.
T= (E) Hypertension. T= (C) Anxiolytic.
F= (D) Local anesthetic.
(19) In chronic renal failure following drugs can be
T= (E) Skeletal muscle relaxant.
given safely
F= (A) Gentamycin. (27) Captopril produces its antihypertensive effects by
T= (B) Erythromycin. inhibition of
F= (C) Sulfonamides. F= (A) Noradrenaline formation.
F= (D) Rifampin. T= (B) Angiotensin-II formation.
T= (E) Digoxin. F= (C) Angiotensin-II receptors.
F= (D) Bradykinin inactivation.
(20) Morphine can be given in
F= (E) Renin release.
F= (A) Head injury.
F= (B) Diabetes mellitus. (28) Drugs which mainly block beta-1 adrenoceptors
T= (C) Myocardial infarction. include
T= (D) Biliary colic. F= (A) Timolol.
F= (E) Right ventricular hypertrophy. T= (B) Atenolol.
F= (C) Propranolol.
(21) Neostigmine reverses skeletal muscle relaxation
F= (D) Pindolol.
caused by
T= (E) Metoprolol.
T= (A) Gallamine.
T= (B) Tubocurarine. (29) Aminoglycoside antibiotics are
F= (C) Diazepam. F= (A) Well absorbed from GIT.
F= (D) Suxamethonium. T= (B) Nephrotoxic.
T= (E) Pancuronium. T= (C) Bactericidal.
T= (D) Ototoxic.
(22) Rifampicin
F= (E) Eliminated mainly by hepatic inactivation.
29: True / False Type MCQs 215

(30) Drug actions which have been attributed to genetic T= (D) Vasoconstriction by adrenaline.
polymorphism include T= (E) Bronchodilation by albuterol.
T= (A) Prolonged apnea with suxamethonium.
T= (B) Peripheral neuritis with isoniazid. (37) Following have vasoconstrictor effects when
F= (C) Gingival hyperplasia with phenytoin. applied locally
F= (D) Hemolysis with primaquine. T= (A) Ephedrine.
T= (E) Lupus erythematosus like syndrome with F= (B) Procaine.
hydralazine. F= (C) Timolol.
F= (D) Cocaine.
(31) Oxytetracycline T= (E) Phenylephedrine.
T= (A) Absorption from GIT is decreased by antacids.
T= (B) Stains & damages teeth if used in children. (38) Drugs which need daily dose reduction in case of
F= (C) Is bactericidal in usual doses. renal failure include
F= (D) Resistant micro-organisms do not show T= (A) Chloramphenicol.
resistance to other tetracyclines. T= (B) Gentamicin.
T= (E) Is liable to cause superinfections in GIT. F= (C) Erythromycin.
F= (D) Doxycycline.
(32) Renal excretion of drugs by glomerular filtration is F= (E) Rifampicin.
reduced by
T= (A) Extensive binding of the drug to plasma proteins. (39) Bioavailability of a drug depends on
F= (B) Probenecid. T= (A) Route of administration.
F= (C) Induction of hepatic microsomal enzymes. F= (B) Route of excretion.
T= (D) Old age. T= (C) Extend of first pass metabolism.
F= (E) Alkalinization of urine. F= (D) Extent of plasma protein binding.
T= (E) Dosage form.
(33) Dopamine
F= (A) Produces renal & mesenteric vasoconstriction. (40) Drug interactions of pharmacokinetic type include
T= (B) Is administered by continuous intravenous T= (A) Prolongation of procaine local anesthesia by
infusion. adrenaline.
T= (C) Is useful in cardiogenic shock. F= (B) Reversal of morphine induced respiratory
F= (D) Produces no inotropic actions on heart. depression by naloxone.
T= (E) Adverse effects are usually rapidly reversed on F= (C) Reversal of hydralazine induced tachycardia by
stopping administration. propranolol.
T= (D) Increased toxicity of methotrexate by aspirin.
(34) Pain of peptic ulcer is relieved by T= (E) Decreased peripheral adverse effects of levodopa
T= (A) Substances which neutralize acid. by carbidopa.
T= (B) Taking normal food in small quantity more
frequently. (41) Muscarinic effects of acetylcholine are produced at
F= (C) Drugs which stimulates vagus. F= (A) Skeletal muscle.
F= (D) Drugs which interfere with the action of T= (B) Cardiac muscle.
cholinesterase. T= (C) Gastrointestinal smooth muscle.
F= (E) Oral administration of beta blockers. T= (D) Sweat glands.
F= (E) Autonomic ganglions.
(35) Xanthine
T= (A) Oxidase inhibitor allopurinol is used in gout to (42) Recognized side effects of the propranolol include
block uric acid production. T= (A) Bronchospasm.
F= (B) Is oxidized to form purines. T= (B) Heart failure.
T= (C) Is a substrate as well as a product of the enzyme F= (C) Retinal degeneration.
xanthine oxidase. F= (D) Tachycardia.
F= (D) Is an intermediate product during catabolism of T= (E) Hypoglycemia.
pyrimidines.
T= (E) Is the precursor of uric acid.
(36) Pharmacological actions resulting from known (43) Gallamine causes paralysis of muscles by
drug-receptor interactions include F= (A) Blocking the synthesis of acetylcholine in motor
T= (A) Miosis by pilocarpine. nerve endings.
F= (B) Diuresis by mannitol. F= (B) Blocking release of activator Ca2+ in the
F= (C) Decreased gastric acidity by aluminium sarcoplasm.
hydroxide. T= (C) Competing with acetylcholine at motor endplate.
F= (D) Depolarizing motor endplate.
M. Shamim’s PHARMACOLOGY 216

F= (E) Blocking interneurones in spinal cord. (51) When following two drugs are used in combined
form, the first drug tends to increase the adverse
(44) For the treatment of Parkinsonism carbidopa is effects of second
used in combination with levodopa because it F= (A) Methotrexate & aspirin.
F= (A) Facilitates dopamine entry into brain. T= (B) Allupurinol & mercaptopurine.
F= (B) Inhibits dopamine inactivation in brain. T= (C) Verapamil & digitalis.
T= (C) Inhibits the peripheral conversion of levodopa F= (D) Halothane & nitrous oxide.
into dopamine. F= (E) Phenobarbital & oral anti-coagulants.
F= (D) Acts as a dopamine receptor agonist.
T= (E) Significantly decreases the peripheral adverse (52) Regarding non-steroidal anti inflammatory drugs
effects of levodopa. (NSAIDs)
T= (A) Aspirin has short half life.
(45) Use of propranolol is better avoided in patients T= (B) Phenylbutazone has long half life.
having F= (C) None of the NSAIDs interact with methotrexate.
T= (A) Bronchial asthma. F= (D) All NSAIDs except sulindac interact with
F= (B) Hypertension. antihypertensive & diuretic agents.
T= (C) Congestive heart failure. T= (E) Non-steroidal anti inflammatory drugs do not
T= (D) Heart block. cause bronchospasm & pulmonary edema.
F= (E) Angina of effort.
(53) Atropine given intravenously in therapeutic doses
(46) The main actions of digoxin when used in T= (A) Increases the resting heart rate.
congestive cardiac failure include T= (B) Produces vasodilation of the skin.
T= (A) Positive inotropic effects. T= (C) Reduces the flow of saliva.
F= (B) Positive chronotropic effects. F= (D) Produces over activity of the small intestine.
F= (C) Decrease in AV nodal conduction time. T= (E) Reduces gastric secretion.
F= (D) Increase in atrial effective refractory period.
T= (E) Inhibition of Na-K-ATPase. (54) Halothane
F= (A) Causes good muscle relaxation.
(47) Thiazide diuretics are capable of producing T= (B) Causes hypotension.
F= (A) Hypolipidemia. T= (C) Causes bronchodilation.
T= (B) Hypokalemia. F= (D) Is a good analgesic.
F= (C) Hypoglycemia. T= (E) Increases the risk of hepatitis.
F= (D) Hypouricemia.
T= (E) Hyponatremia. (55) Following drugs act as an coagulant by acting
against warfarin
(48) Antiboitics which are bactericidal in usual F= (A) Aspirin.
therapeutic dosage include T= (B) Phenobarbital.
T= (A) Ampicillin. T= (C) Vit. K.
F= (B) Chloramphenicol. F= (D) Phenylbutazone.
F= (C) Oxytetracycline. F= (E) Amiodarone.
T= (D) Streptomycin.
T= (E) Cephalexin. (56) When injected subcutaneously noradrenaline
causes
(49) The benefits of dopamine therapy in cardiogenic F= (A) Decreased diastolic blood pressure.
shock include T= (B) Increased systolic blood pressure.
T= (A) Rise in diastolic blood pressure. T= (C) Increased peripheral resistance.
T= (B) Arteriolar constriction. F= (D) Relaxation of bronchial smooth muscles.
F= (C) Bradycardia. F= (E) Relaxation of smooth muscles of blood vessels.
T= (D) Increased force of cardiac contraction.
T= (E) Vasodilatation in kidneys. (57) Following are nephrotoxic drugs
T= (A) Gentamycin.
(50) Regarding oxytetracycline F= (B) Cephalothin.
T= (A) Antacids inhibit its absorption. T= (C) Cephaloridine.
F= (B) Is bactericidal. T= (D) Rifampin.
T= (C) Causes yellow discoloration of teeth. F= (E) Amoxycillin.
T= (D) May cause superinfections.
T= (E) Show cross sensitivity to other tetracyclines. (58) Prolonged use of corticosteroids causes
T= (A) Osteoporosis.
F= (B) Hypotension.
F= (C) Weight loss.
29: True / False Type MCQs 217

F= (D) Increased ACTH. T= (C) High blood solubility.

T= (E) Worsening of clinical diabetes. F= (D) Quick recovery.
F= (E) Good skeletal muscular relaxation.
(59) Tubocurarine
T= (A) Is a non-depolarizing blocker. (66) Recognized side effects of phenytoin include
T= (B) Is antagonized by neostigmine. T= (A) Gingival hyperplasia.
T= (C) Causes bronchospasm. T= (B) Ataxia.
T= (D) Causes hypotension. T= (C) Hirsutism.
T= (E) Used frequently in electroconvulsive therapy. F= (D) Epileptic seizures.
T= (E) Folate depletion.
(60) Cimetidine
F= (A) Decreases salivary secretion. (67) Loop diuretics
F= (B) Decreases gastric motility. F= (A) Inhibits reabsorption of chlorides in distal tubule.
T= (C) Inhibit hepatic enzymes. T= (B) Act independent of changes in acid base balance.
F= (D) Is a proton pump inhibitor. F= (C) Inhibit carbonic anhydrase.
T= (E) Decreases gastric acid secretion. T= (D) Produce metabolic alkalosis.
T= (E) Produce hyperuricemia.
(61) Following intravenous administration, rapid
redistribution of the drug is responsible for the (68) Nitrous oxide inhalations may lead to
short duration of F= (A) Pulmonary edema.
T= (A) General anaesthesia by thiopentone. F= (B) Bronchogenic carcinomas.
F= (B) Cardiovascular effects of dopamine. F= (C) Mesothelioma.
F= (C) Hypotensive effects of trimethaphan. F= (D) Asthma.
T= (D) Anticonvulsant effect of diazepam. F= (E) Respiratory distress syndrome.
F= (E) Skeletal muscle relaxation by succinylcholine
(suxamethonium). (69) Regarding antithyroid drugs
T= (A) Carbimazole interfere with synthesis of thyroid
(62) Durgs known to be associated with fetal hormone.
abnormalities when used during pregnancy F= (B) Propylthiouracil is not suitable during pregnancy.
include T= (C) Propylthiouracil crosses the placenta.
T= (A) Phenytoin. T= (D) Carbimazole does not causes fetal scalp defects.
F= (B) Ampicillin. F= (E) Propylthiouracil is not transferred to breast milk.
T= (C) Captopril.
T= (D) Valproic acid. (70) Drugs having a half life exceeding 12 hours include
F= (E) Chloroquin. T= (A) Chlorpropamide.
F= (B) Atropine.
(63) Chlorpromazine T= (C) Amitriptyline.
T= (A) Effectively controls nausea & vomiting in motion F= (D) Chlordiazopoxide.
sickness. T= (E) Lithium carbonate.
T= (B) Acts mainly by blocking D2 dopamine receptors.
(71) Drugs which are known to have teratogenic effects
T= (C) Can cause cholestatic jaundice.
& should be avoided in pregnancy include
T= (D) Effectively controls hicoughs.
F= (A) Cephalexin.
F= (E) Can cause hypertensive episodes.
T= (B) Captopril.
(64) Succinylcholine (suxamethonium) T= (C) Lithium carbonate.
T= (A) Is a depolarizing type of neuromuscular blocker. T= (D) Valproic acid.
T= (B) Rate of metabolism markedly differs in different F= (E) Methyldopa.
persons.
(72) Regarding acetylcholine in the nervous system
T= (C) Muscle paralysis is preceded by muscle
T= (A) It is the chemical transmiter of the
fasiculations.
parasympathetic nervous system.
T= (D) Overdose effects are reversed by neostigmine in
F= (B) It is absent from the brain.
phase II.
T= (C) Some receptors are blocked by atropine.
T= (E) Use with halothane may sometimes cause
T= (D) Some receptors are blocked by curare.
malignant hyperthermia.
T= (E) It stimulates b receptors in the sympathetic
(65) If the blood gas partition coefficient of an nervous system.
inhalation general anaesthetic is high, it will result
(73) Regarding the biosynthesis of noradrenaline from
in
tyrosine
T= (A) Slow induction.
F= (A) Dopamine beta-hydroxylase is required.
F= (B) Good analgesia.
M. Shamim’s PHARMACOLOGY 218

F= (B) Phenylalanine is an intermediary. F= (E) Ovarian cancer.

F= (C) Dopamine is formed by the addition of a
hydroxyl group to DOPA. (80) Plasma half life of a drug depends on
F= (D) Tryptophan is an intermediary. F= (A) Dose administered.
F= (E) Noradrenaline is formed by the action of N- T= (B) Renal plasma flow.
methyl transferase on adrenalin. T= (C) Rate of drug metabolizm.
T= (D) Rate of elimination.
(74) Concerning the rate of uptake of drugs from the T= (E) Addition of a 2nd drug.
blood into the brain
F= (A) Dopamine is taken up more rapidly than (81) Drugs which are capable of enhancing the anti-
levodopa. coagulant effects of warfarin include
T= (B) Serotonin is taken up more rapidly than F= (A) Oxytetracycline.
tryptophan. T = (B) Aspirin.
T= (C) Thiopentone is taken up more rapidly than other F= (C) Phenobarbitone.
barbiturate. F= (D) Vitamin K.
T= (D) Physostigmine is taken up more rapidly than T= (E) Phenylbutazone.
neostigmine.
T= (E) Lithium ions are takes up more rapidly than
dopamine.
(75) Nalorphine
T= (A) Causes dilation of the pupils in narcotic addicts.
F= (B) Is used in the treatment of thiamine deficiency.
F= (C) Causes constriction of the pupils in non-norcotic
subjects.
F= (D) Prevents withdrawal symptoms in morphine
addicts.
F= (E) Is effective when taken by mouth.
(76) The adverse effects of the first drug usually
increase when it is used concurrently with the
second drug
T= (A) Aminophylline with tricyclic antidepressants.
T= (B) Methotrexate with aspirin.
F= (C) Halothane with nitrous oxide.
T= (D) Verapamil with propranolol.
F= (E) Sulphamethoxazole with trimotheprim.
(77) The characteristics of general anesthesia produced
by intravenous thiopentone sodium include
T= (A) Quick induction.
F= (B) Good analgesia.
F= (C) Good skeletal muscular relaxation.
T= (D) Short lived anesthesia.
T= (E) Quick recovery.
(78) Pharmacological actions of cimetidine include
inhibition of
F= (A) Gastric motility.
T= (B) Gastric acid secretion.
F= (C) H+ - K+ ATPase (proton pump).
F= (D) Salivary secretion.
T= (E) Hepatic microsomal drug metabolizing enzymes.
(79) Long term use of estrogen increases the risk of
T= (A) Gallstone formation.
T= (B) Breast cancer.
T= (C) Deep vein thrombosis.
F= (D) Osteoporosis.
M. Shamim’s PHARMACOLOGY 219

30 ONE BEST TYPE MCQs

(6) A 20-years-old male has severe chest pain, due to

SEE ANSWERS AT THE END OF CHAPTER rib fracture; which of the following long acting
local anesthetic should be given
(1) A patient is having herpes simplex ophthalmitis; (A) Lignocaine
this disease can be treated with (B) Procaine
(A) Trifluridine (C) Bupivacaine
(B) Sulfacetamide (D) Prilocaine
(C) Chloramphenicol (E) Mepivacaine
(D) Ganciclovir
(7 ) A known patient of myasthenia gravis comes to
(E) Zidovudine
you, with his disease previously well control on
(2) Curare act to atropine & neostigmine; but now he feels weakness
(A) Prevent depolarization in neuromuscular junction & the disease is not under control. He is given
(B) Inhibit transmission of impulses in the nerve injection stigma & his condition improved; the
fibers next step is to
(C) Compete with acetylcholine for nicotinic receptor (A) Reduce the dose of neostigmine
sites (B) Withdraw atropine
(D) Produce hypertension (C) Increase the dose of atropine
(E) Produce hyperkalemia (D) Increase the dose of neostigmine
(E) Corticosteroid treatment
(3) The anesthetic used along with the halothane to
give excellent analgesia & rapid induction is (8) Effect of curare on acetylcholine is to
(A) Nitrous oxide (A) Block competitively the transmitter action of
(B) Thiopental acetylcholine
(C) Desflurane (B) Increase the action of acetylcholine
(D) Propofol (C) Decrease the action of acetylcholine
(E) Chloroform (D) Block Na+ pump
(E) Increase Ca++ influx
(4) A 42-years-old asthamatic is on salbutamol,
prednisolone and theophylline. He also uses (9) A patient already receiving digitalis, when given
diazepam for depression and also takes aspirin. He the hydrochlorothiazide will result in
develops bone fracture; the drug most likely to (A) Hypokalemia
cause this effect is (B) Hypercalcemia
(A) Salbutamol (C) Its decreased renal excretion
(B) Prednisolone (D) Its increased GIT absorption
(C) Theophylline (E) Hyperglycemia
(D) Diazepam
(10) A drug is at blood level of 16 mg/dl, has a ½ life of
(E) Aspirin
8 hrs. If clinical effects appear at 4 mg/dl, for how
(5) Mechanism of action of local anesthetic is many hrs will its action last following stopping of
(A) Blockage of Na+ current its constant infusion
(B) Increase Na+ current (A) 8 hours
(C) Increase Ca++ influx (B) 16 hours
(D) Increase of K+ outflow (C) 32 hours
(E) None of the above (D) 24 hours
(E) 64 hours
M. Shamim’s PHARMACOLOGY 220

(11) Dopamine exerts its effect when it reached a steady Cap/ Pres Blood Flow Limb wt AV/O2/Diff.
state. If its ½ life is 2 min., after how many minutes (A) dec. dec. dec. dec.
it will show its effect (B) inc. inc. dec. dec.
(A) 2 min (C) inc. inc. dec. inc.
(B) 4 min (D) inc. inc. inc. dec.
(C) 9 min (E) inc. inc. inc. inc.
(D) 15 min
(E) More than 20 min (18) A patient is taking the oral contraceptives, & now
she is also taking the anti-tuberculous drugs. She
(12) The antiepileptic drug which result in nystagmus, has gone pregnant. Which of the following drug is
ataxia, & gum hypertrophy is responsible for her pregnancy
(A) Phenytoin (A) Rifampin
(B) Phenobarbitone (B) Isoniazid
(C) Carbamazepine (C) Ethambutol
(D) Ethosuximide (D) Streptomycin
(E) Valproic acid (E) Pyrazinamide
(13) The insulin used in case of a patient suffering from (19) A 54-year-old woman suffers from hypertension
diabetic ketoacidosis is due to excessive sympathetic activity. In particular,
(A) Lente insulin she complains of frightening palpitations and pain
(B) Ultralente insulin in the extremities due to poor blood supply.
(C) NPH Labetalol was tried successfully and the physician
(D) Regular insulin decides to prescribe a similar agent with a longer
(E) NPH iletin I duration of action. Which of the following
medications would be the most appropriate in this
(14) A 35-years-old male after having checked up by an case?
ophthalmologist, feels blurring of vision. This is (A) Acebutolol
most likely due to (B) Atenolol
(A) Homatropine (C) Carteolol
(B) Pilocarpine (D) Carvedilol
(C) Xylocaine (E) Pindolol
(D) Edrophonium
(E) Phenylephrine (20) Injection of penicillin is given to a patient; after 2
to 3 hours, the patient become unconscious & his
(15) A 12-years-old boy has tonsillitis, caused by beta BP becomes low. Which drug should be given
hemolytic streptococci; which drug is most suitable (A) Dopamine
(A) Ampicillin (B) Dobutamine
(B) Benzyl penicillin (C) Norepinephrine
(C) Benzathine penicillin (D) Adrenaline
(D) Gentamicin (E) Aminophylline
(E) Chloramphenicol
(21) The drug of choice for the tape worm infestation is
(16) A cancer patient is on cyclophosphamide. A second (A) Niclosamide
drug is added to his regimen and the patient (B) Albendazole
experiences a sharper decline in pulmonary and (C) Mebendazole
renal function. The added drug most likely is (D) Dichlorophen
(A) dactinomycin (E) Oxamniquine
(B) methotrexate
(C) prednisone (22) A patient is suffering from streptococcal
(D) vinblastine pharyngitis; one injection of the following will
(E) vincristine treat the patient
(A) Benzyl penicillin
(17) A patient with a catheter advanced into a forearm (B) Benzathin penicillin
artery is infused with an alpha blocker at a rate (C) Amoxycillin
that produces a local effect, but not a systemic (D) Procaine penicillin
effect. Assume that the patient is resting quietly (E) Methicillin
during the procedure. Which of the following
changes would most likely occur in the forearm?
30: One Best Type MCQs 221

(23) A 54-year-old obese white male with a history of (29) A Parkinson’s patient presents to you complaining
hypertension is managed by captopril and a of a purplish-red mottling of the skin of the lower
diuretic. Which of the following clinical situations leg. The patient denies any associated itching or
is most clearly a contraindication for the use of pain and reports that the color intensifies upon
captopril? standing or with cold temperatures. Physical exam
(A) Congestive heart failure reveals slight pitting edema of the ankles. Therapy
(B) Essential hypertension with which drug would most likely account for
(C) High LDL levels these observations?
(D) Post-myocardial infarction (A) Amantadine
(E) Renovascular hypertension (B) Benztropine
(C) Bromocriptine
(24) The component of a local anesthetic agent that is (D) Levodopa
directly responsible for neuronal conduction block (E) Selegiline
is the
(A) free base inside the neuron (30) A 47-years-old male with CHF develops symptoms
(B) free base outside the neuron & signs of digoxin toxicity, while he is also on
(C) ionized base inside the neuron other CHF drugs. Digoxin levels found to be in
(D) ionized base outside the neuron normal range. The reason for this is
(A) Decreased renal function
(25) Tumor cells from a person with cancer are being (B) Wrong time to take digoxin level
analyzed to determine which oncogene is involved (C) Hypokalemia by diuretics
in the transformation. After partial sequencing of (D) Decreased protein bounding of digoxin due to
the gene, the predicted gene product is identified competition
as a tyrosine kinase. Which of the following (E) Abnormal LFTs
proteins would most likely be encoded by this gene?
(A) Alpha-1 adrenergic receptor (31) Mountain sickness can be corrected with the use
(B) Corticosteroid receptor of
(C) Epidermal growth factor receptor (A) Acetazolamide
(D) Nicotinic cholinergic receptor (B) Metoclopramide
(E) N-menthyl-D-aspartate (NMDA) receptor (C) Furosemide
(D) Promethazine
(26) An old patient with compromised renal function (E) Cyclizine
develops gram-positive infection. The best drug
that does not require renal adjustment is (32) A women which is on phenytoin, wants to conceive.
(A) Vancomycin What advice you can give to her about the drug
(B) Penicillin-G (A) Increase the dose of phenytoin
(C) Cloxacillin (B) Change to valproic acid
(D) Erythromycin (C) Addition of valproic acid
(E) Clarithromycin (D) Change to phenobarbitone.
(E) Decrease the dose of phenytoin
(27) Cimetidine & warfarin are given to a patient, &
the bleeding time is prolonged. What is the cause (33) A 49-year-old frequent business traveler presents
(A) Inhibition of drug metabolism to his physician requesting medication to help him
(B) Impairment of platelet aggregation with nausea and dizziness that he gets during
(C) Increased half life turbulent flights. A scopolamine patch is
(D) Impaired absorption prescribed for his motion sickness. Which of the
(E) Promote platelet aggregation following is the most likely side effect from this
patch?
(28) Which of the following drugs is associated with (A) Bradycardia
cumulative cardiotoxicity? (B) Diaphoresis
(A) Digoxin (C) Diarrhea
(B) Doxorubicin (D) Salivation
(C) Etoposide (E) Urinary retention
(D) Ifosfamide
(E) Procarbazine
M. Shamim’s PHARMACOLOGY 222

(34) A 56-year-old male presents with fatigue, a malar (E) Cough

rash on his cheek, and arthralgia/myalgia. He
reports that even with sunscreens, he “burns (39) A 33-year-old female with a history of IV drug use
easily”. Laboratory tests are positive for and AIDS is being treated for Pneumocystis carinii
antinuclear antibodies (ANA). He has been treated pneumonia with IV pentamidine after having
for essential hypertension for the past 3 years. developed severe hematological side effects to co-
Antihypertensive therapy with which of the trimoxazole. Her last CD4+ cell count was below
following drugs would be most consistent with this 100 cell/mm3 and she is moderately hypocalcemic
patient’s presentation? and hyponatremic. She complains of difficulty
(A) Captopril reading and says she “sees spots”. Which of the
(B) Hydralazine following drugs would be most appropriate for the
(C) Hydrochlorothiazide treatment of her visual problems?
(D) Procainamide (A) Acyclovir
(E) Propranolol (B) Foscarnet
(C) Ganciclovir
(D) Zalcitabine
(E) Zidovudine

(35) A 45-year-old female with metastatic breast cancer (40) A 65-year-old man with an 18-year history of non-
is placed on a combination of antineoplastics, insulin dependent diabetes mellitus (NIDDM)
including an anthracycline antibiotic. Which of the presents to clinic. Despite oral hypoglycemic
following drugs can act as a cytoprotective agent medications, his HbA1c levels are 15%, indicating
that will minimize the cumulative cardiotoxicity persistent, sustained hyperglycemia. Which of the
from the antineoplastic agents? following drugs could be added to this man’s
(A) Amifostine regimen in order to blunt the postprandial
(B) Dexrazoxane increase in plasma glucose?
(C) Leucovorin (A) Acarbose
(D) Mesna (B) Chlorpropamide
(E) Ondansetron (C) Metformin
(D) Regular insulin
(36) A 45-year-old man came in emergency department (E) Troglitazone
with pin-point pupil, unconsciousness & history of
taken morphine. Which will be the antidote (41) A 31-year-old female is diagnosed as schizophrenic,
(A) Naloxone disorganized type. Her symptoms include blunt
(B) Nalorphine affect, motor retardation, mutism, and apathy. In
(C) Flumazenil the past, she has had severe extrapyramidal side
(D) Benztropine effects and has an extreme fear of developing
(E) Neostigmine tardive dyskinesia. Which of the following drugs
would be most appropriate for this patient?
(37) A 48-year-old hypertensive male is diagnosed with (A) Amantadine
benign prostatic hyperplasia (BPH). He is (B) Clozapine
currently taking hydrochlorothiazide, but his (C) Fluphenazine
blood pressure is still not adequately controlled. (D) Phenelzine
Addition of which of the following drugs would (E) Triazolam
constitute rational treatment of both of the
patient’s disorders? (42) Indomethacin is an useful drug to be given in
(A) Captopril neonates for the closure of
(B) Clonidine (A) Foramen ovale
(C) Finasteride (B) Ductus arteriosus
(D) Nifedipine (C) VSD
(E) Terazosin (D) Ductus venosus
(E) Septum primum
(38) A women G3P2A0 at 28 weeks of pregnancy, gone in
(43) A 46-year-old woman with debilitating rheumatoid
preterm labor pains. Tocolytics was given; which
arthritis is being treated with a non-steroidal ant-
is the most common side effect.
inflammatory (NSAID) drug. After 3 months, she
(A) Palpitation
develops renal tubular acidosis. Which of the
(B) Pallor
following drugs is she most likely taking?
(C) Tachycardia
(A) Aspirin
(D) Hypotension.
30: One Best Type MCQs 223

(B) Ibuprofen (49) A 5-year-old child presents to his pediatrician with

(C) Indomethacin abdominal pain, irritability, loss appetite, and
(D) Misoprostol slurred speech. On physical exam, he is pale and
(E) Naproxen ataxic. Upon questioning, his mother says that she
is in the process of remodeling her home, and
(44) A 39-year-old female is seen in the emergency states that her child may have ingested paint chips.
room because of acute diarrhea of 3 days duration Which of the following drugs could be given orally
and a fever of 103.5 degrees F. Her blood pressure to treat the child’s condition?
is 96/60, her heart rate is 130/min. and her (A) CaNa2EDTA
respiratory rate is 321/min. No bowel sounds are (B) Deferoxamine
heard, and the patient is unable to produce a (C) Dimercaprol
specimen for urinalysis. She is confused and (D) Sodium thiosulfate
disoriented. Which of the following drugs would (E) Succimer
initially increase her renal blood flow and cardiac
output, but would increase peripheral resistance at (50) In a child with tapeworm infestation drug of
higher doses? choice is
(A) Dobutamine (A) Albendazole
(B) Dopamine (B) Mebendazole
(C) Isoproterenol (C) Pyrantal pamoate
(D) Prazosin (D) Niclosamide
(E) Terbutaline (E) Piperazine
(45) The drug of choice for HSV kerato-conjunctivitis (51) A 50-year-old, 175 lb female with a 10-year history
is of high blood pressure controlled with propranolol
(A) Chloramphenicol and furosemide returns to clinic because of high
(B) Tetracycline LDL levels. She is evaluated, and treatment is
(C) Neomycin initiated for her high cholesterol levels. Initially,
(D) Aciclovir she experiences gastrointestinal disturbances, but
(E) Gentacin over the next two weeks, her blood pressure
gradually increases. Which of the following drugs
(46) Thiopentone sodium was used as an anesthetic is most likely to have interacted with her previous
agent, but the patient awake just after 15 minutes. antihypertensive treatment?
What is the cause of this short duration of action (A) Cholestyramine
(A) Redistribution of drug (B) Gemfibrozil
(B) Excretion thru kidneys (C) Lovastatin
(C) Excretion thru lungs or in air (D) Niacin
(D) Metabolism in liver
(E) B & D (52) Metronidazole can be given in all of the followings,
except
(47) Acetylcholine is given to the patient, after which (A) Amebiasis
the patient remained unconscious for very long (B) Candidiasis
time. What is the cause? (C) Giardiasis
(A) Deficiency of acetylcholinesterase (D) Trichomoniasis
(B) Deficiency of pseudo-acetylcholinesterase (E) Balantidiasis
(C) Reuptake of acetylcholine.
(D) Decreased excretion by liver (53) A 65-year-old man presents to his physician
(E) Decreased excretion by kidney complaining of his need to make frequent trips to
the bathroom during the day and the night. He
(48) A patient is on aspirin, which has antiplatelet also admits to occasional urinary incontinence.
action. He needs surgery, & the surgeon advises Which of the following drugs would most likely be
him to stop aspirin; he can be operated after helpful to this patient?
(A) 1-3 days (A) Bethanechol
(B) 3-4 days (B) Glycopyrrolate
(C) 15 days (C) Neostigmine
(D) 7 days (D) Phenoxybenzamine
(E) 20 days (E) Phentolamine
M. Shamim’s PHARMACOLOGY 224

(54) A 4-year-old girl is sent home from daycare after (C) Chlordiazepoxide
complaining of abdominal pain. The mother takes (D) Cortisone
her daughter to the pediatrician and states that she (E) Ibuprofen
has been continually scratching around her anus.
On examination, the pediatrician notes red (60) Epinephrine will cause all of the following except
excoriations in the perianal area. He places a strip (A) Increase diastolic BP
of clear cellulose acetate tape on her perianal (B) Increase systolic BP
region and subsequently removes it. The (C) Increase peripheral resistance
pediatrician views the tape under the microscope (D) Increase pulse rate
and notes diagnostic structures. Which of the (E) Increase coronary resistance
following drugs would be most efficacious in (61) A 67-year-old male with severe refractory
eradicating this infection. congestive heart failure is being treated by
(A) Mebendazole afterload reduction. An intravenous infusion of
(B) Metronidazole nitroprusside is begun. Which of the following
(C) Praziquantel signaling molecules would most likely be elevated
(D) Pyrimethamine-sulfonamides in this patient’s vascular smooth muscle during
(E) Stibogluconate this treatment?
(55) Which of the following conditions is the most (A) cAMP
appropriate indication for buspirone? (B) cGMP
(A) Bipolar disorder (C) Potassium
(B) Generalized anxiety disorder (D) Thromboxane A2
(C) Obsessive compulsive disorder (E) Tyrosine kinase
(D) Psychosis (62) On routine checkup a physician prescribe
(E) Stage fright acetazolamide, to a team of mountaineer, to be
(56) A patient who did not disclose frequent use of taken from 5 days prior; this is to prevent
aspirin to the physician is placed on warfarin and (A) Respiratory acidosis
develops severe bleeding episodes. These episodes (B) Respiratory alkalosis
are best explained by (C) Loss of HCO3-
(A) decreased efficacy of antithrombin III (D) Gain of H+
(B) decreased production of vitamin K dependent (E) Decrease pH
clotting factors
(C) drug action on platelets (63) A 20-year-old female being treated for acute
(D) potentiation of PGI2 production lymphocytic leukemia (ALL) complains of pain
and weakness in her knees. Neurological
(57) Which drug is given in the form of injection when examination reveals severe bilateral foot drop, loss
40 weeks uterus is contracting of deep tendon reflexes, and decreased vibratory
(A) FSH sensation. Which of the following agents is most
(B) LH likely to be involved in the etiology of her current
(C) ACTH problem?
(D) Prolactin (A) Bleomycin
(E) Oxytocin (B) Daunorubicin
(C) L-Asparaginase
(58) If a patient has renal compromise, which drug (D) Prednisone
should be avoided (E) Vincristine
(A) Gentamicin
(B) Chloramphenicol (64) Which of the following antibiotics directly affects
(C) Furosemide bacterial nucleic acid synthesis?
(D) Digoxin (A) Ciprofloxacin
(E) Phenytoin (B) Doxycycline
(C) Gentamicin
(59) A patient on a particular medication complains of (D) Pyrimethamine
severe dizziness. His blood pressure in a supine (E) Sulfadiazine
position is 115/80 mm Hg; on standing it drops to
82/50 mm Hg. Which of the following drugs is
most likely responsible for these symptoms?
(A) Carabamazepine
(B) Chlorpromazine
30: One Best Type MCQs 225

(65) A patient presents to the emergency room (70) A 60-years-old male is brought to ER. He is
complaining of tremors, insomnia, sweating, and comatose and his pupils are constricted. Physician
generalized anxiety. While waiting to be seen, he suspects opium overdose. What is best to
becomes delirious, disoriented, and eventually goes administer
into shock. The patient is most likely suffering (A) Flumazanil
from withdrawal from (B) Calcium gluconate
(A) amphetamines (C) Naltraxone
(B) barbiturates (D) Naloxone
(C) hashish (E) Atropine
(D) heroin
(E) inhalants (71) A 16-years-old boy is a know patient of epilepsy.
Following several years of a drug therapy, he is
(66) A 30-year-old woman being treated for observed to have gingival hyperplasia. The
hypertension has the sudden onset of fever and common drug causing this side effect is
malaise. Temperature is 38.3 C (101 F) orally and (A) Alprazolam
blood pressure is normal. She has a malar rash, (B) Carbamazepine
swelling and tenderness of the wrists and knees, (C) Valproic acid
and a friction rub at the left lower sternal border. (D) Ethosuximide
Which of the following drugs is the most likely (E) Phenytoin
cause of these findings?
(A) Captopril (72) A 60-years-old lady is put on oral anticoagulant
(B) Hydralazine therapy. To monitor the optimum performance of
(C) Minoxidil drug, it is most wise to observe her
(D) Nitroprusside (A) PT
(E) Propranolol (B) APTT
(C) Bleeding time
(67) A subject who is given one dose of a drug (D) Platelet count
intravenously 16 hours ago still retains 16 mg of (E) Fibrinogen time
the drug in his body. Assuming that the half-life of
the drug is 8 hours, how much drug was originally (73) A 38-year-old man presents to the emergency
given to the subject? room complaining of a painful right eye and
(A) 4 mg blurred vision. Ophthalmological examination
(B) 32 mg reveals injection of the conjunctiva, corneal edema,
(C) 64 mg and increased intraocular pressure. The patient
(D) 108 mg states that he had just returned from a boat ride
(E) 256 mg for which he used a scopolamine patch to prevent
sea sickness. Which of the following drugs would
(68) Various anesthetics are used for different purposes. be most appropriate to treat this patient’s
The drug that is used for rapid anesthesia and has condition?
got good analgesia is (A) Amiloride
(A) Nitrous oxide (B) Chenodiol
(B) Halothane (C) Hydrochlorothiazide
(C) Diazepam (D) Mannitol
(D) Thiopental (E) Triamterene
(E) Propofol
(74) A 74-year-old man with urinary frequency &
(69) Consultant gynecologist wants to induce ovulation urgency has benign prostatic hypertrophy. He
in premenopausal women; most likely she gets refuses operative intervention but agrees to a trial
benefit from of finasteride therapy. During the trial, synthesis
(A) Clomiphene citrate of which of the following substances is most likely
(B) LH to be inhibited?
(C) GnRH (A) Androstenedione
(D) FSH (B) Dihydrotestosterone
(E) Octreotide (C) Estradiol
(D) Estrone
(E) Testosterone
M. Shamim’s PHARMACOLOGY 226

(75) Escherichia coli strains X and Y are both resistant (81) A 56-year-old man has progressive shortness of
to ampicillin. Ampicillin resistance is stable in breath, a cough, & a low-grade fever. He began
strain X when it is grown for multiple generations taking a drug for recurrent ventricular
in the absence of the antibiotic. However, strain Y arrhythmias 5 months ago. Erythrocyte
loses ampicillin resistance when it is grown in sedimentation rate is increased. Pulmonary
media without the antibiotic. Which of the function tests show decreased diffusing capacity.
following best explains the acquisition of X-ray film of the chest shows diffuse interstitial
ampicillin susceptibility in strain Y? pneumonia. Which of the following drugs is the
(A) Downregulation of the resistance gene most likely cause of these findings?
(B) Insertion of a transposon into the resistance gene (A) Amiodarone
(C) Loss of a plasmid carrying the resistance gene (B) Angiotensin-converting enzyme (ACE) inhibitor
(D) Point mutations in the resistance gene (C) Atenolol
(E) Recombination with a defective copy of the (D) Furosemide
resistance gene (E) Metronidazole
(76) Following will be given for staphylococcus aureus (82) A patient is brought to emergency room in
infection subconscious state, who has taken some drug at
(A) Ceftazidime home. Bicarbonate is given as a treatment; which
(B) Aminoglycoside is the drug that patient has taken
(C) Tetracycline (A) Tricyclic antidepressant
(D) Cloxacillin (B) Pethidine
(E) Ciprofloxacin (C) Phenobarbitone
(D) Benzodiazepine
(77) Most earliest effect of warfarin is seen on which of (E) Aspirin
the following clotting factor
(A) Fibrinogen (83) Which of the following drugs applied topically
(B) Prothrombin produces mydriasis without producing cycloplegia?
(C) von Wille brand (A) Atropine
(D) Thromboplastin (B) Neostigmine
(E) Antihemophilic (C) Phentolamine
(D) Phenylephrine
(78) A 32-year-old man is brought to the emergency (E) Pilocarpine
department because of confusion, wheezing,
vomiting, and diarrhea for the past 6 hours. He is (84) A 35-years-old male otherwise healthy, given a
sweating and salivating profusely. There is drug for his nausea during his mountain climbing.
generalized muscle weakness. Which of the He also started having excess urine. The most
following substances is the most likely cause of likely prescribed drug is
these findings? (A) Scopolamine
(A) Glutethimide (B) Metochlopramide
(B) Heroin (C) Domperidone
(C) Jimson weed (belladonna alkaloids) (D) Acetozolamide
(D) Parathion (E) Cyclizine
(E) Phencylidine (PCP)
(85) The most important benefit of Tamoxifen is to the
(79) Tamoxifen, an anti estrogen, affects the following following structure
(A) Breast (A) Breast
(B) Reproductive system (B) Liver
(C) Cardiovascular system (C) Kidney
(D) Gastrointestinal system (D) Stomach
(E) Urinary system (E) Ovary
(80) The most important complication for (86) The most important complication, optic neuritis is
discontinuation of oral contraceptive pills is caused by which of the following anti-tuberculous
(A) Migraine drug
(B) Heavy menstrual period (A) INH
(C) Vaginal discharge (B) Ethambutol
(D) Acne (C) Rifampicin
(E) Dysmenorrhea (D) Pyrazinamide
(E) Streptomycin
30: One Best Type MCQs 227

(87) A patient with 10 weeks pregnancy develop (E) Increase in Ca++ concentration in parietal cells
hyperthyroidism; which treatment should be given
(A) Beta-blockers (94) A patient given succinylcholine for skeletal muscle
(B) Thyroidectomy relaxation during operation, is not recovering for
(C) Propylthiouracil the last 1 hour; this may be due to congenital
(D) Wait till end of pregnancy deficiency of
(E) Iodinized salt (A) N-acetyl transferase
(B) Cholinesterase
(88) A mountaineer climbing rapidly to a height of (C) G-6-P dehydrogenase
3000 feet develops general body weakness, (D) Uridly transferase
headache, nausea & malaise. These symptoms can (E) Phospho-fructo kinase
be relieved by
(A) Paracetamol (95) A 59-year-old man develops excessive sweating
(B) Acetazolamide and salivation, diarrhea, and bradycardia while
(C) Aspirin being treated with neostigmine for myasthenia
(D) Caffeine gravis. Which of the following is the most
(E) Amphetamine appropriate therapy for these symptoms and signs?
(A) Atropine
(89) A patient with rheumatoid arthritis is on disease (B) Carbachol
modifying drug. His Hb is 8.1 gm/dl & MCV is 115. (C) Edrophonium
This can be due to (D) Epinephrine
(A) Azathioprine (E) Pralidoxime
(B) Gold salts
(C) Methotrexate (96) A patient is on digoxin for congestive heart failure.
(D) Hydrocortisone He develops digoxin toxicity. His plasma level of
(E) Chloroquine digoxin is 4 nano gm/dl. Plasma half life of digoxin
is 36 hours. For how much time digoxin is
(90) During pregnancy the diabetes is managed by withheld so that its plasma level drops to a safe
(A) Sulfonylureas level (1 nano gm/dl)
(B) Insulin (A) 36 hours
(C) Insulin + sulfonylureas (B) 52 hours
(D) Biguanide (C) 72 hours
(E) Acarbose (D) 92 hours
(E) 112 hours
(91) Regarding mechanism of action of different
diuretics, the mannitol acts on (97) A patient is taking digoxin & hydrochlorothiazide.
(A) Proximal convoluted tubule He develops digoxin toxicity, but the plasma level
(B) Distal convoluted tubule (late) of digoxin is within safe range. Digoxin toxicity in
(C) Early distal convoluted tubule this case is due to
(D) Ascending limb of loop of Henle (A) Hyponatremia
(E) Collecting duct (B) Hyperlipidemia
(C) Hypokalemia
(92) A 10-year-old girl is brought to emergency (D) Hyperuricemia
department; her chest is full of wheezes, & she is (E) Hyperglycemia
cyanosed & dyspneic. The best treatment will be
(A) Salbutamol (98) Warfarin is administered to a 56-year-old man
(B) Steroid inhaler following placement of a prosthetic cardiac valve.
(C) Oxygen The warfarin dosage is adjusted to maintain a
(D) Aminophylline prothrombin time of 18 sec. Subsequently,
(E) Systemic steroid + salbutamol trimethoprim-sulfamethoxazole therapy is begun
for recurring urinary tract infection. In addition to
(93) Amongst the mechanism of action of antiulcer monitoring prothrombin time, what action should
drugs, the way that cimetidine act is the physician take to maintain adequate
(A) Decrease in acid production due to achlorhydria anticoagulation?
and gastrin (A) Begin therapy with vitamin K
(B) Decrease in acid production due to gastrin, but (B) Increase the dosage of warfarin
not achlorhydria (C) Make no alterations in the dosage of warfarin
(C) Decrease in cAMP (D) Reduce the dosage of warfarin
(D) Increase in H+ in parietal cells (E) Stop the warfarin and change to low-dose aspirin
M. Shamim’s PHARMACOLOGY 228

(99) A patient on anti-tuberculous therapy develops eye (D) Gentamicin

symptoms; which drug is responsible (E) Nafcillin
(A) INH
(B) Rifampin (104) A 42-years-old patient with known case of
(C) Ethambutol tuberculosis developed visual disturbance. Which
(D) Streptomycin drug he used for T.B. is responsible for causing
(E) Pyrazinamide this disturbance
(A) INH
(100) Compared with normal persons, the dosage (B) Ethambutol
regimen of a drug for a patient known to be a (C) Rifampicin
“rapid metabolizer” is modified most rationally by (D) Pyrazinamide
which of the following loading and maintenance (E) Pholcodine
doses?
Loading Maintenance (105) A 14-year-old girl is brought to the physician
(A) Increased increased because of severe dysmenorrhea over the past year.
(B) Increased normal The dysmenorrhea is accompanied by nausea and
(C) Decreased normal vomiting the first 2 days of her menstrual period
(D) Normal decreased and causes her to miss 2 days of school each month;
(E) Normal increased aspirin does not relieve the pain. Menarche was at
11 years of age. Pelvic examination shows no
(101) A 22-year-old woman, gravida 1, para 1, comes to abnormalities. Serum studies show luteinizing
the physician because of vaginal discharge and hormone level of 7 mIU/mL, follicle-stimulating
vulvar pruritus for 7 days. She is allergic to hormone level of 7 mIU/mL, and thyroid-
penicillin. Her last menstrual period was 1 week stimulating hormone level of 4.0 mU/mL. A
ago. There is a thin, bubbly, pale green discharge. pregnancy test is negative. Which of the following
A wet mount preparation shows a mobile, pear- is the most appropriate next step in mangement?
shaped, flagellated organism. Select the most (A) Doxycycline therapy for 10 days
appropriate pharmacotherapy. (B) Acetaminophen therapy prior to expected menses
(A) Acyclovir (C) Ibuprofen therapy prior to expected menses
(B) Cefazolin (D) Codeine therapy during menses
(C) Ceftriaxone (E) Danazol therapy daily
(D) Erythromycin
(E) Metronidazole (106) Poisoning the Na+ - K+ pump with digitalis causes
which of the following changes in large axons?
(102) A 25-year-old woman, gravida 2, para 2, comes to (A) decreased intracellular Cl-concentration
the physician because of vaginal discharge and (B) decreased intracellular K+ concentration
vulvar pruritus and burning, and dyspareunia for (C) decreased intracellular Na+ concentration
3 days. She has no drug allergies. The vagina is (D) Immediate block in propagation of action
tender and erythematous. A KOH wet mount potentials
preparation shows spores and hyphae. Select the (E) Slow heperpolarization of membrane potentials
most appropriate pharmacotherapy.
(A) Acyclovir (107) A 30-year-old, over-weight, male is diagnosed as
(B) Miconazole diabetic with blood glucose 20 mmol/L; what
(C) Ceftriaxone treatment should you advised with diet & exercise
(D) Griseofulvin (A) Sulfonylurea
(E) Gentamicin (B) Biguanides
(C) Insulin
(103) A 20-year-woman is brought to the emergency (D) Insulin with sulfonylurea
department because of fever, severe myalgias, (E) Insulin & low energy diet
diarrhea, and a diffuse scarlatiniform rash for 4
hours. She recovered from a similar illness 6 (108) An otherwise healthy 55-year-old man is given
months ago. She is menstruating and using a isoniazid and vitamin B6 (pyridoxine) after
tampon. She appears very ill. Her temperature is conversion of his PPD skin test. An x-ray film of
40 C (104 F), blood pressure is 75/30 mm Hg, and the chest shows no abnormalities. Four weeks later
pulse is 130/min. Which of the following is the he develops abdominal pain & jaundice. Which of
most appropriate pharmacotherapy? the following is the most likely explanation?
(A) Ampicillin (A) Hepatic tuberculosis
(B) Chloramphenicol (B) Hepatitis B
(C) Doxycycline (C) Isoniazed-induced hepatitis
30: One Best Type MCQs 229

(D) Pyridoxine-induced cholecystitis (C) Metabolism to false neurochemical transmitters

(E) Tuberculous pancreatitis (D) Potent alpha1-adrenergic agonism
(E) Potent B2-adrenergic agonism
(109) An 24-year-old newly married nulligravid woman
comes to the physician because of temperatures to (114) A mother brings her 2-year-old daughter to the
39 C (102.2 F), malaise, and multiple painful emergency dept after finding her bottle of iron
blisters on her vulva for 2 days; she has been pills spilled on the floor & noticing that her
unable to void for 12 hours. She has bilateral daughter’s mouth was discolored. The child’s
inguinal adenopathy. There are shallow-based plasma iron conc. is 400 mg/dL. Which of the
ulcers on the vulva, vaginal mucosa, and following agents is most appropriate for chelation
ectocervix. The most appropriate treatment is therapy?
administration of which of the following? (A) Acetylcysteine
(A) Acyclovir (B) Calcium disodium edetate (EDTA)
(B) Ganciclovir (C) Deferoxamine
(C) Immune globulin (D) Dimercaprol
(D) Interferon (E) Penicillamine
(E) Zidovudine (AZT)
(115) A patient is on digoxin & diuretics; digoxin level is
(110) A 78-year-old man comes to the physician because within normal limits but its toxicity appears. The
of swelling of both ankles for 4 days. He has been likely reason is
taking indomethacin for low back pain for 2 weeks (A) Decreased K+
with partial relief of symptoms. Examination (B) Decreased PO4_
confirms the pedal edema but is otherwise (C) Decreased Cl_
unremarkable; the bladder is not distended. His (D) Decreased Na+
serum urea nitrogen (BUN) level is 56 mg/dL and (E) Decreased HCO3_
creatinine level is 2.9 mg/dL; these values were
previously within normal limits. Which of the (116) A 45-year-old woman who is being treated for
following is the most appropriate next step? hypertension and hypercholesterolemia develops
(A) Discontinuation of indomethacin diffuse muscle pain and weakness. Serum creatine
(B) Prescription of a thiazide diuretic kinase activity is increased. Which of the
(C) Evaluation for multiple myeloma following drugs is most likely to have caused this
(D) Measurement of urine sodium and creatinine clinical picture?
levels (A) Captopril
(E) Renal ultrasonography (B) Hyrdochlorothiazide
(C) Lovastatin
(111) A patient with acute inferior wall myocardial (D) Nicotinic acid
infarction is having rhonchi (upto mid-chest), (E) Propranolol
dyspnea, sweating, pulse 120 bpm, BP 130/90
mmHg. What treatment should you give to relieve (117) A 58-year-old man with chronic congestive heart
both the pain & dyspnea failure requires ongoing hydrochlorothiazide
(A) Furosemide therapy. His monthly serum chemistry profile
(B) Sublingual GTN shows persistent hypokalemia. The most
(C) Morphine appropriate next step is to add which of the
(D) Aspirin following diuretics to the regimen?
(E) Anticoagulants (A) Acetazolamide
(B) Amiloride
(112) The labs of a patient shows MCV 120, & Hb 9 g/dl; (C) Furosemide
patient is on what drug (D) Mannitol
(A) Azathioprine (E) Metolazone
(B) Methotrexate
(C) Cisplatin (118) H2-receptor blocker will
(D) Chloroquin (A) Inhibit gastrin induced H+ release
(E) Cyclophosphamide (B) Inhibit vagally induced H+ release
(C) Inhibit vagally + gastrin induced H+ release
(113) Which of the following characteristics of (D) Doesn't inhibit gastrin induced H+ release
amphetamines is most likely to be responsible for (E) Doesn't inhibit insulin induced H+ release
increasing blood pressure?
(A) Indirect release of endogenous catecholamines
(B) Inhibition of catecholamine metabolism
M. Shamim’s PHARMACOLOGY 230

(119) A pregnant woman taking phenytoin for epilepsy. (125) Release of neurotransmitter is blocked by
The least likely teratogenic effects of phenytoin is (A) Hemicholinium
(A) Nail hypoplasia (B) Acetylcholinesterase
(B) Cleft lip (C) Botulinum toxin & spider venom
(C) Spina bifida (D) Choline
(D) IUGR (E) Ca++
(E) Cardiac defects
(126) Drug which act on cell wall synthesis of bacteria is
(120) A 52-year-old man with chronic obstructive (A) Quinolones
pulmonary disease who has been taking (B) Macrolides
theophylline for 14 weeks now requires treatment (C) Tetracycline
for hypertension, peptic ulcer, and tuberculosis. (D) Penicillin
After 2 weeks of therapy, he has a toxic plasma (E) Co-trimoxazole
theophylline concentration. The drug most likely
to have caused the theophylline toxicity is (127) A patient with myocardial infarction is having
(A) Cimetidine rhonchi, dyspnea, & sweating. What treatment
(B) ‘hydrochlorothiazide should be given to relieve pain & dyspnea
(C) prazonsin (A) Aspirin orally
(D) rifampin (B) Morphine
(C) Nitroglycerine
(121) An 18-year-old primigravid woman at term has (D) Anticoagulant
been in spontaneous labor with ruptured (E) Diuretics
membranes for 14 hours. Her cervix is 7 cm
dilated. Fetal heart rate monitoring shows a (128) An asthmatic patient, on multiple drugs for his
baseline of 180/min with decreased variability. Her asthma treatment & also uses diazepam for
temperature is 38.5 C (101.3 F), and her uterus is depression, develops bone fracture; this is likely to
tender to palpation. Gram’s stain of the amniotic be from
fluid shows multiple organisms. Which of the (A) Diazepam
following is the most appropriate (B) Theophylline
pharmacotherapy? (C) Salbutamol
(A) Ampicillin and gentamicin (D) Prednisolone
(B) Ciprofloxacin and clindoamycin (E) Aspirin
(C) Erythromycin (129) An old epileptic patient on phenytoin is having an
(D) Metronidazole attack now. What you give to this patient in
(E) Penicillin emergency
(122) Antidote of morphine is (A) Phenytoin
(A) Naloxone (B) Carbamazepine
(B) Naltrixone (C) Diazepam
(C) Amphetamine (D) Valproic acid
(D) Fluconazole (E) Primidone
(E) Meperidine (130) A patient suffering from congestive heart failure,
(123) Fluconazole, an antifungal drug, act by inhibiting has difficulty is swallowing. Barium studies shows
synthesis of esophageal constriction; this is likely to be due to
(A) DNA the following drug
(B) RNA (A) Aspirin
(C) Fungal membrane ergosterol (B) Captopril
(D) Protein (C) Atenolol
(E) Folic acid (D) Fosinopril
(E) Estrialol
(124) Halothane is a weak analgesic & is co-
administrated with (131) Nitrous oxide can not be given in an old man
(A) Thiopental undergoing laparotomy because
(B) Nitrous oxide (A) It causes analgesia
(C) Oxygen (B) It causes intestinal dilatation
(D) Ketamine (C) It causes bronchoconstriction
(E) Enflurane (D) It supports combustion
(E) It lowers blood pressure
30: One Best Type MCQs 231

(132) In a patient, who is under general anaesthesia with (139) Diazepam

spontaneous ventilation, Halothane with 66% N2O (A) 50% bound with proteins
& 33% O2 can cause (B) Has no toxic metabolites
(A) Bronchoconstriction (C) Not easily absorbed on intramuscular injection
(B) Increase in airway resistance (D) Cannot cross placenta readily
(C) Increase in alveolar ventilation (E) Twice more potent than midazolam
(D) Increase in tidal volume (140) Morphine causes
(E) Decrease in PaCO2 (A) Decrease in gastroesophageal reflux
(B) Decrease in tone of sphincters
(133) Sevoflurane is preferred over isoflurane for
(C) Increase in peristalsis
induction because
(D) Increase in acid production
(A) It has got pleasant smell
(E) Increase in gastric emptying time
(B) It has low blood gas solubility coefficient
(C) Metabolites are less active (141) Fentanyl is used because
(D) Don’t sensitize myocardium to exogenous (A) It has minimal cardiac effects
catecholamines (B) Metabolites are inactive
(E) Causes bronchodilatation (C) On high doses it cause anaesthesia
(D) Its half life (t 1/2) is 30-40 minutes
(134) Hypotensive effects of propofol are mainly due to
(E) It is lipid soluble
(A) Peripheral vasodilation
(B) Splanchnic vasodilation (142) Following a dose of local anaesthetic which of the
(C) Cerebral vasodilation fibres will be affected first
(D) Alpha 1 & alpha2 blockage (A) A alpha
(E) Beta 1 & beta 2 blockage (B) A beta
(C) A gamma
(135) Ketamine is use in repeated burn dressings
(D) B
because of its
(E) C
(A) Analgesic effects
(B) Antihypotensive effects (143) A 50 kg person is schedule to stitch a 10 cm long
(C) Less cardiac depression wound on the scalp, which recommended dosage of
(D) Less respiratory depression lidocaine will you choose
(E) Early recovery (A) 150 mg plain
(B) 250 mg 1% with adrenaline
(136) A young boy with burns is brought to emergency
(C) 250 mg 2% with adrenaline
ward. There is history of death of one of his family
(D) 250 mg 3% with adrenaline
members due to succinylcholine induction. So we
(E) 350 mg 3% with adrenaline
will avoid succinylcholine because it
(A) Causes hyperkalemia (144) Roivacain is preferred over bupivacaine for
(B) Causes hepatotoxicity epidural in labor because
(C) Causes muscle pains (A) It is less toxic to baby
(D) Can trigger malignant hyperthermia (B) It is less cardiotoxic
(E) Can cause spasm of masseter muscle (C) Dose is equipotent
(D) Toxicity can easily be reversed
(137) Which of the following benzodiazepines have not
(E) Produces a block of longer duration
active metabolites
(A) Chlordiazepoxide (145) Glycopyrrolate is preferred over atropine because
(B) Diazepam (A) It is quaternary compound
(C) Clonazepam (B) Can cross blood brain barrier
(D) Midazolam (C) Increases sympathetic activity
(E) Oxazepam (D) Cardiac acceleration is less
(E) Causes amnesia
(138) Midazolam is given before induction because
(A) It causes retrograde amnesia (146) Ketorolac can be given safely for postoperative
(B) It decreases post operative sedation analgesia in
(C) It decreases MAC value (A) A patient undergone thoracic surgery without any
(D) It is a short acting systemic disease
(E) Side effect can easily be reversed with flumazenil (B) A patient undergone laparotomy with asthmatic
history
(C) Hip replacement of a patient with IHD
M. Shamim’s PHARMACOLOGY 232

(D) Patient with increased creatinine (154) Isoflurane

(E) In a patient of known peptic ulcer (A) Blood gas solubility coefficient is 1.4
(B) Maintains peripheral vascular resistance
(147) A drug which is used against enemies in war. Its (C) Increases end tidal CO2 when use spontaneously
mechanism of action can be
(D) Very pleasant to smell
(A) Inhibition of acetylcholine
(E) Can cause seizures
(B) Inhibition of alpha & beta receptors
(C) Inhibition of acetyl transferase (155) Suxamethonium is avoided is burn patients
(D) Inhibition of cholinesterase because it causes
(E) Inhibition of dopamine (A) Bradycardia
(B) Hyperkalemia
(148) Which of the following antibiotic can block
(C) Muscle pain
neuromuscular transmission
(D) Increased intracranial pressure
(A) Ceftriaxone
(E) Increased intraocular pressure
(B) Crentamycine
(C) Penicillin (156) Morphine
(D) Metronidazole (A) Causes diarrhea
(E) Chloramphenicol (B) Causes mydriasis
(C) Prevents Nausea & vomiting
(149) Atropine is given before reversal with neostigmine
(D) Prevents histamine release
because it
(E) Acts on all receptors
(A) Decreases secretions
(B) Increases sympathetic activity (157) Which of the following in imidazole derivative
(C) Increases heart rate (A) Thiopentone sodium
(D) Causes bronchodilatation (B) Methohexitone
(E) Causes mydriasis (C) Propofol
(D) Etomidate
(150) A patient was given 450 mg of thiopentone sodium
(E) Ketamine
but after 15 minutes the patient awoke, what had
happened to the drug (158) Dopamine increases urine production in a shocked
(A) Inactivated by liver patient because it
(B) Excreted by kidneys (A) Increase cardiac output
(C) Redistribution (B) Decreases aldosterone release
(D) Settled in brain (C) Decreases ADH release
(E) Drug bound to plasma proteins (D) Causes peripheral vasodilatation
(E) Causes renal arterial vasodilatation
(151) A patient with history of injury & has broken ribs
6 & 7 on right side which local anaesthetic will you (159) A patient is on antiarrhythmic therapy. During the
give for prolonged pain relief period of treatment CNS toxicity appears with
(A) Bupivacaine adverse cardiac effects. Which is the drug
(B) Ropivacain responsible for these effects
(C) Lidocaine (A) Phenytoin
(D) Cinchocaine (B) Lidocaine
(E) Phenoles (C) Bretylium
(D) Verapamil
(152) Bupivacaine
(E) Propranolol
(A) Can be made hyperbaric with 8% glucose
(B) Is aminoester (160) A patient of congestive cardiac failure is taking
(C) 0.5% contain 50 mg/ml digoxin. Which of the following change will occur
(D) Short duration of action in his ECG
(E) Can cause allergic reactions (A) Increase in PR interval
(B) Increase in QT interval
(153) Lignocaine on local anaesthesia
(C) A tall T wave
(A) Cause vasodilatation
(D) A tall P wave
(B) Increase Cl- transfer
(E) QRS complex more than 0.2 sec
(C) Block Na+ channel
(D) Block K+ channel (161) What is the drug of choice in prinzmeatal angina
(E) Decreases pH of tissue (A) Lignocaine
(B) Verapamil
(C) Nitroglycerine
30: One Best Type MCQs 233

(D) Nifedipine (A) Acetylation of disulfiram

(E) Diltiazem (B) Hydroxylation of phenytoin
(C) Glucoronidation of chloramphenicol
(162) Loop diuretics & thiazide diuretics act (D) Conjugation of isoniazid
synergistically at which site of nephron (E) Oxidation of cimetidine
(A) Proximal convoluted tubule
(B) Descending limb of loop of Henle (170) A drug is injected intravenously. After half hour
(C) Ascending limb of loop of Henle its plasma concentration following first order
(D) Distal convoluted tubule kinetics was 400 mg/ml & after 12 hrs its plasma
(E) Collecting ducts concentration was 50 mg/ml. What is the half life
of drug
(163) Paracetamol (A) 2 hrs
(A) Has poor antiinflammatory effects (B) 4 hrs
(B) Inhibit platelet aggregation (C) 6 hrs
(C) Causes renal function worsening (D) 8 hrs
(D) Does not bind to plasma proteins (E) 10 hrs
(E) Plasma half life is 30 minutes
(171) Cimetidine is given preoperatively because
(164) A patient with IHD undergoing anaesthesia (A) It reduces gastric motility
suddenly have increased blood pressure. Which (B) It blocks H2 receptors
one of the following drug will you prefer to give (C) It decreases acidity
(A) I/V nitroglycerine (D) It increases bioavailability of some drugs
(B) I/V nifedipine (E) It decreases release of histamine
(C) I/V hydralazine
(D) I/V sodium nitroprusside (172) Cimetidine is not given with warfarin because it
(E) I/V esmolol causes
(A) Increased destruction of warfarin
(165) In a patient of IHD intravenous fentanyl is (B) Decreased protein binding of warfarin
preferred to analgesia because (C) Inhibit excretion of warfarin thru kidney
(A) It has minimal cardiac effects (D) Inhibit excretion of warfarin thru feces
(B) At high doses it causes anaesthesia (E) Inhibit its metabolism thru liver
(C) Can be reversed with naloxone
(D) Its duration is 30-40 minutes (173) An asthmatic patient comes in emergency ward
(E) It is lipid soluble with severe shortness of breath. Which of the drug
will you give to relieve his symptoms
(166) Labetalol is (A) Salbutamol
(A) Alpha 1 blocker (B) Terbutaline
(B) Alpha 2 blocker (C) Corticosteroids
(C) Beta 1 blocker (D) Theophylline
(D) Beta 2 blocker (E) Ipratropium
(E) Both alpha & beta blocker
(174) A patient of IHD undergoing anaesthesia suddenly
(167) Dopamine increases systolic & diastolic blood develops bronchospasm. Which drug will you
pressure by acting primarily on choose to relieve his bronchospasm
(A) Beta 1 receptors (A) Salbutamol
(B) Beta 2 receptors (B) Terbutaline
(C) On both Beta 1 & beta 2 receptors (C) Corticosteroids
(D) Alpha 1 receptors (D) Theophylline
(E) Alpha 2 receptors (E) Ipratropium
(168) In hyperkalemia which of the following drug (175) A patient comes to you with bacterial infection. His
should be avoided serum creatinine is 150 mmol/liter, urea 40
(A) Frusemide mmol/liter & TLC is 8 x 1012 / liter. Which of the
(B) Ethacrynic acid following drug will you avoid to give
(C) Bumetanide (A) Quinolones
(D) Spironolactone (B) Ceftriaxone
(E) Chlorthiazide (C) Gentamicin
(169) Cytochrome P-450 induces which one of the (D) Ampicillin
following (E) Chloramphenicol
M. Shamim’s PHARMACOLOGY 234

(176) In the treatment of nausea & vomiting (E) Ganglion blocker

(A) Metoclopromide has no role
(B) Metoclopromide has less effects as compared to (184) Which one of the following is cardioselective Beta-
ondansetron following cytotoxic drug therapy blocker
induced nausea & vomiting (A) Esmolol
(C) Glucocorticoids are contraindicated (B) Pindolol
(D) Phenothiazines have no role (C) Practolol
(E) Ipecac is very effective (D) Propranolol
(E) Labetalol
(177) Following combination is used effectively
(A) Halothane & adrenaline (185) Which one of the following is a calcium channel
(B) Sevoflurane & phenytoin blocker
(C) Isoflurane & verapamil (A) Propranolol
(D) Monoamine oxidase inhibitors & pethidine (B) Captopril
(E) Ephedrine & amphetamine (C) Hydralazine
(D) Nifedipine
(178) Monoamine oxidase inhibitors can be used safely (E) Glyceryl trinitrate
with
(A) Fentanyl (186) Hydralazine acts by
(B) Ephedrine (A) Blocking alpha receptors
(C) Pethidine (B) Blocking beta receptors
(D) Morphine (C) Directly acting on vascular smooth muscular
(E) Nalbuphine (D) Ganglion blocking
(E) Blocking renin-angiotensin system
(179) In atrial fibrillation which drug can be given
(A) Propranolol (187) Low molecular weight heparin
(B) Digoxin (A) Antagonize anti thrombine III
(C) Verapamil (B) Inhibit factor V
(D) Nifedipine (C) Inhibit factor VIII
(E) Lidocaine (D) Inhibit factor X
(E) Decrease platelet aggregation
(180) A patient on digoxin therapy has to undergo a
surgery & you are on a pre operative round. (188) Which one of the following drug lowers blood
Which toxicity would you suspect glucose level
(A) Hyperkalemia (A) Adrenaline
(B) Ventricular arrhythmias (B) Chlorpromazine
(C) Pain abdomen (C) Chlorpropamide
(D) Third degree heart block (D) Propranolol
(E) Renal failure (E) Hydrocortisone

(181) In a patient of severe asthmatic attack which of the (189) Ephedrine

following drug will you give intravenously (A) Has actions on both alpha & beta receptors
(A) Propranolol (B) Has actions on nicotinic receptors
(B) Phentolamine (C) Has actions on muscarinic receptors
(C) Isoprenaline (D) Actions can be blocked by adrenaline
(D) Theophylline (E) It causes mydriasis
(E) Esmolol (190) Adrenaline causes
(182) The mechanism of action of theophylline is (A) Mydriasis
(A) Antagonism of adenosine (B) Cutaneous vasoconstriction
(B) Alpha blocker (C) Renal vasodilation
(C) Beta blocker (D) Muscle spasm
(D) Phosphodiesterase inhibitor (E) Glycogenesis
(E) Ganglion blocker (191) A patient is admitted in ICU with TCA poisoning.
(183) Ondansetron is Which is the most likely presentation
(A) Alpha blocker (A) Acute urine retention
(B) Beta blocker (B) Convulsions
(C) Ca++ channel blocker (C) Coma
(D) 5-HT3 blocker (D) Tinnitus
30: One Best Type MCQs 235

(E) Hypertension
(192) What is the drug of choice in supraventricular
arrhythmias
(A) Verapamil
(B) Propranolol
(C) Lidocaine
(D) Quinidine
(E) Procainamide
M. Shamim’s PHARMACOLOGY 236

Answers of One Best Type MCQs

1. A 2. C 3. B 4. B 5. A 6. C 7. D 8. A
9. A 10. B 11. C 12. A 13. D 14. A 15. C 16. B
17. D 18. B 19. D 20. D 21. A 22. A 23. E 24. C
25. C 26. A 27. A 28. B 29. A 30. C 31. A 32. E
33. E 34. B 35. B 36. A 37. E 38. C 39. C 40. A
41. B 42. B 43. C 44. B 45. D 46. A 47. A 48. D
49. E 50. D 51. A 52. B 53. B 54. D 55. B 56. B
57. E 58. B 59. B 60. E 61. B 62. B 63. E 64. A
65. B 66. B 67. C 68. A 69. A 70. D 71. E 72. A
73. D 74. B 75. D 76. D 77. B 78. D 79. A 80. A
81. A 82. A 83. D 84. D 85. A 86. B 87. C 88. B
89. C 90. B 91. A 92. E 93. C 94. B 95. A 96. C
97. C 98. D 99. C 100. E 101. E 102. B 103. E 104. B
105. C 106. B 107. E 108. C 109. A 110. A 111. C 112. B
113. A 114. C 115. A 116. C 117. B 118. C 119. A 120. A
121. A 122. A 123. C 124. B 125. C 126. D 127. B 128. D
129. D 130. A 131. B 132. C 133. B 134. A 135. A 136. D
137. D 138. B 139. C 140. E 141. A 142. E 143. C 144. D
145. D 146. A 147. D 148. B 149. C 150. C 151. E 152. A
153. C 154. A 155. B 156. E 157. D 158. E 159. B 160. A
161. C 162. C 163. A 164. E 165. A 166. E 167. A 168. D
169. B 170. B 171. C 172. E 173. A 174. B 175. C 176. B
177. E 178. B 179. B 180. B 181. D 182. A 183. D 184. A
185. D 186. C 187. D 188. C 189. A 190. B 191. A 192. A
M. Shamim’s PHARMACOLOGY 237

31 GET THRU PHARMA VIVA

(6) Classification of sympatholytics.

INTRODUCTION (7) Phenoxybenzamine (complete).
(8) Propranolol (complete).
Clinico-Basic PHARMACOLOGY is quite different from
other publications available in market in that it contains:  CHAPTER 3: PARASYMPATHETIC NERVOUS
(1) Complete, comprehensive, & update classification. SYSTEM DRUGS
(2) Details of almost all drugs, including dosage. (1) Effects produced by cholinoceptor stimulation.
This will help in comprehensive preparation of MCQ exam., (2) Classification of parasympathomimetics (complete).
but for viva you need not to "memorize" a comprehensive (3) Direct & indirect acting parasympathomimetics
classification & detail of "all drugs". This section will (mechanism of action & pharmacological effects).
therefore reduce your burden by pointing out toward (4) Clinical uses of direct & indirect acting parasym-
important aspects of each chapter. pathomimetics (Methacholine, Bethanechol,
Neostigmine, Ecothiofate).
 CHAPTER 1: GENERAL PHARMACOLOGY (5) Adverse effects of direct & indirect acting
(1) Pharmacology, Pharmacokinetics, Pharmaco- parasympathomimetics (complete).
dynamics. (6) Contraindications of direct-acting parasympatho-
(2) Drug, pharmacopoeia. mimetics.
(3) Formulae for children's dose. (7) Classification of parasympatholytics (complete).
(4) Routes of administration of drugs. (8) Atropine & scopolamine (mechanism of action,
(5) Oral & parenteral routes: Advantages & pharmacological effects, clinical uses, adverse
disadvantages. effects, contraindications).
(6) 1st order & zero order kinetics.
(7) Bioavailability (def).  CHAPTER 4: OPHTHALMOLOGICAL DRUGS
(8) Vol. of distribution (def). (1) Miotics (complete).
(9) Enzyme induction & inhibition. (2) Mydriatics (complete).
(10) First - pass effect. (3) Anti-glaucoma drugs (complete).
(11) Enterohepatic circulation. (4) Sulfonamides used in eye infections (systemically
(12) Clearance of drug (def). & locally).
(13) Half - life.
(14) Receptor & its regulation.  CHAPTER 5: CENTRAL NERVOUS SYSTEM
(15) Affinity & Intrinsic activity. DRUGS
(16) Agonist, Partial agonist & Antagonist. (1) Classification of sedative-hypnotics (complete).
(17) Potentiation, Potency & Efficacy. (2) Benzodiazepines (complete).
(18) Therapeutic index. (3) Barbiturates (clinical use & adverse effects).
(19) Idiosyncrasy & Hypersensitivity. (4) Alcohol (chronic alcoholism).
(20) Tolerance & Tachyphylaxis. (5) Classification of anti-epileptics (complete).
(6) Phenytoin & Ethosuximide (mechanism of action &
 CHAPTER 2: SYMPATHETIC NERVOUS adverse effects).
SYSTEM DRUGS (7) Classification of anti-Parkinsonism drugs
(1) Effects produced by adrenoceptor stimulation. (complete).
(2) Classification of sympathomimetics according to (8) Levodopa, Bromocriptine & Amantadine
receptor selectivity. (mechanism of action & adverse effects).
(3) Mechanism of action of sympathomimetics. (9) Classification of anti-psychotic drugs (complete).
(4) Pharmacological effects of sympathomimetics (10) Anti-psychotic drugs (mechanism of action,
(complete). clinical uses & adverse effects).
(5) Epinephrine (Clinical uses, Adverse effects, (11) Drugs for bipolar affective disorder (complete).
Contraindications, Dosage). (12) Lithium (complete).
M. Shamim’s PHARMACOLOGY 238

(13) Classification of anti-depressants. (4) Saralasin, Captopril & Enalapril (complete).

(14) Tricyclic anti-depressants & MAO inhibitors (5) Classification of anti-anginal drugs (complete).
(mechanism of action, adverse effects & (6) Nitrates & nitrites, Beta-blockers & Ca channel
contraindications). blockers (complete).
(15) Classification of CNS stimulants. (7) Classification of anti-congestive cardiac failure
(16) Amphetamine (mechanism of action, clinical uses drugs (complete).
& adverse effects). (8) Digitalis (complete).
(17) Classification of antimigrain drugs (complete). (9) Classification of anti-arrhythmic drugs (complete).
(18) Ergotamine tartarate (complete). (10) Quinidine, Amiodarone (complete).

 CHAPTER 6: ANESTHETICS  CHAPTER 12: RENAL DRUGS

(1) Classification of general anesthetics (complete). (1) Classification of diuretics.
(2) Mechanism of action of general anesthetics. (2) Osmotic, High-ceiling (loop), Thiazide, & K+ -
(3) Halothane (complete). sparing diuretics (complete).
(4) Chloroform & Diethyl ether (disadvantages).
(5) Classification of local anesthetics (complete).  CHAPTER 13: DRUGS AFFECTING
(6) Local anesthetics (mechanism of action, RESPIRATORY SYSTEM
pharmacological effects, clinical uses, & adverse  (1) Classification of anti-asthmatic drugs (complete).
effects). (2) Methylxanthine drugs (complete).
(3) Beta 2 selective sympathomimetics (complete).
 CHAPTER 7: SKELETAL MUSCLE RELAXANTS (4) Cromolyn sodium (clinical uses).
(1) Classification (complete). (5) Classification of analeptic (complete).
(2) Neuromuscular blockers (complete). (6) Nikethamide (complete).
(7) Classification of anti - tussives (complete).
 CHAPTER 8: OPIOID ANALGESICS & (8) Expectorants.
ANTAGONISTS
(1) Classification (complete).  CHAPTER 14: GASTROINTESTINAL DRUGS
(2) Opioid agonists (complete).  (1) Classification of anti - peptic ulcer drugs (complete).
(3) Opioid antagonists (clinical uses). (2) Antacids (Na bicarbonate, Mg trisilicate, Ca
carbonate).
 CHAPTER 9: NSAIDS, NONOPIOID  (3) H2 - receptor antagonists (complete).
ANALGESICS & ANTI-GOUT DRUGS (4) Emetics (classification, indication & contra-
(1) Classification of NSAIDs (complete). indications).
(2) Aspirin (complete). (5) Anti-emetics (classification).
(3) Classification of Nonopioid analgesics (complete). (6) Purgatives (classification, indications &
(4) Acetaminophen (complete). contraindications).
(5) Classification of anti-gout drugs (complete). (7) Anti-diarrheals (classification).
(6) Colchicine & allopurinol (complete). (8) Appetite stimulants & suppressants (classification).

 CHAPTER 10: DRUGS AFFECTING BLOOD  CHAPTER 15: HEPATO-PANCREATICO-

(1) Classification of anti-anemic drugs (complete). BILIARY DRUGS
(2) Iron (adverse effects, toxicity, contraindications). (1) Classification of anti - hepatitis drugs.
(3) Vit. B12 & folic acid (clinical uses). (2) Drugs used to dissolve gall stones.
(4) Classification of anticoagulants (complete).
(5) Warfarin & heparin (complete).  CHAPTER 16: AUTACOIDS & ITS
(6) Classification of coagulants (complete). ANTAGONISTS
(7) Vit. K (complete). (1) Clinical uses of histamine.
(8) Classification of antihyperlipidemic agents (2) Drugs that cause histamine release.
(complete).  (3) H1 - receptor antagonists (classification, clinical
(9) Anaphylaxis (complete). uses & adverse effects).
(4) Biosynthesis of kinins.
 CHAPTER 11: CARDIOVASCULAR SYSTEM (5) Clinical uses of prostaglandins.
DRUGS
(1) Classification of antihypertensive drugs (complete).  CHAPTER 17: ENDOCRINOLOGY
(2) Methyldopa & Reserpine (complete).  (1) Adrenal corticosteroids (classification, clinical uses,
(3) Diazoxide (complete). adverse effects & contraindications).
31: Get Thru Pharma Viva 239

(2) Estrogen, Progestins & Testosterone (clinical uses (6) Classification of anti-trypanosomiasis.
& adverse effects). (7) Suramin (mechanism of action & adverse effects).
 (3) Oral contraceptive (classification, clinical uses,
adverse effects, & contraindications).  CHAPTER 22: CHEMOTHERAPY OF
 (4) Classification of anti-diabetic drugs (complete). HELMINTIC INFECTIONS
(5) Insulin preparations (clinical uses, & adverse (1) Classification of anti-schistosomiasis drugs.
effects). (2) Praziquantal (mechanism of action, clinical uses &
(6) Sulfonylureas & Biguanides (mechanism of action, adverse effects).
clinical uses & adverse effects). (3) Classification of drugs used in tape worm infections.
 (7) Classification of anti-thyroid drugs (complete). (4) Niclosamide (mechanism of action & adverse
(8) Thioamides, Iodides, Radioactive iodine effects).
(mechanism of action & adverse effects). (5) Classification of drugs used in round worm
infections.
 CHAPTER 18: CHEMOTHERAPY OF (6) Pyrantal pamoate (mechanism of action & adverse
BACTERIAL INFECTIONS effects).
(1) Penicillins (complete).
(2) Cephalosporins (complete).  CHAPTER 23: CANCER CHEMOTHERAPY
(3) Chloramphenicol (complete). (1) Classification of anti-cancer drugs.
(4) Tetracyclines (complete). (2) Methotrexate (mechanism of action, clinical uses &
(5) Aminoglycosides (complete). adverse effects).
(6) Sulfonamides (complete).
(7) Trimethoprim (complete).  CHAPTER 24: VITAMINS & MINERALS
(8) Cotrimoxazole (complete). (1) Vit. A, Vit. B1, Nicotinamide, Vit. B6, Vit. C, Vit.
(9) Erythromycin (complete).
D3, Vit. E (only clinical uses & adverse effects).
(10) Fluoroquinolones (complete).
(11) Classification of anti-tuberculous drugs (complete). (2) Calcium (clinical uses, adverse effects &
(12) Isoniazid, Rifampin, & Ethambutol (mechanism of contraindications).
action & adverse effects).
(13) Classification of anti-leprosy drugs (complete).  CHAPTER 25: DRUG INTERACTIONS
(14) Sulfones (mechanism of action & adverse effects). Not important to get thru.
(15) Classification of drugs used in urinary tract
infections.  CHAPTER 26: ANTIDOTES
(16) Nitrofurantoin & Nalidixic acid (mechanism of All are important.
action, clinical uses & adverse effects).
 CHAPTER 27: COMPARATIVE
 CHAPTER 19: CHEMOTHERAPY OF FUNGAL PHARMACOLOGY
INFECTIONS Following are important;
(1) Classification of anti-fungal agents (complete). (1) Physostigmine & Neostigmine.
(2) Amphotericin B, Nystatin, Griseofulvin (2) Atropine & Hyoscine.
(mechanism of action, clinical uses & adverse (3) Epinephrine & Norepinephrine.
effects). (4) Cocaine & Procaine.
(5) Halothane & Ether.
 CHAPTER 20: CHEMOTHERAPY OF VIRAL (6) Tubocurarine & Suxamethonium.
INFECTIONS (7) Morphine & Pethidine.
(1) Classification of anti-viral drugs (complete). (8) Morphine & Codeine.
(2) Amantadine (complete). (9) Heparin & Warfarin.
(10) Digoxin & Digitoxin.
 CHAPTER 21: CHEMOTHERAPY OF
PROTOZOAL INFECTIONS  CHAPTER 28: PRACTICAL PHARMACOLOGY
(1) Classification of anti - malarial drugs. Do completely.
(2) 4-Aminoquinolines, Quinine, Primaquine &
Pyrimethamine & Fansidar (mechanism of action,
& adverse effects).
(3) Metronidazole, (mechanism of action, clinical uses
& adverse effects).
(4) Classification of anti-leishmaniasis drugs.
(5) Pentavalent antimonials (mechanism of action).
M. Shamim’s PHARMACOLOGY 240

32 ANSWERS OF SELF
ASSESSMENT QUESTIONS

A B C D E A B C D E

(1) T F T T T (45) T F F T T
(2) T F T F T (46) T T F F T
(3) F F T F F (47) T T F F T
(4) T T F F T (48) F F F T F
(5) T T F T F (49) T F T T T
(6) T T T F F (50) T T F F T
(7) T F T F F (51) T T T T F
(8) T F F F F (52) F T F T T
(9) F T F T F (53) T F F F F
(10) F F T F F (54) T T F T F
(11) F T F T T (55) T T T T F
(12) T T T T F (56) T T F T F
(13) T T T T F (57) T F F T F
(14) T F T T T (58) F T T T F
(15) F F F T F (59) T T F T F
(16) F T F F F (60) T T F T T
(17) T F F F T (61) T F T T F
(18) F T T F F (62) T T T T F
(19) F F F T F (63) F T T T F
(20) T T T F F (64) T F F T F
(21) T F T F T (65) T T T F T
(22) T F T F T (66) F F T T F
(23) F T T F F (67) T F T F T
(24) T T T F F (68) F T F T T
(25) F F T F T (69) F F T T T
(26) T T F T T (70) T F T T F
(27) T F T F T (71) F T T T F
(28) F T T T F (72) T F F T T
(29) T T T T F (73) T F T T F
(30) T F T T F (74) F T T F T
(31) F F F F T (75) T T F T T
(32) T F T F F (76) T F F T T
(33) T T T T F (77) T F F F T
(34) T F T F T (78) T T T F T
(35) T F F T T
(79) T T T F F
(36) F F T T T
(80) T T T F T
(37) T T T F T
(38) T F F F F (81) F T T T T
(39) T T F T F (82) F F T T T
(40) F F T F F (83) T T T T F
(41) F T F T F (84) F T F T T
(42) T T T F T (85) F F F T F
(43) T F T T T (86) F T T T T
(44) T F T T T (87) F T T T T
32: Answers of Self Assessment Questions 241

A B C D E A B C D E

(88) T T T F T (131) T T T F T
(89) T T F T F (132) F T F F F
(90) T T F T F (133) T T F T T
(91) F T T F T (134) T T F F T
(92) F T T T T (135) F F T F F
(93) T F T T T (136) F T T T T
(94) T T T T F (137) F T T T F
(95) T T F F T (138) T T T F F
(96) T T F T T (139) T T F F F
(97) T T F T T (140) T T T F T
(98) F F F T F (141) T F T T T
(99) T T F T T (142) F F T F F
(100) T T T T F (143) T T F T T
(101) F T T T T (144) T T F T T
(102) T T T T F (145) F T T T F
(103) T T F F T (146) F T T T F
(104) T F T T T (147) T T T F T
(105) F T F T F (148) T T F T F
(106) T F T F T (149) T T T F T
(107) F T F F T (150) T T T T T
(108) T T T T T (151) F F F T F
(109) T T T F T (152) T F T T T
(110) F T F T T (153) T F T T F
(111) F F F T F (154) T F T F T
(112) T F F T T (155) T T T F T
(113) T F T F F (156) T T T F F
(114) T T F T T (157) T T T F T
(115) F T F F F (158) T F T F T
(116) T F F F F (159) T T F T T
(117) F F F T T (160) T T F F F
(118) F F T T T (161) T T T T F
(119) F T T F F (162) T T T F T
(120) T T T T T (163) T T T F F
(121) T T F T T (164) F T T T T
(122) T T T F F (165) F T F T F
(123) T T F F T (166) T F F T F
(124) T T T T F (167) T F T T F
(125) F T T T T (168) T T T F T
(126) F F T F F (169) T T T F F
(127) T T T F T (170) T T F T T
(128) T T F T T (171) T T T T F
(129) T F F F F
(130) T T T T F