Module CPGAP (Cell Pathology, General & Autonomic Pharmacology)

Pharmacology LOs (Learning Objectives)

Theme ---- DEFENDERS
At the end of the THEME the student should be able to:
1) Define different terms related to Pharmacology.
2) Define Different Branches of Pharmacology.
3) Define Pharmacopoeias with examples.
4) Describe the drug nomenclature and Illustrate with one example.
5) Classify the different sources of drugs with examples.
6) Define the active principle and list and define their types, List the names of active principles
7) Define different types of active principles with examples of drugs.
8) Calculate the dose of a drug according to age and weight
9) Define the different dosage forms
10) Describe the advantages & disadvantages of the different routes of drug administration.
11) Discuss the means by which drug transport across cell membrane, Illustrate with examples.
12) Define the term Drug Absorption.
13) Describe different factors affecting absorption of drugs.
14) Define Bioavailability. Demonstrate its calculation and discuss it’s clinical importance
15) Discuss factors affecting Bioavailability
16) Define First- pass metabolism and discuss its significance
17) Define the terms Bioequivalence and therapeutic equivalence
18) Define drug distribution in the body.
19) Analyze how different factors affect distribution of a drug in the body
20) Describe the distribution of a drug through various body compartments
21) Define volume of distribution. Describe factors affect the distribution of drugs.
22) Describe the importance of distribution and the volume of distribution and its clinical application.
23) Describe the characteristics/features of a drug that is bound to plasma proteins? Discuss its clinical
significance and explain with examples.
24) Define Biotransformation.
25) List sites of biotransformation
26) Describe the aims and outcomes of Biotransformation
27) Define phase I and phase II biotransformation reactions and their types
28) List examples of drugs undergoing Phase 1 and phase 2 metabolic reactions
29) Discuss the characteristics of Phase 1 and Phase 2 biotransformation reactions
30) Explain the microsomal and non- microsomal biotransformation reactions
31) Describe factors affecting biotransformation of Drugs.
32) Define enzyme induction and its significance with examples
33) Define enzyme inhibition and its significance with examples
34) Define and Describe Prodrugs.
35) Define and describe Suicide inhibition.
36) Define plasma half life of a drug.
37) Enumerate and explain the factors affecting half-life of a drug?
38) Describe the importance of plasma half life.
39) Define steady state concentration and give its significance
40) Define the terms First order kinetics and Zero Order Kinetics with examples
41) Differentiate between First order kinetics and Zero Order Kinetics
42) Describe characteristic features of First order kinetics and Zero Order Kinetics
43) Define and calculate the Loading dose and Maintenance Dose, and describe their clinical significance.
44) Define the drug excretion and clearance, Describe formulas involved for calculating these, and their
Clinical significance.
45) List various routes through which drugs are excreted from the body with examples.
46) Explain the basic principles by which drugs are excreted from the kidneys
47) Discuss factors affecting excretion of drugs
48) Describe different mechanisms by which drugs produce their action
49) Describe different types of mechanisms by which drugs act through receptors, with their examples.
50) Describe different types of G-Proteins with examples of drugs?
51) Discuss the role of second messengers involved in receptors transduction
52) Differentiate between Receptor Down regulation and up regulation with examples. And Describe their
significance
53) Differentiate between the terms potency and efficacy
54) Describe the characteristics of Graded Dose Response Curve and Quantal Dose Response Curve
55) Describe the information that can be obtained from a Graded Dose Response curve and Quantal Dose
Response Curve and its clinical significance
56) Define the terms ED50, LD50
57) Define Therapeutic Index and Therapeutic Window with examples, Calculate these, and Describe their
clinical significance
58) Differentiate between Graded and Quantal Dose Response curves.
59) Discuss factors that can affect the actions of different drugs
60) Define with examples the term Agonist, Partial Agonist, Antagonist and Inverse Agonist,
61) Define Spare Receptors, and discuss their importance
62) Describe different types of Antagonists and Antagonism with examples, their characteristics and clinical
significance.
63) Enumerate types of adverse drug reactions, explain with examples.
64) Define drug dependence, addiction, abuse.
65) Differentiate between psychological dependence and physical dependence with examples
66) Define Tolerance. Differentiate different types of Tolerance with their mechanisms and examples.
67) Explain difference between Pharmacokinetic and Pharmacodynamic Tolerance
68) Define Tachyphylaxis, it’s mechanisms and examples.
69) Differentiate between Tolerance and Tachyphylaxis
70) Define Pharmacogenetics and Pharmacogenomics. Discuss their importance. Illustrate with examples.
71) Define idiosyncrasy with examples.
72) Define Drug interactions
73) Differentiate between various types of Drug interactions with examples.
74) Define Synergism, Summation (addition) and Potentiation with examples.

Theme ---- Palpitation

At the end of theme student should be able to:

1 (review anatomy & physiology of ANS
2) Describe autonomic receptors and explain their role in functional organization of autonomic activity
3 ( Explain how different drugs act to modify the autonomic function
4 (Describe the clinical importance of autonomic pharmacology
5 ( Classify Drugs acting on autonomic nervous system.
6 ( List subtypes & characteristic of cholinergic receptors?
7 ( Enumerate various direct and Indirect acting cholinomimetics and write their pharmacokinetics
properties
8 (Describe the mechanism of Action, Pharmacological effects and uses of direct and Indirect acting
cholinergic drugs?
9 (Describe the adverse effects, toxic effects, precautions/contraindications and drug interactions of direct
and Indirect acting cholinomimetics.
10 (Describe the drug treatment of Alzheimer’s disease
11 (Describe the features of overdose toxicity of organophosphates and their management
12 ( Classify Anticholinergic drugs and differentiate between antimuscarinic & antinicotinic drugs.
13 (Describe the pharmacokinetic properties of antimuscarinics.
14 (Discuss mechanism of action, Pharmacological effects & uses of Anti-muscarinics.
15) Describe the adverse effects, toxic effects, precautions /contraindications & drug interactions of
antimuscarinic drugs
16) Describe the features of overdose toxicity of antimuscarinics and the management
17 (Describe the pharmacokinetic properties of antinicotinics.
18 (Discuss mechanism of action, Pharmacological effects & uses of antinicotinics.
19 (Describe the adverse effects, toxic effects, precautions /contraindications & drug interactions of
antinicotinics.
20 (Describe the role of Ganglion-blocker drugs in modern pharmacology
21 ( Classify Adrenomimetic drugs.
22 (List types & subtypes of Adrenoceptors?
23 (Describe the pharmacokinetic properties of Adrenomimetic drugs.
24 (Describe the mechanism of action and pharmacological effects of Adrenomimetics.
25 (Describe the therapeutic uses, adverse effect, toxic effects, precautions/ contraindications & drugs
interactions of Adrenomimetics
26 ( classify of Antiadrenergic drugs
27 (Describe the pharmacokinetics of Antiadrenergic drugs
28) Describe the mechanism of action, pharmacological effects and clinical uses of Antiadrenergic drugs.
29) Describe the adverse effect, toxic effects, precautions/contraindications & drug interactions of
Antiadrenergic drugs
30) Describe the drug treatment of pheochromocytoma & benign prostatic Hyperplasia
31 (Discuss the limitations of beta blockers in patients of Diabetes Mellitus and Hyperlipidemia.
32 (Describe the drugs used in treatment of Glaucoma along with their mechanism of actions.
33) Write down the clinical importance of adrenergic neuron blockers in modern day therapy.
34) Describe the Management of Pheochromocytoma. Describe two different pharmacological drug groups
which can be used to control hypertension in Pheochromocytoma with their benefits and limitations with
respect to their effects on Cardiovascular system
35) Discuss the clinical Application of Autonomic drugs in Horner’s syndrome
Define Graded dose response curve of a
drug. What is/are its use(s)? Explain with
the help of figure.

Plotting the magnitude of response against

increasing doses of a drug produces a
graded dose-response curve.

As the concentration of a drug increases,

its pharmacologic effect also gradually
increases until all the receptors are
occupied (the maximum effect).

The important properties of drugs, affinity,

potency and efficacy, can be determined
by graded dose-response curves.

The curve can be described as a

rectangular hyperbola.
Drugs for rare diseases—so-called orphan drugs—can be difficult

to research, develop, and market.

Kat 14th Page 21

ORPHAN DRUGS

An orphan drug is a drug for a rare disease (in the United States, defined as one affecting fewer than
200,000 people). The study of such agents has often been neglected because profits from the sales of
an effective agent for an uncommon ailment might not pay the costs of development. In the United
States, current legislation provides for tax relief and other incentives designed to encourage the
development of orphan drugs.

Orphan drugs are drugs that are no longer produced by the original manufacturer

Kat Rev 12th Page 11, Page 13 Q.13

Q. Define Quantal dose response curve of a drug. What informations can be obtained from it?
Explain with the help of figure.

Answer.

1. Quantal dose response curve is the relationship between the dose of the drug and the
proportion of a population that responds to it. The minimum dose required to produce a
specified response is determined in each member of a population. These curves plot the
percentage of a population responding to a specified drug effect versus dose or log dose.

2. The median effective dose (ED50), median toxic dose (TD50), and (in animals) median
lethal dose (LD50) are derived from Quantal dose response curves. The data used to
determine the therapeutic index, therapeutic window, standard margin of safety, etc.

3. Quantal dose-response data provide information about the variation in sensitivity to the
drug in a given population. Steep D-R curves reflect little variability; flat D-R curves
indicate great variability in patient sensitivity to the effects of a drug.
Q. Define Therapeutic index. How it is calculated? What is its significance?

Answer.

Marks
Define Therapeutic index:

The therapeutic index is the ratio of the TD50 (or LD50) to the ED50, determined from
Quantal dose-response curves.
How it is calculated?

Therapeutic index = TD50 (or LD50) / ED50

ED50 = Median effective dose = dose at which 50% of the tested population exhibit
specified (desired / therapeutic) effect
TD50 = Median toxic dose = dose at which 50% of the tested population exhibit Toxic
effect
LD50 = Median lethal dose = dose at which 50% of the tested population of animals
exhibit lethal effect
What is its significance?

Higher the index, more safer will be the drug, and vice versa

References:
Katzung & Treveor’s Pharmacology, Examination & Board Review, 12th ed Chapter 2, Page 20
Lippincott’s Illustrated Reviews: Pharmacology 7th Ed. Chapter 2, Page 33
Basic and Clinical Pharmacology Katzung 14th ed, Chapter 2, Page 37

Q. Define therapeutic window and what is its significance?

Answer.

Marks
The therapeutic window describes the dosage range between the minimum
effective therapeutic concentration or dose, and the minimum toxic
concentration or dose.
The therapeutic window is a more clinically useful index of safety. Higher
the therapeutic window, safer will be the drug, and vice versa.

Reference.
Katzung & Treveor’s Pharmacology, Examination & Board Review, 12th ed Chapter 2, Page 20
Basic and Clinical Pharmacology Katzung 14th ed, Chapter 2, Page 37
Q. Define the Terms:
(i) Tolerance
Answer.
(i) Tolerance
Tolerance can be defined as the gradual reduction in response to the drug after repeated
administrations, thus a higher dose is required to produce the same effect that was once
obtained at a lower dose.

Q. Define Enteric-coated preparations of drugs. Write two different Uses (advantages) of

Enteric-coated preparations with one drug example in each case.

Answer.

Marks
An enteric coating is a chemical envelope that protects the drug from stomach acid,
delivering it instead to the less acidic intestine, where the coating dissolves and
releases the drug.
Enteric coating is useful for certain drugs (for example, Omeprazole) that are acid
unstable.
Drugs that are irritating to the stomach, such as Aspirin, can be formulated with an
enteric coating that only dissolves in the small intestine, thereby protecting the
stomach.

Q. Define Extended-release preparations of drugs. What are their advantages.

Answer.

Extended-release preparations of drugs:

Extended-release medications have special coatings or ingredients that control slow drug
release, thereby allowing for:
1. Slower absorption and prolonged duration of action.
2. Dose frequency less
3. Improve patient compliance
4. Maintain concentrations within the therapeutic range over a longer duration, Less
fluctuation in Plasma concentration with smaller peaks and troughs.
5. Advantageous for drugs with short half-lives.
Q. What are the advantages of intravenous route of administration of drugs?

Answer.

1. Rapid onset of action , useful in emergency

2. No first pass effect, 100% bioavailability, maximal degree of control over the circulating
levels of the drug.
3. Suitable in vomiting , motion sickness, migraine, unconscious patients, or when a patient
can not swallow , & when cooperation is lacking
4. Large volume (doses) of drug can be given
5. Following drugs which can not be given by oral rout, can be given intravenously
a. Drugs destroyed by Stomach pH: ------- e.g., Some Penicillins
b. Drugs destroyed by Intestinal enzymes: ----- e.g., Insulin
c. Hydrophilic drugs which can not absorbed: ------- e.g., Aminoglycosides
6. Drugs that are too irritant to be given by other routes
7. In I.V. infusion: ---- Rapid modification of dose and immediate cessation of administration
if unwanted effects occur

Q.. What are the advantages of oral route of administration of drugs?

Answer.

1. Used for both the systemic effects and local effects in G.I.T.
2. Commonest
3. Cost ---- Cheap
4. Most easy and convenient, No skill required, self administration, Painless, & most
acceptable
5. Safest in most of the situations: Due to comparatively slow Rate of absorption, adverse
effects are less in magnitude & severity
6. No maximal sterilization
7. Large amounts (doses) can be given to an extent.
Q. Write disadvantages of oral route of administration of drugs.

Answer.
ANY “FIVE” OF THE FOLLOWINGS:
1. Absorption varies (delay, decrease, or increase ); affected by food, drugs that affect GI
motility, and conditions / diseases of GIT. Dose may not accurately delivered.
2. Irritation of gastric mucosa, can cause nausea, vomiting, heart burn.
3. Patient compliance not ensured --- not suitable in uncooperative patients.
4. First pass metabolism ( First pass effect, Presystemic elimination) decrease the
bioavaiabilioty of drug
5. Not suitable for Unconscious patients, Vomiting patients, and in Emergency due to
Slow onset of action
6. Following drugs can not be given by oral route:
a. Drugs destroyed by Stomach pH: e.g., Some Penicillins
b. Drugs destroyed by Intestinal enzymes: e.g., Insulin
c. Hydrophilic drugs which can not absorbed: e.g., Aminoglycosides
7. Drugs having bad taste or odor, ---- inconvenient for patient ---- e.g. Quinine
8. Discoloration of teeth may occur: ---- e.g., Iron
Q. Compare the characteristic features of First Order Kinetics of elimination (Metabolism) of
drugs with respect to Zero order kinetics. Also formulate the Michaelis Menten equation for
that, and draw graphs of Plasma concentration Versus time and Log Plasma concentration
Versus time in this case
(Cognitive domain C5, Evaluating)

Answer.

Characteristic features of First Order Kinetics of elimination (Metabolism) of drugs.

1. Constant percentage (proportion/fraction) of drug is metabolized (eliminated) per unit of

time
2. Most of the drugs in clinical use demonstrate first order kinetics.
3. Drugs have a constant half life.
4. Enzymes (Elimination Processes) are not saturated because free drug concentration is low
5. Rate of Metabolism / Elimination (V) Concentration of free drug (C)
From Michaelis Menten equation:

In most clinical situations, concentration of drug is much less than Michaelis Constant ,
therefore “C” can be neglected in denominator and equation can be written as:
Q. Predict the consequences and significance of Hepatic microsomal enzyme induction
and inhibition.
(Cognitive domain C6, Creating)

Answer

Consequences and Significance of Hepatic microsomal enzyme inducers

include:
1) decreased plasma drug concentrations, decreased drug activity if the
metabolite is inactive with decreased therapeutic drug effect (Therapeutic
failure).
2) increased drug activity if the metabolite is active, and
3) Toxic effect if metabolite is toxic, reactive. (Kat)
Consequences and Significance of Hepatic microsomal enzyme inducers
include Increased plasma drug concentrations, Increased drug activity with
Increased chances of adverse effects.

Lip 7th Page 14

Inducer Drugs Whose Metabolism Is Enhanced

Benzo[a]pyrene Theophylline
Carbamazepine Carbamazepine, clonazepam, itraconazole
Chlorcyclizine Steroid hormones
Ethchlorvynol Warfarin
Glutethimide Antipyrine, glutethimide, warfarin
Griseofulvin Warfarin
Phenobarbital Barbiturates, chloramphenicol, chlorpromazine, cortisol, coumarin
and other anticoagulants, desmethyl imipramine, digitoxin, doxorubicin,

barbiturates1 estradiol, itraconazole, phenylbutazone, phenytoin, quinine,

testosterone
Phenylbutazone Aminopyrine, cortisol, digitoxin
Phenytoin Cortisol, dexamethasone, digitoxin, itraconazole, theophylline
Rifampin Coumarin anticoagulants, digitoxin, glucocorticoids, itraconazole,
methadone, metoprolol, oral contraceptives, prednisone,
propranolol, quinidine, saquinavir
Ritonavir2 Midazolam
St. John’s wort3 Alprazolam, cyclosporine, digoxin, indinavir, oral contraceptives,
ritonavir, simvastatin, tacrolimus, warfarin
Inhibitor Drug whose metabolism inhibited
Allopurinol Antipyrine, dicumarol, probenecid, tolbutamide
chloramphenicol,
isoniazid
Chlorpromazine Propranolol
Cimetidine Chlordiazepoxide, diazepam, warfarin, others
Dicumaroal Phenytoin
Diethylpentenamide Diethylpentenamide

Disulfiram Antipyrine, ethanol, phenytoin, warfarin

Ethanol Chlordiazepoxide (?), diazepam (?), methanol
Grapefruit juice Alprazolam, atorvastatin, cisapride, cyclosporine, midazolam,
triazolam
Itracomazole Alfentanil, alprazolam, astemizole, atorvastatin, buspirone,
cisapride, cyclosporine, delavirdine, diazepam, digoxin,
felodipine, indinavir, loratadine, lovastatin, midazolam,
nisoldipine, phenytoin, quinidine, ritonavir, saquinavir,
sildenafil, simvastatin, sirolimus, tacrolimus, triazolam,
verapamil, warfarin
Ketocomazoloe Astemizole, cyclosporine, terfenadine
Nortriptyline Antipyrine
Oral contraceptives Antipyrine
Phenyldutazone Phenytoin, tolbutamide
Ritonavir Amiodarone, cisapride, itraconazole, midazolam, triazolam
saquinavir Cisapride, ergot derivatives, midazolam, triazolam
Scovarbital Secobarbital
Spironolactone Digoxin
troleandonycin Theophylline, methylprednisolone
Q. Justify the use of Lactulose in the treatment of hepatic encephalopathy.
(Cognitive domain C5, Evaluating)

Answer.
Marks
(Brunton, pp 1330-1332; Katzung, p 1093.) Pretest Answer 345
Lactu-lose is a synthetic, nonabsorbable disaccharide (galactose-fructose).
In moderate doses it acts as an osmotic laxative.
In higher doses it binds intestinal ammonia and other toxins that accumulate in the
intestine in severe liver dysfunction.
These toxins, and perhaps more so the ammonia, contribute to the signs and
symptoms of encephalopathy.
Gut bacteria metabolize lactulose to lactic acid, acidifying the fecal masses and
causing ammonia to become ammonium. This decreases the amount of ammonia to
be absorbed from GIT and decreasing its
toxicity. Therefore, lactulose is useful in hepatic encephalopathy. (USMLE)

Define Loading dose. How it is calculated. Describe its significance.

Amount of drug required to achieve desired plasma concentration rapidly.

Loading dose = Vd x Desired Plasma concentration / F
Vd = Volume of distribution
F = Bioavailability (If bioavailability is 100%, it is taken as 1)
Achieve desired therapeutic effect from the start of treatment. Need careful
administration with drugs having low therapeutic index, otherwise may
results in adverse effects.
If the loading dose is large (Vd much larger than blood volume), the dose
should be given slowly to prevent toxicity due to excessively high plasma
levels during the distribution phase (K/R 12th Page 30)
Variation in Vd, e.g. pregnancy, hypoalbuminemia, edema, ascites. Pleural
effusion, may need to adjust the loading dose accordingly (Myself).

Define Maintenance dose. How it is calculated? Describe its significance.

Amount of drug required to maintain desired plasma concentration.

Maintenance dose = Clearance x Desired Plasma concentration / F
F = Bioavailability (If bioavailability is 100%, it is taken as 1)
Need careful administration with drugs having low therapeutic index,
otherwise may results in adverse effects. Maintenance dose needs to
adjusted in patients with Liver or Renal failure depending upon the route of
elimination of drug (Myself).
Q. Relate the properties / characteristics of drugs that determine their distribution in different body
fluid compartments and thus their Volume of distribution. Explain with one drug example in each
case.
(Cognitive domain C4, Analyzing)

Answer.

a Drug distributed into Plasma compartment:

If a drug has a high molecular weight or is extensively protein bound, it is too
large to pass through the slit junctions of the capillaries and, thus, is effectively
trapped within the plasma (vascular) compartment. As a result, , it has a
low Vd that approximates the plasma volume or about 4 L in a 70-kg individual.
Therefore if Vd is Less than extracellular volume, (less than 12 to 14 liters), it
means Concentration of drug is greater in plasma as compared to extraplasmic
space.
Example: Heparin shows this type of distribution.
b Drug distributed into Extracellular fluid:
If a drug has a low molecular weight but is hydrophilic, it can pass through the
endothelial slit junctions of the capillaries into the interstitial fluid. However,
hydrophilic drugs cannot move across the lipid membranes of cells to enter the
intracellular fluid. Therefore, these drugs distribute mostly into a volume that
approximates the sum of the plasma volume and the interstitial fluid, which
together constitute the extracellular fluid (about 20% of body weight or 14 L in a
70-kg individual). Therefore if the Vd is greater than plasma volume but less than
total body water (less than 40 to 44 liters), it means that drug is distributed into
extracellular fluid (Plasma plus interstitial fluid).
Example: Aminoglycoside antibiotics show this type of distribution.
c Drug distributed into Total body water:
If a drug has a low molecular weight and is lipophilic, it can move into the
interstitium through the slit junctions and also pass through the cell membranes
into the intracellular fluid.
Therefore, these drugs distribute into whole body water, that is a volume that
approximates the sum of the plasma volume, interstitial fluid, and intracellular
fluid.
These drugs distribute into a volume of about 60% of body weight or about 42 L
in a 70-kg individual.
Example: Ethanol exhibits this apparent Vd.

If Drug has volume of distribution greater than total body water, it means it has
more affinity to tissue binding sites and its concentration is greater in
extraplasmic space as compared to plasma concentration.
Example: Chloroquine has Vd 13000 liters.
50,000 liters is the average Vd for the drug quinacrine in persons whose average
physical body volume is 70 liters. (Kat Rev 12th Page 28)

Reference:
Lippincott’s Illustrated Reviews: Pharmacology 7th Ed. Chapter 1, Page 10 - 11
Q. Compare the characteristic features of Zero Order Kinetics of elimination (Metabolism) of
drugs with respect to First order kinetics. Also formulate the Michaelis Menten equation for
that, and draw graphs of Plasma concentration Versus time and Log Plasma concentration
Versus time in this case
(Cognitive domain C5, Evaluating)
Answer.
Characteristic Features of Zero Order Kinetics
1. Constant amount of drug is metabolized (eliminated) per unit of time.
2. Only few drugs follow zero order; e.g., This is typical of Ethanol (over most of its plasma
concentration range) and of Phenytoin and Aspirin at high therapeutic or toxic
concentrations.
3. Drugs don’t have a constant half life (Depend on Dose)
4. Enzymes are saturated because free drug concentration is high

From Michaelis Menten equation:

Rate of metabolism/elimination remains constant over time ( that is not directly proportion to
concentration of free drug) and is at maximum

Dose is very large, thus C (Concentration) is much greater than Km, therefore “Km” can
be neglected in denominator and Velocity equation can be written as:
Define:

Biased agonist

An agonist that activates the same receptor as other drugs in its group but also causes additional
downstream effects that are not seen with other agonists in the group. (0.5 Marks)

Katzung & Treveor’s Pharmacology, Examination & Board Review, 12th ed Chapter 2, Page
17.

Q. Describe the Therapeutic Potential / significance of Biased Agonists at Beta Receptors

Biased agonist

An agonist that activates the same receptor as other drugs in its group but also causes additional
downstream effects that are not seen with other agonists in the group. (Kat Rev)

Therapeutic Potential of Biased Agonists at Beta Receptors:

Traditional β agonists like epinephrine activate cardiac β1 receptors, increasing heart rate and cardiac
workload through coupling with G proteins. This can be deleterious in situations such as myocardial
infarction. Beta1 receptors are also coupled through G protein-independent signaling pathways
involving β-arrestin, which are thought to be cardioprotective. A “biased” agonist could potentially
activate only the cardioprotective, β-arrestin–mediated signaling (and not the G protein-
coupled–mediated signals that lead to greater cardiac workload). Such a biased agonist would be of
great therapeutic potential in situations such as myocardial infarction or heart failure. Biased agonists
potent enough to reach this therapeutic goal have not yet been developed. (Kat 14th )

Attempts over at least half a century to dissociate the powerful analgesic

effects of opioids from their undesirable effects have failed (Corbett et al.,

2006). However, with our advancing understanding of biased agonism,

prospects are looking up. (GG 13th )

Q. Write the characteristic features of inverse agonists with the help of Figure

Answer.

characteristic features of Inverse agonists:

1. Stabilize the R (inactive form of Receptor) and cause R* (Active form of Receptor) to
convert to R (reverse the activation state of receptors).
2. Decreases the number of activated receptors to below that observed in the absence of
drug.
3. Have an intrinsic activity less than zero. Produce a response below the base-line response
measured in the absence of agonist (a response below the constitutive activity)
4. Exert the opposite pharmacological effect of agonists.

A drug that binds to the non-active state of receptor molecules and decreases constitutive activity (K Rev)

In contrast, inverse agonists have a higher affinity for the inactive Ri state than for Ra and decrease or
abolish any constitutive activity. (K Rev)

(1) Lippincott’s Illustrated Reviews: Pharmacology 7th ed, Chapter 2, Page 31

(2) Katzung & Treveor’s Pharmacology, Examination & Board Review, 12th ed Chapter 2,
Page 17, 19.
Q. Describe Ionotropic and Metabotropic Receptors with one example in each case from autonomic
receptors.
.
Answer.

Marks
1 Ionotropic Receptors:
Membrane receptors affecting ion permeability are ionotropic receptors.
Neurotransmitter receptors are membrane proteins that provide a binding
site that recognizes and responds to neurotransmitter molecules.

Some receptors are directly linked to membrane ion channels.

Therefore, binding of the neurotransmitter occurs rapidly (within fractions
of a millisecond) and directly affects ion permeability.
These types of receptors are known as ionotropic receptors.
Examples: Nicotinic receptors in the skeletal muscle cells
2 Metabotropic Receptors:
Membrane receptors coupled to second messengers are metabotropic
receptors
Many receptors are not directly coupled to ion channels. Rather, the
receptor signals its recognition of a bound neurotransmitter by initiating a
series of reactions that ultimately result in a specific intracellular response.
Second messenger molecules, so named because they intervene between
the original message (the neurotransmitter or hormone) and the ultimate
effect on the cell, are part of the cascade of events that translate
neurotransmitter binding into a cellular response, usually through the
intervention of a G protein.
The two most widely recognized second messengers are the adenylyl
cyclase system and the calcium/phosphatidylinositol system.
The receptors coupled to the second messenger system are known as
metabotropic receptors.
Examples: Muscarinic and adrenergic receptors are examples of
metabotropic receptors.

References.
Basic and Clinical Pharmacology Katzung 14th ed, Chapter 21, Page 370
Katzung & Treveor’s Pharmacology, Examination & Board Review, 12th ed Chapter 21, Page 179-
180.

Orphan receptors, so-called because their natural ligands are

presently unknown; these may prove to be useful targets for future
drug development.
Kat 14th Page 21
Write down the characteristic features of Partial agonists (Marks 1.5)

Partial agonists

Marks
Have intrinsic activities greater than zero (greater than constitutive 0.5
activity) but less than one. Even if all the receptors are occupied, partial
agonists cannot produce the same Emax as a full agonist.

Have an affinity that is greater than, less than, or equivalent to that of a full 0.5
agonist.

When a receptor is exposed to both a partial agonist and a full agonist, the 0.5
partial agonist may act as an antagonist.
A drug that binds to its receptor but produces a smaller effect (Emax) at full dosage than a full agonist. (K Rev)
By definition, partial agonists have lower maximal efficacy than full agonists. (K Rev)
A partial agonist produces less than the full effect, even when it has saturated the receptors (Ra–Dpa + Ri–Dpa),
presumably by combining with both receptor conformations, but favoring the active state. In the presence of a
full agonist, a partial agonist acts as an inhibitor. (K Rev)
(1) Lippincott’s Illustrated Reviews: Pharmacology 7th ed, Chapter 2, Page 31
(2) Katzung & Treveor’s Pharmacology, Examination & Board Review, 12th ed
Chapter 2, Page 17.

Q. Define the Terms:

(i) Spare Receptors.
Answer.
(i) Spare Receptors:
When only a fraction of the total receptors for a specific ligand may need to be occupied to
elicit a maximal response, the Systems that exhibit this behavior are said to have spare
receptors.
(OR)
Receptors are said to be “spare” for a given pharmacologic response if it is possible to elicit a
maximal biologic response at a concentration of agonist that does not result in occupancy of
all of the available receptors.
(OR)
Receptor that does not bind drug when the drug concentration is sufficient to produce
maximal effect; present if Kd > EC50, (Kd = , EC50 =)

Q. Describe Up-regulation and Down-regulation of receptors.

Answer:
Up-regulation of receptors:
Repeated or continuous administration of an antagonist to a receptor or denervation (Kat
Rev) may result in up-regulation of receptors, in which receptor reserves are inserted into
the membrane, increasing the total number of receptors available.
Up-regulation of receptors can make the cells more sensitive to agonists and / or more
resistant to the effect of the antagonist.

Down-regulation of receptors:
Repeated or continuous administration of an agonist may lead to down-regulation of
Receptors, such that they are internalized and sequestered within the cell, unavailable for
further agonist interaction.
Lip 7th Page 27
K/R 12th Page 22
Allosteric antagonists:

This type of antagonist binds to a site ("allosteric site") other than the agonist-binding site
and prevents the receptor from being activated by the agonist.

An allosteric antagonist also causes a downward shift of the Emax, that is decrease
efficacy of agonist, No Parallel shift to right

Receptor blocking effect of antagonist cannot be overcome by increasing agonist

concentration (unless the spare receptors are present)
No Increase in ED50 (Median effective dose) (or EC50, Median effective concentration)
of Agonist, that is No change in Potency of Agonist.
Decrease efficacy of agonist
Q. Write characteristic features of Competitive Pharmacological Antagonism.

Answer.

Characteristic Features of Competitive Pharmacological Antagonism

1. Antagonist compete and bind reversibly to same receptor and same site as that of Agonist
2. Receptor blocking effect of antagonist can be overcome by increasing agonist concentration
3. Dose response curve of Agonist in presence of Antagonist shifts Parallel to right
4. Increase ED50 (Median effective dose) (or EC50, Median effective concentration) of Agonist,
that is Decrease Potency of Agonist
5. No change in efficacy of Agonist
Q. Write characteristic features of Non-Competitive pharmacological antagonism. Illustrate with
the help of dose response curve.

Answer 1. A.

Characteristic Features of Non-Competitive Pharmacological Antagonism:

1. Antagonist bind irreversibly to (i) same receptor as that of Agonist by covalent binding or (ii)
Allosteric site ( a site different from that of agonist at same receptor)
2. Receptor blocking effect of antagonist cannot be overcome by increasing agonist concentration
(unless the spare receptors are present)
3. Dose response curve of agonist in presence of Antagonist : Shifts downward; No Parallel shift to
right
4. No Increase in ED50 (Median effective dose) (or EC50, Median effective concentration) of
Agonist, that is No change in Potency of Agonist
5. Decrease efficacy of agonist
6. Figure

References.
Lippincott’s Illustrated Reviews: Pharmacology 7th ed, Chapter 2, Page 32, Figure 2.13, Page 33.
Basic and Clinical Pharmacology Katzung 14th ed, Chapter 2, Page 23-24, Figure 2.3
Katzung & Treveor’s Pharmacology, Examination & Board Review, 12th ed Chapter 2, Page 19-20,
Figure 2.5

Q. Define Physiological Antagonism. How adrenaline is beneficial in anaphylactic shock

explain with receptor(s) and effector(s) involved.
Answer.
Marks

Definition
If a drug counters the effects of another drug by binding to a different
receptor and causing opposing effects is called Physiological antagonism.
Bronchoconstrictor action of histamine by histamine receptor stimulation is
antagonized by epinephrine’s bronchodilator action due to β2 receptor
stimulation
Vasodilator (Hypotensive) action of histamine by histamine receptor
stimulation is antagonized by epinephrine’s Vasoconstrictor action due to α1
receptor stimulation
Adverse effects of Antimuscarinic drugs:

Mydriasis, Cycloplegia, Near vision blurred, Precipitate Glaucoma

Lacrimal secretions decrease, dry, sandy eyes, Photophobia / light reflex ( -
ve )
Amnesia
Tachycardia
Decrease Salivary secretions, Dryness of mouth (Xerostomia), Difficulty
in swallowing and speaking
Urinary retention
Constipation
Inhibition of sweating: Skin Dry, hot, scarlet, Hyperpyrexia
CNS: Ataxia, restlessness, and excitement; hallucinations and delirium;
Coma

C/I / Precautions of Cholinomimetics

 Mechanical obstruction of GIT ; (Intestinal colic)

 Mechanical obstruction of Urinary tract (Renal colic)
 Peritonitis
 IBD (Inflammatory bowel disease)
 Asthma
 Peptic ulcer
 Bradycardia
 Hypotension
Write the important clinical uses of Antimuscarinics related to different system tissues /
sites with drug examples in each case.

1 CNS:
 Parkinsonism: Benztropine.
Trihexyphenidyl,
Biperiden,
Orphenadrine,
Procyclidine
 Motion Sickness: seasickness: Scopolamine
2 Eye: To produce Mydriasis , Cycloplegia:
 Accurate measurement of --- refractive Tropicamide
error in uncooperative patients, eg, young Cyclopentolate
children, ---- requires ----- ciliary Homatropine
paralysis, thus no interference by the
accommodative capacity of the eye.
 Ophthalmoscopic examination of the ----
retina is greatly facilitated by --- mydriasis.
 Use to prevent synechia (adhesion)
formation in uveitis and iritis.
3 Bronchodilatation ---- COPD --- Asthma Ipratropium. Tiotropium
4 Preanesthetic medication: Atropine
 Anti-secretory ------ Bronchial secretions - Hyoscine
-- block secretions in the upper and lower
respiratory tracts prior.
 Amnesia
 Prevent vagal inhibition, badycardia, heart
block
 Bronchodilation
 Decrease gastric secretions
5 GIT:
 To Decrease motility Dicyclomine
Anti-spasmodic, Antidiarrheal, for Glycopyrrolate
Hypermotility ---- Propantheline
 Peptic ulcer Pirenzepine
 6 Genitourinary Oxybutynin
Urinary Urgency, Trospium
Spasm (Antispasmodic) Darifenacin
Incontinence (enuresis) Solifenacin
BPH Tolterodine
Overactive urinary bladder Fesoteradine
7 Hyperhidrosis (Increase sweating) --- Use --- Propantheline,
Glycopyrronium
bromide or
glycopyrrolate,
oxybutynin,
methantheline, and
benzatropine.
8 Cardiovascular: Bradycardia Atropine, & Others
9 Antidote for cholinomimetics: Atropine
Organophosphate (insecticides, nerve gases)
poisoning,
Reversible anticholinesterases, e.g.
physostigmine, some types of mushroom
poisoning

Q. A 41 year lady prescribedoral Albuterol (Salbutamol) for asthma. Enlist important

adverse effects of Beta-2 agonists, each involving different system / tissues / sites.

Answer.

Adverse effects of Beta-2 agonists.

Tachycardia, Arrhythmia
Hyperglycemia,
Hypokalemia, and
Hypomagnesemia
Skeletal muscle tremors.
Worsened hypoxemia
Vasodilating action of β2-agonist treatment may increase perfusion of poorly ventilated
lung units, transiently decreasing arterial oxygen tension (PaO2),
Tachyphylaxis.

Lip 6th ------Page 383

Kat 14th ------ Page 351
What is / are the advantage(s) of Dobutamine over Other Sympathomimetics in the treatment of acute
cardiac failure

It has relatively greater inotropic than chronotropic effect compared with isoproterenol. [Davidson 22
ed Ch 18 CVDs (Cardiovascular Diseases)]

Because they are less effective in activating vasodilator β2 receptors, they may increase cardiac output
with less reflex tachycardia than occurs with nonselective agonists such as isoproterenol.
Less increase in oxygen demand by heart as compared to other sypathomimetics (Myself , lip)
Not produce vasoconstriction [Davidson 22 ed Ch 18 CVDs (Cardiovascular Diseases)]

The drug increases cardiac output with little change in heart rate, and it does not significantly elevate
oxygen demands of the myocardium a major advantage over other sympathomimetic drugs.

Kat 15th ------

Beta1-selective agents (Figure 9–8) increase cardiac output without lowering diastolic blood pressure
because they do not activate vasodilator β2 receptors.
Dobutamine was initially considered a relatively β1-selective agonist, but its actions are more complex.
Its chemical structure resembles dopamine, but its actions are mediated mostly by activation of α and β
receptors.
Clinical formulations of dobutamine are a racemic mixture of (–) and (+) isomers, each with contrasting
activity at α1 and α2 receptors.
The (+) isomer is a potent β1 agonist and an α1-receptor antagonist.
The (–) isomer is a potent α1 agonist, which is capable of causing significant vasoconstriction when given
alone.
The resultant cardiovascular effects of dobutamine reflect this complex pharmacology.
Dobutamine has a positive inotropic action caused by the isomer with predominantly β-receptor
activity.
It has relatively greater inotropic than chronotropic effect compared with isoproterenol.
Activation of α1 receptors probably explains why peripheral resistance does not decrease significantly.

GG 13th ---------
INE: isoproterenol (Isopropyl NE)
Dobutamine
Dobutamine resembles DA structurally but possesses a bulky aromatic substituent on the amino group
(Table 12–1).
The pharmacological effects of dobutamine are due to direct interactions with α and β receptors; its
actions do not appear to result from release of NE from sympathetic nerve endings, and they are not
exerted by dopaminergic receptors.
Dobutamine possesses a center of asymmetry; both enantiomeric forms are present in the racemate
used clinically.
The (–) isomer of dobutamine is a potent α1 agonist and can cause marked pressor responses.
In contrast, (+)-dobutamine is a potent α1 receptor antagonist, which can block the effects of (–)-
dobutamine.
Both isomers are full agonists at β receptors; the
(+) isomer is a more potent β agonist than the (–) isomer by about 10-fold.
Cardiovascular Effects
The cardiovascular effects of racemic dobutamine represent a composite of the distinct pharmacological
properties of the (–) and (+) stereoisomers.

Compared to INE [isoproterenol (Isopropyl NE)], dobutamine has relatively more prominent inotropic
than chronotropic effects on the heart.

Although not completely understood, this useful selectivity may arise because peripheral resistance is
relatively unchanged.
Alternatively, cardiac α1 receptors may contribute to the inotropic effect.

At equivalent inotropic doses, dobutamine enhances automaticity of the sinus node to a lesser extent
than does INE;
however, enhancement of AV and intraventricular conduction is similar for both drugs.

In animals, infusion of dobutamine increases cardiac contractility and cardiac output without markedly
changing total peripheral resistance; the
relatively constant peripheral resistance presumably reflects counterbalancing of α1 receptor–mediated
vasoconstriction and β2 receptor–mediated vasodilation.

Heart rate increases only modestly when dobutamine is administered at less than 20 μg/kg per min.

After administration of β receptor antagonists, infusion of dobutamine fails to increase cardiac output,
but total peripheral resistance increases, confirming that dobutamine has modest direct effects on α
adrenergic receptors in the vasculature.

ADME
Dobutamine has a t1/2 of about 2 min; the major metabolites are conjugates of dobutamine and 3-O-
methyldobutamine. The onset of effect is rapid.
Steady-state concentrations generally are achieved within 10 min of initiation of the infusion by
calibrated infusion pump. The rate of infusion
required to increase cardiac output typically is between 2.5 and 10 μg/kg
per min, although higher infusion rates occasionally are required. The rate
and duration of the infusion are determined by the clinical and hemodynamic
responses of the patient.
Therapeutic Uses
Dobutamine is indicated for the short-term treatment of cardiac decompensation that may occur
after cardiac surgery or
in patients with congestive heart failure or
acute myocardial infarction.

Dobutamine increases cardiac output and stroke volume in such patients, usually without a marked
increase in heart rate.
Alterations in blood pressure or peripheral resistance usually are minor, although some patients may
have marked increases in blood pressure or heart rate.
An infusion of dobutamine in combination with echocardiography is useful in the noninvasive
assessment of patients with coronary artery disease.
Adverse Effects
Blood pressure and heart rate may increase significantly during dobutamine administration requiring
reduction of infusion rate. Patients with a history of hypertension may exhibit an exaggerated pressor
response more frequently.
Because dobutamine facilitates AV conduction, patients with atrial fibrillation are at risk of marked
increases in ventricular response rates;
digoxin or other measures may be required to prevent this from occurring. Some patients may develop
ventricular ectopic activity.
Dobutamine may increase the size of a myocardial infarct by increasing myocardial O2 demand, a
property common to inotropic agents.
The efficacy of dobutamine over a period of more than a few days is uncertain;
there is evidence for the development of tolerance.

Q. A adult patient is given treatment with Dopamine in intensive care unit. Write down the dose
dependent actions of dopamine on cardiovascular system with their significance?

Answer 2.

Marks
In Low dose: Dopamine stimulates D1 receptors of coronary and renal vessels→
vasodilation → increase blood flow.
In intermediate dose: Dopamine stimulates B1 receptors of heart→ increase heart
rate and force of contraction.
In high close: Dopamine stimulates α1 receptors causing vasoconstriction→
increased blood pressure.
Clinical application:
Advantage: in low dose dopamine increases renal blood flow and enhances
glomerular filtration rate causing diuresis. In this regard dopamine is far superior
to norepinephrine in the treatment of cardiogenic and septic shock.
Disadvantage: in high dose dopamine causes vasoconstriction which diminishes
blood flow to the kidneys and may cause renal shut down.

References.
Lippincott’s Illustrated Reviews: Pharmacology 7th ed, Chapter 6, Page 82.
Q. How would you differentiate between preganglionic and post-ganglionic lesion in Horner’s
syndrome by using adrenomimetic (sympathomimetic) drugs.

Answer

If the lesion of Horner’s syndrome is postganglionic, indirectly acting sympathomimetics (eg,

cocaine, hydroxyamphetamine) will not dilate the abnormally constricted pupil because
catecholamines have been lost from the nerve endings in the iris. In contrast, the pupil dilates
in response to phenylephrine, which acts directly on the α receptors on the smooth muscle of
the iris.
A patient with a preganglionic lesion, on the other hand, shows a normal response to both
drugs, since the postganglionic fibers and their catecholamine stores remain intact in this
situation.

Post-ganglionic Lesion Preganglionic Lesion

Indirectly acting sympathomimetics (eg, Not dilate the abnormally Dilate
cocaine, hydroxyamphetamine) constricted pupil
Phenylephrine Dilate Dilate

Q. Name two different pharmacological drug groups which can be used to control
hypertension in Pheochromocytoma with their benefits and limitations with respect to their
effects on Cardiovascular system.

Answer

Marks
1 Alpha adrenoceptor antagonists:
Benefit: Vasodilation, decrease Total Peripheral Resistance, decrease
Blood Pressure
Limitation: Not decrease Heart Rate, may produce tachycardia
2 Beta adrenoceptor antagonists:
Benefit: decrease Heart Rate, decrease Cardiac Output, decrease Blood
Pressure
Limitation: No Vasodilation, May produce Vasoconstriction, Increase
Total Peripheral Resistance, Increase Blood Pressure. Therefore Should
not be used alone. Always given in presence of Alpha antagonists.
Q. What are the limitations / hazards of using beta adrenoceptor antagonists in patients of
Diabetes Mellitus and Hyperlipidemia.

Answer.

Limitations of Beta Blockers in Patients of Diabetes Mellitus and Hyperlipidemias:

1. Diabetes Mellitus:

 Non selective beta blockers such as propranolol inhibit glycogenolysis in the human liver
after β2 receptor blockade and thus inhibit recovery from hypoglycemia.(Kat) in type 1
(insulin-dependent) diabetes mellitus, but infrequently in type 2 diabetes mellitus (GG 13th).
Decrease glucagon secretion (Lip).
 Thus, β adrenergic receptor antagonists should be used with great caution in patients with
labile diabetes and frequent hypoglycemic reactions. If such a drug is indicated, a β1-
selective antagonist is preferred because these drugs are less likely to delay recovery from
hypoglycemia (GG).
 Prevent counter regulatory effects of catecholamines during hypoglycemia (Lip , GG).
Premonitory signs and symptoms of hypoglycemia due to insulin overdosage ( tachycardia,
palpitation, tremor, nervousness, anxiety) may be masked (blunted) by β blockers.
Diaphoresis with hypoglycemia still occur, as this is mediated through neurotransmitter
acetylcholine (Lip) involving muscarinic receptors.
 β blockers should be used with caution in insulin dependent diabetic patients. This may be
particularly important in patients with inadequate glucagon reserve and in
pancreatectomized patients
 β1 receptor selective drugs may be less prone to inhibit recovery from hypoglycemia
 β blockers are much safer in those type 2 diabetic patients who do not have hypoglycemic
episodes

2. Hyperlipidemias:

 A major role of beta receptor is to mobilize energy molecules such as free fatty acids (Lip).
This increased flux of fatty acids is an important source of energy for exercising muscle
(GG). Hormone sensitive (GG) Lipases in fat cells are activated mainly by beta receptor
 stimulation, leading to metabolism of trglycerides into free fatty acids (Lip) . β Receptor
antagonists can attenuate the release of free fatty acids from adipose tissue (GG).
 Chronic use of β blockers has been associated with increased plasma concentration of
VLDL and decreased concentration of HDL cholesterol. LDL concentration generally do
not change (Kat). LDL cholesterol increases (GG)
 These changes may increase the risk of coronary artery disease
 These changes tend to occur with both selective and non-selective β blockers though they
may be less likely to occur with β blockers possessing Intrinsic Sympathomimetic Activity
(ISA) (Kat). These effects on serum lipid profile may be less pronounced with use of beta 1
selective antagonists such as propranolol (Lip).
 In contrast, β1-selective antagonists, including celiprolol, carteolol, nebivolol, carvedilol,
and bevantolol, reportedly improve the serum lipid profile of dyslipidemic patients. While
drugs such as propranolol and atenolol increase triglycerides, plasma triglycerides are
reduced with chronic celiprolol, carvedilol, and carteolol (GG).
 When β blockers are required, β1-selective or vasodilating β receptor antagonists are
preferred. In addition, it may be necessary to use β receptor antagonists in conjunction with
other drugs, (e.g., HMG CoA reductase inhibitors) to ameliorate adverse metabolic effects
(GG).

In contrast to classical β blockers, which decrease insulin sensitivity, the vasodilating β receptor
antagonists (e.g., celiprolol, nipradilol, carteolol, carvedilol, and dilevalol) increase insulin sensitivity in
patients with insulin resistance. Together with their cardioprotective effects, improvement in insulin
sensitivity from vasodilating β receptor antagonists may partially counterbalance the hazard from
worsened lipid abnormalities associated with diabetes (GG).

Lip 7th Page 95-96

Enlist the important clinical uses of Beta adrenoceptors antagonists
Hypertension
Chronic management of stable angina.
Myocardial infarction
Supraventricular and ventricular arrhythmias
Long term management of chronic heart failure
Obstructive cardiomyopathy
Dissecting aortic aneurysm
Chronic open angle Glaucoma
Prophylaxis of Migraine:
Hyperthyroidism and thyroid storm
Reduce certain tremors
prophylactically.to control somatic manifestations of anxiety.
For example, in performance anxiety (“stage fright”).
Symptomatic treatment of alcohol withdrawal
to diminish portal vein pressure in patients with cirrhosis.
- decrease the incidence of bleeding from esophageal varices

Infantile hemangiomas

Q. Enlist important adverse effects of Beta antagonists, each involving different system /
tissues / sites.

1 Hypotension
2 Bradycardia, Heart block
3 Precipitate heart failure
4 Bronchoconstriction
5 Impaired sexual activity in men.
6 Hypoglycemia. Mask symptoms of Hypoglycemia. Prevent
the counterregulatory effects of catecholamines during hypoglycemia.
7 increased lowdensity lipoprotein ("bad" cholesterol), increased
triglycerides, and reduced high-density lipoprotein ("good" cholesterol).
8 CNS: depression, dizziness, lethargy, fatigue, weakness,
visual disturbances, hallucinations, short-term memory
loss, emotional lability, vivid dreams (including nightmares),
and depression.
9 Abrupt withdrawal may precipitate Arrhythmias, Ischemic heart disease,
Hypertension, heart failure
10 Beta blockers may increase the number of attacks of chest pain in patients
with Prinzmetal ' s angina; this occurs especially with non -cardioselective
beta blockers, which should be avoided.
11 Mask Hyperthyroidism
12 Precipitate peripheral arterial disease,

13 Mask symptoms of hypoglycemia, Delay recovery from hypoglycemia

14 Precipitate Psoriasis
Role of beta blockers in Angina Pectoris: Limitations and advantages:

Beta blockers may increase the number of attacks of chest pain in patients with Prinzmetal ' s
angina; this occurs especially with non -cardioselective beta blockers, which should be avoided.
(Martindale)

Not used for acute attack.

Used for prophylaxis.

β Blockers and serum K

The β receptor agonists decrease the plasma concentration of K+ by

promoting its uptake, predominantly into skeletal muscle. At rest, an

infusion of EPI causes a decrease in the plasma concentration of K+. The

marked increase in the concentration of EPI that occurs with stress (such

as myocardial infarction) may cause hypokalemia, which could predispose

to cardiac arrhythmias. The hypokalemic effect of EPI is blocked by an

experimental antagonist, ICI 118551, which has a high affinity for β2 and,

to a lesser degree, β3 receptors. Exercise causes an increase in the efflux of

K+ from skeletal muscle. Catecholamines tend to buffer the rise in K+ by

increasing its influx into muscle. β Blockers negate this buffering effect. (GG 13th)
Beta1-Adrenoceptor Agonists

Dobutamine and dopamine

Dobutamine β1 > β2 >>>> α

Dopamine D1 = D2 >> β >> α

are not appropriate for chronic failure because of

tolerance,

lack of oral efficacy, and

significant arrhythmogenic effects.

Role of beta blockers in Heart failure: Limitations and advantages:

Although beta blockers are used in the management of heart failure, they should not be given to
patients with uncontrolled heart failure and treatment should be begun with great care, starting
with a low dose and cautiously titrating upwards. (Martindale)

Although it may seem counterintuitive to administer drugs with negative inotropic activity to a
patient with HF,

several clinical studies have clearly demonstrated

improved systolic functioning and

reverse cardiac remodeling in patients receiving β-blockers.

These benefits arise in spite of occasional initial exacerbation of symptoms.

[can ppt. acute decompensation of cardiac function]

Treatment should be started at low doses and gradually titrated to effective doses based on patient
tolerance.

The benefit ---- attributed, in part, to their ability to prevent the changes that occur because of the
chronic activation of the sympathetic nervous system, including:

decreasing the heart rate and

inhibiting the release of renin.

In addition, also prevent the direct deleterious effects of norepinephrine on the cardiac muscle fibers,
decreasing remodeling,

hypertrophy and cell death.

A full understanding of the beneficial action of blockade is lacking, but suggested mechanisms include

1. attenuation of the adverse effects of high concentrations of catecholamines (including

apoptosis),

2. up-regulation of receptors,

3. decreased heart rate, and

4. reduced remodeling through inhibition of the mitogenic activity of catecholamines.

β Blockers contraindications Precautions

Martindale

Respiratory system:

Bronchospasm
or asthma or
to those with a history of obstructive airways disease.

This contra-indication generally applies even to those beta blockers considered to be

cardioselective. However, cardioselective beta blockers may be used with extreme caution when
there is no alternative treatment (see Obstructive Airways Disease, p. 1 3 2 1 . 1 ) .

Other contra-indications include

metabolic acidosis,

CVS:

cardiagenic shock,
hypotension,
severe peripheral arterial disease,
sinus bradycardia, and
second- or third-degree AV block;
caution should be observed in first-degree block.

Beta blockers may increase the number of attacks of chest pain in patients with Prinzmetal ' s
angina; this occurs especially with non -cardioselective beta blockers, which should be avoided.

Although beta blockers are used in the management of heart failure, they should not be given to
patients with uncontrolled heart failure and treatment should be begun with great care, starting
with a low dose and cautiously titrating upwards.

Patients with phaeochromocytoma should not be given beta

blockers without alpha-adrenoceptor blocking therapy as
well.

Beta blockers may mask the symptoms of hyperthyroidism

and of hypoglycaemia. (Diabetes Mellitus, myself)

Hyperlipidemia (myself)

They may unmask myasthenia gravis.

Psoriasis may be aggravated.

Allergy:

Beta blockers increase sensitivity to allergens and also the

severity of anaphylactoid reactions; patients with a history
of anaphylaxis to an antigen may be more reactive to
repeated challenge with the antigen while taking beta
blockers (see Hypersensitivity, p. 1 32 1 . 1 ) .

Abrupt withdrawal o f beta blockers has sometimes

resulted in angina, myocardial infarction, ventricular
arrhythmias, and death. Patients on long-term treatment
with a beta blocker should have their medication stopped
gradually over a period of I to 2 weeks.

In patients
undergoing surgery, beta blockers may reduce the risk of
arrhythmias but increase tbe risk of hypotension; the
decision to withdraw or continue therapy depends on
individual patient risk-see Cardiovascular Risk Reduction,
p. 1 3 1 7 .2.

If beta blockers arc withdrawn, this should take

place at least 24 to 48 hours before surgery; if they are
continued, atropine may be given to counter increases in
vagal tone and anaesthetics causing myocardial depression,
such as ether, cyclopropane, and trichloroethylene, are best
avoided. It is of the greatest importance that the anaesthetist
is aware that beta blockers are being taken.

Use of beta blockers in pregnancy shortly before delivery

has occasionally resulted in bradycardia and other adverse
effects such as hypoglycaemia and hypotension in the
neonate. Many beta blockers are distributed into breast
milk.

Similar precautions apply when beta blockers are used as

eye drops since systemic absorption can occur.

Peripheral arterial disease (Myself)

In contrast to classical β blockers, which decrease insulin sensitivity,

the vasodilating β receptor antagonists

(e.g., celiprolol (+ Martindale),

nipradilol,

carteolol,

carvedilol (+ Martindale), and

dilevalol) increase insulin sensitivity in patients with insulin resistance.

Together with their cardioprotective effects, improvement in insulin sensitivity from vasodilating β
receptor antagonists may partially counterbalance the hazard from worsened lipid abnormalities
associated with diabetes (GG).

Labetalol ( Martindale)

Nebivolol ( Martindale)
Q. 2. B. A 60 year old female diagnosed with Acute, closed angle glaucoma. Write any two drug
groups with one example from each group preferred in treatment of acute, closed angle glaucoma
with their mechanism of effectiveness to lower intraocular pressure (IOP). (Marks 2)

Answer 2. B.

Any two drug groups of the followings with one example from each group (1 x 2 = 2 Marks)

One mark for two drug names and One mark for their mechanism of effectiveness to lower
intraocular pressure (IOP).

Drugs (0.5 x 2 = 1 Mark) Mechanism (0.5 x 2 = 1 Mark)

1 Cholinomimetics 0.5 Ciliary muscle contraction, opening of 0.5
Any one example of the trabecular meshwork; increased
followings: outflow
Pilocarpine, carbachol,
physostigmine, echothiophate,
demecarium
2 Carbonic anhydrase inhibitors 0.5 Decreased aqueous secretion due to 0.5
Any one example of the lack of HCO3 −
followings:
Dorzolamide, brinzolamide,
Acetazolamide, dichlorphenamide,
methazolamide
3 Osmotic Agents 0.5 By exerting osmotic pressure, causing 0.5
Any one example of the a marked reduction in aqueous humor
followings: production, and vitreous volume.
Mannitol, Glycerol Vitreal “dehydration” directly decrease
IOP and allows the intact lens to move
posteriorly, increasing outflow of
aqueous humor and reducing pupillary
block.

References.
Basic and Clinical Pharmacology Katzung 14th ed, Chapter 10, Page 165, Table 10.3, Page 166.
Katzung & Treveor’s Pharmacology, Examination & Board Review, 12th ed Chapter 10, Table 10.2,
Page 89.
Q. A 60 year old female diagnosed with Chronic, wide angle glaucoma. Write two drug groups
with one example from each group preferred in treatment of chronic, wide angle glaucoma with
their mechanism of effectiveness to lower intraocular pressure. (Marks 2)

Answer 2. B.

Drugs Marks Mechanism Marks

Beta blockers 0.5
Any one of the followings: decreased aqueous secretion 0.5
Timolol, betaxolol, carteolol, from the ciliary epithelium
levobunolol, metipranolol
Prostaglandins 0.5
Any one of the followings: Increased outflow of aqueous 0.5
Latanoprost, bimatoprost, travoprost, humor
unoprostone

References.
Basic and Clinical Pharmacology Katzung 14th ed, Chapter 10, Page 165, Table 10.3, Page 166.
Katzung & Treveor’s Pharmacology, Examination & Board Review, 12th ed Chapter 10, Table 10.2,
Page 89.
BLOCK 1; PAPER 2; Pharmacology; SEQs; Key
Q. 2. B. Write three drug groups with one example from each group preferred in treatment of
acute, closed angle glaucoma with their mechanism of effectiveness to lower intraocular
pressure. (Marks 2.5)

Answer 2. B.
Marks

0.5

BLOCK 1; PAPER 1; Pharmacology; SEQs; Key

Q. 2. B. A 60 year old female diagnosed with Chronic, wide angle glaucoma. Write two
drug groups with one example from each group preferred in treatment of chronic, wide
angle glaucoma with their mechanism of effectiveness to lower intraocular pressure.
(Marks 2.5)

Answer 2. B.

More Preferable Drug Groups

Drugs Mechanism
Beta blockers
Timolol, betaxolol, decreased aqueous secretion from the ciliary
carteolol, levobunolol, epithelium
metipranolol
Prostaglandins
Latanoprost, bimatoprost, Increased outflow
travoprost, unoprostone
1
BLOCK 1; PAPER 3; Pharmacology; SEQs; Key
Q. 2. B. Write two drug groups with one example from each group preferred in treatment of
chronic, wide angle glaucoma with their mechanism of effectiveness to lower intraocular
pressure. (Marks 2.5)

Answer 2. B.

More Preferable Drug Groups

Marks

1.5

BLOCK 1; PAPER 1; Pharmacology; SEQs; Key

Q. 2. B. A 60 year old female diagnosed with Chronic, wide angle glaucoma. Write
TWO drug groups with TWO example from each group preferred in treatment of
chronic, wide angle glaucoma with their mechanism of effectiveness to lower intraocular
pressure. (Marks 2.5)

Answer 2. B.

More Preferable Drug Groups with Example any one of the following drugs

Drugs Marks Mechanism

1 Beta blockers: 0.25 decreased aqueous secretion 0.5
from the ciliary epithelium
Example any TWO of the
following drugs:
Timolol, betaxolol, carteolol, 0.25 +
levobunolol, metipranolol 0.25
2 Prostaglandins: 0.25 Increased outflow 0.5

Example any TWO of the 0.25 +

following drugs 0.25
Latanoprost, bimatoprost, 1
travoprost, unoprostone
Q. 2 A patient is prescribed Antimuscarinic drug for some ailment. Enlist the three
important clinical uses of Antimuscarinics related to different system tissues / sites with
one drug example in each case. (3 Marks)
Answer:
Any three of the followings: (1 x 3 = 3 Marks)

1 CNS: (Any one of the followings)

 Parkinsonism: Benztropine.
Trihexyphenidyl,
Biperiden,
Orphenadrine,
Procyclidine
 Motion Sickness: seasickness: Scopolamine
2 Eye: To produce Mydriasis , Cycloplegia:
(Any one of the followings)
 Accurate measurement of --- refractive error Tropicamide
in uncooperative patients, eg, young children, Cyclopentolate
---- requires ----- ciliary paralysis, thus no Homatropine
interference by the accommodative capacity of
the eye.
 Ophthalmoscopic examination of the ----
retina is greatly facilitated by --- mydriasis.
 Use to prevent synechia (adhesion) formation
in uveitis and iritis.
3 Bronchodilatation ---- COPD --- Asthma Ipratropium.
Tiotropium
4 Preanesthetic medication: Atropine
 Anti-secretory ------ Bronchial secretions --- Hyoscine
block secretions in the upper and lower
respiratory tracts prior.
 Amnesia
 Prevent vagal inhibition, bradycardia, heart
block
 Bronchodilation
 Decrease gastric secretions
5 GIT: (Any one of the followings)
 To Decrease motility Dicyclomine
Anti-spasmodic, Antidiarrheal, for Hypermotility Glycopyrrolate
Propantheline
 Peptic ulcer Pirenzepine
6 Genitourinary Oxybutynin
Urinary Urgency, Trospium
Spasm (Antispasmodic) Darifenacin
Incontinence (enuresis) Solifenacin
Overactive urinary bladder Tolterodine
Fesoteradine
7 Hyperhidrosis (Increase sweating) --- Use --- Propantheline,
Glycopyrronium
bromide or
glycopyrrolate,
oxybutynin,
methantheline, and
benzatropine.
8 Cardiovascular: Bradycardia Atropine, & Others
9 Antidote for cholinomimetics: Atropine
Organophosphate (insecticides, nerve gases)
poisoning,
Reversible anticholinesterases, e.g.
physostigmine, some types of mushroom
poisoning

BLOCK 1; PAPER 3; Pharmacology; SEQs; Key

Q. 3. A. What is the mechanism by which Low dose Atropine may produces bradycardia?
(Marks 2)

Answer 3. A.

Low dose Atropine may produces bradycardia which results from blockade of the Muscarinic
receptors on the inhibitory prejunctional (presynaptic) neurons of Postganglionic
parasympathetic nerve terminal (Autoreceptors) on SA node of heart, thus permitting increased
Acetylcholine release. Then Acetylcholine stimulate Postsynaptic M2 receptors on SA node to
produce bradycardia until these M2 receptors are also blocked by Atropine.
Contraindications / Precautions of Cholinomimetics

 Mechanical obstruction of GIT ; (Intestinal colic)

 Mechanical obstruction of Urinary tract (Renal colic)
 Peritonitis
 IBD (Inflammatory bowel disease)
 Asthma
 Peptic ulcer
 Bradycardia
 Hypotension

BLOCK 1; PAPER 3; Pharmacology; SEQs; Key

Q. 2. B. A 50 years male using a Muscarinic receptor antagonists for some ailment,

developed some undesirable effects. Enlist any SIX important adverse effects of the
Muscarinic receptor antagonists involving different system /tissues / sites. (Marks 3)

Answer 2. B.
Adverse effects of Antimuscarinic drugs:
Any SIX of the followings:

Mydriasis, Cycloplegia, Near vision blurred, Precipitate Glaucoma

Lacrimal secretions decrease, dry, sandy eyes, Photophobia / light reflex ( -
ve )
Amnesia
Tachycardia
Decrease Salivary secretions, Dryness of mouth (Xerostomia), Difficulty
in swallowing and speaking
Urinary retention
Constipation
Inhibition of sweating: Skin Dry, hot, scarlet, Hyperpyrexia
CNS: Ataxia, restlessness, and excitement; hallucinations and delirium;
Coma
BLOCK 1; PAPER 2; Pharmacology; SEQs; Key

Q. 2. B. Write the SIX important clinical uses of Antimuscarinics related to different

systems / tissues / sites. (3 Marks)

Answer 2. B.
uses of Antimuscarinics
Any SIX of the followings: (0.5 x 6 = 3 Marks)

1 CNS:
 Parkinsonism: Benztropine.
Trihexyphenidyl,
Biperiden,
Orphenadrine,
Procyclidine
 Motion Sickness: seasickness: Scopolamine
2 Eye: To produce Mydriasis , Cycloplegia:
 Accurate measurement of --- refractive Tropicamide
error in uncooperative patients, eg, young Cyclopentolate
children, ---- requires ----- ciliary Homatropine
paralysis, thus no interference by the
accommodative capacity of the eye.
 Ophthalmoscopic examination of the ----
retina is greatly facilitated by --- mydriasis.
 Use to prevent synechia (adhesion)
formation in uveitis and iritis.
3 Bronchodilatation ---- COPD --- Asthma Ipratropium. Tiotropium
4 Preanesthetic medication: Atropine
 Anti-secretory ------ Bronchial secretions - Hyoscine
-- block secretions in the upper and lower
respiratory tracts prior.
 Amnesia
 Prevent vagal inhibition, badycardia, heart
block
 Bronchodilation
 Decrease gastric secretions
5 GIT:
  To Decrease motility Dicyclomine
Anti-spasmodic, Antidiarrheal, for Glycopyrrolate
Hypermotility ---- Propantheline
 Peptic ulcer Pirenzepine

6 Genitourinary Oxybutynin
Urinary Urgency, Trospium
Spasm (Antispasmodic) Darifenacin
Incontinence (enuresis) Solifenacin
Overactive urinary bladder Tolterodine
Fesoteradine
7 Hyperhidrosis (Increase sweating) --- Use --- Propantheline,
Glycopyrronium
bromide or
glycopyrrolate,
oxybutynin,
methantheline, and
benzatropine.
8 Cardiovascular: Bradycardia Atropine, & Others
9 Antidote for cholinomimetics: Atropine
Organophosphate (insecticides, nerve gases)
poisoning,
Reversible anticholinesterases, e.g.
physostigmine, some types of mushroom
poisoning

BLOCK 1; PAPER 1; Pharmacology; SEQs; Key

Q. 3. A. What is the mechanism by which Low dose Atropine may produces

bradycardia? (Marks 1)

Answer 3. A.

Low dose Atropine may produces bradycardia which results from blockade of the
Muscarinic receptors on the inhibitory prejunctional (presynaptic) neurons of
Postganglionic parasympathetic nerve terminal (Autoreceptors) on SA node of heart, thus
permitting increased Acetylcholine release. Then Acetylcholine stimulate Postsynaptic
M2 receptors on SA node to produce bradycardia until these M2 receptors are also blocked
by Atropine.
Write the SIX important clinical uses of Antimuscarinics related to different system
tissues / sites with atleast one drug example in each case. (3 Marks)

1 CNS:
 Parkinsonism: Benztropine.
Trihexyphenidyl,
Biperiden,
Orphenadrine,
Procyclidine
 Motion Sickness: seasickness: Scopolamine
2 Eye: To produce Mydriasis , Cycloplegia:
 Accurate measurement of --- refractive Tropicamide
error in uncooperative patients, eg, young Cyclopentolate
children, ---- requires ----- ciliary Homatropine
paralysis, thus no interference by the
accommodative capacity of the eye.
 Ophthalmoscopic examination of the ----
retina is greatly facilitated by --- mydriasis.
 Use to prevent synechia (adhesion)
formation in uveitis and iritis.
3 Bronchodilatation ---- COPD --- Asthma Ipratropium. Tiotropium
4 Preanesthetic medication: Atropine
 Anti-secretory ------ Bronchial secretions - Hyoscine
-- block secretions in the upper and lower
respiratory tracts prior.
 Amnesia
 Prevent vagal inhibition, badycardia, heart
block
 Bronchodilation
 Decrease gastric secretions
5 GIT:
 To Decrease motility Dicyclomine
Anti-spasmodic, Antidiarrheal, for Glycopyrrolate
Hypermotility ---- Propantheline
 Peptic ulcer Pirenzepine
6 Genitourinary Oxybutynin
Urinary Urgency, Trospium
Spasm (Antispasmodic) Darifenacin
Incontinence (enuresis) Solifenacin
BPH Tolterodine
Overactive urinary bladder Fesoteradine
7 Hyperhidrosis (Increase sweating) --- Use --- Propantheline,
Glycopyrronium
bromide or
glycopyrrolate,
oxybutynin,
methantheline, and
benzatropine.
8 Cardiovascular: Bradycardia Atropine, & Others
9 Antidote for cholinomimetics: Atropine
Organophosphate (insecticides, nerve gases)
poisoning,
Reversible anticholinesterases, e.g.
physostigmine, some types of mushroom
poisoning

Adverse effects of Antimuscarinic drugs:

Mydriasis, Cycloplegia, Near vision blurred, Precipitate Glaucoma

Lacrimal secretions decrease, dry, sandy eyes, Photophobia / light reflex ( -
ve )
Amnesia
Tachycardia
Decrease Salivary secretions, Dryness of mouth (Xerostomia), Difficulty
in swallowing and speaking
Urinary retention
Constipation
Inhibition of sweating: Skin Dry, hot, scarlet, Hyperpyrexia
CNS: Ataxia, restlessness, and excitement; hallucinations and delirium;
Coma
C/I / Precautions of Cholinomimetics

 Mechanical obstruction of GIT or Urinary tract

 Peritonitis
 IBD (Inflammmatory bowel disease)
 Asthma
 Peptic ulcer
 Bradycardia / Hypotension

BLOCK 1; PAPER 1; Pharmacology; SEQs; Key

Q. 2. B. Enlist any five important uses of Cholinomimetics (Marks 2.5)

Answer 2 B

ANY “FIVE” OF THE FOLLOWINGS:

1. Glaucoma
2. Intestinal Atony
3. Urinary Bladder Atony
4. Reflex esophagitis
5. To increase salivary secretions in Xerostomia, Sjogren’s syndrome
6. Myasthenia Gravis ----- Diagnosis and Treatment
7. Tachycardia
8. Antimuscarinic drugs intoxication
9. Alzheimer’s disease
10. Insecticides / Pesticides / Antihelminthics (Anthelmintics) / Chemical warfare
BLOCK 1; PAPER 3; Pharmacology; SEQs; Key
Q. 2. B. A 50 years male using a Muscarinic receptor agonist for some ailment,
developed some undesirable effects. Enlist any SIX important adverse effects of the
Muscarinic receptor agonists involving different system /tissues / sites. (Marks 3)

Answer 2. B.
Adverse effects of Cholinomimetics:
Any SIX of the followings:
DUMBBELSS

Miosis, Cyclospasm, Far vision blurred,

Lacrimal secretions increase, watery eyes,
Bronchoconstriction
Bradycardia
Increase Salivary secretions, Increase stomach and other exocrine secretions
Urinary urgency, Urination
Diarrhea
Excitation of Skeletal muscle and CNS
Lacrimation,
Salivation,
Sweating

BLOCK 1; PAPER 3; Pharmacology; SEQs; Key

Q. 3. A. A 35 years male patient needs treatment with a Cholinomimetics. Enlist
important Contraindications / Precautions of Cholinomimetics. (2.5 Marks).

Answer 3. A. Contraindications / Precautions of Cholinomimetics. (2.5 Marks).

 Mechanical obstruction of GIT or Urinary tract

 Peritonitis
 IBD (Inflammmatory bowel disease)
 Asthma
 Peptic ulcer
 Bradycardia / Hypotension
Q. 3. A. Write any three drug interactions of Neuromuscular blockers (Anticholinergics,
Antinicotinics). (Marks 2.5)

Answer 3. A.

ANY “THREE” OF THE FOLLOWINGS:

1. Cholinesterase inhibitors; Drugs such as neostigmine, physostigmine, pyridostigmine, and

edrophonium : Decrease the effect of nondepolarizing (competitive) neuromuscular blockers
e.g. atracurium, cisatracurium.
2. Halogenated hydrocarbon general anesthetics; e.g. desflurane: Increase the effect of
neuromuscular blockers.
3. Aminoglycoside antibiotics; e.g. gentamicin and tobramycin : Inhibit ACh release from
cholinergic nerves by competing with calcium ions; Increase the effect of neuromuscular
blockers.
4. Calcium channel blockers; e.g. Verapamil: Increase the effect of Neuromuscular blockade
of nondepolarizing (competitive) neuromuscular blockers e.g. atracurium, cisatracurium.

BLOCK 1; PAPER 1; Pharmacology; SEQs; Key

Q. 3. A. A 55 year male develop bradycardia after administration of low dose atropine.

What is the mechanism by which Low dose Atropine may produce bradycardia?
(Mark 1)
Answer 3. A.
Low dose Atropine may produces bradycardia which results from blockade of the
Muscarinic receptors on the inhibitory prejunctional (presynaptic) neurons of
Postganglionic parasympathetic nerve terminal (Autoreceptors) on SA node of heart, thus
permitting increased Acetylcholine release. Then Acetylcholine stimulate Postsynaptic
M2 receptors on SA node to produce bradycardia until these M2 receptors are also blocked
by Atropine.
BLOCK 1; PAPER 3; Pharmacology; SEQs; Key
Q. 3. A. What is the mechanism by which Low dose Atropine may produces bradycardia?
(Marks 2)
Answer 3. A.

Low dose Atropine may produces bradycardia which results from blockade of the Muscarinic
receptors on the inhibitory prejunctional (presynaptic) neurons of Postganglionic
parasympathetic nerve terminal (Autoreceptors) on SA node of heart, thus permitting increased
Acetylcholine release. Then Acetylcholine stimulate Postsynaptic M2 receptors on SA node to
produce bradycardia until these M2 receptors are also blocked by Atropine.

BLOCK 1; PAPER 2; Pharmacology; SEQs; Key 1

Q. 3. A. Enlist five important adverse effects of succinylcholine involving different system /
tissues / sites. (Marks 2.5)

Answer 3. A.

ANY “FIVE” OF THE FOLLOWINGS:

.

1. Malignant Hyperthermia
2. Apnea
3. Hyperkalemia
4. Initial muscle fasciculations (Twiching) ; Myalgias (muscle pain)
5. Increase Intragastric Pressure --- due to --- Fasciculations; Increase risk of regurgitation &
aspiration of gastric contents; more likely in pts. with Delayed gastric emptying and such as
those with esophageal dysfunction or diabetes
6. Slight histamine release; can produce a fall in blood pressure, flushing, and
bronchoconstriction.
7. Increase Intraocular Pressure: may precipitate glaucoma
8. With Halothane more chances of Cardiac arrhythmias
Autonomic Pharmacology

BLOCK 1; Set 3; Pharmacology; SEQs; Key

Q. 2.A. An adult patient is given a Neuromuscular blocker in operation theatre who is also
receiving some other drugs for certain conditions. Describe any two drug interactions of
Neuromuscular blockers (Anticholinergics, Antinicotinics) with the mechanism of interaction and
the resultant effect in each case. (2 Marks)

Answer 2. A. (2 Marks)

Any Two of the followings: (2 x 1 = 2 Marks)

Drug Mechanism of interaction Resultant effect

1 Cholinesterase Pharmacodynamic interaction, Decrease the effect of
inhibitors; Drugs such (Competitive Pharmacological nondepolarizing
as neostigmine, Antagonism). (competitive)
physostigmine, Increasing the concentration of neuromuscular
pyridostigmine, and Acetylcholine at the nicotinic receptor site blockers e.g.
edrophonium : (Skeletal neuromuscular junction) atracurium,
cisatracurium
2 Halogenated Skeletal muscle relaxation Increase the effect of
hydrocarbon general neuromuscular
anesthetics; e.g. blockers.
desflurane:
3 Aminoglycoside Pharmacodynamic interaction, Increase the effect of
antibiotics; e.g. Inhibit ACh release from cholinergic neuromuscular
gentamicin and nerves by competing with calcium ions; blockers.
tobramycin :
4 Calcium channel Pharmacodynamic interaction, Increase the effect of
blockers; e.g. Block Ca Channels, Relax skeletal muscles Neuromuscular
Verapamil: blockade of
nondepolarizing
(competitive)
neuromuscular
blockers e.g.
atracurium,
cisatracurium.

Reference.
Lippincott’s Illustrated Reviews: Pharmacology 8 th ed, Chapter 5, Page 68-69.
Autonomic Pharmacology

BLOCK 1; PAPER 3; Pharmacology; SEQs; Key

Q. 2.A. Write any Three drug interactions of Neuromuscular blockers (Anticholinergics,
Antinicotinics) with the resultant effect. (3 Marks)

Answer 2. A. (3 Marks)

Any THREE of the followings:

1 Mark for each of the followings: (1 x 3 = 3 Marks)

1. Cholinesterase inhibitors; Drugs such as neostigmine, physostigmine, pyridostigmine, and

edrophonium : Decrease the effect of nondepolarizing (competitive) neuromuscular
blockers e.g. atracurium, cisatracurium.
2. Halogenated hydrocarbon general anesthetics; e.g. desflurane: Increase the effect of
neuromuscular blockers.
3. Aminoglycoside antibiotics; e.g. gentamicin and tobramycin : Inhibit ACh release from
cholinergic nerves by competing with calcium ions; Increase the effect of neuromuscular
blockers.
4. Calcium channel blockers; e.g. Verapamil: Increase the effect of Neuromuscular
blockade of nondepolarizing (competitive) neuromuscular blockers e.g. atracurium,
cisatracurium.

Q. A patient attended OPD is prescribed a Beta adrenoceptors antagonist for some ailment. Enlist
the SIX important clinical uses of Beta adrenoceptors antagonists (3 Marks)
Answer:
Any Six of the followings: (0.5 x 6 = 3 Marks)
Hypertension
Chronic management of stable angina.
Myocardial infarction
Supraventricular and ventricular arrhythmias
Long term management of chronic heart failure
Obstructive cardiomyopathy
Dissecting aortic aneurysm
Chronic open angle Glaucoma
Prophylaxis of Migraine:
Hyperthyroidism and thyroid storm
Reduce certain tremors
prophylactically.to control somatic manifestations of anxiety.
For example, in performance anxiety (“stage fright”).
Symptomatic treatment of alcohol withdrawal
to diminish portal vein pressure in patients with cirrhosis.
- decrease the incidence of bleeding from esophageal varices
Infantile hemangiomas
General Pharmacology BLOCK 1; Set 1; Pharmacology; SEQs; Key

Q. 2.A. A beta adrenoceptor antagonist with additional vasodilating effect is prescribed to a

patient with chronic cardiac failure. Enlist:
i. any three beta adrenoceptor antagonist which have additional vasodilating effect.
ii. any three putative additional mechanisms by which beta adrenoceptor antagonist
produce vasodilation
(Marks 1.5 + 1.5 = 3)
Answer 2. A. (Marks 1.5 + 1.5 = 3)

Marks
1 i. Enlist any three beta adrenoceptor antagonist has additional 1.5
vasodilating effect.
Any three of the followings: (0.5 x 3 = 1.5 Mark)
 Betaxolol
 Bevantolol
 Bopindolol
 Bucindolol
 Carteolol
 Carvedilol
 Celiprolol
 Labetalol
 Nebivolol
 Nipradilol
 Tilisolol
2 ii. Enlist any three putative additional mechanisms by which beta 1.5
adrenoceptor antagonist produce vasodilation
Any three of the followings: (0.5 x 3 = 1.5 Mark)
 Nitric oxide Production
 β2 receptor Agonism
 α1 receptor Antagonism
 Ca2+ entry Blockade
 K+ channel Opening
 Antioxidant Activity
Q. Name two different pharmacological drug groups which can be used to control
hypertension in Pheochromocytoma with their benefits and limitations with respect to their
effects on Cardiovascular system.

Answer

Marks
1 Alpha adrenoceptor antagonists:
Benefit: Vasodilation, decrease Total Peripheral Resistance, decrease
Blood Pressure
Limitation: Not decrease Heart Rate, may produce tachycardia
2 Beta adrenoceptor antagonists:
Benefit: decrease Heart Rate, decrease Cardiac Output, decrease Blood
Pressure
Limitation: No Vasodilation, May produce Vasoconstriction, Increase
Total Peripheral Resistance, Increase Blood Pressure. Therefore Should
not be used alone. Always given in presence of Alpha antagonists.

Q. How would you differentiate between preganglionic and post-ganglionic lesion in Horner’s
syndrome by using adrenomimetic (sympathomimetic) drugs.

Answer

If the lesion of Horner’s syndrome is postganglionic, indirectly acting sympathomimetics (eg,

cocaine, hydroxyamphetamine) will not dilate the abnormally constricted pupil because
catecholamines have been lost from the nerve endings in the iris. In contrast, the pupil dilates
in response to phenylephrine, which acts directly on the α receptors on the smooth muscle of
the iris.
A patient with a preganglionic lesion, on the other hand, shows a normal response to both
drugs, since the postganglionic fibers and their catecholamine stores remain intact in this
situation.

Post-ganglionic Lesion Preganglionic Lesion

Indirectly acting sympathomimetics (eg, Not dilate the abnormally Dilate
cocaine, hydroxyamphetamine) constricted pupil
Phenylephrine Dilate Dilate
Autonomic Pharmacology

BLOCK 1; PAPER 3; Pharmacology; SEQs; Key

Q.2.B. A 55 year male is prescribed an alpha adrenoceptor blocker for some ailment. Write
down the FOUR important uses of alpha adrenoceptor blockers with one drug example in
each case. (2 Marks)

Answer 2. B. (2 Marks)

Uses of alpha adrenoceptor blockers

0.5 Mark for each of the followings: (0.5 x 4 = 2 Marks)

Any four of the followings: with one drug example in each case:

1. Treatment of pheochromocytoma:
 Phentolamine
 Phenoxybenzamine
2. Hypertensive emergencies: Phentolamine
3. Chronic hypertension:
 Prazosin
 Doxazosin
 Terazosin
4. Peripheral vascular disease: in Raynaud’s disease. e.g.,
 Phenoxybenzamine
5. Benign prostate hypertrophy (BPH):Drugs used are
 Tamsulosin
 Terazosin
 Prazosin
 Doxazosin
 Alfuzosin
6. Erectile dysfunction: Drugs used are
 Yohimbine
 Phentolamine
BLOCK 1; PAPER 2; Pharmacology; SEQs; Key
Q. 3. B. Write down the Clinical uses of adrenaline. (Marks 2.5)
Answer 3. B.

1. Acute Asthma, to relieve bronchospasm

2. Type I Hypersensitivity reactions (Anaphylaxis, Anaphylactic shock), to relieve
bronchospasm, & to increase blood pressure
3. Cardiac arrest, Complete heart Block, Bradycardia
4. With Local Anesthetics to increase the duration of action and decrease systemic adverse
effects of anesthetics.
5. Priapism
6. Chronic wide angle Glaucoma
7. Topical application to control bleeding, Epistaxis, Gingivectomy
8. Hypotension / Postural Hypotension
9. Anti-dote for Vasodilators (Anti-Hypertensive drugs)

BLOCK 1; PAPER 1; Pharmacology; SEQs; Key

Q. 3. C. A 50 years male using an Alpha adrenoceptor antagonists for some ailment,

developed some undesirable effects. Enlist important adverse effects of the Alpha
adrenoceptor antagonists. (Marks 2)

Postural hypotension
Dizziness
Lack of energy
Headache
Drowsiness
Reflex tachycardia
Precipitate Arrhythmias and Angina
Nasal stuffiness / congestion,
Nausea, and vomiting.
Sexual dysfunction, inhibition of ejaculation and retrograde ejaculation.
''Floppy iris syndrome"

1
BLOCK 1; PAPER 1; Pharmacology; SEQs; Key (Marks 2.5)

1
Q. 3. B. Compare the effects of Adrenaline and Noradrenaline on cardiovascular system.
Answer 3. B.

Marks

0.5

…………………………………………………………………………………………
1

Small doses decrease, large doses increase.

1

↑ = Increase; ↓ = Decrease; 0 = No change.

BLOCK 1; PAPER 1; Pharmacology; SEQs; Key

Q. 4. A. Write the Uses of Antihistamine H1 Receptor Antagonists with one drug example for
each indication. (Marks 2.5)
1
BLOCK 1; PAPER 1; Pharmacology; SEQs; Key

Q. 3. B. A 50 year male suffering from Diabetes Mellitus and Hyperlipidemia, needs

treatment with beta adrenoceptors antagonist for some ailment. What are the limitations
of beta adrenoceptors antagonist in patients of Diabetes Mellitus and Hyperlipidemia.
(Marks 2)

Answer 3. B.

Limitations of Beta Blockers in Patients of Diabetes Mellitus and Hyperlipidemias:

1. Diabetes Mellitus:

 Non selective beta blockers such as propranolol inhibit glycogenolysis in the human
liver after β2 receptor blockade and thus inhibit recovery from hypoglycemia
 Premonitory signs and symptoms of hypoglycemia due to insulin overdosage (
tachycardia, palpitation, tremor, anxiety) may be masked by β blockers
 β blockers should be used with caution in insulin dependent diabetic patients. This
may be particularly important in patients with inadequate glucagon reserve and in
pancreatectomized patients
 β1 receptor selective drugs may be less prone to inhibit recovery from hypoglycemia
 β blockers are much safer in those type 2 diabetic patients who do not have
hypoglycemic episodes

2. Hyperlipidemias:

 Chronic use of β blockers has been associated with increased plasma concentration of
VLDL and decreased concentration of HDL cholesterol. LDL concentration generally
do not change
 These changes may increase the risk of coronary artery disease
 These changes tend to occur with both selective and non-selective β blockers though
they may be less likely to occur with β blockers possessing Intrinsic
Sympathomimetic Activity (ISA)
Q. 3. C. A 50 years male need an Alpha adrenoceptor antagonists for some ailment.
Enlist important Adverse effects of the Alpha adrenoceptor antagonists. (Marks 2)

Postural hypotension
Dizziness
Lack of energy
Headache
Drowsiness
Reflex tachycardia
Precipitate Arrhythmias and Angina
Nasal stuffiness / congestion,
Nausea, and vomiting.
Sexual dysfunction, inhibition of ejaculation and retrograde ejaculation.
''Floppy iris syndrome"

BLOCK 1; PAPER 2; Pharmacology; SEQs; Key

Q. 3. A. A 41 year lady prescribedoral Albuterol (Salbutamol) for asthma. Enlist any

THREE important adverse effects of Beta-2 agonists, each involving different system /
tissues / sites. (1.5 Marks)

Answer 3. B.

Adverse effects of Beta-2 agonists.

Any “THREE” of the followings

Tachycardia, Arrhythmia
Hyperglycemia,
Hypokalemia, and
Hypomagnesemia
Skeletal muscle tremors.
Worsened hypoxemia
Vasodilating action of β2-agonist treatment may increase perfusion
of poorly ventilated lung units, transiently decreasing arterial
oxygen tension (PaO2),
Tachyphylaxis.
Lip 6th ------Page 383
Kat 14th ------ Page 351
Q. 4. B. Enlist three important adverse effects of Beta antagonists, each involving
different system / tissues / sites. (1.5 Marks)

Hypotension
Bradycardia, Heart block
Precipitate heart failure
Bronchoconstriction
Impaired sexual activity in men.
Hypoglycemia. Mask symptoms of Hypoglycemia. Prevent
the counterregulatory effects of catecholamines during hypoglycemia.
increased lowdensity lipoprotein ("bad" cholesterol), increased
triglycerides, and reduced high-density lipoprotein ("good" cholesterol).
CNS: depression, dizziness, lethargy, fatigue, weakness,
visual disturbances, hallucinations, short-term memory
loss, emotional lability, vivid dreams (including nightmares),
and depression.
Abrupt withdrawal may precipitate Arrhythmias, Ischemic heart disease,
Hypertension, heart failure

Enlist the SIX important clinical uses of Beta adrenoceptors antagonists (3 Marks)

Hypertension
Chronic management of stable angina.
Myocardial infarction
Supraventricular and ventricular arrhythmias
Long term management of chronic heart failure
Obstructive cardiomyopathy
Dissecting aortic aneurysm
Chronic open angle Glaucoma
Prophylaxis of Migraine:
Hyperthyroidism and thyroid storm
Reduce certain tremors
prophylactically.to control somatic manifestations of anxiety.
For example, in performance anxiety (“stage fright”).
Symptomatic treatment of alcohol withdrawal
to diminish portal vein pressure in patients with cirrhosis.
- decrease the incidence of bleeding from esophageal varices

Infantile hemangiomas
Q. 3. B. What are the limitations of beta blockers in patients of Diabetes Mellitus and
Hyperlipidemia. (Marks 3)

Answer 3. B.

Limitations of Beta Blockers in Patients of Diabetes Mellitus and Hyperlipidemias:

1. Diabetes Mellitus:

 Non selective beta blockers such as propranolol inhibit glycogenolysis in the human liver
after β2 receptor blockade and thus inhibit recovery from hypoglycemia
 Premonitory signs and symptoms of hypoglycemia due to insulin overdosage ( tachycardia,
palpitation, tremor, anxiety) may be masked by β blockers
 β blockers should be used with caution in insulin dependent diabetic patients. This may be
particularly important in patients with inadequate glucagon reserve and in pancreatectomized
patients
 β1 receptor selective drugs may be less prone to inhibit recovery from hypoglycemia
 β blockers are much safer in those type 2 diabetic patients who do not have hypoglycemic
episodes

2. Hyperlipidemias:

 Chronic use of β blockers has been associated with increased plasma concentration of VLDL
and decreased concentration of HDL cholesterol. LDL concentration generally do not change
 These changes may increase the risk of coronary artery disease
 These changes tend to occur with both selective and non-selective β blockers though they
may be less likely to occur with β blockers possessing Intrinsic Sympathomimetic Activity
(ISA)

BLOCK 1; PAPER 3; Pharmacology; SEQs; Key

1
BLOCK 1; PAPER 1; Pharmacology; SEQs; Key

Q. 3. B. A 53 year lady suffering from Diabetes Mellitus and Hyperlipidemia, needs

treatment with beta adrenoceptors antagonist for some ailment. What are the limitations
of beta adrenoceptors antagonist in patients of Diabetes Mellitus and Hyperlipidemia?
(Marks 2)

Answer 3. B.

Limitations of Beta Blockers in Patients of Diabetes Mellitus and Hyperlipidemias:

1. Diabetes Mellitus:

 Non selective beta blockers such as propranolol inhibit glycogenolysis in the human
liver after β2 receptor blockade and thus inhibit recovery from hypoglycemia
 Premonitory signs and symptoms of hypoglycemia due to insulin overdosage (
tachycardia, palpitation, tremor, anxiety) may be masked by β blockers
 β blockers should be used with caution in insulin dependent diabetic patients. This
may be particularly important in patients with inadequate glucagon reserve and in
pancreatectomized patients
 β1 receptor selective drugs may be less prone to inhibit recovery from hypoglycemia
 β blockers are much safer in those type 2 diabetic patients who do not have
hypoglycemic episodes

2. Hyperlipidemias:

 Chronic use of β blockers has been associated with increased plasma concentration of
VLDL and decreased concentration of HDL cholesterol. LDL concentration generally
do not change
 These changes may increase the risk of coronary artery disease
 These changes tend to occur with both selective and non-selective β blockers though
they may be less likely to occur with β blockers possessing Intrinsic
Sympathomimetic Activity (ISA)
BLOCK 1; PAPER 3; Pharmacology; SEQs; Key
Q. 3. B. Enlist the SIX important clinical uses of Beta adrenoceptors antagonists (3
Marks)
Answer 3. B.
Any SIX of the followings:
Hypertension
Chronic management of stable angina.
Myocardial infarction
Supraventricular and ventricular arrhythmias
Long term management of chronic heart failure
Obstructive cardiomyopathy
Dissecting aortic aneurysm
Chronic open angle Glaucoma
Prophylaxis of Migraine:
Hyperthyroidism and thyroid storm
Reduce certain tremors
prophylactically.to control somatic manifestations of anxiety.
For example, in performance anxiety (“stage fright”).
Symptomatic treatment of alcohol withdrawal
to diminish portal vein pressure in patients with cirrhosis.
- decrease the incidence of bleeding from esophageal varices
Infantile hemangiomas

BLOCK 1; PAPER 2; Pharmacology; SEQs; Key

Q. 3. B. A 50 years male using an Beta adrenoceptor antagonists for some ailment,
developed some undesirable effects. Enlist important adverse effects of Beta antagonists.
(2.5 Marks)
Answer 3. B.

1 Bradycardia, Heart block

2 Precipitate heart failure
3 Bronchoconstriction
4 Impaired sexual activity in men.
5 Hypoglycemia. Mask symptoms of Hypoglycemia. Prevent
the counterregulatory effects of catecholamines during hypoglycemia.
6 increased lowdensity lipoprotein ("bad" cholesterol), increased
triglycerides, and reduced high-density lipoprotein ("good" cholesterol).
7 CNS: depression, dizziness, lethargy, fatigue, weakness,
visual disturbances, hallucinations, short-term memory
loss, emotional lability, vivid dreams (including nightmares),
and depression.
8 Abrupt withdrawal may precipitate Arrhythmias, Ischemic heart disease,
Hypertension
9 Hypotension rarely
BLOCK 1; PAPER 2; Pharmacology; SEQs; Key
Q. 3. A. A 41 year lady using oral Albuterol (Salbutamol) for asthma, developed some
undesirable effects. Enlist important adverse effects of Beta-2 agonists (2.5 Marks)
Answer 3. A.
Adverse effects of Beta-2 agonists.
1. Tachycardia, Arrhythmia
2. Hyperglycemia,
3. Hypokalemia,
4. Hypomagnesemia
5. Skeletal muscle tremors.
6. Worsened hypoxemia
7. Vasodilating action of β2-agonist treatment may increase perfusion of poorly
ventilated lung units, transiently decreasing arterial oxygen tension (PaO2),
8. Tachyphylaxis.
Lip 6th ------Page 383
Kat 14th ------ Page 351

BLOCK 1; PAPER 2; Pharmacology; SEQs; Key

Q. 4. A. Compare First generation and second generations Antihistamine H1 Receptor
Antagonists . (Marks 2.5)

Answer 4. A.
Comparison between 1st generation and 2nd generation Antihistamines H1 Receptor Antagonists

1st generation 2nd generation

1 Penetrate CNS and cause sedation These are polar, do not penetrate the blood
brain barrier causing less or no sedation
2 Also block other receptors such as α1- No such effects
adrenergic (causing postural hypotension,
dizziness, reflex tachycardia, palpitation),
Muscarinic (causing dry mouth, urinary
retention, constipation, sinus tachycardia)
and serotonin receptors (causing increase
appetite).
3 Use in motion sickness and nausea vomiting No
4 Shorter duration (6-8 hours) Longer duration (12-24 hours)
5 Inexpensive More expensive
Autacoids and Related Drugs

BLOCK 1; PAPER 3; Pharmacology; SEQs; Key

Q.3.B. An adult male is prescribed an antihistamine H1 receptor antagonists for some ailment,
complains of excessive sedation and wants to switch the drug to avoid this effect. Name one
drug example from each category having marked potential, weak potential, and no potential
for producing sedation. (1.5 Marks)

Answer 3.B.

Any one drug example from each category: (0.5 x 3 = 1.5 Marks)

1. Marked potential for producing sedation

 Brompheniramine
 Chlorphenamine
 Clemastine
 Cyproheptadine
 Diphenhydramine
 Doxylamine
 Hydroxyzine
 Promethazine

2. Weak potential for producing sedation

 Acrivastine
 Cetirizine
 Levocetirizine

3. No potential for producing sedation (Nonsedating)

 Desloratadine
 Fexofenadine
 Loratadine
BLOCK 1; PAPER 3; Pharmacology; SEQs; Key

Q. 4. A. A 40 year lady needs treatment with Antihistamine H1 Receptor Antagonists for

some allergy. She is also using certain other drugs for some ailments, Write FIVE
important Drug interactions of Antihistamine H1 Receptor Antagonists with the resultant
effect (2.5 Marks)

Answer 4. A.

Drug interactions of Antihistamine H1-receptor antagonists: (2.5 Marks)

1 CNS depressants, (eg, benzodiazepines and alcohol): additive / 0.5

Potentiation of sedative and other CNS depressant effects
2 Monoamine oxidase inhibitors (MAOls): can exacerbate the 0.5
anticholinergic effects of the antihistamines.
3 First-generation antihistamines having anticholinergic (antimuscarinic) 0.5
actions may decrease the effectiveness of cholinesterase inhibitors
(donepezil, rivastigmine, and galantamine) in the treatment of Alzheimer's
disease.
4 Drugs that inhibit hepatic metabolism may result in dangerously high 0.5
levels of certain antihistaminic drugs (e.g. terfenadine or astemizole ) that
are taken concurrently.
For example, azole antifungal drugs (ketoconazole, itraconazole, or),
macrolide antibiotics such as erythromycin, and certain other CYP3A4
inhibitors interfere with the metabolism of astemizole and terfenadine, and
can precipitate lethal arrhythmias.
5 First-generation antihistamines having α-blocking effect: Additive effect 0.5
with α-blockers
BLOCK 1; PAPER 3; Pharmacology; SEQs; Key
Q. 4. A. Enlist the five adverse effects of Antihistamine H1 Receptor Antagonists involving
different system / tissues / sites. (2.5 Marks)
1
Answer 4. A.

Adverse Effects of H1 Antagonists

ANY “FIVE” OF THE FOLLOWINGS:

1. Sedation; due to block of H1 receptors in CNS

2. Hypotension, dizziness, reflex tachycardia; due to block of α-adrenergic receptors
3. Dry mouth, urinary retention, sinus tachycardia, blurred vision; due to block of
muscarinic receptors
4. Increased appetite; due to block of serotonin receptors
5. Headache; due to 1st generation H1 antihistamines
6. Topical formulations of diphenhydramine can cause hypersensitivity reaction
7. Potentiation of effects of other CNS depressants including alcohol
8. MAO inhibitors can exacerbate anticholinergic effects of antihistamines
9. 1st generation drugs with anticholinergic effects may decrease the effectiveness of
cholinesterase inhibitors
BLOCK 1; PAPER 1; Pharmacology; SEQs; Key
Answer 4. A.
Uses of Anti Histamines H1 Receptor Antagonists:

Any “ONE” Drug example

1 Prevention and treatment of Allergic conditions:
a. Allergic rhinitis (hay fever), atopic Any of first or second generation
dermatitis, urticarial, angioedema antihistamines
b. Allergic conjunctivitis: Opthalmic antihistamines such as
azelastine, olopatadine, ketotifen.
2 Motion sickness and vestibular disturbance Diphenhydramine, dimenhydrinate,
promethazine, cyclizine, meclizine,
Hydroxyzine
3 Nausea and vomiting of Pregnancy (Morning Doxylamine
sickness)
4 Chemotherapy-induced vomiting. Diphenhydramine

5 For Insomnia (As somnifacients) 1st generation antihistamines:

Brompheniramine,
Chlorpheniramine, Clemastine,
Cyproheptadine, Diphenhydramine,
Doxylamine, Hydroxyzine,
Meclizine, Promethazine
6 As Antimuscarinic, e.g. in Nonallergic Carbinoxamine, dimenhydrinate,
rhinorrhea diphenhydramine), Promethazine

7 Extrapyramidal symptoms & Acute Dystonia Drugs with antimuscarinic effects,

due to antipsychotic drugs e.g. Diphenhydramine
8 Appetite stimulant Drug with serotonin antagonist effect
e.g., cyproheptadine
9 Local anesthesia Diphenhydramine, Promethazine
Autacoids and Related Drugs

BLOCK 1; PAPER 2; Pharmacology; SEQs; Key

Q. 3. B. A patient needs treatment with a Prostaglandin for some ailment. Write down any five
important clinical uses of Prostaglandins with one example of Prostaglandins in each case . (2.5
Marks)

Answer 3. B.

Prostaglandins: Clinical Uses:

ANY “Five” OF THE FOLLOWINGS:

1 Abortifacients: PGE2 and PGF2α ; PGE1 analog Misoprostol with the Methotrexate or
progesterone antagonist Mifepristone
2 To soften the cervix at term before induction of labor with oxytocin -----
PGE2 (as Dinoprostone)
3 To maintain patency of the ductus arteriosus in infants with transposition of the great
vessels until surgical correction ------ PGE1
4 In severe Pulmonary hypertension — Prostacyclin (PGI2) ----- (as Epoprostenol)
5 To prevent platelet aggregation in dialysis machines. ----- Prostacyclin (PGI2) ----- (as
Epoprostenol)
6 Prevention of peptic ulcers associated with NSAIDs use ---- Misoprostol
7 Treatment of impotence: PGE1 (as Alprostadil)
8 Treatment of glaucoma: PGF2α derivatives, Latanoprost, Bimatoprost,
Travoprost, and Unoprostone.
9 Eyelash growth: Treatment of eyelash hypotrichosis. ----- Bimatoprost
10 Chronic idiopathic constipation, Opioid-induced constipation, Irritable Bowel Syndrome
with constipation: Lubiprostone (PGE1 derivative, Prostanoic acid derivative)

References.
Basic and Clinical Pharmacology Katzung 14th ed, Chapter 18, Page 334-335
Katzung & Treveor’s Pharmacology, Examination & Board Review, 12th ed Chapter 18, Page 160-
161
Lippincott’s Illustrated Reviews: Pharmacology 7th ed, Chapter 38, Page 510-511.
Autacoids and Related Drugs

BLOCK 1; PAPER 1; Pharmacology; SEQs; Key

Q.3.A. A 35 year female needs treatment with an Ergot Alkaloid for some ailment. Enlist the
Five important uses of Ergot Alkaloids with one drug example for each condition. (2.5
Marks)

Answer 3.A.

Ergot Alkaloids Uses:

Any Five of the followings. (0.5 x 5 = 2.5 Marks)

1. Acute attacks of Migraine — Ergotamine;

For prophylaxis of Migraine ------ Methysergide, dihydroergonovine, and ergonovine
2. Obstetric bleeding — Ergonovine and ergotamine ----- for the reduction of postpartum
bleeding by producing a powerful and long-lasting contraction of uterus.
3. Hyperprolactinemia ----- Bromocriptine, pergolide, and cabergoline ----- used to reduce
prolactin secretion
Bromocriptine also appears to reduce the size of pituitary tumors of the prolactin-secreting
cells.
4. Treatment of Acromegaly: Bromocriptine and cabergoline .
5. Treatment of Parkinson’s disease: Bromocriptine, pergolide, and cabergoline
6. Diagnosis of Variant Angina: Ergonovine, methylergometrine.
7. Senile Cerebral Insufficiency and Alzheimer’s dementia: Dihydroergotoxine, a mixture of
dihydro-α-ergocryptine and three similar dihydrogenated peptide ergot alkaloids (ergoloid
mesylates),
Autacoids and Related Drugs

BLOCK 1; PAPER 3; Pharmacology; SEQs; Key

Q.3.A. An adult female is prescribed a 5-HT Antagonist for some ailment. Enumerate Two
important uses of 5-HT Antagonist with one drug example for each condition. (Mark 1)

Answer 3.A.

Uses of 5-HT Antagonist

Any Two of the followings. (0.5 x 2 = 1 Mark)

1. As Antihypertensive: Ketanserin
2. Carcinoid trumor: Ketanserin, cyproheptadine, and phenoxybenzamine
3. Antiemetics: Ondansetron and its congeners
4. Irritable bowel syndrome associated with diarrhea: Alosetron

Autacoids and Related Drugs

BLOCK 1; PAPER 2; Pharmacology; SEQs; Key

Q.3.A. An adult female is prescribed an Ergot Alkaloid for some ailment, develop some
undesirable effects. Enlist the Four important adverse effects of Ergot Alkaloids. (Marks
2)

Answer 3. A.

ANY “FOUR” OF THE FOLLOWINGS: (0.5 x 4 = 2 Marks)

1. Severe prolonged vasoconstriction can result in ischemia and gangrene. Precipitate

Angina and Peripheral vascular disease.
2. Hyperplasia of connective tissue. This fibroplasias may be retroperitoneal, retropleura,
or subendocardial and can cause hydronephrosis or cardiac valvular and conduction
system malfunction.
3. Gastrointestinal effects—gastrointestinal upper upset (nausea, vomiting, diarrhea)
4. Uterine effects—Marked uterine contraction, abortion .
5. CNS effects—Hallucinations resembling psychosis
NSAIDs and Related Drugs

BLOCK 1; Set 3; Pharmacology; SEQs; Key

Q. 3.A. An adult patient is prescribed Colchicine by his physician for the treatment of Gout,
experienced some undesirable effect. Enlist any Five important adverse effects of Colchicine each
from a different system /tissue / site. (Marks 3)
Answer 3.A.
Colchicine: Adverse effects:
Any Five of the followings: (0.5 x 5 = 2.5 Marks):

1 Diarrhea, nausea, vomiting, and abdominal pain.

2 Hepatic necrosis
3 Acute renal failure
4 Disseminated intravascular coagulation
5 Seizures
6 Hair loss
7 Bone marrow depression
8 Peripheral neuritis
9 Myopathy
10 Death

References.
Lippincott’s Illustrated Reviews: Pharmacology 8th ed, Chapter 38, Page 524.
Basic and Clinical Pharmacology Katzung 14th ed, Chapter 36, Page 661
Katzung & Treveor’s Pharmacology, Examination & Board Review, 13th ed Chapter 36, Page 312

NSAIDs and Related Drugs

BLOCK 1; PAPER 2; Pharmacology; SEQs; Key

Q.3.B. Name the syndrome which can be fatal if aspirin is given to children with viral fever.
Name the drug which is preferred as antipyretic in children with viral fever. Also write the
mechanism of action of that drug. (Marks 2)

Answer 3.B. (Marks 2)

 Name the syndrome: Reye’s syndrome. (Mark 0.5)

 Drug preferred as antipyretic in children with viral fever: Acetaminophen (Paracetamol).

(Mark 0.5)
 Mechanism of action of Acetaminophen (Paracetamol) as antipyretic. (Mark 1)
nonselective COX inhibitor, inhibits prostaglandin synthesis in the CNS, leading to
antipyretic and analgesic effects.
NSAIDs and Related Drugs
BLOCK 1; PAPER 3; Pharmacology; SEQs; Key
Q.3.C. An adult male presented in emergency department with overdose toxicity of Aspirin.
Enumerate any five important clinical features of Aspirin overdose toxicity each involving
different system / tissue / site. (Marks 2.5)
Answer 3.C.
Clinical features Aspirin overdose Toxicity:
Any FIVE of the followings: (0.5 x 5 = 2.5 Marks)
 Mild salicylate toxicity is called salicylism and is characterized by

1. Nausea, vomiting,
2. Sweating
3. Marked hyperventilation, respiratory alkalosis
4. Headache, mental confusion,
5. Dizziness, and tinnitus (ringing or roaring in the ears), Deafness
 Moderately severe poisoning.

6. Peripheral vasodilatation with bounding pulses and profuse sweating

 Severe salicylate intoxication:

7. Hypoprothrombinaemia,
8. Hyperglycaemia,
9. Hyperpyrexia,
10. Renal failure,
11. Pulmonary oedema,
12. Shock
13. Cerebral oedema Restlessness, agitation, confusion, delirium, hallucinations,
convulsions, coma,
14. Respiratory and metabolic acidosis, and
15. Vasomotor collapse
16. Dehydration
17. Death from respiratory failure may occur.
 In severe salicylate intoxication death may occur due to:

Hypothermia
Cerebral infarct results from Hypoglycemia
Liver failure
Renal failure
Respiratory failure

 Which of the following is a feature of salicylate toxicity:

Hypothermia
Hypoglycemia
Metabolic alkalosis
Hypoprothrombinaemia
Increase blood pressure
Tachycardia?????
BLOCK 1; PAPER 3; Pharmacology; SEQs; Key

Q. 4. B. A 10 Year old boy accidently ingested several tablets of acetaminophen. What is

the most probable lethal effect in Acetaminophen overdose toxicity? What is the
mechanism of injury in that Lethal effect? In this case what is the antidote and its
mechanism of effectiveness? (Marks 2.5)

Answer 4. B.

Liver toxicity: ------ Hepatic necrosis 0.5

With large doses of acetaminophen, the available glutathione in the liver 1
becomes depleted, and NAPQI (N-acetyl-p-benzoquinoneimine) reacts
with the sulfhydryl groups of hepatic proteins, forming covalent bonds
causing Hepatic necrosis, a very serious and potentially life threatening
condition.
N-acetylcysteine: 1
It contains sulfhydryl groups, acts as a glutathione substitute, to which the
toxic metabolite can bind.

BLOCK 1; PAPER 2; Pharmacology; SEQs; Key

Q. 4. B. What is the use of Allopurinol in cancer chemotherapy? What drug interaction

occur between Allopurinol and 6-mercaptopurine (Marks 2)

Answer 4. B.

Marks
Allopurinol is also used as an adjunct to cancer chemotherapy to slow the 1
formation of uric acid from purines released by the death of large numbers
of neoplastic cells.
6-MP is converted in the liver to the 6-methylmercaptopurine derivative or 1
to thiouric acid (an inactive metabolite).
The latter reaction is catalyzed by xanthine oxidase.
Allopurinol, a Xanthine oxidase inhibitor, interferes with the metabolism
of 6-mercaptopurine, increase the chances of adverse effects by 6-
mercaptopurine.
If allopurinol is used adjunctively in cancer chemotherapy to offset
hyperuricemia, the dosage of Mercaptopurine should be reduced.
BLOCK 1; PAPER 1; Pharmacology; SEQs; Key

Q. 4. B. Which agent is used to counter the methotrexate toxicity. What is the

mechanism of effectiveness of that agent (2.5 Marks)

Answer 4. B.

Agent used to counter the effect of Methotrexate toxicity is leucovorin or folinic acid or
N5-formyl-FH4.
Leucovorin is converted to N5, N10-methylene-FH4 and therefore bypass the inhibited
dihydrofolate reductase
What is the use of Allopurinol in cancer chemotherapy
What drug interaction occur between Allopurinol and 6-mercaptopurine

Allopurinol is also used as an adjunct to cancer chemotherapy to slow the

formation of uric acid from purines released by the death of large numbers
of neoplastic cells.
6-MP is converted in the liver to the 6-methylmercaptopurine derivative or
to thiouric acid (an inactive metabolite).
The latter reaction is catalyzed by xanthine oxidase.
Allopurinol, a Xanthine oxidase inhibitor, interferes with the metabolism
of 6-mercaptopurine, increase the chances of adverse effects by 6-
mercaptopurine.
If allopurinol is used adjunctively in cancer chemotherapy to offset
hyperuricemia, the dosage of Mercaptopurine should be reduced.
BLOCK 1; PAPER 3; Pharmacology; SEQs; Key

Q. 4. B. Mention the differences between the effects on gastrointestinal and cardiovascular

systems of non-selective cyclooxygenase inhibitors and selective cyclooxygenase-2 inhibitors.
(Marks 2.5)

Answer 4. B.

Difference in the effects of Non-Selective and Selective COX-2 inhibitors on CVS and GIT

1. GIT:
Non-selective COX inhibitors inhibit PGI2 (PGI2 inhibits gastric acid secretion), PGE2 and
PGF2α (PGE2 and PGF2α stimulate synthesis of protective mucus).
Thus reduce level of these prostaglandins resulting in increased gastric acid secretion,
diminished mucus protection and increased risk for epigastric distress, Peptic ulcer and
bleeding.
Selective COX-2 inhibitors have reduced risk of these Gastrointestinal adverse effects

2. CVS:
Non-selective COX inhibitors such as aspirin inhibits TXA2 and thus inhibits platelet
aggregation and vasoconstriction.
Benefit of antiplatelet effect of aspirin is that it reduces the risk of cardiovascular events but
disadvantage is that it increases the risk of bleeding.
Selective COX-2 inhibitors have greater inhibitory effect on endothelial prostacyclin (PGI2)
formation than effect on platelet TXA2 formation, thus stimulates platelet aggregation and
vasoconstriction.
Selective COX-2 inhibitors thus increases the risk of cardiovascular events including Myocardial
infarction and Stroke.