Knowing how drugs works make these tasks easier to handle, thus enhancing drug therapy.

B.

History
o o o

Introduction to Nursing Pharmacology

A. Introduction to Drugs
The human body works through a complicated series of chemical reactions and processes. Drugs are chemicals that are introduce into the body to cause some sort of change.

Early drug plants, animals & minerals 2700 BC earliest recorded drug use found in Middle East & China 1550 BC Egyptians created Ebers Medical Papyrus

Castor oil laxative Opium pain Moldy bread wounds & bruises

Drugs will undergo process with in the body which involve breaking and eliminating the drugs, in turn affect the bodys complex series of chemical reactions.

Galen (131-201 AD) Roman physician; initiated common use of prescriptions 1240 AD introduction of apothecary (pharmacy) system (Arab doctors)

Understanding how drugs act on the body to cause changes and applying that knowledge in the clinical setting are important aspects of nursing practice. The nurse is in a unique position regarding drug therapy because nursing responsibilities include the following:

1st set of drug standards & measurements (grains, drams, minims), currently being phased out

15th century apothecary shops owned by barber, surgeons, physicians, independent merchants 18th century small pox vaccine (by Eward Jenner, British Doctor)

Administering drugs Assessing drug effects Intervening to make the drug regimen more tolerable Providing patient teaching about drugs and drug regimen. Monitoring the overall patient care plan to prevent medication error

Digitalis from foxglove plant for strengthening & slowing of heartbeat Vitamin C from fruits

19th century morphine & codeine extract from opium

Introduction of atropine & iodine

Amyl nitrite used to relieve anginal pain Discovery of anesthetics (ether, nitrous oxide)

what the body does to the drug deals with beneficial effects of the drugs (medicines) source of drugs

Early 20th century aspirin from salicylic acid - Introduction of Phenobarbital, insulin, sulforamides Mid-20th century

ex: penicillin from penicillium (fungi) 3. Pharmacotherapeutics study of drugs used in the diagnosis, prevention, suppression, & treatment of diseases 4. Pharmacognonsy study of drugs in their original unaltered state; origin of drugs 5. Toxicology study of biologic toxins: study of poison & its effects deals with deleterious effects of physical & chemical agents (including drugs) in human Nurses deal with Pharmacotherapeutics, or Clinical Pharmacology, the branch of pharmacology that uses drugs to treat, prevent, and diagnose diseases.

1940 Discovery antibiotics (penicilline, tetracycline,streptomycin), antihistamines, cortisone 1950 Discovery antipsychotic drug, antihypertensives, oral contraceptives, polio vaccine

C.
-

Pharmacology

Is the study of the biological effects of chemicals

It is the scientific study of the origin, nature, chemistry, effects and uses of drugs. In clinical practice, health care providers focus on how chemicals act on living organisms.

Clinical Pharmacology

Addresses two key concerns The drugs effects on the body The bodys response to the drug

Subdivisions of Pharmacology
1. Pharmacodynamics study of the biochemical & physiological effects of drugs & mechanisms of action o what the drug does to the body 2. Pharmacokinetics deals with the absorption, distribution, biotransformation & excretion of drugs

Because drug can have many effects the nurse must know which ones may occur when a particular drug is administered.

Effects of the Drug

1. Therapeutic Effect

- The primary effect intended, that is the reason the drug is prescribed. - Also called desired effect. 2. Side Effect - The effect of the drug that is not intended. - Also called secondary effect. 3. Drug Allergy - The immunologic reaction to the drug. 4. Anaphylactic Reaction - A severe allergic reaction which usually occurs immediately following administration of the drug. 5. Drug Tolerance - A decreased physiologic response to the repeated administration of a drug or chemically related substance. Excessive increase in the dosage is required in order to maintain the desired therapeutic effect. 6. Drug Interaction - Effects of one drug are modified by the prior or concurrent administration of another drug, thereby increases or decreases the pharmacological action. Drug Antagonism the conjoint effects of two drugs is less than the drugs acting separately.

Summation The combined effect of two drugs produces a result that equals the sum of the individual effect of each agent. Synergism The combined effects of drugs is greater than the sum of each individual agent acting independently. Potentiation The concurrent administration of two drugs in which one increases the effect of the other drug.

Therapeutic Effects of Drugs

1. Palliative Relieves the symptoms of a disease but not affect the disease itself. 2. 3. Ex. Analgesic for pain Curative Treats the disease condition Ex. Antibiotic for infection Supportive Sustains body functions until other treatment of the bodys response can take over. Ex Mannitol to reduce/ICP in a client for surgery due to brain tumor. 4. Substitutive Replaces body fluids or substances.

5. 6. -

Ex. insulin injection for diabetes mellitus Chemotherapeutic

1. Plants roots, bark, sap, leaves, flowers, seeds of medicinal plants

Destroys malignant cells Ex. Cyclophophamide for cancer of the prostate gland. Restorative Returns the body to health.

D.

Drug Nomenclature
1. CHEMICAL NAME atomic/molecular structure of drug Ex. acetylsalicylic acid

digitalis (use as a heart stimulant) from wildflower, purple foxglove, dried leaves of plant active principles of plants o alkaloids alkaline in reaction, bitter in taste, powerful in physiologic activity o atropine & scopolamine o morphine sulfate, cocaine, quinine, nicotine, caffeine o procaine o glycosides digitalis o resin soluble in alcohol; example colonic irritant found in laxative cascara o gums used in bulk-type laxatives: some used in certain skin preparations for their soothing relief o oils castor oil, oil of wintergreen

2. GENERIC NAME/NON-PROPERTY NAME original designation given to the drug when the drug company applies for approval patents

universally accepted & not capitalized; before drug becomes official, used in all countries protected by law; not capitalized ex. aspirin

3. TRADE/BRAND/PROPRIETY NAME name given by the drug company that developed it

followed by the symbol R or TM, 1st letter is capitalized ex. Aspilet

2. Animal Products from organs, organ secretion or organ cells o Used to replace human chemical not produces because of disease or genetic problems o Thyroid drugs & growth hormones preparations from animal thyroid & hypothalamus tissue (many of these preparations are now created synthetically safer & purer) o Insulin from pancreas of animals (hog, cattle, sheep): thru genetic engineering cld produce human insulin by altering E. coli bacteria making it a better product without impurities that come with animal products 3. Inorganic Compounds from free elements, both metallic & non-metallic usually in form of acids bases, salts found in food

E.

Sources of Drugs

Dilute HCI control/prevent indigestion

Calcium, aluminum, fluoride, iron, gold, potassium more potent, more stable, less toxic steroids arthritis & other diseases sulfonamides/chemotherapeutic agents kill microorganism slow their growth meperidine HCI (Demerol)

4. Synthetic Sources many drugs developed synthetically after chemical in plants, animals, or environment have been screened for signs of therapeutic activity 4.1 Genetic engineering alter bacteria to produce chemicals that are therapeutic and effective.

CNS (+)/(-) actions of neural pathways & centers; ex. Phenobarbital ANS governs several bodily functions so that drugs that affect ANS will at the same time affect other systems functions; ex. scopolamine GIT acts on muscular & glandular tissues; ex. loperamide Respiratory System act on resp. tract, tissues, cough center, suppress, relax, liquefy & stimulate depth & rate of respiration; salbutamol Urinary system act on kidney & urinary tract; ex. furosomide Circulatory system act on heart, blood vessels, blood; ex. Metroprolol

Reordering of genetic information enables scientists to develop bacteria that produce insulin for human.

4.2 Chemical alterations Scientists alter chemical with proven therapeutic effectiveness to make it better.

G.
1. -

Kinds of Drugs
Prescription Drugs Also known as legend drugs

Sometimes a small change in a chemicals structure can make that chemical more useful as a drug, more potent, more stable, less toxic.

F.

Drug Classification

1. By Action o Ant- infective antiseptics, disinfectants, sterilants o Antimicrobials, metabolic, diagnostic materials, vitamins & minerals o Vaccine & serums, antifungals, antihistamines, antineoplastics, antacids 2. By Body System

Can be dispensed if with prescription order; with specific name of drug & dosage regimen to be used by patient. 2. Non-Prescription Drugs Also known as Over the Counter Drugs can be dispensed without prescription order for self-treatment of variety of complaints

Vitamin supplements, cold/cough remedies, analgesics, antacids, herbal products Cautions in use of OTC drugs: 3. 4. Delay in professional diagnosis & treatment of serious/potentially serious condition may occur Symptoms may be masked making the diagnosis more complicated Clients health care provider/pharmacist should be consulted before OTC preparations are taken Labels/instructions should be followed carefully Ingredients in OTC drug may interact with prescribed drug Inactive ingredients may result in adverse reactions Potential for overdose Multiple medication users are at risk as more medications are added to therapy regimen Interactions of medications are potentially dangerous Investigational drug new drugs undergoing clinical trails Illicit/street drug used/distributed illegally for non-medical purposes to alter mood of feeling

Drugs and the Body (Pharmacodynamics)

Pharmacodynamics
- The study of the drug mechanisms that produce biochemical or physiologic changes in the body. - What happens to the body in response to the drug. - Interactions between chemical components of living systems & foreign chemicals including drugs that enter these systems.

1. Agonist Drugs interact directly with receptor sites to cause the same activity that natural chemicals would cause at that site. Ex. Insulin 2. Antagonist A drug has an affinity for a receptor but displays little or no intrinsic activity. A. Competitive antagonist o Competes with the agonist for receptor sites B. Non-competitive antagonist o Binds to receptor sites and blocks the effects of the agonist B. Drug Enzyme Interactions o Interferes with enzyme systems that act as catalyst from various chemical reactions. o Enzyme systems: Cascade effect; one enzyme activating another, causing cellular reaction. If single step in one of enzyme system is blocked, normal cell function is disrupted o Ex. ACE inhibitors, inhibiting the release of angiotensin converting enzyme in the lungs, preventing the conversion of Angiotensin I to Angiotensin II which is a powerful vasocontrictor, preventing an increase in blood pressure. C. Selective Toxicity o All chemotherapeutic agent would act only on 1 enzyme system needed for life of a pathogen or neoplastic cell & will nor affect

Drug Actions:
a. To replace or act as substitutes for missing chemicals. b. To increase or stimulate certain cellular activities. c. To depress or slow cellular activities. d. To interfere with the functioning of foreign cells, such as invading microorganisms or neoplasm.

Theories of Drug Actions

A. Drug Receptors Interaction o Receptor sites location on a cell surface where certain molecules such as enzymes, hormones, drugs attach to interact with cell component. o Receptor sites react with certain chemicals to cause an effect within the cell. o lock and key theory o Drug action may be:

healthy cells. o Ex. Penicillin

Classifications of Drug Action (in terms of speed of action)

a. Rapid o few seconds to minutes. o intravenous, sub-lingual, inhalation b. Intermediate o 1-2 hours after administration o intramuscular, subcutaneous c. Delayed/Slowed o Several hours after administration o oral and rectal

Parameters of Drug Action

Parameters notable characteristics a. Onset of action o Latent period, interval between time the drug is administered and 1st sign of its effect. b. Duration of action o Period from onset until drug effect is no longer seen. o Length of time the drug exerts pharmacologic effect. c. Peak of action o drug reaches its highest blood / plasma concentration d. Termination of action o point from onset at which drug effect is no longer seen

Drugs and the Body (Pharmacokinetics)

Drugs and the Body I. Pharmacokinetics
- The term kinetics refers to movement. - Pharmacokinetics deals with a drugs actions as it moves through the body - What happens to the drug when it enters the body. - Involves the study of the following: o Absorption o Distribution o Metabolism/Biotransformation o Excretion

A. Cell Absorption - Drugs can be absorbed into cells through various processes 1. Passive Absorption (diffusion) o Movement of drug particles from an area of higher concentration to an area lower concentration. o No energy required: occurs when smaller molecules diffuse across membrane o Stops when drug concentration on both sides of the membrane is equal o Major process through which drugs are absorbed into the body o Oral drugs use passive transport

A. Absorption
- In order to reach reactive tissues, a drug must first make its way into the circulation. - Absorption refers to what happens to a drug from the time it is introduced to the body until it reaches the circulating fluids. - Drugs can be absorbed from many different areas in the body: o GIT o Mucous membranes o Through the skin o Through the lungs o Through the muscle o Through subcutaneous tissues

2. Active Absorption o Movement of drugs particles from an area of low concentration to an area of high concentration. o Energy is required o Used to absorb electrolytes (Ex. sodium, potassium) 3. Pinocytosis o Cells engulf the drug to carry it across the membrane. o Transport fat-soluble vitamins (vitamin A,D,E,K) B. Factors Affecting Drug Absorption: 1. Blood Flow 2. Pain 3. Stress 4. Foods (High fat and solid foods) 5. Exercise 6. Solubility 7. Nature of the absorbing surface

8. pH 9. Concentration 10. Dosage form c. Oral Administration of Drug

1. Free/unbound portion (+) pharmacologic response

B. Distribution
- Process by which drug becomes available to body fluids & tissues - The ways a drug is transported from the site of absorption to the site of action (transportation) - Happens in the circulation (circulatory system) A. Factors Affecting Distribution 1. Size of the organ 2. Blood flows drug is quickly distributed to organs with large supply of blood (heart, liver, kidneys) distribution to other internal organs, skin, fat, muscle is slower 3. Solubility Lipid-soluble or non-lipid-soluble Lipid-soluble drugs can cross the blood-brain barrier & enter the brain 4. Protein binding B. Protein Binding - as drug travels through the body, it comes in contract with proteins (albumin) - the drug can remain free or bind to protein - Portion of drug bound to protein is inactive, no therapeutic affect

2. Highly protein bound drug 89% of drug is bound to protein diazepam, piroxicam, valproic acid

3. Moderately high protein bound drugs 61-89% bound protein Erythromycin, phenytoin

4. Moderately protein bound drugs 30-60% bound to protein aspirin, lidocaine, pindolol, theophyline 5. Low protein-bound drugs 30% bound to protein amikacin, amoxicillin

C. Metabolism/Biotransformation
- Also called detoxification. - Refers to the bodys ability to change a drug from its dosage form to a more water soluble form that can be excreted - A sequence of chemical events that change a drug to a less active form after it enters the body

- Permits the body to inactivate a potent drug before it accumulates & produces toxic effects - Drugs can be metabolized several ways: o Most drugs metabolized into inactive metabolites (products of metabolism), which are then excreted o Other drugs converted to active metabolites capable of exerting their own pharmacologic action May undergo further metabolism or may be excreted from body unchanged Pro-drugs some drugs administered as inactive drugs which dont become active until theyre metabolized A. Sites of Metabolism 1. Liver Through the drug metabolizing enzymes (microsomal enzymes, non-microsomal enzymes) 1st pass effect/hepatic 1st pass some drugs do not directly go into circulation but pass thru intestinal lumen to liver via portal vein 2. Plasma 3. Kidneys 4. Membranes B. Factors Affecting Drug Metabolism 1. Diseases Liver cirrhosis and heart failure 2. Genetics People metabolize drugs rapidly, other more slowly. 3. Environment Smoking and stressful environment 4. Age Infants have immature livers that reduce the rate of metabolism.

Elderly patients experience a decline in liver size, blood flow and enzyme production that also slows metabolism 5. Nutrition Liver enzymes involved in metabolism rely on adequate amounts of amino acids, lipids, vitamins and carbohydrates. 6. Insufficient amounts of major body hormones Decrease amounts of insulin and adrenal corticosteroids can reduce metabolism of drugs in the liver.

D. Excretion
- Removal of drug from the body - Is the process by which drugs are eliminated from the body - Drug is changed into inactive form & excreted by the body A. Sites of Excretion 1. Kidney Free/unbound/water soluble drugs are filtered in kidneys Protein bound drug cannot be filtered in kidney 2. Lungs, exocrine (sweat, salivary, mammary) glands, skin, intestinal tract B. Factors Affecting Excretion 1. Urine pH Normal urine pH is 4 5.8 Acidic urine promotes elimination of weak base drugs Ex. Cranberry juice decreases urine pH Alkaline urine promotes elimination of weak acid drugs Ex. Nabicarbonate increases urine pH, use to eliminate as excess aspirin in the system due to overdose

2. Glomerular Filtration Rate The amount of glomerular filtrate in the glomerulus Glomerular Filtration Passive Reabsorption Active Secretion Nephron Glomerulus Proximal Tubule Bladder When there is a decrease in glomerular filtration rate drug excretion are slowed/impaired. Can result to drug accumulation

3. Half-life Time it takes for one half of drug concentration to be eliminated. Short half-life 4-8 hrs: given several times a day (ex. penicillin G) Long half-life More than 12 hrs: given 2x or 1x a day (ex. digoxin)

Medications and Calculations

A.
1.

meter (m, M) for length. Apothecary System Common system used by most practitioner s before the

Systems of Measurements
There are 3 systems of measurements

universal acceptance of the International Metric System Metric system

o o 2.

Was developed in the late 18th century The internationally accepted system of measure Was replaced by the metric system Dates back to the middle ages and had been used in England since the 17thcentury.

labels. -

Now all pharmaceuticals are manufactured using the metric

system, and the apothecary system is no longer included on any drug

Apothecary system
o o

All medication should be prescribed and calculated using

metric measures, but occasionally the use of the fluid ounce and grains is found. For those rare circumstances, nurses should have a general understanding of the apothecary system. The apothecary system uses Roman numerals instead of

3.

Household system
o

Commonly used in community and home settings.

Metric System The metric system is a decimal system based on the

Arabic numbers to express the quantity. The Roman numeral is placed after the symbol or abbreviation for the unit of measure.

power of 10. The basic units of measure are: gram (g, gm, G, Gm) for weight; liter (l, L) for volume; and

A. Ex. gr x stands for 10 grains.

In the apothecary system: the unit of weight is the grain (gr)

 the units of fluid volume are the ounce (fluidounce), the dram (fluidram), and the minim (min). Household System

Pharmaceutical companies usually label their drugs with the

brand name of the drug in large letters and the generic name in smaller letters. The dose per tablet, capsule, or liquid (for oral and injectable

Uses household containers such as spoons, cups and glasses

doses) is printed on the drug label. 1. Method 1: Basic Formula (BF)

as measuring devices. Not as accurate as metric system because of the lack of The basic formula is easy to recall and is most frequently used in calculating drug dosages.

standardization.

B. Methods for Calculation

DxV=A The four general methods for the calculation of drug dose are H D = desired dose (drug dose ordered by the health care the (1) basic formula, (2) ration and proportion, (3) fractional equation, (4) and dimensional analysis. These methods are used to calculate oral and injectable drug doses. For drugs that require individualized dosing, calculation by H = on hand dose (drug dose on label of container) V = vehicle (drug form in which the drug comes (tablet, capsule, liquid) A = the amount calculated to be given to the client provider) body weight (BW) or by body surface area (BSA) may be necessary. Before calculating drug doses, all units of measure must be

converted to a single system. Interpreting Oral and Injectable drug Labels

2. Method 2: Ratio and Proportion The ratio and proportion method is the oldest method

H = dosage on hand

V = vehicle D = desired dosage X = unknown

currently used in the calculation of drug dosages.

H -

V ::

D = desired dose (drug dose ordered by the health care 4.

provider) H = on hand dose (drug dose on label of container) V = vehicle (drug form in which the drug comes (tablet, capsule, liquid) x = the amount calculated to be given to the client 3. Method 3: Fractional Equation The fractional equation method is similar to ratio and

Cross multiply and solve for x Method 4: Dimensional Analysis Dimensional analysis is a calculation method known as units

and conversions. The advantage of DA is that it decreases a number of steps required to calculate a drug dosage. It is set up as one equation. Identify the unit/form (tablet, capsule, ml) of the drug to be calculated. If the drug comes in tablet, then tablet = (equal sign) The known dose and unit/form from the drug label follows the equal sign. H=D Order: amoxicillin 500 mg V x On the drug label: 250 mg per 1 capsule

proportion except it is written as a fraction.

Capsule =

1cap 250 mg

Drug dose x body weight = clients dose per day III. Follow the basic formula, ratio and proportion, fractional equation, or dimensional analysis method to calculate the drug dosage.
6.

The mg (250 mg) is the denominator and it must match the next numerator, which is 500 mg (desired dose or order). The NEXT denominator would be 1 or blank. Capsule = 1cap 250 mg X 500 mg = 1 -

Method 6 : Body surface area (BSA) The body surface area (BSA) method is considered the most

accurate way to calculate the drug dose for infants, children, older adults, andclients who are on antineoplastic agents or whose BW is low. The BSA, in square meters, is determined by where the persons height and weight intersect the nomogram scale. To calculate the drug dosage the BSA method, multiply the drug dose ordered by number of square meters. 100 mg x 1.8 m2 (BSA) = 180 mg/day

Cancel out the mg, 250 and 500. What remains is the capsule and 2. Answer is 2 capsules

5.

Method 5: Body Weight The body weight method of calculation allows for the

Other computation: 1. Clark's Rule for Infants or Children: Clarks rule is based upon the weight of the child. To determine the proper dosage for children, divide childs weight in pounds by 150 to get the correct fraction of adult dose. Example: For a 50 pound child give 50/150 (or 1/3) of the adult dose. Therefore, if the adult dose is 30 drops taken 3 times per day, the childs dose will be 10 drops taken 3 times per day (not 30 drops taken 1 time per day!)

steps:

individualization of the drug dose and involves the following three

I. Convert pounds to kilograms if necessary (lb / 2.2 = kg) II. Determine drug dose per BW by multiplying as follows:

(Weight in pounds x (Adult dose) 150

2. Fried's Rule for Infants and Children up to 1 to 2 Years:

(Age in Months) x (Adult Dose) 150

3. Young's Rule for Children from 1 year to 12 Years: Youngs rule is based upon the age of the child, regardless of its weight. It is a rule of the thumb method for calculating the dose of medicine to be administered to a child. The childs age divided by age plus 12 represents the fraction of the adult dose suitable for the child.

(Age in Years) x (Adult Dose) Age + 12

9. Tetracyclines Bacteria one-celled organisms visible only through a microscope. Bacteria live all around us and within us. The air is filled with bacteria, and they have even entered outer space in spacecraft. Bacteria live in the deepest parts of the ocean and deep within Earth. They are in the soil, in our food, and on plants and animals. Even our bodies are home to many different kinds of bacteria. Our lives are closely intertwined with theirs, and the health of our planet depends very much on their activities. Bacteria can invade the body the human body through many routes, ex. Respiratory, gastrointestinal and skin. The human immune response is activated when bacteria invade. Many of the sign s and symptoms of an infection are related to the immune response as the body tries to rid itself of the foreign cells. Ex. Fever, lethargy, classic sign s of inflammation (redness, swelling, heat and pain) To determine which antibiotic will effectively treat a specific infection, the causative agent must be identified. Culture and sensitivity testing is performed.

Antibiotics
Antibiotics Are chemicals that inhibit a specific bacteria

Used to treat a wide variety of systemic and topical infections. Antibacterial

Antibiotics are made in three ways: 1. By living microorganisms 2. By synthetic manufacture 3. Through genetic engineering Major classes: 1. 2. 3. 4. 5. 6. 7. 8. Aminoglycosides Cephalosporins Fluoroquinolones Lincosamides Macrolides Monobactams Penicillins Sulfonamides

Types of Bacteria

1. Gram-positive Bacteria are those whose cell wall retains a stain, known as Gram stain. They are commonly associated with infection of the respiratory tract. Ex Streptococcus pneumonia. 2. Gram-negative Bacteria are those whose cell walls loose a stain. Frequently related with infections of the genitourinary or GI tract. Ex. Escherichia coli. 3. Aerobic bacteria depends on oxygen for survival. 4. Anaerobic bacteria does not depend on oxygen.

Pharmacokinetics Because aminoglycosides are absorbed poorly from the GI tract, theyre usually given parenterally. After IV or IM administration, absorption is rapid and complete. Aminoglycosides are distributed widely in extracellular fluid. They readily cross the placental barrier but dont cross the blood brain barrier. Aminoglcosides arent metabolized. Theyre excreted primarily by the kidneys.

1. Aminoglycosides Aminoglycosides are bactericidal. Theyre effective against:

Pharmacodynamics Bactericidal

Gram-negative bacilli Some aerobic gram-positive bacteria

Binds to the bacterias 30S subunit in the ribosome inhibiting protein synthesis. Aminoglycosides currently in use include: 1. 2. 3. 4. 5. 6. Amikacin sulfate Gentamicin sulfate Kanamycin sulfate Neomycin sulfate Streptomycin sulfate Tobramycin Pharmacotherapeutics

Infections caused by gram-neagtive bacilli Nosocomial infections such as peritonitis and pneumonia UTI CNS infections

Adverse Reactions

Peripheral nerve toxicity Ototoxicity Renal toxicity

Cefazolin sodium Cephalexin hydrochloride Cephradine

Oral administration causes:

1. Second Generation Cephalosporins

Nausea Vomiting Diarrhea

Effective against gram-positive bacteria Haemophilus influenza, Enterobacter aerogenes and Neisseria species

Some of the Second Generation Cephalosporins 1. Cephalosporins

The cephalosporins were first introduce in the 1960s. These drugs are similar to the penicllins in structure and in activity. Over time, four generations of cephalosporins have been introduced, each group with its own spectrum of activity. 1. First Generation Cephalosporins

Cefaclor Cefrozil Ceftibuten Cefoxitin Cefuroxime axetil Cefuroxime Sodium

1. Third Generation Cephalosporins

Effective against gram-positive bacteria Also effective against some gram-negative bacteria such as Proteus mirabilis, E. Coli, and Klebsiella pneumoniae

Effective against gram negative bacilli, as Serratia marcescens

Some of the Third Generation Cephalosporins

Some of the First Generation Cephalosporins

Cefadroxil

Cefdinir Cefoperazone sodium Cefotaxime sodium

Cefpodoxine proxetil Ceftazidine Ceftizoxime sodium Ceftriaxone sodium

Adverse Reactions:

Confusion Seizures Nausea and vomiting Diarrhea

1. Fourth Generation cephalosporins

Effective against cephalosporins resistant-staphylococci and P. Aeruginosa

1. Penicillin

Some of the Fourth Generation Cephalosporins

Cefditoren pivoxil Cefepine hydrochloride

Penicillin remain one of the most important and useful antibacterial drugs. Discovered by Sir Alexander Flemming in the 1920s The Penicillin can be divided into four groups: 1. Natural Penicillin

Pharmacokinetics Administered parenterally, because they arent absorbed from the GI tract.

Pharmacodynamics Inhibit cell-wall synthesis by binding to the bacterial Penicillin Binding Protein enzy,es located on the cell membrane.

Penicillin G benzathine Penicillin G potassium Penicillin G procaine Penicillin G sodium Penicillin V potassium

1. Penicillinase Resistant Penicillin

Dicloxacillin sodium

Nafacillin sodium Oxacillin sodium

Pharmacodynamics Bactericidal

1. Aminopenicillins

Ampicillin

Binds to an enzyme outside the bacterial cell wall known as penicillin-binding proteins which is involved in cell wall synthesis and cell division. Interference with these processes inhibits cell wall synthesis, causing rapid destruction of the cell.

1. Extended Spectrum Penicillin Pharmacotherapeutics

Amoxicillin No other class of antibacterial drugs provides as wide spectrum of antimicrobial activity as the penicillin

Pharmacokinetics After oral administration, penicillin are absorbed mainly in the duodenum and upper jejunum of the small intestine.

Gram-positive Gram-negative Anaerobic organisms

Adverse Reactions Factors affecting absorption of penicillin

Types of penicillin used pH of the patients stomach and intestine presence of food in the GI tract (penicillin should be given on an empty stomach, 1 hour before meals or 2 hours after meal).

Hypersensitivity reactions are the major reactions to penicillin Anaphylactic reactions Skin rashes Tongue inflammation Nausea and Vomiting Diarrhea

1. Fluoroquinilones

Bacteriostatic

Fluoroquinilones interrupt DNA synthesis during bacterial replication by inhibiting DNA gyrase, an essential enzyme of replicating DNA. As a result, the bacteria cant reproduce.

Structurally similar synthetic antibacterial drugs. They;re primarily administered to treat UTIs, upperrespiratory tract infections, pneumonia and gonorrhoea Pharmacotherapeutics Fluorquinolones can be used to treat a wide variety of UTIs.

Examples of fluoroquinilones:

Cifrofloxacin Gemifloxacin Levofloxacin Moxifloxacin Norfloxacin Ofloxacin

Pharmacokinetics After oral administration, fluoroquinilones are absorbed well. They arent highly protein bound, minimally metabolized in the liver, and are excreted primarily in the urine

Ciprofloxacin is used to treat lower respiratory tract infections, infectious diarrhea and skin, bone and joint infection. Gemifloxacin is used to treat bronchitis, community acquired pneumonia, UTIs, and gynaecologic infections. Levofloxacin is indicated for treatment of lower respiratory tract infections, skin infections and UTIs. Moxifloxacin is used to treat bacterial sinusitis and mild to moderate community acquired pneumonia. Norfloxacin is used to treat UTIs and prostatitis Ofloxacin is used to treat selected sexually transmitted diseases, lower respiratory tract infection, skin infections and prostatitis

Pharmacodynamics

Adverse Reactions

Fluoriquinilones are well tolerated by most patients, but some adverse effects may occur, including:

Tetracyclines are excreted primarily by the kidneys. Doxycyclline is also excreted in feces. Minocycline undergoes enterhepatic recirculation.

Dizziness Nausea and vomiting Diarrhea Abdominal pain

Pharmacodynamics All tetracyclines are primarily bacteriostatic, meaning they inhibit the growth or multiplication of bacteria. They penetrate the bacterial cell by an energy-dependent process. Within the cell, they bind primarily to a subunit of the ribosome, inhibiting the protein synthesis required for maintaining the bacterial cell. The long acting compounds doxycycline and minocycline provide more action against various organisms than other tetracyclines

1. Tetracycline

Tetracyclines are broad-spectrum antibacterial drugs. They may be classified as: Intermediate-acting compounds, such as demeclocycline hydrochloride Long-acting compounds, such as doxycycline hyclate and minocycline hydrochloride

Pharmacotherapeutics Pharmacokinetics Tetracyclines are absorbed from the duodenum when taken orally. Theyre distributed widely into the body tsiisues and fluids and concentrated bile. Tetracyclines provide a broad spectrum of activity, which means they cover a wide range of organisms, including:

Gram-positive and gram-negative aerobic and anaerobic bacteria Spirochetes Mycoplasmas Rickettsiae Chlamydiae Some protozoa

Rocky Mountain spotted fever Q fever Lyme disease

Because erythromycin is acid sensitive, it must be buffered or have an enteric coating to prevent destruction by gastric acid. Erythromycin is absorbed in the duodenum. Its distributed to most tissues and body fluids except, in most cases, cerebrospinal fluid. However, as a class, macrolides can enter the CSF when menenges are inflamed. Erythromycin is metabolized by the liver and excreted in bile in high concentrations; small amounts are excreted in urine. It also crosses the placental barrier and is secreted in breast milk.

1. Macrolides

Macrolides are used to treat a number of common infections. They include erythromycin and its derivatives, such as:

Erythromycin estolate Erythromycin ethylsuccinate Erythromycin glucepate Erythromycin lactobionate Erythromycin stearate

Pharmacodynamics

Macrolides inhibit RNA-dependent protein synthesis by acting on a small portion of the ribosome.

Other macrolides include:

Azithromycin Clarithromycin Dirithromycin

Pharmacotherapeutics

Pharmacokinetics

Erythromycin has a range of therapeutic uses: It provides a broad spectrum of antimicrobial activity against gram-positive and gram-negative bacteria, including Mycobacterium, Treponema, Mycoplasma, and Chlamydia.

Its effective against pneumococci and group A streptococci. Staphylococcis aureus is sensitive to erythromycin; however, resistant strains may appear during therapy. Its drug of choice for treating Mycoplasma pneumonia infections as well as pneumonia caused by Legionella pneumophila.

Adverse Reactions

Although macrolides produces few adverse effects, they may produce: o Epigastric distress o Nausea and vomiting o Diarrhea o Rashes o Fever o Eosinophilia (an increase in the number of eosinophils, a type of WBC) o Anaphylaxis

Drugs Affecting the Cardiovascular System

Drugs Affecting the Cardiovascular System The Heart 1. I. Introduction to the Cardiovascular system Circulatory System, or cardiovascular system, in humans, the combines the function of the 3 major components of the body. 1. Heart 2. Blood Vessels 3. Blood

5. when foreign substances or organisms invade the body, the circulatory system swiftly conveys disease-fighting elements of the immune system, such as white blood cells and antibodies, to regions under attack 6. in the case of injury or bleeding, the circulatory system sends clotting cells and proteins to the affected site, which quickly stop bleeding and promote healing.

The human heart is a hollow, pear-shaped organ about the size of a fist. The heart is made of muscle that rhythmically contracts, or beats, pumping blood throughout the body.

Structure of the Heart 1. a. Chambers of the Heart

1. A. Functions of the Cardiovascular System 1. transport oxygen and nutrients to organs and tissues throughout the body 2. carry away waste products. 3. increases the flow of blood to meet increased energy demands during exercise 4. regulates body temperature

The heart has four chambers. The upper two are the right and left atria. The lower two are the right and left ventricles. The atria are the receiving chambers of the heart, receiving blood flowing back to the heart. The ventricles are the chambers of the heart that pump the blood out of the heart.

1. b.
o

The Heart Valves The valves of the heart are located within the chambers of the heart and are critical to the proper flow of blood through the heart. Tricuspid Valve - between the right atrium and right ventricle Pulmonary Valve - between the right ventricle and the pulmonary artery Mitral Valve - between the left atrium and left ventricle Aortic Valve - between the left ventricle and the aorta

The Cardiac Cycle Although the right and left halves of the heart are separate, they both contract in unison, producing a single heartbeat. The sequence of events from the beginning of one heartbeat to the beginning of the next is called the cardiac cycle. The cardiac cycle is a two step process which includes: Diastole resting period when the veins carry blood back to the heart Systole contraction period when the heart pumps blood out to the arteries for distribution to the body Deoxygenated blood is carried by the veins to the right side of the heart, which directs the blood to lungs where it takes on oxygen. Oxygenated blood form the lungs circulate circulates to the left side of the heart to be pumped out to every cell in the body through the arteries

o o o o

1. Septum divides the heart to left and right 4. Layers of the Heart
o o o

Pericardium (Outer layer) Myocardium (Muscular layer) Endocardium (Inner layer) Coronary Arteries

1. e.
o

The heart is nourished not by the blood passing through its chambers but by a specialized network of blood vessels. Known as the coronary arteries, these blood vessels encircle the heart like a crown, supplying the cardiac muscle with blood.

Conduction System of the Heart Each cycle of cardiac contraction and relaxation is controlled by impulses that arise spontaneously in certain pacemakers cells.

 These continuous, rhythmic contractions are controlled by the heart itself; the brain does not stimulate the heart to beat. Impulses:

The Blood vital fluid found in humans that provides important nourishment to all body organs and tissues and carries away waste materials. The Composition of the Blood 1. The Plasma (Fluid) makes up 55% of the blood volume. Blood Plasma :Blood Plasma 97% Water Other 3% -Antibodies and Proteins Nutrients and Wastes 2. The Solids (Cells) make up 45% of the blood volume. o Red Blood Cells -Carry oxygen, Contain Hemoglobin o White Blood Cells -Attack bacteria & other invaders o Platelets -Control the blood clotting process Drugs Affecting Blood Pressure The cardiovascular system is a closed of blood vessels that is responsible for delivering oxygenated blood to the tissue and removing waste products from the tissue. The blood in this system flows from areas of higher pressure to areas of lower pressure. The maintenance of this pressure system is controlled by specific areas of the brain and various hormones.
o o o

Sinoatrial node Atrial bundles Atrioventricular node Bundle of His Bundle branches Purkinje fibers

The Blood Vessels any of the veins, arteries, and capillaries that transport blood through the body. 1. Arteries
o o

Carries oxygen rich blood away from the Heart for distribution in the body. The Aorta is the largest artery

2. Veins Carries oxygen poor blood towards the Heart and into the lungs for reoxygenation. o The Vena Cava is the largest vein 3. Capillaries o Known as the Distribution Pipes
o

Helping the patient to maintain the blood pressure within normal limits is the goal when drug therapy is instituted. Blood Pressure-pressure of circulating blood against the walls of the arteries Blood Pressure Control The pressure in the cardiovascular system is determined by three elements:

If the pressure is high, the medulla stimulates vasodilation and a decrease in cardiac rate and output causing the pressure in the system to drop. If the pressure is low, the medulla directly stimulates an increase in cardiac rate and output and vasoconstriction. The medulla mediates these effects through the autonomic nervous system. Renin-Angiotensin System

Heart Rate Stroke volume or the amount of blood that is pumped out of the ventricle with each heartbeat (primarily determined by the volume of blood in the system). Total peripheral resistance or the resistance of the muscular arteries to the blood being pumped through.

Another compensatory system is activated when the blood pressure within the kidney falls. Because the kidneys require a constant perfusion to function properly, they have a compensatory mechanism to help This mechanism is known as the Renin-Angiotensin System. RENIN-ANGIOTENSIN SYSTEM

Baroreceptors As the blood leaves the left ventricle through the aorta, it influences specialized cells in the arch of the aorta called baroreceptors. Baroreceptors pressure receptors located in different arteries in the body. Detects pressure within the arteries and sends a stimulus in the medulla, in area called the cardiovascular center (vasomotor center)

Hypertension When a persons blood pressure is above normal limits for a sustained period 90% of people with hypertension have what is called Essential Hypertension

If the blood pressure becomes too low, the vital centers in the brain as well as the rest of the tissues of the body may not receive enough oxygenated blood to continue functioning. Hypotension can progress to shock

Waste products accumulate Cells die from lack of oxygen

Hypertension with no known cause Hypotensive state can occur in the following situations:

The underlying danger of hypertension is the prolonged force on the vessels of the vascular system. Untreated hypertension increases a persons risk for the following: Coronary artery disease Cardiac death Stroke Renal failure Loss vision Hypotension When a persons blood pressure is below normal limits for a sustained period.

When the heart muscle is damaged and unable to pump effectively. With severe blood loss, when volume drops dramatically. When there is extreme stress in the bodys levels of norepinephrine are depleted, leaving the body unable to respond to stimuli to raise blood pressure. Antihypertensive Agents Because an underlying cause of hypertension is usually unknown, altering the bodys regulatory mechanisms is the best treatment currently available. Treatment for hypertension does not cure the disease but is aimed at maintaining the blood pressure within normal limits to prevent the damage that hypertension can cause.

Diuretics Diuretics are drugs that increase the excretion of sodium and water from the kidney. These drugs are often the first agents tried in mild hypertension; they affect blood volume levels and blood volume. Diuretics increase urination and can disturb electrolyte and acid-base balances they are usually tolerated well by most patients. Symphatetic Nervous System Blockers Drugs that block the effects of the sympathetic nervous system are useful in blocking many of the compensatory effects of the sympathetic nervous system.

Angiotensin Converting Enzyme Inhibitor The ACE inhibotors block the conversion of angiotesin I to angitensin II in the lungs. ACE inhibitors prevent ACE from converting angitensin I to angiotensin II. Angiotensin II is a powerful vasocontrictor and a stimulator of aldosterone release. These drugs are indicated for the treatment of hypertension. Pharmakokinetics Well absorbed Widely distributed Metabolized in the liver Excreted through the urine Cross the placenta and joins the breast milk

Betablockers blocks vasoconstriction, decreased heart rate, decreased cardiac muscle contraction, increase blood flow in the kidneys, decrease renin release. Alpha-adrenergic blockers inhibit the post synaptic alpha 1-adrenergic receptors, decreasing synaphatethic tone in the vascularate and causing vasodilation, which leads to a lowering of blood pressure.

Not indicated during pregnancy and lactation

Adverse effects Tachycardia Chest pain

 Angina CHF Cardiac arrhythmias GI irritation Ulcers Constipation Renal insufficiency Renal failure Liver injury Protenuria Rash Alopecia Dermatitis Photosensitivity

Common ACE inhibitors Benazepril Captopril Enalapril Fosinopril Lisinopril Moexipril Perindopril Quinapril Ramipril Trandolapril Calcium Channel Blockers Inhibit the movement of calcium ions across the membranes of myocardial and arterial muscle cells, altering the action potential and blocking muscle cell contraction. This effect depresses myocardial contractility, slows cardiac impulse formation in the conductive tissues, and relaxes and dilates arteries, causing a fall in blood pressure and decrease in venous return.

Pharmacokinetics

Heart block Skin flushing Rash

Well absorbed Metabolized in the liver Excreted in the urine Cross placenta and enters breast milk Can cause fetal toxicity Not indicated for pregnant and lactating women

Common Calcium Channel Blockers Amlodipine Diltiazem Felodipine Isradipine Nicardipine Nifedipine Nisoldi

Adverse Effect Dizziness Lightheadedness Headache Fatigue Nausea Hepatic injury Hypotension Bradycardia Peripheral edema

Drugs Acting on the Immune System

Drugs Acting on the Immune System 1. Introduction to the Immune Response And Inflammation The body has many defense systems in place to keep it intact and to protect from EXTERNAL STRESSORS. These stressors can include:

1. Barrier Defenses Certain anatomical barriers exist to prevent the entry of foreign pathogens and to serve as important lines of defense in protecting the body.

Skin
o o

Bacteria Viruses Other foreign pathogens Trauma Exposure to extremes of environmental conditions

The same defense systems that protect the body also help to repair it after cellular trauma or damage. Understanding the basic mechanisms involved in these defense systems helps to explain the actions of drugs that affect the immune system and inflammation. Body Defenses

The bodys defenses include: Barrier defenses Cellular defenses Inflammatory response Immune response

The skin is the first line of defense The skin acts as a physical barrier to protect the internal tissues and organs of the body. The acid pH of skin secretions inhibits bacterial growth. Glands in the skin secrete chemicals that destroy or repel many pathogens. Ex. Sebum contains chemicals that are toxic to bacteria. The skin sloughs off daily, making it difficult for any pathogen to colonize on the skin. An array of normal flora bacteria lives on the skin and destroys many disease causing pathogens. Mucous membrane Mucous membranes line the areas of the body that are exposed to external influences but do not have the benefit of skin protection. Respiratory tract The mucous membrane is lined with tiny, hair-like processes called cilia. The cilia sweep any captured pathogens or foreign

materials upward toward the mouth, either to be swallowed or to cause irritation to the area and be removed by a cough or a sneeze. Gastrointestinal tract The mucous membrane serves as a protective coating, preventing erosion of GI cells by the acidic environment of the stomach, the digestive enzymes of the small intestines, and the waste products that accumulate in the large intestine. The stomach mucosa secretes hydrochloric acid and protein digesting enzymes. Both kill pathogens. The mucous membrane also secretes mucus that serves as a

lubricant throughout the GI tract to facilitate movement of the food bolus and of waste products.

1. Cellular Defenses Any foreign pathogen that manages to get past the barrier defenses will encounter the human immune system, or mononuclear phagocyte system (MPS) composed of:

Thymus gland Lymphatic tissue Leukocytes Lymphocytes chemical mediators

1. Leukocyte

White blood cells Two types of WBC o Lymphocytes- key components of the immune system and consist of T cells, B cells and natural killer cells o Myelocytes- different cell types those are important in both the basic inflammatory response and the immune response. Myelocytes include neuthrophils, basophils, eosinophils and monocytes or macrophages.

1. Neuthrophils

1. Monocytes

Polymorphonuclear lukocytes that are capable of diapedesis and phagocytosis. o Diapedesis- moving outside of the bloodstream. o Phagocytosis-engulfing and digesting foreign material o When the body is injured or invaded by a pathogen, neuthrophils are rapidly produced and moved to the site of the insult to attack the foreign material. o Able to identify nonself-cells by use of MHC.

1. Basophils

Monuclear phagocytes also called macrophages Mature leukocytes that are capable of phagocytizing an antigen. o Antigen- an substance capable of exciting our immunne system and provoking an immune response. As far as our immune system is concern, they are foreign intruders in the body o A major role of macrophages is to engulf foreign particles and present fragments of these antigens, like signal flags, on their own surfaces, where theyczn be recognized by immunocompetent T cells.

Myelocytic leukocytes that are not capable of phagocytosis. Full of chemical substances that are important for intiating and maitaining an immune or inflammatory response. Ex histamine and heparin

1. Mast cells

Fixed basophils that do not circulate Can be found in the respiratory and GI tracts and in the skin.

1. Eosinophils

Circulating myelocytic leukocytes. Often found at the site of allergic reaction and responsible for removing proteins and active componets of the immune reaction from the site of an allergic response.

1. The Inflammatory Response

The inflammatory response is the local reaction of the body to invasion or injury. Any insult to the body that injures cells or tissues sets into action a sereis of events and chemicals reactions. Cell injuries causes the activation of a chemical in the plasma called factor XII or Hageman Factor.

Hageman Factor-responsible for activating the Kinin System: Clottting cascade- which starts blood clotting + Hageman factor activates kallikrein, a bustance found in the local tissues. Kallikrein causes the precursor substance kininogen to be converted to bradykinin. Bradykinin Causes local vasodilation to bring more blood to the injured area Allow white blood cells to ecape into the tissues. Increase permeability. Stimulates nerve ending to cause pain,which alerts the body to the injury. Bradykinin also causes the release of arachidonic acid from the cell memebrane. Arachidonic acid causes the release of autochoids. Autochoids act like local hormes release from the cell and cause an eefect in the immediate area: Protaglandins- augments the inflamatory reaction and stimulates nerve ending which causes pain. 1. The Immune Response

Leukotrines- causes vasodilation and increased capillary permeability. Leukotrines has a property called chemotaxis, which is the ability to attarct neuthrophils and to stimulate them and other macrophages in the area to be very aggressive. Thromboxanes- cause local vasoconstriction and facilitates aggregation and blood coagulation. Injury to the cell membrane causes the release of Histamine. Histamine causes vasodilation, which bring more blood and blood components to the area. Histamine also increases the permeability of the capillary, making it easier for neuthrphils and blood chemicals to leave the blood sream and enter the injured area.

More specific invasion can stimulate a more specific response through the immune system. A major component of the immune response are the lymphocytes

1. Suppresor T cells

Responds to the rising levels of chemicals associated w/ an immune response to suppress or slow reaction.

2 major types of lymphocytes: The balance of the helper and suppresor T cells allow for rapid response to body injury or invasion. And slowing allows the body to conserve energy and the component of the immune and inflammatory reaction.

1. T cells

T cells are programmed in the thymus gland It provides to what is called a cell mediated immunity Cell mediated immunity is an immune response that does not involve antibodies but rather involves the activation of macrophages and antigen specific cytotoxic T cells, and the release of various cytokines in response to an antigen. T cells develop into at least 3 different cell types

1. B cells

1. Effector or cytotoxic T cells

Are found throughout the body Aggressive against non-self cells Releases cytokines, or chemicals that can either directly destroy a foreighn cell or mark it for aggressive destruction. Attacks bodys own cells that have been invaded by a virus, neoplastic cancer, or transplant foreign cells.

1. Helper T cells

Stimulates other lymphocytes to be more aggressive and responsive.

Are programmed to identifay specific protein, or antigens. They provide what is called humoral immunity. Humoral immunity is the aspect of immunity that is mediated by secreted antibodies. Antibodies also known as immunoglobulins, are used by the immune system to identify and neutralize foreign objects or microorganms. When B cells reacts w/ its specific antigen, it changes to become a plasma cell. Plasma cells produce antibodies, w/c circulate in the body and react w/ this specific antigen when it is encounterd. Reaction between an antigen ang antibodies will form a Ag-Ab complex will cause an activation of complement.

Complement is a biochemical cascade of the innate immune system that helps clear pathogens fron an organism.

Several diffrent types of drugs are used as anti-inflammatory agents: 1. Corticosteroids- are used sytemically to block the inflammatory and immune systems. Blocking these important protective processes may produce many adverse effects, including decreased resistance to infection and neoplasm. 2. Antihistamines- are use to block the release of histamine in the initiation of the inflammatory response. 3. Salicylates- are popular anti-inflammatory agebts, not only because of their ability to block the inflammatory response but also because of their antipyretic and analgesic properties. They are generally available without prescription and are relatively nontoxic when used as directed. 4. Nonsteroidal anti-inflammatory drugs (NSAIDS)- are some of the most widely used drugs. They provide strong anti-inflammatory and analgesic effects yet do not have the adverse effects that are associated with the corticosteroids. 5. Acetaminophen- also is widely used agent. It has antipyretic and analgesic properties but does not have the anti-inflammatory effects of salicylates or the NSAIDs.

Anti-inflammatory Agents

The inflammatory response is designed to protect the body from and pathogens. It employs a variety of potent chemical mediators to produce reactions that helps to destroy pathogens and promote healing. As the body reacts to these chemicals, it produces some signs and symptoms of disease:

Swelling Pain Redness Heat/fever

Anti iiflammatory agenys generally block or alter the chemical reactions associated with the inflammatory response to stop one or more of the signs and symptoms of inflammation.

Because many anti-inflammatory drugs are available over the counter, there is the potential for abuse and overdosing.

Patients may take these drugs and block the signs and symptoms of a present illness, thus potentially causing the misdiagnosis of a problem. Patients also may combine these drugs and unknowingly induce toxicity.

effect in ulcerative colitis or other condition involving inflammation of the large intestine. Olsalazine- is a drug that is converted to mesalamine in the colon and has the same direct anti-inflammatory effects. Salsalate- is used treat pain, fever, and inflammation. Sodium thiosalicylate- is used mainly for episodes of acute gout and muscular pain, and to treat rheumatic fever.

SALICYLATES Are some of the oldest anti-inflammatory drugs used. Therapeutic Actions Ancient peoples extract salicylates from willow bark and poplar trees, used to treat fever, pain and inflammation.

Nowadays synthetic salicylates are commonly used. Synthetic salicylates includes the following drugs: Aspirin- one of the most widely used drugs for treating inflammatory conditions, it is available OTC. Balsalazide- a new type of anti-inflammatory drug that is delivered intact to the colon, where it delivers a local anti-inflammatory effect for patients with ulcerative colitis. Choline magnesium trisalicylate- is used to treat mild pain and fevers, as well as arthritis. Choline salicylate- is used to treat mild pain and fevers, as well as arthritis, it is available only as an OTC. Mesalanine- is a unique compound that release aspirin in the large intestine for a direct anti-inflammatory

Salicylates inhibit the synthesis of prostaglandin The antipyretic effect of salicylates maybe related to blocking of a prostaglandin mediator of pyrogen. o Pyrogen are chemicals that can cause an increase in body temperature and that are released by active WBC, they act at the thermoregulatory of the hypothalamus. o At low levels , aspirin also affects platelet aggregation by inhibiting the synthesis of thromboxane A2, a potent vasoconstrictor that normally increases platelet aggregation and blood clotting. o At high levels, aspirin inhibits the synthesis of prostacyclin , a vasodilator that inhibits platelet aggregation.

Indications

Salicylates are indicated for the treatment of:

Adverse Reactions

Mild to moderate pain Fever Numerous inflammatory conditions: o Rheumatoid arthritis o Ostheoarthritis Low doses indicated for the prevention of transient ischemic attack Stroke in adults with a history of emboli Reduce the risk of death and myocardial infarction in patients with history of MI or unstable angina.

Pharmacokinetics

Salicylates are readily absorbed in the stomach Metabolized in the liver Excreted in the urine Crosses the placenta barrier and enter breast milk Not indicated for use during pregnancy and lactation because of the potential adverse effect on the neonates

Contraindications

Allergy to salicylates Bleeding abnormalities

Stomach (gastric irritant) o Nausea o Dyspepsia o Heartburn o Epigastric discomfort Clotting systems o Blood loss o Bleeding abnormalities Salicylism (high levels of salicylates) o Dizziness o Ringing in the ears o Difficulty hearing o Nausea vomiting o Diarrhea o Mental confusion o Lassitude Acute salicylate toxicity (occurs at doses of 20-40g in adults, 4 g in children) o Hyperpnea (increase depth in breathing) o Tachypnea o Hemorrhage o Excitement o Confusion o Pulmonary edema o Convulsions o Tetany (spasms due to decrease calcium) o Metabolic acidosis o Fever o Coma o Cardiovascular collapse o Renal failure

Respiratory collapse

Acetic Acids 1. Diclofenac- is used to treat acute and long term pain associated with inflammatory conditions. 2. Etodolac- is widely used for arthris pain. 3. Indomethacin- is available in oral, topical, and rectal preparations for the relief of moderate to severe pain associated with inflammatory conditions and in intravenous form to promote closure of the patent ductus arteriosus in premature infants. 4. Ketorolac- is used for short-term management of pain and topically to relieve ocular itching. 5. Nabumetone- is used treat acute and chronic arthritis pain. 6. Sulindac- is used for long-and short term treatment of the signs and symptoms of various inflammatory conditions. 7. Tolmetin- is used to treat acute attacks of rheumatoid arthritis and juvenile arthritis.

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS

The NSAIDs are a drug class that has become one of the most commonly used types. This group of drugs includes the following agents:

Propionic Acid 1. Fenopropen- is used to treat pain and manage arthritis. 2. Flurbipropen- is used for the long-term management of arthritis and as atopical preparations for managig pain after eye surgery. 3. Ibufrofen- is used as an OTC pain medication and for long-term management of arthritis pain and dysmenorrhea; it is the most widely used of the NSAIDs. 4. Ketoprofen- is available for short-term management of pain and as atopical agent to relieve ocular itching caused by seasonal rhinitis. 5. Naproxen- is available for OTC pain relief and to treat arthritis and dysmenorrhea. 6. Oxaprozin- is very successfully used to manage arthritis.

Fenamates 1. Mefenamic acid- is used only for short-term tratment of pain. 2. Piroxicam- is used to treat acute and chronic arthritis. 3. Diflunisal- is used for moderate pain and for the treatment of arthritis

Oxicam Derivative

1. Meloxicam- is used for the relief of juvenile arthritis, osteoarthritis, and rheumatoid arthristis.

Cyclooxygenase-2 Inhibitor 1. Celcoxib- is used for the acute and long term treatment of arthritis, particularly in patients who cannot tolerte the GI effects of other NSAIDs.

The adverse effects associated with most NSAIDs are related to blocking of both of these enzymes and changes in the functions that they influence: Changes in bleeding time GI effects Water retention

Therapeutic Actions

Indications

The anti-inflammatory, analgesic and antipyretic effects of NSAIDs are largely related to the inhibition of prostaglandin. The NSAIDs block 2 enzymes: o Cyclooxygenase-1 (COX-1)- involves in many body functions including: Blood clotting Protecting the stomach lining Maintaining sodium and water balance COX-1 turns arachidonic acid into prostaglandins as needed in a variety of tissues. Cyclooxygenase-2 (COX-2) Is active at sites of trauma or injury when more prostaglandins are needed, but it does not seem to be involved in the other tissue function, unlike COX-2.

The NSAIDs are indicated for relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis, for relief of mild to moderate pain, for treatment of primary dysmenorrhea, and for fever reduction.

Pharmacokinetics

Rapidly absorbed from the GI tract Metabolized in the liver Excreted in the urine NSAIDs cross the placenta and cross into breast milk Not recommended during pregnancy and lactation because of the potential adverse effects on the fetus or neonate.

Contraindications

Allergy to any NSAIDs or salicylates. Celecoxib is also contraindicated in the presence of allergy to sulphonamides. Cardiovascular dysfunction Hypertension Peptic ulcer or known GI bleeding Renal or hepatic dysfunction

Adverse Effects

Nausea Dyspepsia GI pain Constipation Diarrhea Flatulence Potential for GI bleeding Headache Dizziness Fatigue Bleeding Platelet inhibition Bone marrow depression Rash and mouth sores Anaphylactic shock in cases of severe hypersensitivity.