Introduction to Pharmacology Download Notes PDF BPharmacy 4th Semester 2020

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UNIT – I

General Pharmacology

a) Introduction, definition and scope of Pharmacology

b) Routes of administration of drugs

c) Pharmacokinetics (Absorption, Distribution, Metabolism and Elimination)

d) Pharmacodynamic-receptor and non-receptor mediated mechanism of drug, receptor drug interactions and adverse

drug reactions

e) Factors modifying drug effects

(A) Introduction, definition and scope of Pharmacology

 DEFINITION OF PHARMACOLOGY

 Pharmacology is the study of the therapeutic value and/or potential toxicity of chemical agents on biological

systems.

 It targets every aspect of the mechanisms for the chemical actions of both traditional and novel therapeutic

agents.

 Two important and interrelated areas are: pharmacodynamic and pharmacokinetics.

i. Pharmacodynamic (what drug does with the body) are the study of the molecular, biochemical, and

physiological effects of drugs on cellular systems and their mechanisms of action.

ii. Pharmacokinetics (what body does with the drug) deals with the absorption, distribution, and excretion

of drugs.

 SCOPE OF PHARMACOLOGY

A. History

 It is of intellectual interest to know how drugs are discovered and developed. Often in the past, this was

based on folklore or intelligent observation (e.g. digitalis leaf, penicillin). Nowadays, new drugs are

mostly developed by the organic chemist working with a pharmacologist, increasingly from basic

knowledge about key molecular targets. Usually some sort of biological screen is used to select among

organic molecules for optimum pharmacological activity.

1. Francois Magendie (1783-1855), a French physiologist laid down the dictum “Facts and facts alone are

the basis of science.” Experimental procedures with animals are the testing grounds for determination of

drug action.

2. Claude Bernard (1813-1878), investigated the plant extract curare and proposed a site of action for this

agent.

3. Rudolph Buchheim (1820-1879). In 1847 Buchheim established the first laboratory devoted to

experimental pharmacology in the basement of his home in Dorpat which is known as the cradle of

experimental pharmacology.

4. Oswald Schmiedeberg (1838-1921). In 1872 set up an institute of pharmacology in Strasbourg, France

(Germany at that time) which became a mecca for students who were interest in pharmacological

problems.

5. J.N. Langley (1852-1925 and Sir Henry Dale (1875-1968) pioneered pharmacology in England, taking a

physiological approach.

6. John J. Abel (1857-1938) established the first chair of pharmacology in the U.S.A. (U. Michigan, 1891) after

training in Germany. Able went to Johns Hopkins in 1893, and trained many U.S. pharmacologists. He is

known as “The Father of American Pharmacology”.

7. The Second World War was the impetus for accelerated research in pharmacology (the war time

antimalarial program) in the U.S., and introduced strong analytical and synthetic chemical approaches.

UNIT – I: General Pharmacology

Lecture Notes_Dr. Sumanta Mondal_ PHARMACOLOGY – I (PPH 206)_B.Pharm-VI Sem_GITAM University. Page | 2

B. Chemistry

 Chemical structures of drugs can provide information about mechanism of action, pharmacokinetics,

stability, and metabolic fate.

1. Structure-Activity Relationship: A modification of the chemical structure of a drug may accentuate or

diminish its pharmacological effects, often providing clues as to the mechanism of action. A picture of the

biological reactive site (the receptor) can be developed in such studies. Also, drugs are metabolized by

body systems, which may convert the parent drug to a more active or a less active form. The drug structure

can be modified to enhance or diminish the rate of metabolic conversion.

2. Sites of Action: The organ or cellular target of drug action.

3. Drug Receptors: Macromolecules in cells or cell membranes with which drugs interact to exert their

effects. Usually the interacting forces are reversible ionic and Van der Waals bonds of relatively low energy,

but sometimes covalent bonds are formed (e.g. organophosphate insecticides).

C. Pharmacodynamic

 The effect of the drug on the body. Pharmaco-dynamics is the study of the relationship of drug

concentration and the biologic effect (physiological or biochemical).

 For most drugs it is necessary to know the site of action and mechanism of action at the level of the

organ, functional system, or tissue. For example, the drug effect may be localized to the brain, the

neuromuscular junction, the heart, the kidney, etc. Often the mechanism of action can be described in

biochemical or molecular terms. Most drugs exert effects on several organs or tissues, and have

unwanted as well as therapeutic effects. There is a dose-response relationship for wanted and

unwanted (toxic) effects.

 Patient factors affect drug responses – age, weight, sex, diet, race, genetic factors, disease states, trauma,

concurrent drugs, etc.

D. Pharmacokinetics

 The effect of the body on the drug. To produce its characteristic effects, a drug must be present in

appropriate concentrations at its sites of action. Thus, it is important to know the interrelationship of

the absorption, distribution, binding, biotransformation, and excretion of a drug and its concentration

at its locus of action.

1. Absorption (oral or parenteral): A drug must be absorbed and achieve adequate concentration at its site of

action in order to produce its biological effects. Thus, when a drug is applied to a body surface (e.g., G.I.

tract, skin, etc.), its rate of absorption will determine the time for its maximal concentration in plasma and

at the receptor to produce its peak effect.

2. Distribution: The blood, total body water, extracellular, lymphatic and cerebrospinal fluids are involved in

drug movement throughout the body. Depending upon its chemical and physical properties, the drug may

be bound to plasma proteins or dissolved in body fat, delaying its progress to its sites of action or excretory

mechanism.

3. Metabolism: This is how certain drugs are handled by the body in preparation for their elimination and

includes the fate of drugs-biotransformation (e.g., hydrolysis, conjugation, oxidation-reduction).

4. Excretion: The kidney is the most important organ for drug excretion but the liver, lung and skin are also

involved in drug elimination. Drugs excreted in feces are mostly derived from unabsorbed, orally ingested

drugs or from metabolites excreted in the bile and not reabsorbed by the intestine. The physical and

chemical properties, especially the degree of ionization of the drug, are important in the rate of excretion.

5. Biological Factors Modifying Pharmacokinetic Aspects: Normal variations occur in population

pharmacokinetic constants (absorption rates, elimination rates). Other factors include age, weight, obesity,

edema, concurrent diseases, other drugs (various interactions including effects on protein binding or

metabolic rate), diet, dose interval and route of administration, genetic variations in elimination rate.

UNIT – I: General Pharmacology

Lecture Notes_Dr. Sumanta Mondal_ PHARMACOLOGY – I (PPH 206)_B.Pharm-VI Sem_GITAM University. Page | 3

E. Clinical Pharmacology and Therapeutics

1. Indications and Therapeutic Uses: Emphasis is placed on the therapeutic use of drugs for the treatment of

disease in clinical pharmacology, internal medicine and therapeutics. There are specific clinic disorders or

disease entities for which a given drug may be prescribed and the physician must weigh the potential

benefit of drug use against the risks of adverse effects.

2. Contraindications and Factors (e.g., liver disease) May Modify Drug Action: Where detoxification of the

drug by the liver is important. It is important to know that the presence of disease or organ pathology may

influence the actions of a drug. Conditions such as age, pregnancy, concomitant administration of other

drugs and disease may alter the patient’s response to a given drug.

3. Posology: It is an archaic term describing dosage regimens. Consideration of dosage schedules is a part of

pharmacokinetics.

4. Bioavailability: The fraction of drug administered which is actually absorbed and reaches the systemic

circulation following oral dosing. Preparations of the same drug by different manufacturers may have a

different bioavailability.

5. Prescription writing: It is important that the physician write clear, error-free directions for the drug

provider (pharmacist) and for the patient. Physicians must guard against prescribing too many drugs, or

preparations of little value. Drugs of unproven clinical value should be avoided, as well as potentially toxic

agents if drugs equally effective but less dangerous are available. Risk-benefit and cost-benefit should be

considered. Drugs may be prescribed by generic name, since often a less expensive drug product can be

obtained in this way. A particular manufacturer may be specified if the physician has reason to believe a

better or more reliable preparation is available from that manufacturer.

6. Drug Nomenclature: In addition to its formal chemical name, a new drug is usually assigned a code name

by the pharmaceutical manufacturer. If the drug appears promising and the manufacturer wishes to place it

on the market, a United States Adopted Name (USAN) is selected by the USAN Council which is sponsored

by:

i. The American Medical Association

ii. The American Pharmaceutical Association

iii. The United States Pharmacopoeial Convention

F. Toxicology

 The aspect of Toxicology deals with the adverse effects of chemical agents.

 Toxicology is concerned not only with drugs used in therapy but also with the other chemicals that may

be responsible for household, environmental or industrial intoxication.

1. Forensic Toxicology: Addresses medicolegal aspects of the use of chemicals that are harmful to animals or

man. Analytical chemistry and fundamental toxicological principles are hybridized to underlie this aspect

of toxicology. Nonetheless accidental poisoning with drugs is a health problem of major significance. More

than 1/4 of the fatalities and about 1/2 of all poisonings occur in children under 5 years of age. All common

household articles that are poisonous should be made unavailable to children, and poisonous rodenticides

and insecticides should not be placed in the home.

2. Clinical Toxicology: Focuses on toxic events that are caused by or are uniquely associated with drugs or

other chemicals

UNIT – I: General Pharmacology

Lecture Notes_Dr. Sumanta Mondal_ PHARMACOLOGY – I (PPH 206)_B.Pharm-VI Sem_GITAM University. Page | 4

G. Pharmacovigilence

 The area of Pharmacovigilence that focuses on the effects of drugs on patient safety.

 It involves the characterization, detection, and understanding of adverse events associated with drug

administration, including adverse drug reactions, toxicities, and side effects that arise as a consequence

of the short- or long-term use of drugs.

 Adverse drug reactions, including drug-drug interactions, are estimated to be a major cause of

mortality of inpatients and also lead to significant increases in duration of hospitalization. No drug is

free of toxic effects. Some untoward effects of drugs are trivial, but others are serious and may be fatal.

Side effects often are predictable from knowledge of the pharmacology of a particular drug.

 Examples of chemicals or drug-induced toxicities are given below:

1. Allergic reactions: The number of serious allergic reactions to drugs involving antigen-antibody reactions

is low but when they occur the physician must have sufficient knowledge to manage these problems.

2. Blood dyscrasias: These are very serious and sometimes fatal complications of drug therapy. They

include: agranulocytosis, aplastic anemia, hemolytic anemia, thrombocytopenia and defects in clotting

factors.

3. Hepatotoxicity and nephrotoxicity: Because many chemicals and drugs are eliminated and metabolized

by the liver and kidney, damage to these organs is seen commonly.

4. Teratogenic effects: The thalidomide tragedy dramatically emphasized that drugs may adversely

influence fetal development.

5. Behavioral toxicity: This is a term used to describe suppression of normal anxiety, reduction in

motivation, impairment of memory and learning, distortion of judgement, impairment of reflexes, adverse

effects on mood, etc.

6. Drug dependence and drug abuse: The repeated administration of some chemicals may lead to drug

dependence. Drugs likely to be abused and upon which drug dependence may develop are the various

psychopharmacological agents such as opiates, barbiturates, amphetamines, nicotine and ethanol.

Dependence on tobacco (nicotine) is also well known.

7. Carcinogenesis: Carcinogenesis is a delayed type of toxicity with a latency of many years.

8. Pharmacogenetic toxicities: Certain genetically-predisposed individuals have a markedly toxic reaction

to certain otherwise safe drugs. Examples are prolonged apnea after succinylcholine, or malignant

hyperthermia associated with anesthetics.

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