Introduction to Pharmacology B.Pharmacy 4th Semester 2020 (2019-2020) Previous Year's Question Papers/Notes Download - HK Technical PGIMS

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

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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.