PHARMACOLOGY: Basic concepts
Pharmacology is the study of drugs and their actions on the body.
Pharmacon – DRUG: is a chemical substance that alters the function of any
physiological system for the treatment, prevention and diagnosis.
Logos – Study.
It consists of detailed study of drugs, particularly their actions on living
animals, organs or tissues.
It is an official code containing a selected list of the established drugs and
medicinal preparations with descriptions of their physical properties and tests
for their identity, purity and potency.
IP (Indian Pharmacopoeia)
BP (British Pharmacopoeia)
USP (United States Pharmacopoeia)
Names of Drugs
Chemical…states its chemical composition and molecular structure.
Generic…usually suggested by the manufacturer.
Official…as listed in the I.P., B.P., U.S. Pharmacopeia.
Brand…the trade or proprietary name.
Chemical Name 1,4 benzodiazepine analog
Generic Name Alprazolam
Official Name Alprazolam, USP
Brand Name Alprax®
Dose vs. Dosage
Dose: the quantity of drug administered at one time
E.g.10 mg of amlodipine
Dosage: the amount of the drug that should be given over time
e.g. 3.125 mg carvedilol twice daily for one month
Routes of drug administration
What is Pharmacology ?
What the body does to drug What the drug does to body
The study of the use of drugs Preparing suitable dosage forms
How the drug is given?
Advantages and disadvantages of oral, IV, IM and SC administration
In terms of safety and convenience, orally administered drugs score over the
drugs administered through parenteral routes like subcutaneous, intramuscular
Advantages and disadvantages of oral, IV, IM and SC administration
It is the study of absorption, distribution, metabolism and excretion of
• How the drug is moved into blood stream from the site of
• How much drug is moved to various body tissues / organs?
Depends on blood flow through tissue.
• How the drug is altered – broken down?
• How much of the drug is removed from the body?
Low &/or Variable
High and Reliable IV > IM = SC > ORAL
IV > IM > SC > Oral
ONSET OF ACTION
Oral > SC > IM > IV
Oral > SC > IM > IV
IV > IM > SC > ORAL
IV > IM > SC > ORAL
Absorption and Bioavailability:
Absorption is the movement of drug from its site of administration into
Not only the fraction of the administered dose that get absorbed, but also
the rate of absorption is important
Bioavailability: Fraction of administered dose of a drug that reaches the
systemic circulation in the unchanged form.
Bioavailability of IV route : 100 %
It is a time required for 50% of elimination of the plasma concentration
of the administered drug.
1st t1/2 - 50 % drug is eliminated
CURVE FOR A DRUG
MEC for Adverse
Half-life is the time taken for the concentration of drug in blood to fall by a half.
Half-life is 2hrs in this example.
2nd t1/2 - 50+25 ( 75 % ) drug is eliminated
3rd t1/2 - 50+25 +12.5( 87.5 % ) drug is eliminated
4th t1/2 - 50+25 +12.5+6.25( 93.7 % ) drug is eliminated
Thus, nearly complete drug elimination occurs in 4-5 half lives.
It is the maximum concentration of drug achieved in the plasma.
It is the minimum time required to achieve the maximum plasma concentration of
Means chemical alteration of the drug in the body.
Site of drug metabolism: Liver (primary site), others are intestine, lungs,
kidney, skin etc.
Biotransformation of drugs lead to following
Inactivation : Amlodipine, Morphine
Active metabolite from an active drug: Atorvastatin - ortho &
parahydroxylated derivatives; Ezetimibe - glucuronide metabolite.
Activation of inactive drug (Prodrug): Enalapril-enalaprilat.
Cytochrome P450 (Microsomal enzymes):
Located on smooth endoplasmic reticulum.
Primarily in liver.
They catalyze most of the oxidations, reductions, hydrolysis etc.
First- pass metabolism:
Refers to metabolism of a drug during its passage from the site of
absorption into the systemic circulation.
All orally administered drugs are exposed to drug metabolizing enzymes
in the intestinal wall and liver.
Drugs having high first pass metabolism
Not given orally :
High oral dose required :
Drugs &/or its metabolites are irreversibly eliminated from the body
Elimination of the drug
Unchanged (Parent form)
Routes of excretion
Kidneys – Urine
GIT – Stools ( feces)
Skin - Perspiration
Eyes – Tears
Saliva and milk
It the quantitative study of the biological and therapeutic effects of drugs.
The way in which a drug causes its effects; its pharmacodynamics.
Mechanism of actions.
What the drug does to the body.
A protein on the cell membrane or within the cytoplasm or cell nucleus
that binds to a specific molecule (a ligand) such as a neurotransmitter or a
hormone or other substance, and initiates the cellular response to the ligand.
Affinity : Force of attraction between drug and a receptor
Intrinsic activity ( Efficacy ) : Ability of drug to activate receptor once
Drug at Receptor
Agonist: It activates a receptor to produce an effect similar to that of the
physiological signal molecule.
Antagonist: It prevents the action of an agonist on a receptor but does not
have any effect of its own.
Partial agonist: It activates a receptor to produce sub maximal effect but
antagonizes the action of full agonist.
Agonist v/s Antagonist
Drug + Receptor Maximum Effect
Drug = complete or full agonist
Drug + Receptor Less than maximal effect
Drug = partial agonist
Drug + Receptor Block effect
Drug = Antagonist
Efficacy VS Potency
The amount of drug needed to produce a certain response.
The maximal response that can be elicited by the drug.
Comparing Dose-Effect Curves
Effects of combination of drug
Addition (1 + 1 = 2)
Response elicited by combined drugs is equal to the combined
response of the individual drugs
E.g. atenolol + amlodipine
Synergism (1 + 1 = 3 )
1 10 100 1000
Two drugs with the same effect are given together and produce a
response greater than the sum of their individual responses
E.g. Losartan + hydrochlorothiazide
Drug devoid of intrinsic pharmacological activity and it works by
Uses: treatment and research.
Factors affecting drug response
Dose & Route of administration
Duration of treatment
Co-administration of other drugs
Age & Weight
Psychological factor : Placebo effect
Diet & environment
Therapeutic / safety window
It is the range of the dose of the drug which is bounded by the dose which
produces minimal therapeutic effect and the dose which produces
maximal acceptable adverse effects.
Drugs having narrow Therapeutic Window
Steady State Levels- For Multiple Dosages
Dosing Interval - how often the drug should be given
Loading dose – when plateau must be achieved quickly
Routine smaller doses to maintain the steady state (Plateau) –
Indication & Contraindication
o A clinical circumstance indicating that the use of a particular drug
would be appropriate
o Any condition which renders a particular line of treatment
improper or undesirable.
Adverse effects of drugs
Adverse drug reaction: A response to a drug that is noxious and
unintended and that occurs at therapeutic dose and as a possibility of
causal relationship between drug and response.
E.g. Nitrates and headache
Adverse events: Response at therapeutic dose without known causal
E.g. Rabeprazole and headache
Toxic effects: Response due to excessive pharmacological action of the
drug due to overdose or prolonged dose.
E.g. Heparin leads to bleeding
Understanding Clinical Trial Terminology
What is clinical trial?
Methodological experimentation of investigational drugs or devices (like stents)
in human beings / (volunteers/patients).
Randomized Controlled Trials
Participants randomly allocated to either study drug OR another like a
different drug or placebo
Follow up is for a specified period
Analyses in terms of outcomes defined at the outset
Objective of randomization is to rule out bias on part of investigator
(doctor) for a specific treatment.
Two or more groups of people are selected on the basis of their exposure
to a particular agent.
Subsequently followed up to see how many from each group develop the
For example: smokers ( one group ) and non-smokers ( other group ) are
selected and followed-up for a period of say 5 years to see how many from
the smoker group and non-smoker group develop bronchitis (outcome).
Case- Control Studies
Patients with a particular disease are identified and matched with controls
Data is collected on past exposure to a possible causal agent
For example, diabetic patients (one group) and no-diabetics (other group)
otherwise matching with each other are selected and evaluated for a risk
factor (say obesity) for diabetes.
Data are collected at a single time
o e.g. Lipid profiles of 25 year old males in Ahmedabad.
Medical history of a single patient
Not very reliable as evidence
Conveys information which might have been lost
Hierarchy of Evidence:
In terms of clinical evidence, systemic reviews & meta-analyses have rated as the
highest evidence followed by randomized controlled trials.
1 2 3 4 5 6 7 8 9 10
A A B B B A A B B A
Systematic reviews: Summarize primary studies according to a systematic
Meta-analyses: Integrate numerical data from more than one study/trial on a
single product and analyze data.
Guidelines: Conclusions from primary studies on clinical decisions.
For example JNC (Joint National Committee) VIII Guidelines on hypertension,
NCEP ATP IV (National Cholesterol Education Program Adult Treatment Plan)
Guidelines on dyslipidemia management.
Surveys: Something defined is measured in individuals (may be patients).
Placebo controlled: Subjects in control group receive a placebo whereas
subjects in other group receives drug.
Treatment controlled: Subjects in control group receive a standard treatment
whereas subjects in other group receives drug under investigation.
Single blind: Patients do not know which treatment they are receiving.
Double blind: The investigators and the patient both do not know which of the
two treatment options is being administered.
Parallel group comparison: Each group receives a different treatment, both
groups being entered at the same time.
Crossover design: Each subject receives both the new treatment and the
control-treatment, often separated by a washout period.
Multicenter trial: A clinical trial conducted according to a single protocol at
more than one site and thus by more than one investigator.
Systemic reviews and meta-analyses
Randomized controlled trials
Absolute Risk Reduction (ARR) & Relative Risk Reduction (RRR)
Absolute Risk Reduction
ARR is the difference in the event rate between treatment group and control
Relative Risk Reduction
The proportional reduction in rates of bad outcomes between experimental
and control participants in a trial
Example, disease B has a mortality rate of 50% and drug Y reduces mortality
from 50% to 40%.
The absolute risk of death with disease B is .5 or 50% and the relative risk is
.4/.5 = 0.8 or 80%.
The relative risk reduction is 1-0.8 = 0.2 or 20% while the absolute risk
reduction is 0.4-0.5= .1 or 10%.
In this case the relative risk reduction is 20% while the absolute risk
reduction is much higher, 10%.
Null hypothesis: The hypothesis that there is no real difference between two
P value: The probability of any particular outcome having arisen by chance.
Arbitrarily a P value of less than 1 in 20 (expressed as P<0.05, odds of 20 to 1)
is taken as "statistically significant" and a P value of less than 1 in 100
(P<0.01) as "statistically highly significant”.
A result in the statistically significant range (P<0.05) suggests that the null
hypothesis should be rejected.
Confidence Interval (CI)
The range of numerical values in which we can be confident (to a
probability, such as 90 or 95%) that the value being estimated will be
A 95% CI is the range of values within which we can be 95% sure that the
true value for the whole population lies.
Confidence intervals indicate the strength of evidence.
The narrower the confidence interval, the more precise is the estimate of
The larger the trial size, the narrower the interval.