Definitions

Pharmacology Detailed study of drugs

Pharmacy Science of identification,

election, preservation,
standardization,compounding
& dispensing of medical
substances

Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 2

 Definitions (contd)

Pharmacodynamics What the drug does to the body

Study of biological and

therapeutic effects of drugs.

Pharmacokinetics What the body does to the

drug
Study of absorption,
distribution, metabolism
and excretion
Pharmacology of drugs and
& Pharmacotherapeutics, Satoskar,1997, pg 2
 Definitions (contd)

Therapeutics Branch of medicine concerned

with cure of disease or relief of
symptoms

Toxicology Science of poisons.

* Measurement/ detection of
poisons
* Treatment of poisoning.
Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 2
 Definitions (contd)

Chemotherapy Effect of drugs upon microorganisms

and parasites, living and multiplying
in a living organism.

Pharmacopoeia An official published book which

contains a list of the established drugs
and medicinal preparations.
E.g. BP, IP, USP

Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 2

 Nature & Sources of
Drugs
Mineral Liquid paraffin, Magnesium sulfate
Animal Heparin, Insulin
Plant Morphine, Digoxin, Codeine
Synthetic Aspirin, Sulfonamides
Micororganisms Penicillins, Cephalosporins
Genetic Human insulin, Human growth
engineering hormone.
(DNA recombinant
technology)
Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 3
 Drug nomenclature
Patented drug
- Trade name drugs
- Protected by law
- Exclusive marketing rights (in some countries)
- Original drug (pioneer product)

Generic drugs
- Not patented or patent expired
- Any company can market
 Drug nomenclature
Most drugs have three names

- Chemical name: Acetyl salicylic acid

- Generic name: Aspirin
- Trade name: ECOTRIN®
 Drug nomenclature
Prescription drug
- Unsafe to use without medical supervision
- To be dispensed by the order of licensed
physicians, veterinarians, dentists, etc.
Non-prescription drugs
- Sold “over the counter” (OTC)
- Judged safe for use without medical
supervision
Routes of Drug Administration
• Local
• Oral
• Injection
 Local
Local application : Dusting
powder, paste, lotion, drops,
ointment, plaster

Local administration :
Pessaries, suppositories

Enema - local in GIT i.e ‘local’ thru enteral route

Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 4
 Oral or Enteral
Advantages Disadvantage
 Safe  Onset of drug action is slower
 Convenient  Irritant & unpalatable drugs
 Economical cannot be administered
 Not useful - vomiting,
diarrhoea, unconscious/
uncooperative patients.
 Destroyed by digestive juices
eg : Insulin
 Absorption of certain drugs is
irregular/negligible

Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 5

 Enteric Coating

Pills or tablets are coated with substances

which resist the acid juice of the stomach but
disintegrate in intestinal juices.
 To prevent gastric irritation
 To prevent alteration of drug in stomach
 To get desired concentration of the drug in small intestine
 To retard the absorption of the drug.

Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 5

 Injection

Intradermal BCG vaccine

Subcutanecous Insulin, LMWH

Intramuscular Iron preparations, Vaccines

Intravenous
Bolus Cefuroxime
Infusion Dopamine
Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 6
 Injection (contd)

Intraarterial Angiogram

Intrathecal Spinal anaesthesia, antibiotics

Intraperitoneal Peritoneal dialysis

Intraarticular Hydrocortisone in rheumatoid

arthritis
Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 6
 IV Infusion
IV infusion:50-100 ml or larger volume
To slow administration eg : Morphine
of drug

Maintain a constant eg : Insulin or

plasma level of drug dopamine

To administer large volumes eg : fluids in

either rapidly or over shock or
prolonged periods of time dehydration

Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 7

Factors Affecting Drug Absorption

Physical Properties :
 Physical state : Liquids absorbed better than
solids
 Lipid/water solubility
 Particle size
 Disintegration time/ dissolution rate

Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 11

 Dose Concentration Curve
IV
AUC
Cmax

1/2 Cmax

Serum MEC
levels or MIC

Oral Tmax 1/2 life

AUC : Amount of drug absorbed along with rate of absorption and time
required to achieve maximum conc.
Significance - AUC directly proportional to efficacy or action
 Definitions

 AUC - Area Under the Curve - it is the extent of absorption of drug in

the body
 MEC - Minmum Effective Concentration- it is the least concentration
of the drug in the plasma/blood requited to produce therapeutic effect
 Tmax - it is the time required to achieve maximum concentration in
blood/tissues
 Cmax - it is the maximum concentration achieved by the drug in
blood/tissues
 Definitions (contd)
Bioavailability
- The amount (fraction or proportion) of the
given dose of a drug that eventually reach the
systemic circulation in unchanged form.
Bioequivalence
- If two pharmaceutical preparations or
formulations have equal systemic
bioavailability, then they are considered to be
bioequivalent
Bioequivalence

1400
test
1200
reference
concentration

1000
800
600
400
200
0
0 2 4 6 8 10 12
time (hours)
 Half Life T ½
100
50

Time (h) to reduce serum level by 50%

Steady State
50

Levels move up when you add dose Levels “steadier” at higher dose
 Clearance

Volume of plasma cleared from which the

drug is removed in unit time.

Clearance is reduced in renal failure

Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 14

 Blood Brain Barrier

Barrier to the passage of substances from blood to

brain
Lipid insoluble Lipid soluble
Do not cross Enter brain tissue
readily with ease
eg : Streptomycin eg : alcohol

Clinical Pharmacology, Laurence, 1997, pg 92

 Metabolism/ Biotransformation

Metabolism : To make lipid soluble substances

more water soluble & pharmacologically less
active so that they can be excreted easily

Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 15

 Site of Metabolism
 Mainly by enzymes in liver
 Poor function in premature infants and neonates
 Diminishes in liver failure

Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 15-16

 Elimination
Important channels of drug excretion
 Kidneys : Penicillins, Cephalosporins,
Salicylates

 Liver : Erythromycin,

 Lungs : General anaesthetics (gases),

Alcohol

 Others : skin, intestines,

Pharmacology saliva, milk
& Pharmacotherapeutics, etcpg 17-18
Satoskar,1997,
Watch this Animation to understand better
 Mechanism of Action

Cell membrane
Mechanism Metabolic processes
of action within the cells

Outside the cell

Clinical Pharmacology, Laurence, 1997, 78

 Receptor

Receptors are protein macromolecules

When the agonist binds to the receptor, the proteins

undergo an alteration in conformation which induces
changes in systems within the cell that in turn bring
about the response to the drug

Agonists : activate receptors

Antagonists : blockers of receptors
Clinical Pharmacology, Laurence, 1997, pg 78
 Agonist
Receptor = Lock, Drug = Key

Drug + Receptor = Action

 Antagonist
Receptor = Lock, Drug = Key

Antagonist Drug + Receptor = Blocks Action

 Adverse Drug Reaction
Side-effect
Any response to a drug
 that is harmful or unintended
 and that occurs at doses used in man for
prophylaxis, diagnosis or therapy.
Toxic Effect -
An adverse drug reaction which occurs at
higher than usual doses
Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 30
 Carcinogenicity /
Mutagenicity

Carcinogenicity : Liability of the drug to

induce malignancy

Mutagenicity : Certain drugs are known to

produce genetic abnormalities. Abnormal
genes may produce various abnormalities in
subsequent generations.
Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 31-32
 Teratogenicity

Ability of a drug to induce foetal

malformations and / or death in utero

Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 31-32

 Allergy
Greek : Allos - allied
ergos - Energy
Allergic or hypersensitivity reactions occur in
individuals who have been sensitized following the
prior administration of the same drug. Eg : Rash,
Fever, Eosinophilia
Drugs frequently causing allergic reactions -
Salicylates, sulfonamides, tetracyclines etc.
Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 35
 Anaphylaxis
Systemic reaction in a sensitized human
subject following repeat injection of a drug
like penicillin characterised by
•laryngeal edema,
•severe bronchospasm leading to asphyxia, or
•circulatory collapse.
Eg : Penicillin Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 35
 Drug Abuse
The excessive & persistent use of mind altering
substances without medical need.
Commonly abused drugs :
 Alcohol
 Marijuana
 Cocaine
 Benzodiazepines
 Barbiturates
 Heroin
 Amphetamine
The Merck Manual, 1997, pg 27
 Drug Dependence
Behavioural and other responses that always include
• a compulsion to take the drug on a continuous or
periodic basis
• in order to experience its psychic effects and
• sometimes to avoid the discomfort of its absence.

Morphine - severe psychic & physical dependence

Caffeine (Coffee, tea) - Only psychic dependence
Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 50
 Calculation of Paediatric Dose

Paediatric doses are

expressed in terms of
body weight (mg/kg per
dose or daily) or in terms
of body surface area
(mg/M2 per dose or daily)

Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 42

 Additive Effect
1+1=2
When the total pharmacological action of two or
more drugs administered together is equivalent to the
sum of their individual pharmacological actions.

Eg : ephedrine + aminophylline in treatment of

bronchial asthma

Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 45

 Synergism
1+1=3

Synergism Greek Ergo (work) and Syn (with)

When the concomitant use of two or more
drugs produces effect which is more than the
sum of their individual effects

Eg : Codeine and aspirin

Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 45
 Cumulation
If a drug is excreted slowly, its repeated
administration may build up a high
concentration in the body

Non cumulative drug would produce

cumulation in the presence of hepatic and
renal disease.

Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 44

 Clinical Pharmacology
Study of various aspects of drug action and metabolism
in humans
Clinical Evaluation (Trials)
Phase I
Phase II
Phase III
Phase IV
Pharmacology & Pharmacotherapeutics, Satoskar,1997, pg 55
 Phase I
 First human administration
 Safety and toxicity of preparation
 Tolerability of the drug and dosage range
 Pharmacokinetic parameters
Phase II
 Small number of patients
 Metabolic activity & toxicity
 To determine final dosage form of the drug

Phase III
 Large number of patients
 Controlled clinical trials
 Comparison with previously established therapy or placebo

Phase IV
 After marketing
 Therapeutic Window
Toxic dose
IV
AUC
Cmax Therapeutic
Window

1/2 Cmax
Serum MEC
levels or MIC

Oral Tmax 1/2 life

 Dose
Subtherapeutic
Dose
Therapeutic
Dose : Amount of drug to be administered at a
given time e.g.- 100 mg
Dosage : Regimen of doses e.g.- 100 mg bid
Duration : Time for which dosage is administered

e.g.- 100 mg bid for 3 days

 Compliance

Patient compliance is the extent to which the

actual behaviour of the patient coincides
with medical advice and instructions.

Clinical Pharmacology, Laurence, 1997, pg 19

 Definitions (contd)
Bioavailability
- The amount (fraction or proportion) of the
given dose of a drug that eventually reach the
systemic circulation in unchanged form.
Bioequivalence
- If two pharmaceutical preparations or
formulations have equal systemic
bioavailability, then they are considered to be
bioequivalent
 United States FDA has the following definitions for the pregnancy
categories:
United States FDA Pharmaceutical Pregnancy Categories

Adequate and well-controlled human studies have failed to demonstrate a risk to the
Pregnancy
fetus in the first trimester of pregnancy (and there is no evidence of risk in later
Category A
trimesters).

Animal reproduction studies have failed to demonstrate a risk to the fetus and there are
Pregnancy no adequate and well-controlled studies in pregnant women OR Animal studies have
Category B shown an adverse effect, but adequate and well-controlled studies in pregnant women
have failed to demonstrate a risk to the fetus in any trimester.

Animal reproduction studies have shown an adverse effect on the fetus and there are
Pregnancy
no adequate and well-controlled studies in humans, but potential benefits may warrant
Category C
use of the drug in pregnant women despite potential risks.

There is positive evidence of human fetal risk based on adverse reaction data from
Pregnancy
investigational or marketing experience or studies in humans, but potential benefits
Category D
may warrant use of the drug in pregnant women despite potential risks.

Studies in animals or humans have demonstrated fetal abnormalities and/or there is

Pregnancy positive evidence of human fetal risk based on adverse reaction data from
Category X investigational or marketing experience, and the risks involved in use of the drug in
pregnant women clearly outweigh potential benefits.