Important factors Body weight,Age, sex, route of Drug administration,Drug Interactions,Synergism,potentiation,Antagonism,Tolerance.

1. FACTORS MODIFYING DRUG
RESPONSE
Mr. A. S .Khairnar
Assistant. Professor
Ali –Allana college of pharmacy,
Akkalkuwa (M.S.)

2. FACTORS MODIFYING DRUG
RESPONSE
• variations in response to same dose of a drug
between different patients
• in the same patient on different occasions
•The dose of drug is generally expressed in the range,
which gives therapeutic effect in majority of patients.
• The dose range is usually based on the average
requirements of an adult and is not strictly applicable
under all circumstances

3. • IMPORTANT FACTORS MODIFYING DRUG
ACTION ARE:
• • BODY WEIGHT
• • AGE
• • SEX
• • ROUTE OF DRUG ADMINISTRATION
• • TIME OF DRUG ADMINISTRATION
• • GENETIC FACTORS
• • METABOLIC DISTURBANCES
• • PATHOLOGICAL CONDITIONS
• • TOLERANCE
• • TACHYPHYLAXIS
• • CUMMULATION
• • DRUG INTERACTIONS

4. BODY WEIGHT :
• average dose of a drug is mentioned in terms of mg/Kg body
weight. However, the dose mentioned may not be applicable
to all cases.
• in cases of edema weight of patient increases due to the
accumulation of ECF
• in malnutrition metabolizing capacity of drug is reduced
• these factors should be kept in mind while calculating the
dose of drug.

5. AGE:
Pharmacokinetics of many drugs change with age.
- Newborn: liver and renal function less developed
– Elderly: hepatic and renal functions decline
– Glomerular filtration rate: low in infants
– Blood brain barrier: more permeable in infants & may cause
accumulation

6. SEX:
• Females: smaller body size, require doses that are on lower
side of the range.
• Consideration given to menstruation, pregnancy and
lactation.
• Drugs given during pregnancy may affect the fetus.
• Physiological changes during pregnancy alter drug
disposition.
• drugs like methyldopa and  blockers interfere with sexual
function in males but not in females.

7. • Gynecomastia produced by drugs like Digitalis, Cimetidine,
and Metoclopramide occurs in males not in females
ROUTE OF DRUG ADMINISTRATION:
• governs the speed and intensity of drug response.
• In general, intravenous dose of drug is usually smaller than
oral, and time of onset of action is quick with intravenous
route.
• A drug may have entirely different uses through different
routes. For example Magnesium sulfate given orally
produce purgation, applied locally on inflamed area
decreases the swelling while intravenously it produces
CNS depression and hypotension.

8. GENETIC FACTORS:
• The dose of a drug to produce same effects may vary 4–6
folds among different individuals. This is mainly due to the
differing rates of drug metabolism as the amount of
microsomal enzymes is genetically controlled.
• There are some specific genetic defects that lead to variation
in drug response. Example;
• Hemolysis by Primaquine and Sulfonamides in persons with
G.6.P.D. deficiency.
• Slow metabolism of Isoniazid in slow acetylators.

9. • Example; • Hemolysis by Primaquine and
Sulfonamides in persons with G.6.P.D. deficiency.
• Slow metabolism of Isoniazid in slow acetylators.

10. TIME OF ADMINISTRATION:
There is delayed drug absorption when drug is given orally after meals,
which slows down the effects of drug. Under certain circumstances
drugs must be given before meals.
• To prevent mixing of drug with food Anthelminthics.
• To get immediate effect: Drugs used for prevention of motion sickness.
• To prevent formation of insoluble complexes: Tetracycline's.
• To prevent specific side effects, for example to prevent hypoglycemia
insulin and sulfonylureas are given before meals

11. METABOLIC DISTURBANCES:
Changes in water and electrolyte balance body temperature and
acid base balance may modify the effects of drug.
• For example aspirin reduces body temperature only in presence
of fever and have no effect on body temperature when it is
normal.
• Iron is well absorbed in states of iron deficiency.

12. PATHOLOGICAL CONDITIONS
several diseases influence drug disposition and action.
• Hepatic, renal and cardiovascular diseases have important
influence on drug clearance and drug actions.
• Drugs must be carefully used in presence of diseases of these
organs.
DRUG INTERACTIONS:

13. Drug interaction:
• Drugs may modify the response to each other by pharmacokinetic or
pharmacodynamics interaction between them.
• Drug interaction does not necessarily mean that their concurrent use
is contraindicated; many drugs can be used beneficially and some
with dose adjustment.
• Drug combinations can produce:

14. » Additive effect.
» Synergism.
» Potentiation.
» Antagonism.
ADDITIVE EFFECT OR SUMMATION
When total pharmacological effect produced by concomitant use of
two or more drugs is equal to the sum of their individual effects, it is
called “Additive effect.”
1 + 1 = 2.
Example: Combination of ephedrine and Theophylline in the
treatment of asthma. The individual side effects of an additive pair
may be different, and may not add up. The combination is better
tolerated than higher dose of one component.

15. SYNERGISM
• When total pharmacological effect produced by
concomitant use of two or more drugs is higher than the
sum of their individual effects, it is called “Synergism”.
• 1 + 1 = > 2.
• Example: • Codeine + Aspirin > Analgesia.
• Sulfonamide + Trimethoprim > Antibacterial effect.

16. POTENTIATION
• Enhancement of effect of one agent by another; so that the
combined effect is more than the sum of their individual effects is
called “Potentiation.”
• In case of potentiation one agent has no effect when given alone
but increases the effects of other co-administered drug.
• 0 + 1 = > 2.
• Example: • Levodopa + Carbidopa => Parkinsonism.
• Ampicillin + Clavulanic acid = > Antibacterial effect.

17. ANTAGONISM
• The phenomenon of opposing effects when two or more drugs are
given together is called “Antagonism.”
There are three types of antagonism
• Chemical antagonism.
• Physiological antagonism.
• Pharmacological antagonism.
CHEMICAL ANTAGONISM
• In this type of antagonism two or more drugs react chemically to form
inactive product, it occurs without involvement of drug receptors.
Examples: Acids react with Alkalis, Heparin and Protamine sulfate.

18. PHARMACOLOGICAL ANTAGONISM
• When two drugs produce opposite effects on same
physiological function by acting on same receptors it is called
“Pharmacological antagonism.” PHARMACOLOGICAL
ANTAGONISM
• Competitive antagonist
• Non competitive antagonism Equilibrium (reversible). Non
equilibrium (irreversible).

19. COMPETITIVE EQUILIBRIUM
ANTAGONISM
• agonist and antagonist compete for same receptor site. • Drug
receptor binding is weak & non-covalent.
• The extent to which the antagonist opposes the action of agonist is
dependent upon the number of receptors occupied by agonist and
antagonist.
• The antagonism is surmountable i.e. the antagonism can be reversed
by increasing the concentration of agonist at receptor site, for example
atropine and acetylcholine on muscarinic receptors.
• Maximal response of agonist is achieved by increasing the
concentration of agonist at receptor site.

20. COMPETITIVE NON-EQUILIBRIUM
ANTAGONISM
• agonist and antagonist compete with one another for
same receptor site.
• Antagonist binds with receptor by covalent bond.
• Example: Epinephrine and Phenoxybenzamine on 
receptors.

21. NON COMPETITIVE ANTAGONISM
• Agonist and antagonist bind at different sites on the same
receptors.
• The antagonist inactivates the receptor so that effective
complex with agonist cannot be formed irrespective of the
concentration of agonist.
• Example: Acetylcholine and Decamethonium on nicotinic
receptors

22. TOLERANCE
• Reduction in the response due to continued use or repeated
administration of drug is called TOLERANCE
CROSS TOLERANCE: • It is the development of tolerance to
pharmacologically related drugs, e.g. alcoholic need relatively large
doses of barbiturates, as they are tolerant to this class of drugs.
• Closer the drugs are, more complete is the cross-tolerance between
them; e.g. there is partial tolerance between morphine and barbiturates
but complete cross tolerance between morphine and pethidine.

23. MECHANISM OF TOLERANCE:
• Reduction in response may be due to the changes in
absorption, distribution, metabolism and excretion leading to
the decreased effective concentration of drug at the site of
action, e.g. barbiturates on repeated administration enhance
their own metabolism due to enzyme induction, this is called
DISPOSITIONAL OR PHARMACOKINETIC
TOLERANCE.
• Reduction in response may be due to the reduced
responsiveness of target tissues due to down regulation of
receptors; this called FUNCTIONAL OR
PHARMACODYNAMIC TOLERANCE.

24. TACHYPHYLAXIS
• Rapid reduction in responsiveness due to repeated
administration of drug at frequent intervals is called
TACHYPHYLAXIS.
• It is also known as ACUTE TOLERANCE.
• This is usually seen with indirectly acting drugs, e.g.
ephedrine, tyramine, and amphetamine act by releasing
catecholamine in the body, synthesis of which does not match
release and stores deplete rapidly.
• Slow dissociation of drug from receptors is another
mechanism responsible for the development of Tachyphylaxis.

25. •Thank you