Factors modifying the drug action

1. Factors modifying the
DRUG action
Sarita Sharma
Assistant professor
Department of pharmacology
Mumbai

2. On administration of a drug ,a predicted response is
obtained but some times
Variation in response to the same dose of a
drug between different patients and even in
the same patient on different occasions.
 Occasionally individuals exhibit unusual
response IDIOSYNCRACY

3. 1.Body weight/size:
It influences the concentration of drug attained
at the site of action
The average adult dose refers to individuals of
medium built.
For exceptionally obese or lean individuals and for
children dose may be calculated on body weight basis
doseadultAveragex
70
(kg)BW
doseIndividual 

4. 2.Age:
Infants and Children:
 Children may not react in the same manner as
young adults.
The dose of drug for children often calculated
from the adult dose
formula)sYoung'.........(doseadultx
12Age
Age
doseChild


formula)sg'...(Dillindose......adultx
20
Age
doseChild 

5.  Higher proportion of water
 Lower plasma protein levels
More available drug
 Immature liver/kidneys
Liver often metabolizes more slowly
Kidneys may excrete more slowly

6. Elders:
 In elderly, renal function progressively declines
(intact nephron loss) and drug doses have to be
reduced
Chronic disease states
Decreased plasma protein binding
Slower metabolism
Slower excretion
Dietary deficiencies
Use of multiple medications
Lack of compliance

7. 3.Sex:
Evidences show that men and women may respond
differently to same drugs
This may be due to body size, and amount of body
fats, hormonal makeup.
But there are also some less easily explained
differences in gender –specific drug response
Eg: Aspirin shows greater benefit in men than women
in cardiovascular diseases

8. (4)
 SPECIES –
Some drugs resistant with some species
 Rats- Digitalis
 Rabbits-Atropine
 RACE-
 Blacks require higher and Mongols
require lower conc. of Ephedrine and
Atropine for pupilary dilatation.
 Fast acylators and slow acylators of isonizide.

9. Genetically mediated variations in
drug responses
Different rates of metabolism
Ex.
 Pseudocholinestrases
 G6PD defeciency
 Acetylation & hydroxylation

10. (6) Route of drug administration:
 Route governs the speed and intensity of drug
response.
 I.V route dose smaller than oral route
 A drug may have entirely different uses through
different routes.
 Magnesium sulfate:
 Orally –purgative
 Parenterally –sedative
 Locally –reduces inflammation

11. 7.Diet , tobacco, alcohol and environment
 Medicines are usually taken after a meal to reduce the risk of
gastric irritation, nausea and vomiting.
 Food depress the rate and extent of drug absorption.
 Drug may be given on empty stomach
-to prevent mixing with food stuffs-eg; anthelmintics
-to get an immediate action
 Tetracyclines form insoluble chelates with Ca, Al etc which
reduce their absorption. (so avoid ca+ food stuff)

12.  Dose of a hypnotic required to produce sleep during
daytime is higher than that required to produce
sleep at night.
 Polycyclic hydrocarbons present in cigarette smoke
and hydrocarbon pesticides such as DDT induce
hepatic microsomal enzymes P450- accelerates the
biodegradation.
 Alcohol induces hepatic enzymes and cause rapid

13. 8.PSYCHOLOGICAL
FACTOR
 Efficacy of a drug can be affected by patients beliefs ,
attitudes, and expectations.
 This is particularly applicable to centrally acting drugs.
 PLACEBO
 -an inert substance which is given in the grab of a
medicine.
 -it works by psychological rather than pharmacological
means , it often produces responses equivalent to the
active drug.

14. Placebos do induce physiological responses.
Substances commonly used as placebo are
lactose tablets/capsules and distilled water
injection.

15. 9.PATHOLOGICAL STATES
 Gastrointestinal diseases
 These can increase or decrease absorption of
orally administered drug.
 Eg; in coeliac disease absorption of amoxycillin is
decreased.
 Hepatic diseases
 Serum albumin is decreased so free level of acidic
drugs like NSAIDs, alprozolam etc may increase
and so dose should be decreased.

16. 10.Cumulation
 A drug excreted slowly from the system , on
continuous administration , may accumulate in
toxic amount.
 Chloroquine on prolonged action may cause retinal
damage.

17.  Decrease in pharmacological response of a
drug after repeated administration at very
short interval (occurs rapidly)
Ephedrine
Tyramine
Amphetamine
serotonin

18.  Requirement of large dose of a drug to elicit
an effect ordinarily produced by normal
therapeutic dose of the drug
Eg: sulfonamides

19.  Repeated administration of drug
may induce habit and
dependence.
Psychic dependence
Physical dependence
 Eg: Narcotic analgesics

20. 14.Idiosyncrasy:
 Is an abnormal genetic response and is usually harmful
 It occurs in small portion of population.
e.g. Aplastic anaemia due to chlormaphenicol
 haemolysis by primaquine

21. 15. Drug interactions:
 Enzme induction:
 liver micsrosomal enzymes are induced by a wide
variety of drugs and these affect the metabolism of other
drugs reducing their concentration and hence effect.
 e.g oral contraceptive metabolism is enhanced if
Phenytoin is co-administered ,leading to unplanned
pregnancy
 eg loss of anticougulant effect of Warfarin leading to
danger of thrombosis if barbiturates are administered.
 chronic use of alcohal shows tolerance to general
anesthetics.

22.  Enzyme inhibition
 Certain drugs inhibit the liver microsomal enzymes
,hence increase the activity of drugs which are to be
metabolized by these enzymes.
 Eg. Cimetidine potenciates the effects of
propranolol ,theophylline, warfarin and others

23. 16.Synergism:
 when two drugs are administered at the same time , the
effect increases.
 Summation: the effect of two drugs having same action
are added have aditie effect.
e.g. beta blocker + diuretic have additive antihypertensive
effect
 Potenciation: when one drug increases the effect of other
drug
 e.g. levodopa +cabidopa

24. Thank you