Factors modifying the DRUG action

Sarita Sharma Assistant professor Department of pharmacology Mumbai

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

1.Body weight/size:It influences the concentration of drug

attained at the site of actionThe 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

doseadult Average x 70

(kg)BW dose Individual

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'.........( doseadult x 12Age

Age dose Child

formula) sg'...(Dillindose......adult x 20

Age dose Child

Higher proportion of water Lower plasma protein levels

More available drug Immature liver/kidneys

Liver often metabolizes more slowlyKidneys may excrete more slowly

Elders: In elderly, renal function progressively

declines (intact nephron loss) and drug doses have to be reduced

Chronic disease statesDecreased plasma protein bindingSlower metabolismSlower excretionDietary deficienciesUse of multiple medicationsLack of compliance

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

(4) SPECIES AND RACESPECIES –

Some drugs resistant with some speciesRats- DigitalisRabbits-Atropine

RACE-Blacks require higher and Mongols

require lower conc. of Ephedrine and Atropine for pupilary dilatation.

Fast acylators and slow acylators of isonizide.

(5)GENETIC FACTORSGenetically mediated variations in

drug responsesDifferent rates of metabolismEx.

PseudocholinestrasesG6PD defeciencyAcetylation & hydroxylation

(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

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) -

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 metabolism of certain drugs.

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.

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

9.PATHOLOGICAL STATESGastrointestinal 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.

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.

11. TACHYPYLAXIS

Decrease in pharmacological response of a drug after repeated administration at very short interval (occurs rapidly)

EphedrineTyramineAmphetamine serotonin

12.Drug tolerance

Requirement of large dose of a drug to elicit an effect ordinarily produced by normal therapeutic dose of the drug

Eg: sulfonamides

13. DRUG DEPENDENCE

Repeated administration of drug may induce habit and dependence.Psychic dependencePhysical dependence

Eg: Narcotic analgesics

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

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.

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

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

Thank you