FACTORS MODIFYING THE

DRUG ACTIONOPTOM FASLU MUHAMMED

Individuals differ both in the degree and the character of the response that a drug may elicitVariation in response to the same dose of a drug between different patients and even in the same patient on different occasions.

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:Females have smaller body size, and so require doses of drugs on the lower side of the dose range.They should not be given quinine during pregnancy and sedatives during lactation

4.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 -to prevent drug inactivation in the

stomach. eg; penicillin v Tetracyclines form insoluble chelates with

Ca, Al etc which reduce their absorption. -

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.

5.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 –purgativeParenterally –sedativeLocally –reduces inflammation

6.GENETICSThe dose of a drug to produce the same effect may vary by 4-6 fold among different individuals.There are specific genetic defects which leads to discontinuous variation in drug response. eg; G-6 –PD deficiency-haemolysis with primaquine and other oxidizing drugs like sulfonamides , dapsone, quinine, etc.

7.PSYCHOLOGICAL FACTOREfficacy 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, eg: they can release endorphins in brain – causing analgesia.Substances commonly used as placebo are lactose tablets/capsules and distilled water injection.

8.PATHOLOGICAL STATESGastrointestinal diseasesThese can increase or decrease absorption of orally administered drug.Eg; in coeliac disease absorption of amoxycillin is decreased but that of cephalexin and cotrimoxazole is increased.Hepatic diseasesSerum albumin is decreased so free level of acidic drugs like NSAIDs, alprozolam etc may increase and so dose should be decreased.

9.Cumulation A drug excreted slowly from the

system , on continuous administration , may accumulate in toxic amount.

Chloroquine on prolonged action may cause retinal damage.