Factors Modifying the Drug Action
The response to a drug varies from one individual to the other. The followings are the factors which are responsible for variation in drug effects.
Age: Children are hyper reactive to certain drugs. The reasons are immaturity of renal functions or poor development of enzymes needed for in activation. So a lesser dose must be given for children than for adults.
Body Weight: Body weight has a definite influence on the concentration of the drug at the site of action. So the dose of a drug must be suitably adjusted in case of lean or obese individuals.
Sex: Females have smaller body size and require doses that are on the lower side of the range. Subjective effects of drugs may differ in females because of their mental makeup. In women consideration must also be given at menstruation, lactation & pregnancy. e.g. Ketoconazole causes loss of libido in men but not in women.
Species and Race: Rabbits are resistant to atropine. Blacks require higher and Mongals required lower concentrations of atropine and ephedrine to dilate their pupil.
Genetics: The effects of a drug may vary due to genetic factors like inherited enzyme deficiencies. E.g. Primaquine produces haemolysis in individuals with a deficiency of Glucose-6-phosphate dehydrogenase (G-6-PD).
Route of Administration: Route of administration governs the speed and intensity of the drug response. E.g. magnesium sulfate given orally causes purgation, applied locally on inflamed area decrease swelling, while given i.v it produces CNS depression and hypotension.
Environmental Factors: Hypnotics taken at night and in silence surroundings may work more easily.
Time of Administration: This factor has a definite effect on drug absorption and on its effect. E.g. Drug which produces nausea and vomiting (due to gastric irritation) should be taken after food. But anthelmintics should be taken in empty stomach.
Physiological Factors: Body temperature and acid base status are some factors which modify drug effects. E.g. salicylats lower body temperature only in fever but not in normal individuals.
Psychological Factors: The effect of drug may be modified by psychogenic response of the patient. Sometimes it is necessary to please the patient by psychological means. Placebo which is a dummy medication (having the same colour smell etc. as the actual medication) is used for this purpose.
Pathological States: The effect of a drug may be modified in pathological conditions. E.g. hyper thyroid individuals require a large dose of morphine. Hepatotoxic drugs (primaquine) should be avoided in liver disease.
Cumulation: Any drug will cumulate in the body if rate of administration is more than rate of elimination. E.g. digitalis are excreted slowly. Repeated administration is lead to accumulation in the body, so to produce toxicity. Prolonged use of chloroquine causes retinal damage.
Drug interaction: The effects of a drug may be modified by the prior or simultaneous administration of another drug. One drug can increase or decrease the function of another drug. E.g. ammonium chloride increases the action of mercurial diuretics (mersalyl). Atropine decreases the function of acetylcholine at muscarinic receptors.
Tolerance: It is the un usual resistance to normal therapeutic dose of a drug. So large dose is required to produce an effect. Tolerance can be classified as –
True tolerance– It can be produced on both oral and parenteral administration of a drug. When it occurs by nature, it is called as Natural tolerance e.g. tolerance for atropine in rabbits. This can occur even without previous exposure to the drug. Acquired tolerance is produced on repeated administration e.g. tolerance for the euphoria effect of morphine.
Tachyphylaxis– It is an acute type of tolerance. It occurs on repeated administration of a drug at short intervals. e.g. Tyramine (cheese protein) produces decreased rise in blood pressure on repeated administration. This decreased response is due to depletion of noradrenaline stores from sympathetic nerves.