Individual Variation in Responses to Drugs

There are some well-known examples of individual variation in response to drugs. Propranolol is a drug commonly used to treat high blood pressure. About 8% of the general population are poor hydroxylators of propranolol. Because propranolol is extensively metabolized affected individuals show exaggerated and prolonged responses to this drug. 

Many disease states can cause individual variation in response to drugs. Any disease that results in alteration in the pharmacokinetics of a drug will create these variations. Diseases of the liver and kidney, any disease that affects intestinal motility, mal-absorption syndromes and any condition that reduces plasma protein concentration are all implicated. Some diseases can alter the physiological sensitivity to a drug at its site of action. 

Apart from the possibility of adverse drug reactions occurring, individuals show variation in response to drugs and this is particularly likely in the very young and the very old. 

In addition to individual variation in susceptibility to adverse effects of drugs, there is substantial variation in degree of effectiveness. Silber pointed out that in trials of many different drugs for many different conditions, the rates for poor and nonresponders frequently exceeded 50% of the treated subjects. But these drugs are considered effective because the response rate in the treated was greater than that of the controls in a way unlikely due to chance. 

E. Variation in response to a drug among different individuals is most likely to occur with a drug showing a large therapeutic index. 

Defective oxidation. Variation in response to some drugs can be attributed to genetic polymorphisms involving oxidation of their carbon centres (see Metabolism p. 112). The condition was recognised by abnormal metabolism and response to a standard dose of debrisoquine. Individuals may be classed as extensive or poor oxidisers and the latter are at special risk of adverse effects from drugs whose inactivation is strongly dependent on the defective... 

In the final analysis the clinician s question as to which drug is best for the patient in pain cannot be answered by experimental pharmacological studies. A clinical study comparing four NSAIDs found individual variations in response so striking that several drugs may need to be tried to find the right one for a particular patient. 

Ethnic differences have been shown to influence response to psychotropic medications. Much of the focus on the explanation for such differences has been on drug-metabolizing (CYP) enzymes of the liver and their sway over pharmacokinetic factors. It is now well recognized that differences in the distribution of polymorphic variants of CYP enzymes exist between different ethnic groups. However, within ethnic groups there are considerable inter-individual variations in drug kinetics, which may not be accounted for solely by genetic variation. Responses to pharmacotherapy are multifaceted and involve the interaction of environmental and... 

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