Risk factors in elderly taking psychotropic drugs: Significance of genetic polymorphism in drug oxidation

The pattern of adverse drug reactions in elderly is both quantitatively and qualitatively different from that in younger patients. This relates to age-associated changes in physiology, pharmacodynamics and pharmacokinetics. The combination of several risk factors including the use of several drugs concurrently is of special importance in the elderly. Extreme pharmacokinetic variations due to genetic polymorphism in drug action, may, although not in itself age-related, cause particular problems in the elderly. The best-studied drug oxidation polymorphism, related to the model substances sparteine and debrisoquine, is important for several types of drugs, including tricyclic antidepressants, several neuroleptics and several other types of drugs. Sparteine/debrisoquine-poor metabolizers will with standard doses of tricyclic antidepressants or neuroleptics develop very high steady-state blood levels, and this may cause particular problems in the elderly. There are several examples of how the genetic polymorph...