Pharmacogenetics and drug-induced arrhythmias

Drugs are widely recognized to vary in the beneficial and undesirable effects they produce in human subjects. The understanding that variants (polymorphisms and mutations) in the human genome are common and may well modulate both disease and its response to drugs, is a critical new concept in understanding mechanisms of drug action and their variability in human subjects. Variability can arise because of variability in genes encoding molecules of drug disposition, in genes encoding molecules that drugs target, or in genes that modulate the overall activity of the complex biological systems within which drugs act. The evolving understanding of the genetic basis of variability in response to drugs used in the treatment of sudden cardiac death has important implications not only for the treatment of patients who have survived an episode, but also for helping formulate a framework for further understanding mechanisms of drug action at the genetic level. (C) 2001 Elsevier Science B.V. All rights reserved.