Pharmacogenetics in Geriatric Medicine: Challenges and Opportunities for Clinical Practice

Alberto      Pilotto; Francesco      Panza; Davide      Seripa

doi:10.2174/138920011796504545

Abstract

The genetics of drug metabolizing enzymes, drug transporters and drug receptors is a very active area of multidisciplinary research, overlapping the interest of medicine, biology, pharmacology and genetics. Indeed, these proteins are virtually responsible for the metabolism, disposition and efficacy of most of available drugs. Variations in the gene encoding these proteins may account for the interindividual differences observed in drug efficacy, including severe clinical consequences such as therapeutic failures and adverse drug reactions. It is well known that the prevalence of both therapeutic failures and adverse drug reactions strongly increased in older subjects, and this did not seem to be always related to the presence of multiple pharmacological treatments, a common status in subjects aged 65 years and over. The present article explored some basic concepts of human genetics that may have important implications in the pharmacogenetics of drug metabolizing enzymes, drug transporters and receptors. We also focus the current knowledge on the genetic basis of the efficacy and the adverse drug reactions of the most common drugs used in the geriatric patient. Thus we explore the status of what we know and what we need to know to forward the application of pharmacogenetics in clinical practice, in order to introduce a personalized treatment project for the older people.

Keywords: Pharmacogenetics, adverse drug reaction, drug efficacy, genetics, elderly, receptors, human genome project, therapeutic failure (TF), cytochrome P450