[Pharmacogenomics. What is relevant for the internal medicine specialist?].
Epidemiological observational studies have shown existing interindividual and interethnical differences in drug metabolism. This results in a great variety of effects and side effects of drugs. One reason for these variabilities are genetic polymorphisms which occur on the basis of single-nucleotide exchanges or insertional and deletional mutations. Such mutations may involve transport proteins or metabolizing enzymes of phase I and phase II reactions, as cytochrome P450, glucuronidases and enzymes which metabolize cytostatics. The differences in pharmacokinetics and pharmacodynamics have an impact on therapeutical outcome. Dosage adjustments should be undertaken before the initiation of therapy in reflection of modern genotyping. This is particularly important in oncology to avoid life-threatening adverse drug reactions. Examples of cardiovascular and neurological diseases are presented to demonstrate the impact of genetic polymorphisms on the incidence and prevalence of diseases as well as the responses to medications like beta blockers, ACE inhibitors and psychotropic drugs. Finally, additional factors are summarized, which may contribute to the large diversity of drug reactions.
Krüth
P
P
Institut für Klinische Pharmakologie, Fakultät für Klinische Medizin Mannheim der Ruprecht-Karls-Universität Heidelberg.
Wehling
M
M
D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004342:Drug Hypersensitivity / Q000235:genetics*; D004789:Enzyme Activation / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D007388:Internal Medicine; D010597:Pharmacogenetics; D010599:Pharmacokinetics; D011110:Polymorphism, Genetic / Q000235:genetics
D003577:Cytochrome P-450 Enzyme System