Enzymes and pharmacogenetics of cardiovascular drugs.
To select the best drug for a patient, physicians can use pharmacogenomics to optimize the effective drug and to minimize adverse reactions. Many enzymes are involved in the pharmacokinetic and pharmacodynamic sources of cardiovascular drugs. Taking the antihypertensive drugs as an example, the variability in blood pressure response is very high in different individuals, some of them having an increase in blood pressure. The most important proteins involved in the patient response to a drug are cytochrome P450 (CYP) 2D6, CYP2C19, CYP3A4 and the ABCB1 transporter. These enzymes, at the origin of important side effects or drug interactions, are responsible, at a great extent, of the cardiovascular drug response variability. Genotyping of the most important CYP today is easy while no reliable tool has been developed for the ABC transporters ATPase dependent and linked to the other phase I and phase II enzymes. The second relevant group of enzymes are involved in pharmacodynamic action of cardiovascular drugs: enzymes of the renin-angiotensin system and enzymes of the lipid metabolism. Angiotensin converting enzyme (ACE) is the most studied target with a relevant insertion deletion polymorphism. Contradictory reported data could be explained by ethnic differences or patient sample size which are often too small.
Siest
Gérard
G
INSERM U.525, Université Henri Poincaré Nancy 1, Nancy, France. Gerard.Siest@pharma.uhp-nancy.fr
Jeannesson
Elise
E
Visvikis-Siest
Sophie
S
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D002317:Cardiovascular Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004798:Enzymes / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D000960:Hypolipidemic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D010597:Pharmacogenetics
D000806:Angiotensin-Converting Enzyme Inhibitors; D002317:Cardiovascular Agents; D002352:Carrier Proteins; D004798:Enzymes; D000960:Hypolipidemic Agents; D003577:Cytochrome P-450 Enzyme System