Drug-drug interactions of beta-adrenoceptor blockers.
Patients with cardiovascular diseases are often treated by concurrent multiple drug therapy. It is therefore plausible that with an increasing number of drugs the risk of drug interactions increases. Such interactions can be either pharmacodynamic (and are due to the mechanism of the administered drugs) or they can be pharmacokinetic (resulting in a reduction or enhancement of drug elimination). Pharmacokinetic interactions can be either due to interactions at the level of drug metabolizing enzymes (most important cytochrome P450 (CYP) enzymes) or interactions at the level of drug transporter proteins (for example P-glycoprotein (MDR1)). It is important to distinguish between both mechanisms because interactions at transporter proteins can be attributed to those drugs that are not enzymatically metabolized. The scope of this article is to give an overview on clinically relevant interactions of the four beta-blockers widely used in the therapy of cardiovascular diseases namely atenolol (CAS 29122-68-7), bisoprolol (CAS 66722-44-9), metoprolol (CAS 37350-58-6) (each beta-1 selective), and carvedilol (CAS 72956-09-3) (beta-1 and beta-2 nonselective). Among these beta-blockers atenolol is mainly eliminated by renal excretion, bisoprolol is in part excreted as parent compound via the renal route (50%), the other 50% are hepatically metabolised, whereas metoprolol and carvedilol are metabolised by CYP2D6. In addition, evidence is accumulating that carvedilol is a substrate for P-glycoprotein. For these four beta-blockers various pharmacodynamic and pharmacokinetic interactions have been demonstrated. Such interactions that result in an altered pharmacokinetics are mainly observed with those beta-blockers that are excreted via metabolism (metoprolol and carvedilol). Accordingly these drugs have a higher potential for drug interactions. However, it should be emphasized that, in general, beta-blockers are well tolerated safe drugs with a large therapeutic index.
Brodde
Otto-Erich
OE
Klinik für Nephrologie, Institut für Pathophysiologie, Klinikum der Universität Essen, Essen, Germany. otto-erich.brodde@uni-essen.de
Kroemer
Heyo K
HK
D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000503:physiopathology; D002352:Carrier Proteins / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D002352:Carrier Proteins; D011943:Receptors, Adrenergic, beta