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.