Drug interactions of antihypertensive agents

Abstract

Adverse drug-drug interactions may occur when a major therapeutic mechanism of one drug class (such as bradycardia with a beta blocker) is excessively exaggerated by the addition of another heart-rate slowing antihypertensive, such as verapamil. The most important interactions at the molecular level are those of the hepatic enzyme, cytochrome (CYP) 3A4. A classic example is the inhibitory effect of grapefruit juice in large amounts on CYP3A4, which decreases the breakdown of the antihypertensive agent nifedipine, to produce hypotensive side-effects. Common beneficial drug interactions occur when the normal side-effect of one drug, such as potassium loss with the use of diuretics, is opposed by another drug, such as an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB). The first type of drug interaction is when one of the normal actions of one drug becomes exaggerated, to become a side-effect. The second type of interaction is at a molecular level, when the two drugs are both broken down by the same liver enzyme, e.g. amlodipine and simvastatin.