[Drug interactions with antihypertensive drugs]

Numerous of pharmacokinetic and pharmacodynamic interactions with antihypertensive drugs have to be considered. In this review, interactions are analysed in the major organ sites of these interactions and in cardiovascular target sites of arterial hypertension, with respect to the major antihypertensive drugs. Many antihypertensive drugs are metabolized in the liver (calcium antagonists, liposoluble beta-blockers, and some ACE-inhibitors) via the cytochrome-oxidase system. Phenytoin, barbiturates, and rifampin can accelerate the breakdown of these drugs; conversely, cimetidine, which inhibits oxidase system, can increase antihypertensive drug levels, resulted in greater therapeutic effect. Hepatic blood flow can be modified by propranolol and nifedipine with opposite effects. When combined with nifedipine the breakdown of propranolol is accelerated because of an increase of hepatic blood flow. In the kidney, some anti-hypertensive agents interact with other cardiovascular drugs by competing for renal clearance; calcium antagonists alter the renal clearance of digoxin, but the mechanism remains unclear. In vascular muscle cells, excess vasodilatation or vasoconstriction can be observed. The combination of an alpha 1-blocking agent with a dihydropyridine can induce hypotension, which is sometimes severe. Non-steroidal antiinflammatory drugs (NSAIDs) are able to lessen the antihypertensive effects of beta-blockers, diuretics and ACE-inhibitors, via vascular prostaglandin inhibition. The cardiac pharmacodynamic interactions of beta-blockers and calcium antagonists, verapamil and diltiazem, at the sino-atrial node, atrio-ventricular node, conduction system and myocardium are well established and must be avoided. The main interactions with beta-blockers concern calcium antagonists, class I antiarrhythmic drugs and NSAIDs.(ABSTRACT TRUNCATED AT 250 WORDS)