[Drug interactions with calcium inhibitors in man].
The most common interactions concern cardiovascular drugs. The combination of calcium antagonists (CA) and beta-blockers is more effective than single-agent therapy in stable effort angina and hypertension. But there is an increased risk of hemodynamic or electrophysiological side effects in patients with left ventricular or sinus dysfunction, or disturbances of conduction. Pharmacokinetic interactions have been observed in particular with verapamil (VE) which increases propranolol bioavailability. VE increases the T1/2 of elimination and plasma digoxin concentration following single or prolonged administration. The primary mechanism appears to be renal. These modifications increase the risk of digitalis intoxication. Diltiazem (DTZ) inconsistently increases steady state plasma digoxin levels. In healthy subjects, nifedipine (NF) increases plasma digoxin concentrations and decreases digoxin renal clearance. These findings have not been observed in patients with heart failure. NF therefore leads to less marked modifications in digitalis pharmacokinetics than do VE and DTZ. Nitrendipine and nicardipine interact only slightly with digoxin, and consequently there are no pharmacodynamic effects. In healthy subjects, VE increases quinidine t1/2 and markedly decreases its metabolic clearance. Conversely, quinidine increases plasma NF levels. The primary CA are extensively metabolized by liver microsome oxidases. These result in interactions with the drugs that are also metabolized by these enzymes, or able to modify their activity. VE and DTZ decrease antipyrine and carbamazepine clearance. VE, DTZ and nicardipine lead to a marked increase in plasma ciclosporin levels. Cimetidine, but not ranitidine, increases plasma NF levels. The effects on VE are controversial. Prolonged rifampicin treatment decreases plasma VE levels.
Cheymol
G
G
Engel
F
F
D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000818:Animals; D002121:Calcium Channel Blockers / Q000378:metabolism*; D004071:Digitalis Glycosides / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D004071:Digitalis Glycosides
Interactions médicamenteuses observées chez l'homme avec les inhibiteurs calciques.