VASCULAR SELECTIVE CALCIUM-ENTRY BLOCKERS IN THE TREATMENT OF CARDIOVASCULAR DISORDERS - FOCUS ON FELODIPINE

Calcium entry through L-type calcium channels is essential for contrac tion of both arterial smooth muscle and the myocardium, and is importa nt in cardiac conduction. First-generation calcium entry blockers lack or have a modest degree of vascular selectivity and inhibit cardiac f unction at doses producing therapeutic arterial dilatation. Such agent s may cause deterioration in patients with left ventricular dysfunctio n, and their combination with a beta-adrenergic blocker may adversely affect cardiac contractility and conduction. Development of newer agen ts has focused on obtaining a higher degree of vascular selectivity. F elodipine is a highly vascular selective calcium entry blocker, with a vascular selectivity ratio greater than 100, as shown experimentally. Isradipine and nicardipine are also vascularly selective calcium entr y blockers. Hemodynamic studies in patients with hypertension, coronar y artery disease, congestive heart failure, or in patients receiving b eta-adrenergic blockade, show that felodipine can produce profound art eriolar dilatation without the negative effects of left ventricular sy stolic performance. Furthermore, felodipine alone or when added to a b eta-adrenergic blocker does not interfere with cardiac conduction. The primary mechanism that accounts for the efficacy of dihydropyridine c alcium entry blockers in hypertension and angina pectoris is arterial dilation, whereas nondihydropyridines may also derive part of their ef fect from inhibition of cardiac performance. As some of these patients , most commonly the elderly, have concomitant left ventricular dysfunc tion, it should be advantageous to avoid myocardial depression in the treatment of their primary disease. Preliminary studies in patients wi th heart failure indicate that felodipine and amlopidine may improve h emodynamics, reduce neurohormonal activation, and increase exercise to lerance, but final conclusions must await the randomized clinical tria ls now underway.