Clinical pharmacology, pharmacokinetics, and hemodynamic effects of nicardipine.

The dihydropyridine derivatives constitute a distinct subcategory of calcium channel blockers that have marked peripheral vascular effects with minimal or no electrophysiologic actions when administered to intact animals or humans. These dihydropyridine derivatives are structurally similar to nifedipine, the most widely studied dihydropyridine. The derivatives have varying affinities for different regional circulations, and there may be an important relationship between structure and activity of these compounds with respect to the predilection of the site of their action in vascular tissue. It is possible that such differences may be of clinical significance. As a class, the dihydropyridines exert reasonably distinct hemodynamic changes that may be of particular importance in the treatment of hypertension, cardiac failure, and regurgitant valvular lesions. Nicardipine hydrochloride is a newer agent that has undergone extensive evaluation in recent years. Pharmacologically and electrophysiologically, it resembles other dihydropyridines. Unlike nifedipine, however, it can be administered by both the intravenous and oral routes. There are additional differences between its properties and those of other calcium channel blockers. For example, nicardipine appears to produce a greater increase in coronary sinus blood flow than other calcium channel blockers. The clinical significance of this finding is unclear. In addition, nicardipine appears to increase myocardial contractility, even in patients with severe congestive cardiac failure. Nicardipine produces a dose-dependent decrease in blood pressure and systemic vascular resistance with increases in heart rate, left ventricular dP/dt, LV ejection fraction, cardiac output, and stroke work index, but no significant change in LV end-diastolic pressure. Clearly, the drug has negligible venodilator actions.(ABSTRACT TRUNCATED AT 250 WORDS)