Hasegawa G R
Department of Pharmacy, St. Joseph Mercy Hospital, Ann Arbor, MI 48106.
Clin Pharm. 1988 Feb;7(2):97-108.
The chemistry, pharmacology, pharmacokinetics, clinical uses, and adverse effects of nicardipine, nitrendipine, and bepridil are reviewed. Nicardipine, nitrendipine, and bepridil are calcium antagonists under investigation for the treatment of cardiovascular disorders. Nicardipine and nitrendipine share a common dihydropyridine nucleus with the calcium antagonist nifedipine; bepridil is unrelated to other known calcium antagonists. Like nifedipine, nicardipine and nitrendipine produce peripheral vasodilation as their predominant in vivo effect. Bepridil has vascular, sinoatrial and atrioventricular nodal, and myocardial effects qualitatively similar to those of the calcium antagonist verapamil; it also interferes with the fast sodium channel and prolongs refractoriness in atrial and ventricular tissue. Nicardipine and nitrendipine undergo extensive first-pass hepatic extraction after oral administration; oral bioavailability of bepridil is about 60%. All three drugs are highly protein bound and have been reported to increase plasma digoxin concentrations. Both nicardipine and nitrendipine are effective antihypertensive agents used alone or combined with diuretics, beta blockers, or angiotensin-converting enzyme inhibitors. Nicardipine and bepridil effectively control angina, and preliminary studies indicate that nitrendipine has antianginal properties. Bepridil may be useful in the treatment of various cardiac arrhythmias; however, its tendency to cause or worsen cardiac arrhythmias and its association with torsade de pointes may limit its usefulness. Nicardipine and nitrendipine have similar adverse effect profiles, with vasodilation-related complaints being most common. Since nicardipine, nitrendipine, and nifedipine are similar in efficacy and safety, the eventual availability of sustained-release dosage forms may determine how these drugs are ultimately used. Bepridil is an effective antianginal drug, but, because of its proarrhythmic potential, it should probably not be used as a first-line agent.
本文综述了尼卡地平、尼群地平和苄普地尔的化学性质、药理学、药代动力学、临床用途及不良反应。尼卡地平、尼群地平和苄普地尔均为正在研究用于治疗心血管疾病的钙拮抗剂。尼卡地平和尼群地平与钙拮抗剂硝苯地平具有共同的二氢吡啶核；苄普地尔与其他已知钙拮抗剂无关。与硝苯地平一样，尼卡地平和尼群地平在体内的主要作用是产生外周血管舒张。苄普地尔对血管、窦房结和房室结以及心肌的作用在性质上与钙拮抗剂维拉帕米相似；它还干扰快速钠通道并延长心房和心室组织的不应期。尼卡地平和尼群地平口服给药后在肝脏经历广泛的首过提取；苄普地尔的口服生物利用度约为60%。这三种药物均与蛋白质高度结合，据报道都会增加血浆地高辛浓度。尼卡地平和尼群地平都是有效的抗高血压药物，可单独使用或与利尿剂、β受体阻滞剂或血管紧张素转换酶抑制剂联合使用。尼卡地平和苄普地尔可有效控制心绞痛，初步研究表明尼群地平具有抗心绞痛特性。苄普地尔可能对治疗各种心律失常有用；然而，其导致或加重心律失常的倾向以及与尖端扭转型室速的关联可能会限制其用途。尼卡地平和尼群地平的不良反应谱相似，与血管舒张相关的不适最为常见。由于尼卡地平、尼群地平和硝苯地平在疗效和安全性方面相似，最终缓释剂型的可用性可能会决定这些药物的最终使用方式。苄普地尔是一种有效的抗心绞痛药物，但由于其有致心律失常的可能性，可能不应作为一线药物使用。
