Leonard R G, Talbert R L
Clin Pharm. 1982 Jan-Feb;1(1):17-33.
The role of calcium in the cardiovascular system, and the pharmacology, pharmacokinetics, and studies evaluating the clinical use of three calcium-channel blocking agents--verapamil hydrochloride, nifedipine, and diltiazem hydrochloride--are reviewed. Inhibition of calcium conductance and alteration of calcium availability cause profound changes in: slow inward current of the cardiac action potential, myocardial contractility and metabolism, blood pressure regulation, and smooth-muscle activity. Calcium-channel blocking agents affect the movement of calcium through these channels in smooth and cardiac muscle; the specific agents in this class differ markedly in their inhibitory effects. Verapamil hydrochloride is useful intravenously for treating supraventricular rhythm disturbances. It is absorbed well when taken orally, but there is an extensive first-pass effect, so that about 20% enters the systemic circulation. The incidence of side effects in patients receiving verapamil is 9-10%; about 1% require discontinuation of therapy. Verapamil is contraindicated in patients with sinus-node disease, unstable atrioventricular block, and shock. Nifedipine has proven useful for hypertension, coronary-artery spasm, and exertional angina; it has little negative inotropic effect. Approximately 90% of an oral dose is absorbed, and 65-70% reaches the systemic circulation after first-pass metabolism. Protein binding of nifedipine ranges from 92 to 98%. Side effects of nifedipine, usually associated with the peripheral vasodilatory action, occur in approximately 15% of patients, requiring discontinuance in 2-5%. Diltiazem hydrochloride has been shown effective in the treatment of coronary-artery spasm; limited studies indicate it may be useful in treating exertional angina, hypertension, and possibly arrhythmias. Diltiazem's oral bioavailability is good (90% reaches systemic circulation), but there is significant interindividual variability between administered dose and resulting plasma concentration. Geriatric patients have delayed absorption and reduced clearance of diltiazem given in sustained-release tablets. Studies of diltiazem are limited at this time. The exact role of calcium-channel blocking agents has not yet been elucidated. However, their ability to influence the calcium channel greatly expands the therapeutic armamentarium for cardiovascular disease and other disorders.
本文综述了钙在心血管系统中的作用，以及三种钙通道阻滞剂——盐酸维拉帕米、硝苯地平和盐酸地尔硫䓬的药理学、药代动力学和评估其临床应用的研究。钙电导的抑制和钙可用性的改变会导致以下方面的深刻变化：心脏动作电位的缓慢内向电流、心肌收缩力和代谢、血压调节以及平滑肌活动。钙通道阻滞剂影响钙通过平滑肌和心肌中的这些通道的移动；该类中的特定药物在其抑制作用方面有显著差异。盐酸维拉帕米静脉注射可用于治疗室上性心律失常。口服时吸收良好，但有广泛的首过效应，因此约20%进入体循环。接受维拉帕米治疗的患者副作用发生率为9% - 10%；约1%的患者需要停药。维拉帕米禁用于窦房结疾病、不稳定房室传导阻滞和休克患者。硝苯地平已被证明对高血压、冠状动脉痉挛和劳力性心绞痛有效；它几乎没有负性肌力作用。口服剂量约90%被吸收，首过代谢后65% - 70%到达体循环。硝苯地平的蛋白结合率为92%至98%。硝苯地平的副作用通常与外周血管舒张作用有关，约15%的患者会出现，2% - 5%的患者需要停药。盐酸地尔硫䓬已被证明对冠状动脉痉挛有效；有限的研究表明它可能对治疗劳力性心绞痛、高血压以及可能的心律失常有用。地尔硫䓬的口服生物利用度良好（90%到达体循环），但给药剂量与所得血浆浓度之间存在显著的个体差异。老年患者服用缓释片时地尔硫䓬的吸收延迟且清除率降低。目前关于地尔硫䓬的研究有限。钙通道阻滞剂的确切作用尚未阐明。然而，它们影响钙通道的能力极大地扩展了心血管疾病和其他疾病的治疗手段。
