van Zwieten P A
Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
Blood Press Suppl. 1998;2:5-9.
Several types of calcium antagonists (CA) (verapamil, diltiazem, nifedipine and related drugs) may be used as antihypertensives. In practice, the dihydropyridines (nifedipine and related drugs) are the CA used most frequently as antihypertensives. Apart from the lowering of blood pressure CA may lead to other, theoretically beneficial, effects: regression of left ventricular and vascular hypertrophy, renal protection, weak natriuretic, weak antiplatelet, anti-ischaemic and antiatherogenic activity. Several new dihydropyridine CA have been introduced in recent years. The advantages of the newer compounds, such as amlodipine, felodipine, isradipine, lacidipine and lercanidipine, may include: vasoselectivity, hence little or no cardiodepressant activity; an improved kinetic profile, resulting in a slow onset and long duration of action, fewer side-effects such as reflex tachycardia and headache, owing to the slow onset of the antihypertensive action. For a few newer CA a predominant effect on specialized circulatory beds (renal, coronary and cerebral) has been claimed. The new CA, which are clearly lipophilic, deserve special attention. Owing to the lipophilic character of such compounds considerable concentration occurs in lipid-containing membrane depots. The CA thus concentrated are slowly released from these depots and, subsequently, reach their targets, the L-type calcium channels. This phenomenon explains both the slow onset and the long duration of action of these CA. Owing to the slow onset of action reflex tachycardia is virtually absent. The long duration of action allows satisfactory control of blood pressure in hypertensives by means of a single daily dose. A few lipophilic dihydropyridine CA are vasoselective. This property implies that at therapeutic, vasodilatory dosages no cardiodepressant activity occurs. Lercanidipine is a recently introduced example of a lipophilic and vasoselective dihydropyridine CA. It is an effective vasodilator/antihypertensive drug, with a slow onset and long duration of action, which is associated with neither reflex tachycardia nor cardiodepressant activity. Other examples of recently introduced lipophilic CA are lacidipine, barnidipine and manidipine.
几种类型的钙拮抗剂（CA）（维拉帕米、地尔硫䓬、硝苯地平和相关药物）可用作抗高血压药。在实际应用中，二氢吡啶类（硝苯地平和相关药物）是最常作为抗高血压药使用的钙拮抗剂。除了降低血压外，钙拮抗剂还可能产生其他理论上有益的作用：左心室和血管肥厚的消退、肾脏保护、微弱的利钠作用、微弱的抗血小板作用、抗缺血作用和抗动脉粥样硬化作用。近年来已引入了几种新型二氢吡啶类钙拮抗剂。较新化合物（如氨氯地平、非洛地平、伊拉地平、拉西地平和乐卡地平）的优点可能包括：血管选择性，因此几乎没有或没有心脏抑制活性；改善的动力学特征，导致起效缓慢且作用持续时间长，由于抗高血压作用起效缓慢，副作用（如反射性心动过速和头痛）较少。对于一些较新的钙拮抗剂，有人声称它们对特殊循环床（肾、冠状动脉和脑循环床）有主要作用。这些明显具有亲脂性的新型钙拮抗剂值得特别关注。由于这类化合物的亲脂性，它们在含脂质的膜储存库中会大量蓄积。如此蓄积的钙拮抗剂会从这些储存库中缓慢释放，随后到达其靶点——L型钙通道。这一现象解释了这些钙拮抗剂起效缓慢和作用持续时间长的原因。由于起效缓慢，几乎不会出现反射性心动过速。作用持续时间长使得高血压患者每日服用一次就能令人满意地控制血压。一些亲脂性二氢吡啶类钙拮抗剂具有血管选择性。这一特性意味着在治疗性血管舒张剂量下不会出现心脏抑制活性。乐卡地平是最近引入的一种亲脂性且具有血管选择性的二氢吡啶类钙拮抗剂。它是一种有效的血管舒张剂/抗高血压药物，起效缓慢且作用持续时间长，既不伴有反射性心动过速，也没有心脏抑制活性。最近引入的亲脂性钙拮抗剂的其他例子有拉西地平、巴尼地平和马尼地平。
