Fischler M P, Follath F
Departement für Innere Medizin, Universitätsspital, Zürich.
Schweiz Med Wochenschr. 1999 Jul 27;129(29-30):1053-60.
ACE inhibitors are well established in the treatment of arterial hypertension, heart failure and diabetic and/or hypertensive nephropathy with albuminuria. The important trials for the various indications are briefly discussed. In Switzerland 11 ACE inhibitors are available for clinical use, differing mainly in their pharmacokinetic and pharmacodynamic properties. The characteristics of practical relevance regarding oral bioavailability, elimination mechanisms and half-life, as well as the necessary dosage modifications in patients with renal, hepatic and cardiac failure, are presented. All ACE inhibitors except captopril and lisinopril are administered as prodrugs. The bioavailability among ACE inhibitors varies widely with a range from 11% (trandolapril) to more than 60% (captopril). The great majority of ACE inhibitors are eliminated predominantly through the kidneys. However, benazepril, fosinopril, ramipril, spirapril and trandolapril also have a hepatic (metabolic) route of elimination. Since half-life varies from 1 h (captopril) to 30 h (spirapril) we drew up, for simplicity, a table of 3 groups with short, medium and long t1/2. In renal insufficiency dose adjustment is required only below a creatinine-clearance level of 30 ml/min. These dosage reductions are not required in liver diseases, but renally excreted drugs such as lisinopril should be preferred. Treatment with ACE inhibitors in severe heart failure should be initiated carefully, with low doses and concomitant diuretic treatment added or maintained. Most common adverse effects of ACE inhibitors are hypotension, cough, hyperkalaemia and renal failure. Less frequent adverse effects are angioedema, bone marrow suppression and also foetal damage. Thus, ACE inhibitors are contraindicated in pregnancy.
血管紧张素转换酶(ACE)抑制剂在治疗动脉高血压、心力衰竭以及伴有蛋白尿的糖尿病和/或高血压性肾病方面已得到广泛应用。本文简要讨论了针对各种适应症的重要试验。在瑞士,有11种ACE抑制剂可供临床使用,它们的主要区别在于药代动力学和药效学特性。文中介绍了与口服生物利用度、消除机制和半衰期相关的实际特性,以及肾功能不全、肝功能不全和心力衰竭患者所需的剂量调整。除卡托普利和赖诺普利外,所有ACE抑制剂均以前药形式给药。ACE抑制剂之间的生物利用度差异很大,范围从11%(群多普利)到超过60%(卡托普利)。绝大多数ACE抑制剂主要通过肾脏消除。然而,贝那普利、福辛普利、雷米普利、螺普利和群多普利也有肝脏(代谢)消除途径。由于半衰期从1小时(卡托普利)到30小时(螺普利)不等,为简单起见,我们列出了一个分为短、中、长半衰期三组的表格。在肾功能不全时,仅在肌酐清除率低于30 ml/min时才需要调整剂量。在肝脏疾病中不需要进行这些剂量减少,但应优先选择经肾脏排泄的药物,如赖诺普利。在严重心力衰竭中使用ACE抑制剂治疗时应谨慎开始,采用低剂量,并加用或维持利尿剂治疗。ACE抑制剂最常见的不良反应是低血压、咳嗽、高钾血症和肾衰竭。较不常见的不良反应是血管性水肿、骨髓抑制以及对胎儿的损害。因此,ACE抑制剂在妊娠期间禁用。