Leonetti G, Cuspidi C
Istituto Scientifico Ospedale S. Luca, Università degli Studi, Milan, Italy.
Drugs. 1995 Apr;49(4):516-35. doi: 10.2165/00003495-199549040-00003.
To find out if there are one or more criteria to guide selection among the ACE inhibitors for the treatment of arterial hypertension, we have reviewed the principal pharmacokinetic and pharmacodynamic aspects of the more frequently used agents of this class of antihypertensive drugs. Among the pharmacokinetic aspects that we have considered, terminal half-life, as related to the duration of the antihypertensive effect, and the route of elimination may have an impact in the clinical selection among the various ACE inhibitors. On the other hand, all the other characteristics have no pragmatic clinical relevance or may be corrected by dosage adjustment. Among the pharmacodynamic aspects, the antihypertensive efficacy of the different ACE inhibitors seems to be very similar, and some of the differences found in different studies are probably due to the population investigated and to the protocol of the study (time of blood pressure measurements, diet, drug dosage etc.). However, some differences can be found among the various ACE inhibitors when the antihypertensive efficacy is evaluated also as trough to peak ratio of blood pressure reduction. Indeed, in respect of the administration schedule of each ACE inhibitor not all the agents of this class have a trough to peak ratio above 50 to 60%, as suggested by the Food and Drug Administration of the US. According to this criterion, especially when blood pressure is measured with 24-hour noninvasive ambulatory blood pressure monitoring, some drugs such as lisinopril, enalapril and trandolapril should be preferred for their higher trough to peak ratios. Left ventricular hypertrophy is significantly reduced by antihypertensive agents, the ACE inhibitors being the most effective. Indeed, the reduction of left ventricle mass for each 1 mm Hg reduction in mean blood pressure is greater for ACE inhibitors than for other classes of antihypertensive agents. However, this effect seems more class related than characteristic of one or more among the various ACE inhibitors. Insulin resistance is elevated in hypertensive patients and it has been thought responsible for or associated with other metabolic abnormalities. ACE inhibitors seem to correct the insulin resistance of hypertensive patients, but this effect also appears to be class related more than limited to one ACE inhibitor or another. Our knowledge of this field is still limited and more studies are necessary, especially to understand the prognostic impact of insulin resistance and/or insulin resistance improvement.(ABSTRACT TRUNCATED AT 400 WORDS)
为了确定是否存在一种或多种标准来指导在治疗动脉高血压时选择血管紧张素转换酶(ACE)抑制剂,我们回顾了这类抗高血压药物中更常用药物的主要药代动力学和药效学方面的内容。在我们考虑的药代动力学方面,与降压作用持续时间相关的终末半衰期以及消除途径可能会对不同ACE抑制剂的临床选择产生影响。另一方面,所有其他特征在临床实践中并无实际意义,或者可以通过调整剂量来纠正。在药效学方面,不同ACE抑制剂的降压效果似乎非常相似,不同研究中发现的一些差异可能归因于所研究的人群以及研究方案(血压测量时间、饮食、药物剂量等)。然而,当将降压效果评估为血压降低的谷峰比时,不同ACE抑制剂之间会发现一些差异。实际上,就每种ACE抑制剂的给药方案而言,并非所有这类药物的谷峰比都高于美国食品药品监督管理局建议的50%至60%。根据这一标准,特别是在使用24小时无创动态血压监测测量血压时,赖诺普利、依那普利和群多普利等一些药物因其较高的谷峰比而更受青睐。抗高血压药物可显著减轻左心室肥厚,其中ACE抑制剂最为有效。事实上,平均血压每降低1毫米汞柱,ACE抑制剂使左心室质量的降低幅度大于其他类别的抗高血压药物。然而,这种效应似乎更多地与类别相关,而非不同ACE抑制剂中某一种或几种的特性。高血压患者存在胰岛素抵抗升高的情况,并且被认为与其他代谢异常有关或为之负责。ACE抑制剂似乎可以纠正高血压患者的胰岛素抵抗,但这种效应似乎也更多地与类别相关,而非局限于某一种ACE抑制剂。我们在这一领域的知识仍然有限,需要更多的研究,特别是要了解胰岛素抵抗和/或胰岛素抵抗改善的预后影响。(摘要截取自400字)