Brown Teresa, Gonzalez Jimmy, Monteleone Catherine
Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Department of Pharmacy Practice, Western New England University School of Pharmacy, Springfield, MA, USA.
J Clin Hypertens (Greenwich). 2017 Dec;19(12):1377-1382. doi: 10.1111/jch.13097. Epub 2017 Oct 10.
According to the National Health and Nutrition Examination Survey 2012, one third of antihypertensive prescriptions in the United States in the past decade were for angiotensin-converting enzyme inhibitors (ACEIs). An important and serious side effect of ACEIs is angioedema caused by a reduction in bradykinin degradation. In a national medical chart abstraction study conducted at the US Veterans Affairs Health Care System in 2008, 0.20% of ACEI initiators developed angioedema while on the medication. The angiotensin-converting enzyme is a part of the renin-angiotensin system that converts angiotensin I to angiotensin II. It is additionally responsible for the degradation of bradykinin, which is generated from high molecular weight kininogen by kallikrein. Via bradykinin 2 receptors, bradykinin affects vascular permeability and stimulates the release of substance P, which is a peptide that causes vasodilation and fluid extravasation into tissues. Inhibition of the angiotensin-converting enzyme and subsequent blockade of bradykinin degradation is thought to be a likely explanation for ACEI-induced angioedema. Studies have shown that blacks, women, and smokers are at an increased risk for ACEI-induced angioedema. A 2005 study identified black race, history of drug rash, age older than 65 years, and seasonal allergies as independent risk factors for angioedema related to enalapril. Angioedema may occur at any time during treatment with ACEIs and may continue after the medication is discontinued. The degree of ACEI-angiotensin receptor blocker angioedema cross-reactivity is difficult to determine from the literature. However, multiple studies have reported relatively low rates of native angioedema with angiotensin receptor blockers (approximately half that of ACEIs, or 0.1%) and a low incidence of cross-reactivity (<10%). Common treatments for angioedema, such as antihistamines and glucocorticoids, have not been shown to be effective in ACEI-induced angioedema. However, medications that have been used for acute treatment of hereditary angioedema and target the factors that cause ACEI-mediated angioedema are being explored.
根据2012年美国国家健康与营养检查调查，在过去十年中，美国三分之一的抗高血压处方是用于血管紧张素转换酶抑制剂（ACEI）。ACEI的一个重要且严重的副作用是由于缓激肽降解减少导致的血管性水肿。在2008年于美国退伍军人事务医疗保健系统进行的一项全国性医疗图表摘要研究中，0.20%开始使用ACEI的患者在用药期间出现了血管性水肿。血管紧张素转换酶是肾素 - 血管紧张素系统的一部分，它将血管紧张素I转化为血管紧张素II。它还负责缓激肽的降解，缓激肽是由激肽释放酶从高分子量激肽原产生的。通过缓激肽2受体，缓激肽影响血管通透性并刺激P物质的释放，P物质是一种引起血管舒张和液体渗入组织的肽。血管紧张素转换酶的抑制以及随后缓激肽降解的阻断被认为是ACEI诱导血管性水肿的一个可能解释。研究表明，黑人、女性和吸烟者发生ACEI诱导血管性水肿的风险增加。一项2005年的研究确定黑人种族、药物皮疹史、65岁以上年龄以及季节性过敏是与依那普利相关的血管性水肿的独立危险因素。血管性水肿可能在使用ACEI治疗期间的任何时间发生，并且在停药后可能继续。从文献中难以确定ACEI与血管紧张素受体阻滞剂血管性水肿的交叉反应程度。然而，多项研究报告血管紧张素受体阻滞剂引起的原发性血管性水肿发生率相对较低（约为ACEI的一半，即0.1%），交叉反应发生率也较低（<10%）。血管性水肿的常见治疗方法，如抗组胺药和糖皮质激素，在ACEI诱导的血管性水肿中尚未显示有效。然而，正在探索用于遗传性血管性水肿急性治疗且针对导致ACEI介导血管性水肿的因素的药物。
