Thiazide effects and adverse effects: insights from molecular genetics.
Thiazide effects and adverse effects: insights from molecular genetics.
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DOI：
10.1161/hypertensionaha.109.129171
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发表时间：
2009-08
期刊：
影响因子：
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通讯作者：
Loffing J
中科院分区：
文献类型：
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作者：
Ellison DH;Loffing J
临床医学中持续时间最长的争论之一没有消失的迹象；就在噻嗪类药物似乎重新成为治疗高血压的一线药物时，新的担忧出现了，2-4导致一些人再次质疑它们的作用。噻嗪类药物是有效的抗高血压药物，记录时间长，成本低。对其使用的主要担忧来自于它们容易引起低钾血症、损害葡萄糖耐量、增加血清胆固醇和增加血清尿酸。很少有医疗争议能像这样引起如此大的热议，一些成熟的阵营表明了自己的立场，似乎拒绝改变。6-9抗高血压和降脂治疗预防心脏病发作试验是迄今为止进行的最大的抗高血压单一疗法研究，10旨在确定高危高血压患者的最佳一线治疗方法；然而，尽管它的规模和众多的出版物，其影响和权威继续争议。这次审查的目的不是在这场辩论中站队，而是注入一个独特的，有时被忽视的观点；在过去的15年中，分子生物学和人类遗传学的显著发展为高血压的发病机制、利尿剂的机制和不良反应提供了实质性的见解。利尿剂的支持者和反对者在讨论这个话题时往往忽视了这些发展；这篇简要综述的目的是将这些发展纳入辩论，目的是产生可以科学解决的问题。
One of the longest-running debates in clinical medicine shows no sign of disappearing; just when it seems that thiazides have reassumed their role as front-line drugs to treat hypertension, 1 new concerns emerge, 2–4 leading some to question their role once again. 5 Thiazides are effective antihypertensives with long track records and low cost. The major concerns about their use arise from their tendency to cause hypokalemia, impair glucose tolerance, increase serum cholesterol, and increase serum uric acid. Few medical controversies have generated as much heat, with wellestablished camps staking out positions that appear resistant to change. 6–9 The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, the largest study of antihypertensive monotherapy ever performed, 10 was intended to identify the best first-line treatment for high-risk hypertensive individuals; however, despite its size and the numerous resulting publications, its implications and authority continue to be disputed. The goal of this review is not take sides in this debate but rather to inject a distinct, and sometimes neglected, perspective; during the past 15 years, remarkable developments in molecular biology and human genetics have provided substantial insights into the pathogenesis of hypertension and mechanisms and adverse effects of diuretics. Diuretic proponents and antagonists alike often neglect these developments when addressing the topic; it is the purpose of this Brief Review to integrate these developments into the debate with the goal of generating questions that can be addressed scientifically.