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噻嗪类利尿剂在原发性(特发性)高血压患者中的使用

Authors
Johannes FE Mann, MD
Karl F Hilgers, MD
Section Editor
George L Bakris, MD
Deputy Editor
John P Forman, MD, MSc
Translators
牛晓琳, 主治医师

引言

噻嗪型和噻嗪样利尿剂是原发性高血压的主要治疗药物。这类药物中最常用的是氢氯噻嗪，过去的常用剂量为50-100mg/d。这样的剂量可引起代谢性并发症及电解质并发症。后来证实低剂量治疗有效，且副作用的发生率低得多。已有研究证实，与噻嗪型利尿剂氢氯噻嗪相比，噻嗪样利尿剂氯噻酮和吲达帕胺的降压效果更强，更重要的是可以减少心血管事件和死亡[1]。而目前还没有试验证实氢氯噻嗪有死亡率方面的获益。

本专题将总结噻嗪型和噻嗪样利尿剂的降压机制、大剂量使用此类利尿剂的常见副作用以及小剂量使用的益处。这些药物治疗原发性高血压的作用将在别处讨论。 (参见“原发性高血压的药物治疗选择”)

抗高血压的机制

尚未完全理解噻嗪类利尿剂降低血压(blood pressure, BP)的机制。血压反应似乎需要首先减少容量(平均体重减轻1.5kg左右)，因为未在利尿剂抵抗或摄入高盐膳食的患者中观察到这一作用[2]。有反应的患者在用药1周内血压开始下降，而缓慢下降可持续长达12周[3]。对于轻至中度原发性高血压患者，长效利尿剂比短效袢利尿剂更有效，因为前者可以维持血管内容量的降低。 (参见“对比噻嗪类利尿剂与袢利尿剂在高血压治疗中的作用”)

最初的降压反应由血浆容量和心输出量的轻度下降介导[3,4]。然而，低血容量引起的肾素-血管紧张素系统激活会削弱血压降低的幅度[2,5]。因此，对噻嗪型或噻嗪样利尿剂无反应的患者与有反应患者可能有相同的利尿作用，但由于全身血管阻力增加，无反应的患者血压几乎无下降(图 1)[3]。这种关系解释了利尿剂与血管紧张素转化酶抑制剂(angiotensin-converting enzyme inhibitor, ACEI)或血管紧张素Ⅱ受体阻滞剂(angiotensin receptor blocker, ARB)之间的协同作用。ACEI和ARB可以阻断血管紧张素Ⅱ的生成或其作用，从而让利尿剂完全发挥降压作用。 (参见“高血压治疗中的肾素-血管紧张素系统抑制”)

维持血压长期下降可使初始血流动力学变化出现部分逆转：血浆容量和心输出量部分上升至基线水平，而全身血管阻力下降[3,4]。尽管血浆容量接近正常化，但相对于血管扩张引起的血管容量增加，血浆容量很可能仍然偏低。这一假设与以下两项观察结果相一致：(1)血浆肾素活性持续升高；(2)停用利尿剂，在全身血管阻力下降出现任何逆转前，导致快速的液体潴留[6]。

          

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Literature review current through: 2017-06 . | This topic last updated: 2017-03-08.
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