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心房颤动的新药理靶点和治疗方法。

New pharmacological targets and treatments for atrial fibrillation.

机构信息

AstraZeneca R&D Mölndal, Sweden.

出版信息

Trends Pharmacol Sci. 2010 Aug;31(8):364-71. doi: 10.1016/j.tips.2010.05.001. Epub 2010 May 31.

Abstract

Atrial fibrillation (AF) is an arrhythmia of growing clinical concern that is increasing in prevalence and is associated with significant morbidity and mortality. Pharmacological agents remain the first-line therapy for the AF patient, and the potential advantages of sinus rhythm maintenance motivate continued efforts to identify novel pharmacological means to restore and maintain sinus rhythm. Traditional antiarrhythmic agents only moderately suppress AF and present problematic concerns of proarrhythmia and extracardiac toxicity. Current investigational or recently approved strategies for improving efficacy and safety of anti-AF agents include (i) specific or predominant blockade of atrial ion channels; (ii) "upstream therapies" affecting non-ion channel targets that influence electrical and structural remodeling, inflammation and oxidative stress; (iii) amiodarone derivatives with an improved safety profile; (iv) intracellular calcium handling; and (v) therapies aiming at alleviating conduction disturbances (gap junction coupling enhancers). This review provides a succinct overview of some of these strategies.

摘要

心房颤动(AF)是一种日益受到临床关注的心律失常,其发病率不断增加,与显著的发病率和死亡率相关。药物仍然是 AF 患者的一线治疗方法,维持窦性心律的潜在优势促使人们继续努力寻找恢复和维持窦性心律的新的药理学手段。传统的抗心律失常药物仅能适度抑制 AF,并存在致心律失常和心脏外毒性等问题。目前,提高抗 AF 药物疗效和安全性的研究策略包括:(i)对心房离子通道的特异性或主要阻断;(ii)影响电和结构重构、炎症和氧化应激的非离子通道靶点的“上游治疗”;(iii)安全性更好的胺碘酮衍生物;(iv)细胞内钙处理;以及(v)旨在缓解传导障碍的治疗方法(缝隙连接偶联增强剂)。这篇综述简要概述了其中的一些策略。

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