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[关于秋水仙碱作为一种“新型”心血管药物的十个问题]

[Ten questions on colchicine as a "new" cardiovascular drug].

作者信息

Imazio Massimo, Brucato Antonio

机构信息

Cardiologia, Dipartimento Cardiotoracico, Ospedale Santa Maria della Misericordia, Azienda Sanitaria Universitaria del Friuli Centrale (ASUFC), Udine.

Università di Milano, Dipartimento di Scienze Cliniche e Biomediche "Sacco", Ospedale Fatebenefratelli, Milano.

出版信息

G Ital Cardiol (Rome). 2021 Jul;22(7):536-543. doi: 10.1714/3629.36104.

Abstract

Colchicine is one of the more ancient drugs of vegetal origin still in use in clinical practice. It has been used for centuries as drug to treat gout, but its anti-inflammatory effects made it efficacious also in different cardiovascular indications (e.g. pericarditis, acute and chronic coronary syndromes, atrial fibrillation), that are well beyond its original indication. The treatment and prevention of pericarditis is the only registered cardiovascular indication in Italy (allowing prescription in class A by the National Healthcare System), while other indications are off-label. When used at low doses (0.5 mg/day), the drug is safe and efficacious with limited side effects, mainly gastrointestinal. Gastrointestinal absorption is fast since the drug is a small lipophilic molecule that is eliminated by cells through P-glycoprotein. Colchicine is metabolized by cytochrome P450 in the liver and mainly excreted into the biliary tract. It is also excreted, essentially unmodified, by the kidneys. It is concentrated in white blood cells, especially neutrophils, that are without P-glycoprotein. In these cells, blocking tubulin polymerization, colchicine reduces their function, also interfering with endothelial adhesion and platelet interactions. Moreover, it is responsible for a non-specific inhibition of the inflammasome, thus reducing the generation of pro-inflammatory cytokines, such as interleukin-1. The aim of this paper is to provide concise replies to the most common clinical questions on the use of colchicine for cardiovascular indications.

摘要

秋水仙碱是临床实践中仍在使用的较为古老的植物源药物之一。几个世纪以来,它一直被用作治疗痛风的药物,但它的抗炎作用使其在不同的心血管适应症(如心包炎、急性和慢性冠状动脉综合征、心房颤动)中也有疗效,这些适应症远远超出了其最初的适应症范围。心包炎的治疗和预防是意大利唯一注册的心血管适应症(允许国家医疗系统开具A类处方),而其他适应症则属于超说明书用药。当以低剂量(0.5毫克/天)使用时,该药物安全有效,副作用有限,主要是胃肠道副作用。由于该药物是一种小的亲脂性分子,可通过P-糖蛋白被细胞清除,因此胃肠道吸收很快。秋水仙碱在肝脏中通过细胞色素P450代谢,主要排泄到胆道。它也基本上未经修饰地通过肾脏排泄。它集中在没有P-糖蛋白的白细胞中,尤其是中性粒细胞中。在这些细胞中,秋水仙碱通过阻断微管蛋白聚合来降低其功能,还会干扰内皮细胞黏附和血小板相互作用。此外,它还能非特异性抑制炎性小体,从而减少促炎细胞因子如白细胞介素-1的产生。本文旨在对秋水仙碱用于心血管适应症的最常见临床问题提供简要解答。

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