麦角碱类多巴胺受体激动剂对心瓣膜的不良反应

The Side Effects of Ergot-derivative Dopamine Agonists on Cardiac Valves

多巴胺(DA)受体激动剂能够控制帕金森病(PD)症状和延缓PD进程,并具有神经保护作用,在临床上广泛用于治疗PD和不安腿综合征。近年来发现,麦角碱类DA受体激动剂在临床应用过程中存在严重的安全问题,最主要的危害是造成心瓣膜损害而导致其反流增加。本文对培高利特、卡麦角林、溴隐亭和麦角乙脲4种麦角碱类DA受体激动剂与药源性心瓣膜病之间的关系予以探讨。卡麦角林和大剂量(>1.5mg·d-1)的培高利特可以显著增加心瓣膜病发生的风险性,小剂量的(<1.5mg·d-1)培高利特、溴隐亭和麦角乙脲引起心瓣膜病的风险性相对较低。麦角碱类DA受体激动剂引起心瓣膜病的可能分子机制是通过异常激动5-HT2B受体,刺激成纤维细胞增殖,从而使心瓣膜及其附属结构纤维化,导致关闭不全。

Dopamine agonists have neuroprotective effect. They can improve the symptom of Parkinson＇s disease （PD） and postpone the progression of PD, so they have been widely used in the treatment of PD and restless leg syndrome. Recently, however, it was found that ergot derivative dopamine agonists had some severe safe problems in the clinical applications. The most important problem is those drugs which can induce valvular heart disease. They can increase the valvular regurgitation. This paper reviewed the relation of four ergot derivative dopamine agonists and drug-induced valvular heart disease, and concluded that cabergoline and high-dose（〉 1.5 mg·d^-1 ） pergolide can significantly increase the risk of valvular heart disease, low-dose （〈 1.5 mg·d^-1 ） pergolide, bromocriptine and lisuride had low risk of valvular heart disease. The molecular mechanism by which ergot derivative dopamine（DA） receptor induced valvular heart disease may pass through abnormally agitating 5-HT2B receptor, stimulate fibroblast proliferation, then cause the fibrosis of heart valves and accessory structures, lead to valvular insufficiency.