Parker J A
Kingston General Hospital, Ontario, Canada.
Am J Cardiol. 1996 May 30;77(13):38C-40C. doi: 10.1016/s0002-9149(96)00187-7.
The organic nitrates have been used for more than a century in the management of patients with myocardial ischemia. The most commonly used agents at this time include nitroglycerin, isosorbide dinitrate, and isosorbide-5-mononitrate. These agents all exert their therapeutic effects through biodegradation to nitric oxide, which stimulates guanylate cyclase in vascular smooth muscle cells with the production of cyclic guanosine monophosphate. The latter induces vasodilation by reducing the availability of ionized calcium to the contractile proteins. Tolerance to the organic nitrates occurs when the agents are administered in an attempt to provide therapeutic effects throughout 24 hours each day. There are probably several mechanisms responsible for nitrate tolerance, but there is no evidence at this time that concurrent medications will modify the development of tolerance. The only available method at this time is to give these agents intermittently to provide a period of washout. In so doing, it is possible to provide therapeutic nitrate effects for approximately 12 hours throughout each 24-hour period.
有机硝酸盐用于治疗心肌缺血患者已有一个多世纪。目前最常用的药物包括硝酸甘油、异山梨醇二硝酸酯和5-单硝酸异山梨酯。这些药物均通过生物降解产生一氧化氮发挥治疗作用，一氧化氮刺激血管平滑肌细胞中的鸟苷酸环化酶，生成环磷酸鸟苷。后者通过减少离子钙与收缩蛋白的结合来诱导血管舒张。当每天试图24小时持续给药以提供治疗效果时，会出现对有机硝酸盐的耐受性。硝酸盐耐受性可能有多种机制，但目前尚无证据表明同时使用其他药物会改变耐受性的发展。目前唯一可行的方法是间歇性给药，留出一段洗脱期。这样，每24小时内大约有12小时可提供治疗性硝酸盐效应。
