Thadani U, de Vane P J
Cardiovascular Section, University of Oklahoma Health Sciences Center, Oklahoma City 73104.
Am J Cardiol. 1992 Nov 27;70(17):67G-71G. doi: 10.1016/0002-9149(92)90029-x.
The rapid development of tolerance has limited the applicability of oral and transdermal nitrates in the long-term management of patients with chronic stable angina pectoris. Recent well-controlled trials have demonstrated that asymmetrical, or eccentric, dosing of oral isosorbide mononitrate, in which 20-mg doses are taken at 8 A.M. and 3 P.M., provides at least 12 hours of antianginal coverage. There is no evidence for the development of tolerance with this schedule, which allows for a 17-hour nitrate withdrawal period. Likewise, the asymmetrical 20-mg twice daily regimen has not been associated with the zero-hour effect that has been reported with higher oral doses of isosorbide mononitrate and with intermittent nitroglycerin patch therapy. This approach also avoids the development of a clinical rebound phenomenon, as measured by increased episodes of angina and nitroglycerin consumption, compared with the pretreatment period, during the nitrate-free interval at night and the early hours of the morning.
耐受性的快速发展限制了口服和透皮硝酸盐类药物在慢性稳定型心绞痛患者长期治疗中的应用。近期严格对照试验表明，口服单硝酸异山梨酯采用不对称或偏心给药方案，即上午8点和下午3点各服用20毫克剂量，可提供至少12小时的抗心绞痛作用。没有证据表明这种给药方案会产生耐受性，该方案允许有17小时的无硝酸盐期。同样，每日两次20毫克的不对称给药方案与高剂量口服单硝酸异山梨酯及间歇性硝酸甘油贴剂治疗所报道的零时效应无关。与治疗前相比，该方法还可避免在夜间无硝酸盐间隔期和清晨出现临床反跳现象，临床反跳现象表现为心绞痛发作次数增加和硝酸甘油消耗量增加。
