Thadani U
Herz. 1984 Jun;9(3):123-36.
Nitrates are effective in the management of exertional angina pectoris primarily due to their peripheral effects i.e. venodilation and arterial dilation, and thereby reduction in myocardial oxygen demand. These drugs also improve collateral blood flow in ischemic areas and in some patients may increase coronary blood flow by modifying tonus in the conductive or conduit coronary vessels. Sublingual nitroglycerin is the most effective antianginal agent but its prophylactic use is limited by its short duration of action. Until recently, the efficacy of long-acting oral nitrates was seriously questioned. However, recent data suggests that when given acutely in adequate doses, oral nitrates, transcutaneous and buccal preparations of nitroglycerin all exert prolonged hemodynamic and antianginal effects. Development of tolerance to the circulatory and antianginal effects during chronic therapy, however, remains a concern. Published literature suggests that tolerance to the circulatory effects and to headaches develops rapidly during sustained therapy with long-acting nitrates. However, reports regarding the development of tolerance to the antianginal effects and reduction of ST segment depression remain conflicting. Partial tolerance to the antianginal effects has been well-documented during chronic therapy with isosorbide dinitrate. Duration of improvement in exercise tolerance during four times daily therapy with isosorbide dinitrate has been shown to be shortened compared to prolonged effects following acute therapy. Recent data suggests that given in high doses, beneficial effects of ST segment depression during exercise may also diminish during chronic therapy with long acting nitrates. Tolerance to antianginal and circulatory effects can be reversed by withholding long-acting nitrates for 24 to 36 hours. Furthermore, initial studies suggest that tolerance to antianginal effects during sustained therapy can be avoided by giving smaller but effective doses of ISDN (20 to 40 mg) twice a day rather than prescribing larger doses more frequently.
硝酸盐类药物在劳力性心绞痛的治疗中有效，主要是由于其外周效应，即静脉扩张和动脉扩张，从而降低心肌需氧量。这些药物还可改善缺血区域的侧支血流，在一些患者中，通过改变传导性或输送性冠状动脉血管的张力，可能增加冠状动脉血流。舌下含服硝酸甘油是最有效的抗心绞痛药物，但其预防性应用因作用持续时间短而受到限制。直到最近，长效口服硝酸盐类药物的疗效还受到严重质疑。然而，最近的数据表明，当给予足够剂量的急性口服硝酸盐类药物、硝酸甘油的经皮和颊部制剂时，均可产生持久的血流动力学和抗心绞痛作用。然而，长期治疗期间对循环和抗心绞痛作用产生耐受性仍然是一个问题。已发表的文献表明，在用长效硝酸盐类药物进行持续治疗期间，对循环作用和头痛的耐受性迅速发展。然而，关于抗心绞痛作用耐受性的发展以及ST段压低的减轻的报道仍存在矛盾。在用硝酸异山梨酯进行长期治疗期间，对抗心绞痛作用的部分耐受性已有充分记录。与急性治疗后的延长效应相比，每日四次服用硝酸异山梨酯时运动耐量改善的持续时间已显示缩短。最近的数据表明，大剂量给药时，长效硝酸盐类药物长期治疗期间运动时ST段压低的有益作用也可能减弱。停用长效硝酸盐类药物24至36小时可逆转对抗心绞痛和循环作用的耐受性。此外，初步研究表明，通过每日两次给予较小但有效的硝酸异山梨酯剂量（20至40毫克）而非更频繁地开具较大剂量，可避免持续治疗期间对抗心绞痛作用的耐受性。
