ROLE OF NITRATES IN UNSTABLE ANGINA-PECTORIS

被引:18
作者
HOROWITZ, JD
机构
[1] Cardiology Unit, The Queen Elizabeth Hospital, University of Adelaide, Woodville
关键词
D O I
10.1016/0002-9149(92)90595-P
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Unstable angina pectoris is a clinically heterogeneous process with patient symptoms varying between reduced threshold tor exertional angina and the occurrence of multiple episodes of rest pain. The major factors in the pathogenesis of unstable angina appear to be intracoronary platelet aggregation and thrombus formation secondary to fissuring or rupture of atheromatous plaques, with associated coronary vasoconstriction due to release of constrictor materials from aggregating platelets and deficiency of endothelium-related vasodilator activity. The latter factor is of particular interest in view of the similar biochemical mechanisms of action of nitroglycerin (NTG) and endothelium-derived relaxing factor (EDRF). The efficacy of NTG in limiting platelet aggregations is also of particular interest in this condition. Medical therapy in patients with unstable angina usually requires use of multiple agents. In the short term, there is a strong case for the use of intravenous heparin both to relieve pain and to reduce the risk of acute myocardial infarction. Aspirin is perhaps less effective in the short term, but very useful in long-term treatment of such patients. Despite their widespread clinical use, beta adrenoceptor antagonists are probably only marginally beneficial, whereas dihydropyridine calcium antagonists such as nifedipine are potentially harmful as monotherapy and of questionable use in combination with other drugs. Other agents that are effective in relieving ischemic symptoms are the nondihydropyridine calcium antagonists verapamil and diltiazem and the oxygen-sparing agent perhexiline maleate. Despite a paucity of controlled trial data, nitrates are used in the vast majority of patients with unstable angina. In patients with severe symptoms, intravenous infusion is preferable and because of the need for 24-hour prevention of ischemia, the development of nitrate tolerance is a major risk that cannot be reduced by intermittent nitrate administration. There is strong evidence that infusion of NTG at rates >40-mu-g/min induces the development ot extensive hemodynamic tolerance, affecting both the systemic and coronary circulations, in most patients. NTG infusion rates should therefore be kept as low as possible in such patients. An alternative approach is the combined infusion of NTG and N-acetylcysteine (NAC) in patients with "high risk"' unstable angina. This combination may augment the antiaggregatory effects of NTG and prevent nitrate tolerance. In a controlled clinical trial, incidence of acute myocardial infarction was significantly lower with NTG/NAC than with NTG alone. Continuous rather than intermittent administration of NAC is preferable to avoid development of symptomatic hypotension.
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页码:B64 / B71
页数:8
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