Thadani Udho, Rodgers Tiffany
University of Oklahoma Health Sciences, Cardiovascular Section, Department of Medicine, 920 Stanton L. Young Blvd, WP3120, Oklahoma City, OK 73104, Oklahoma, USA.
Expert Opin Drug Saf. 2006 Sep;5(5):667-74. doi: 10.1517/14740338.5.5.667.
Nitrates are very effective antianginal and anti-ischaemic agents. Provision of a long nitrate-free interval or low plasma nitrate levels prior to the morning dose prevents the loss of clinical efficacy by preventing the development of tolerance. However, side effects during nitrate therapy are common. Headache is the most common side effect of nitrates; often dose-related and reported by up to 82% of patients in placebo-controlled trials. Nearly 10% of patients are unable to tolerate nitrates due to disabling headaches or dizziness. In others, headaches are mild-to-moderate in severity and either resolve or diminish in intensity with continued nitrate therapy. Nitrate-induced hypotension is common, but often asymptomatic. In rare instances, nitrate-induced hypotension is severe and accompanied by marked slowing of the heart rate and syncope. Use of nitrates in patients who experience syncope after administration of nitrates is contraindicated. Nitrates rarely cause coronary steal and myocardial ischaemia. Nitrate rebound may occur and patients may experience nocturnal anginal episodes during intermittent therapy with nitroglycerin patches. Administration of nitrates is contraindicated with concomitant use of phosphodiesterase-5 inhibitors used for the treatment of erectile dysfunction, as combination therapy may lead to profound hypotension and even death. There are disturbing observational reports in the literature that continuous, prolonged use of nitrates may lead to increased mortality and recurrent myocardial infarctions. Large, randomised, placebo-controlled studies are needed to confirm or refute these reports; until then, the use of nitrates to treat angina is here to stay.
硝酸盐是非常有效的抗心绞痛和抗缺血药物。在早晨给药前提供较长的无硝酸盐间隔期或较低的血浆硝酸盐水平，可通过防止耐受性的发展来避免临床疗效的丧失。然而，硝酸盐治疗期间的副作用很常见。头痛是硝酸盐最常见的副作用；通常与剂量相关，在安慰剂对照试验中，高达82%的患者报告有此症状。近10%的患者因严重头痛或头晕而无法耐受硝酸盐。在其他患者中，头痛程度为轻度至中度，随着硝酸盐治疗的持续进行，症状会缓解或减轻。硝酸盐引起的低血压很常见，但通常无症状。在极少数情况下，硝酸盐引起的低血压很严重，并伴有心率明显减慢和晕厥。对服用硝酸盐后出现晕厥的患者禁用硝酸盐。硝酸盐很少引起冠状动脉窃血和心肌缺血。可能会发生硝酸盐反跳，患者在使用硝酸甘油贴片进行间歇治疗期间可能会出现夜间心绞痛发作。硝酸盐与用于治疗勃起功能障碍的磷酸二酯酶-5抑制剂同时使用时禁用，因为联合治疗可能会导致严重低血压甚至死亡。文献中有一些令人不安的观察报告称，持续、长期使用硝酸盐可能会导致死亡率增加和心肌梗死复发。需要进行大规模、随机、安慰剂对照研究来证实或反驳这些报告；在此之前，硝酸盐用于治疗心绞痛的情况仍将持续。
