Sorkin E M, Brogden R N, Romankiewicz J A
Drugs. 1984 Jan;27(1):45-80. doi: 10.2165/00003495-198427010-00003.
The recently introduced preparation of intravenous glyceryl trinitrate (nitroglycerin) provides a rapid steady therapeutic blood concentration of nitrates during continuous infusion. Intravenous glyceryl trinitrate causes venodilation at low doses, but at higher doses dilates both arteries and veins. Its principal haemodynamic effects at therapeutic dosages include a decrease in blood pressure in preload (left ventricular filling pressure) and in determinants of afterload, and a decrease in myocardial oxygen demand. Human pharmacokinetic data are few and difficult to interpret due to wide interstudy and interindividual variation. There is no close correlation between infusion rate, blood concentration and haemodynamic effects. The nature of the patient population treated with intravenous glyceryl trinitrate has largely precluded the use of a placebo, but in open trials the drug has been used successfully in the treatment of unstable angina, left ventricular failure accompanying acute myocardial infarction and in the control of hypertension associated with cardiac surgery at dosages titrated to achieve a specific end-point. Favourable haemodynamic responses have been achieved in very short term studies in congestive heart failure, and preliminary studies suggest that institution of intravenous glyceryl trinitrate early after acute myocardial infarction may limit ischaemic damage. However, use of the drug in acute myocardial infarction remains controversial. Intravenous glyceryl trinitrate is generally well tolerated, although hypotension and headache occur occasionally, and sinus tachycardia and bradycardia less frequently. Careful titration of dosage is required (beginning at 5 micrograms/min), and if the infusion sets contain polyvinylchloride, the delivered dose is lower than that calculated, because of adsorption of glyceryl trinitrate onto the plastic tubing.
最近推出的静脉注射硝酸甘油制剂,在持续输注过程中能使硝酸盐在血液中迅速达到稳定的治疗浓度。静脉注射硝酸甘油在低剂量时会引起静脉扩张,但在高剂量时会同时扩张动脉和静脉。其在治疗剂量下的主要血流动力学效应包括降低前负荷(左心室充盈压)和后负荷决定因素中的血压,以及降低心肌需氧量。由于研究间和个体间差异较大,人类药代动力学数据较少且难以解释。输注速率、血药浓度和血流动力学效应之间没有密切相关性。接受静脉注射硝酸甘油治疗的患者群体性质在很大程度上排除了安慰剂的使用,但在开放试验中,该药物已成功用于治疗不稳定型心绞痛、急性心肌梗死伴发的左心室衰竭以及控制心脏手术相关的高血压,剂量经滴定以达到特定终点。在充血性心力衰竭的短期研究中已取得了良好的血流动力学反应,初步研究表明,在急性心肌梗死后早期使用静脉注射硝酸甘油可能会限制缺血损伤。然而,该药物在急性心肌梗死中的应用仍存在争议。静脉注射硝酸甘油一般耐受性良好,尽管偶尔会出现低血压和头痛,窦性心动过速和心动过缓则较少见。需要仔细滴定剂量(从5微克/分钟开始),并且如果输液装置含有聚氯乙烯,由于硝酸甘油会吸附在塑料管道上,实际输送的剂量会低于计算剂量。