Mulrow J P, Crawford M H
Department of Medicine, University of Texas Health Science Center, San Antonio, Texas.
Clin Pharmacokinet. 1989 Feb;16(2):86-9. doi: 10.2165/00003088-198916020-00003.
Hydralazine (1-hydrazinophthalazine) has been used extensively in the treatment of hypertension and congestive heart failure and produces arteriolar vasodilation, in part, mediated by prostaglandins. Its associated reflex baroreceptor-mediated responses of tachycardia and increased ejection velocity are attenuated in congestive heart failure. A direct inotropic effect has been attributed to the drug. Pharmacokinetic data indicate hydralazine is absorbed well from the gastrointestinal tract, and has an extensive and complex metabolism depending on acetylator status: slow acetylators undergo primary oxidative metabolism, while rapid acetylators are acetylated. Half-lives, clearances and bioavailability of the drug are not significantly altered in congestive heart failure compared with hypertensive patients. A wide range of dosages in heart failure has been noted (150 to 3000 mg/24h), and may related to a saturation of the first-pass effect. Hydralazine improves haemodynamics in the short term in patients with increased peripheral vascular resistance, and has variable effects on pulmonary capillary wedge and left ventricular filling pressures. Prediction of the short term clinical response is difficult and appears to be independent of pharmacokinetics. A meta analysis did not demonstrate long term efficacy of hydralazine alone in heart failure, but combination therapy with nitrates has been shown to improve survival and exercise performance in patients with mild to moderate heart failure. Side effects are common and are dependent on dose, duration and acetylator status.
肼屈嗪（1-肼基酞嗪）已广泛用于治疗高血压和充血性心力衰竭，它可产生小动脉血管舒张，部分是由前列腺素介导的。在充血性心力衰竭中，其相关的反射性压力感受器介导的心动过速和射血速度增加的反应会减弱。该药具有直接的正性肌力作用。药代动力学数据表明，肼屈嗪从胃肠道吸收良好，并且根据乙酰化状态具有广泛而复杂的代谢：慢乙酰化者进行主要的氧化代谢，而快乙酰化者则被乙酰化。与高血压患者相比，充血性心力衰竭患者中该药的半衰期、清除率和生物利用度没有明显改变。已注意到心力衰竭患者使用的剂量范围很广（150至3000mg/24小时），这可能与首过效应的饱和有关。肼屈嗪可在短期内改善外周血管阻力增加患者的血流动力学，对肺毛细血管楔压和左心室充盈压有不同影响。预测短期临床反应很困难，而且似乎与药代动力学无关。一项荟萃分析未证明肼屈嗪单独用于心力衰竭的长期疗效，但已表明与硝酸盐联合治疗可改善轻至中度心力衰竭患者的生存率和运动能力。副作用很常见，并且取决于剂量、用药持续时间和乙酰化状态。
