Johnston D, Duffin D
Department of Therapeutics and Pharmacology, The Queen's University of Belfast, Northern Ireland.
Am J Cardiol. 1992 Oct 8;70(10):109C-112C. doi: 10.1016/0002-9149(92)91367-d.
The effects of congestive heart failure (CHF) on drug disposition and elimination are many and varied. Indeed, the pharmacokinetics of many of the drugs used to treat CHF are significantly altered by the patient's underlying condition. Reduced gastric emptying in CHF delays absorption and decreases the peak plasma concentrations of furosemide, bumetanide, and digoxin. Moreover, drugs that have a high hepatic extraction ratio (organic nitrates, morphine, prazosin, and hydralazine) achieve higher than expected plasma concentrations in patients with CHF. In contrast, drugs requiring biotransformation to active forms, e.g., angiotensin-converting enzyme (ACE) inhibitors such as enalapril, perindopril, quinapril, and ramipril, generally have lower than expected plasma concentrations. Nevertheless, ACE inhibitors can impair renal function in CHF, leading to an actual increase in plasma concentrations. However, decreases in absorption and first-pass metabolism are often offset by reduced hepatic and renal clearance. The overall absorption of lisinopril may be reduced in some CHF patients; consequently, the onset of effect is delayed but is often more prolonged.
充血性心力衰竭（CHF）对药物处置和消除的影响是多方面且各异的。实际上，许多用于治疗CHF的药物的药代动力学都会因患者的基础病情而发生显著改变。CHF患者胃排空减慢会延迟吸收，并降低呋塞米、布美他尼和地高辛的血浆峰浓度。此外，肝提取率高的药物（有机硝酸盐、吗啡、哌唑嗪和肼屈嗪）在CHF患者中达到的血浆浓度高于预期。相比之下，需要生物转化为活性形式的药物，如依那普利、培哚普利、喹那普利和雷米普利等血管紧张素转换酶（ACE）抑制剂，其血浆浓度通常低于预期。然而，ACE抑制剂可损害CHF患者的肾功能，导致血浆浓度实际升高。不过，吸收和首过代谢的降低通常会被肝和肾清除率的降低所抵消。某些CHF患者中赖诺普利的总体吸收可能会降低；因此，起效延迟，但作用时间往往会延长。
