Benowitz N L, Meister W
Clin Pharmacokinet. 1976 Nov-Dec;1(6):389-405. doi: 10.2165/00003088-197601060-00001.
Cardiac failure is often associated with disturbances in cardiac output, autonomic nervous system activity, central and systemic venous pressures, and sodium and water metabolism. These disturbances influence the extent and pattern of tissue perfusion, may lead to tissue hypoxia and visceral congestion, and may alter gastrointestinal motility. By these mechanisms, cardiac failure potentially affects absorption and disposition characteristics of drugs, which may necessitate adjustment in dosage regimen for optimum therapy. Lignocaine is the drug which has been studied most extensively in cardiac failure. Volumes of distribution and clearance are decreased. As a drug whose metabolism is largely limited by liver blood flow, decreased blood flow to the liver accounts for some of the change in clearance, but impaired hepatic metabolism appears also to play a role in some patients. Accumulation of active metabolites of lignocaine and procainamide in patients with cardiac failure can influence therapeutic and toxic effects. Theophylline metabolism, which is largely independent of blood flow, appears to be reduced significantly in patients with severe cardiac failure and necessitates reduction of dosage. In the presence of severe cardiac failure, digoxin clearance may be less than anticipated on the basis of estimates of renal function. Quinidine plasma levels may be higher after single doses due to reduced volume of distribution. Quinidine metabolites are believed not to be pharmacologically active but may create confusion with nonspecific assays. Specific assays are recommended in cardiac failure, especially complicated by renal insufficiency. Data are lacking relating pharmacokinetic alterations to haemodynamic measurements in patients with cardiac failure. Whereas the direction of change in pharmacokinetic parameters may be predicted, variability in the magnitude of change is so great that determination of drug concentration in blood remains as essential adjunct to therapy.
心力衰竭常伴有心输出量、自主神经系统活动、中心静脉压和全身静脉压以及钠和水代谢的紊乱。这些紊乱会影响组织灌注的程度和模式，可能导致组织缺氧和内脏充血，并可能改变胃肠蠕动。通过这些机制，心力衰竭可能会影响药物的吸收和处置特性，这可能需要调整给药方案以实现最佳治疗效果。利多卡因是在心力衰竭中研究最为广泛的药物。其分布容积和清除率降低。作为一种代谢在很大程度上受肝血流量限制的药物，肝血流量减少是清除率变化的部分原因，但在一些患者中，肝代谢受损似乎也起了作用。心力衰竭患者体内利多卡因和普鲁卡因酰胺活性代谢物的蓄积会影响治疗效果和毒性作用。茶碱的代谢在很大程度上不依赖于血流量，在严重心力衰竭患者中其代谢似乎显著降低，因此需要减少剂量。在严重心力衰竭的情况下，地高辛的清除率可能低于根据肾功能估计值所预期的水平。由于分布容积减小，单次给药后奎尼丁的血浆水平可能会更高。奎尼丁的代谢产物被认为无药理活性，但可能会在非特异性检测中造成混淆。在心力衰竭患者中，尤其是合并肾功能不全的情况下，建议采用特异性检测方法。目前缺乏关于心力衰竭患者药代动力学改变与血流动力学测量之间关系的数据。虽然可以预测药代动力学参数的变化方向，但变化幅度的变异性非常大，因此测定血药浓度仍然是治疗的重要辅助手段。
