Perry M O
Department of Surgery, New York Hospital-Cornell Medical Center, New York 10021.
Am J Surg. 1988 Feb;155(2):268-76. doi: 10.1016/s0002-9610(88)80712-8.
Heparin combines with antithrombin III, and the resulting complex inactivates several clotting factors (all are serine proteases) in the coagulation cascade, but the most important steps are inhibition of the conversion of factor X to Xa and the antithrombin effect. Heparin pharmacokinetics are poorly understood, but when the usual doses are given intravenously, heparin is rapidly removed from the blood and has a half-life of approximately 90 minutes. Warfarin is not a true anticoagulant but is readily absorbed after oral administration. It interrupts the coagulation mechanism by interfering with the vitamin K-dependent synthesis of prothrombin and factors VII, IX, and X. This process takes 4 to 5 days. The drug has a long half-life, and its activity is enhanced or blunted by many chemicals. The effective treatment of thromboembolism with heparin, followed by warfarin, requires a basic understanding of the complex pharmacologic aspects and drug interactions.
肝素与抗凝血酶III结合，形成的复合物使凝血级联反应中的几种凝血因子（均为丝氨酸蛋白酶）失活，但最重要的步骤是抑制因子X向Xa的转化以及抗凝血酶的作用。肝素的药代动力学了解甚少，但静脉注射常用剂量时，肝素会迅速从血液中清除，半衰期约为90分钟。华法林并非真正的抗凝剂，但口服后易被吸收。它通过干扰维生素K依赖的凝血酶原及因子VII、IX和X的合成来阻断凝血机制。这一过程需要4至5天。该药半衰期长，其活性会被许多化学物质增强或减弱。先用肝素，后用华法林有效治疗血栓栓塞，需要对复杂的药理学方面及药物相互作用有基本的了解。
