Departments of Pathology and Pharmacology, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Annu Rev Pharmacol Toxicol. 2012;52:79-99. doi: 10.1146/annurev-pharmtox-010611-134633. Epub 2011 Aug 5.
Since the discovery of heparin nearly a century ago, there have been large gaps in the development of anticoagulants. The discovery of warfarin was the first step toward using oral anticoagulants, but warfarin use has been associated with its own challenges from the perspectives of the prescribing physician and the patient. Warfarin, along with other coumarins, has a narrow therapeutic index, requires frequent monitoring, exhibits interindividual response variations, and is associated with several adverse effects. Frequent drug and food interactions contribute to potential safety and efficacy compromise. The indications for use of oral anticoagulants have increased, as these drugs are used not only for thrombosis management but also for cardiovascular indications, producing more challenges for oral anticoagulant use. Factor Xa and thrombin targeting has provided a rational approach to develop new oral anticoagulants with improvements over warfarin. In this review, the pharmacology of warfarin and the pharmacology of the newly developed oral anti-Xa and antithrombin agents are discussed.
自近一个世纪前肝素被发现以来，抗凝剂的发展一直存在很大的差距。华法林的发现是朝着使用口服抗凝剂迈出的第一步，但从开处方的医生和患者的角度来看，华法林的使用也存在自身的挑战。华法林和其他香豆素类药物的治疗指数较窄，需要频繁监测，个体间反应存在差异，并且与多种不良反应相关。药物和食物的频繁相互作用可能会导致潜在的安全性和疗效受损。口服抗凝剂的适应证有所增加，因为这些药物不仅用于血栓管理，还用于心血管适应证，这给口服抗凝剂的使用带来了更多的挑战。因子 Xa 和凝血酶靶向治疗为开发新型口服抗凝剂提供了合理的方法，这些新型抗凝剂在改善方面优于华法林。在这篇综述中，讨论了华法林的药理学和新开发的口服抗 Xa 和抗凝血酶药物的药理学。
