title: Old versus new oral anticoagulants: focus on pharmacology.
abstract: 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.
authors.affiliation: Departments of Pathology and Pharmacology, Loyola University Medical Center, Maywood, Illinois 60153, USA. jfareed@lumc.edu
authors.forename: Jawed
authors.initials: J
authors.lastname: Fareed
authors.forename: Indermohan
authors.initials: I
authors.lastname: Thethi
authors.forename: Debra
authors.initials: D
authors.lastname: Hoppensteadt
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000494:pharmacology*; D000991:Antithrombins / Q000009:adverse effects / Q000627:therapeutic use*; D065427:Factor Xa Inhibitors; D018565:Food-Drug Interactions; D006490:Hemostatics / Q000378:metabolism; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D010597:Pharmacogenetics; D011516:Prothrombin / Q000037:antagonists & inhibitors; D013917:Thrombin / Q000627:therapeutic use; D013927:Thrombosis / Q000188:drug therapy; D014812:Vitamin K / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D065427:Factor Xa Inhibitors; D006490:Hemostatics; D006495:Heparin, Low-Molecular-Weight; D014812:Vitamin K; D014859:Warfarin; D011516:Prothrombin; C025337:Factor IIa; D013917:Thrombin