Warfarin
Warfarin is an anticoagulant used as a medication under several brand names including Coumadin. While the drug is described as a "blood thinner", it does not reduce viscosity but rather inhibits coagulation. Accordingly, it is commonly used to prevent blood clots in the circulatory system such as deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who have atrial fibrillation, valvular heart disease, or artificial heart valves. Less commonly, it is used following ST-segment elevation myocardial infarction (STEMI) and orthopedic surgery. It is usually taken by mouth, but may also be administered intravenously. The common side effect, a natural consequence of reduced clotting, is bleeding. Less common side effects may include areas of tissue damage, and purple toes syndrome. Use is not recommended during pregnancy. The effects of warfarin are typically monitored by checking prothrombin time (INR) every one to four weeks. Many other medications and dietary factors can interact with warfarin, either increasing or decreasing its effectiveness. The effects of warfarin may be reversed with phytomenadione (vitamin K1), fresh frozen plasma, or prothrombin complex concentrate. Warfarin decreases blood clotting by blocking vitamin K epoxide reductase, an enzyme that reactivates vitamin K1. Without sufficient active vitamin K1, the plasma concentrations of clotting factors II, VII, IX, and X are reduced and thus have decreased clotting ability. The anticlotting protein C and protein S are also inhibited, but to a lesser degree. Despite being labeled a vitamin K antagonist, warfarin does not antagonize the action of vitamin K1, but rather antagonizes vitamin K1 recycling, depleting active vitamin K1.
A few days are required for full effect to occur, and these effects can last for up to five days. Because the mechanism involves enzymes such as VKORC1, patients on warfarin with polymorphisms of the enzymes may require adjustments in therapy if the genetic variant that they have is more readily inhibited by warfarin, thus requiring lower doses. Warfarin first came into large-scale commercial use in 1948 as a rat poison. It was formally approved as a medication to treat blood clots in humans by the U.S. Food and Drug Administration in 1954. In 1955, warfarin's reputation as a safe and acceptable treatment was bolstered when President Dwight D. Eisenhower was treated with warfarin following a massive and highly publicized heart attack. Eisenhower's treatment kickstarted a transformation in medicine whereby coronary artery disease, arterial plaques, and ischemic strokes were treated and protected against by using anticoagulants such as warfarin. It is on the World Health Organization's List of Essential Medicines. Warfarin is available as a generic medication and under many trade names. In 2021, it was the 56th most commonly prescribed medication in the United States, with more than 11 million prescriptions.
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