In the early 20th century, bis-hydroxycoumarin(dicumarol) was discovered after cows livestock had eaten spoiled Sweet clover and died of a hemorrhagic disease.
Today, coumarin derivatives are used therapeutically as anticoagulants and commercially as rodenticides. Warfarinis the most common oral anticoagulant used today.
Approximately 2 million people in the U.S. start taking warfarin each year.
What is Warfarin?
Warfarin is an oral coumarin anticoagulant widely used to control and prevent thromboembolic disorders.
Warfarin is clinically available as a racemic mixture of R- and S-warfarin. The S-enantiomer has 3–5 times greater anticoagulation potency than its optical congener R-warfarin.
Mechanism of Action
Warfarin acts by antagonizing the antihemorrhagic effect of vitamin K.
It inhibits hepatic synthesis of vitamin K dependent coagulation factors II, VII, IX, and Xby inhibiting vitamin K1 -2,3 epoxidereductase, preventing vitamin K from being reduced to its active form.
The oral bioavailability of warfarinis nearly 100%.
It is highly bound (approximately 99%) to plasma protein, mainly albumin. (The high degree of protein binding is one of several mechanisms whereby other drugs interact with warfarin)
Warfarin is distributed to the liver, lungs, spleen, and kidneys. It does not appear to be distributed to breast milk in significant amounts. It crosses the placenta and is a known teratogen.
The duration of anticoagulant effect after a single dose of warfarin is usually 5-7 days.
Warfarin is metabolized by hepatic cytochrome P-450 (CYP) isoenzymesto inactive metabolites, which are excreted in the bile. (It also is metabolized by reductases to reduced metabolites “warfarin alcohols” , which are excreted in the kidneys).
Warfarin metabolism may be altered in the presence of hepatic dysfunction or advanced age but is not affected by renal impairment.
Indications prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction.