Vitamin K antagonists (VKA) are a class of anticoagulants which, as their name indicates act by inhibiting the action of vitamin K, coumarins are the most commonly used VKA. In medicine the most commonly used VKA is warfarin. Warfarin is an antagonist of Vitamin K, a necessary element in the synthesis of clotting factors II, VII, IX, and X as well as the naturally occuring endogenous anticoagulatant protein C and S which are biologically inactive without the carboxylation of certain glutamic acid residues. This carboxylation process requires reduced Vitamin K as a co-factor. A deficiency of this vitamin or antagonist of vitamin K reduces the rate at which these factors and proteins are produced. This is necessary for a state of anticoagulation.. Vitamin K is measured in micrograms. The recommended daily allowances (RDA) for vitamin K intake is between 70-90 microgams for adults. Vitamin K in the diet lowers the International Normalized Ratio(INR) reading overtime. Consistent diet is important so that warfarin dosing can be stablised.
The focus of anticoagulatant therapy is to administer the lowest possible dose to prevent the clot formation. By using the lowest possible dose of warfarin, the physician can minimize the risk of bleeding. Warfarin can be dectected in the plasma one hour after oral administration . Warfarin is a racemic mixture of stereo isomers, which are 99 percent bound to albumin. The drug is metabolised in the liver and kidneys, the production of inactive metabolites are then excreted in the urine and stool.. The half-life of racemic warfarin ranges from 20 to 60 hours. This means plasma half-life is approximately 40 hours, and the duration of the effect is two to five days. After administration the maximum effect of a dose occurs upto 48 hours, and the effect lingers for the next five days
Limitations of Warfarin
They many limitations in the use of warfarin, they are:
- A therapeutic International Normalized Ratio (INR) has to be properly maintained and monitored frequently.
- Therapeutic level is affected by many factors inluding diet, medication genetics and illness
- Warfarin’s narrow therapeutic range may cause under anticoagulation (causing thrombus formation) or over anticoagulation (leading to hemorrhage).
- Constant monitoring is inconvenient for patients and costly
- The action of the drug takes 72-96 hours to become effective and
- A rapidly acting parenteral anticoagulatant (heparin) has to be administered until a therapeutic (INR) is achieved.
- Many drugs increases or decreases the anticoagulant effect of warfarin , resulting in bleeding or clots.
While on warfarin, it is important not to start or discontinue any new non-prescription drugs or herbal products without letting the doctor know. Warfarin has been the only oral anticoagulant despite their many limitations. There is a need to find a replacement for warfarin for long term therapy, particularly stroke prevention in atrial fribillation. Patients. Drugs in advanced development target factor Xa (rivaroxaban, apixaban) or thrombin inhibitor (dabigatran etexilate). These emerging oral anticoagulants are free from many of warfarin many limitations and many offer a convenient alternative.