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Coumadin : Mechanisms of Action
Coumadin® is an anticoagulant drug. The drug is manufactured and marketed by DuPont Pharma of Wilmington, Delaware, USA. It is only available by prescription, and should only be taken under the supervision of a physician familiar with its indications and actions.
Coumadin® is based on a chemical known as warfarin sodium. Warfarin causes its anti-clotting effect by impairing the production of certain blood clotting proteins by the liver. These proteins, called "cofactors" are necessary elements of a complex series of proteins which the body uses to form a solid clot. The proteins are the fundamental components of the "intrinsic pathway" of clotting, in which many other proteins participate in concert.
The specific action of warfarin is to block the production of Factors VII, IX, X, and II by the liver. Creation of these factors by the liver is normally controlled by Vitamin K. This dietary vitamin is ingested with many different green vegetables. In addition, vitamin K can be produced by bacteria in the large intestine. As it is absorbed from the intestinal tract, Vitamin K is absorbed by, and stored in, the liver. Subsequently vitamin K is used in a vital regulatory step during the production of clotting Factors VII, IX, X, and II by the liver.
Administration of warfarin sodium blocks the action of vitamin K within the liver. The drug effectively competes for the same absorption sites within the liver needed for vitamin K uptake. Thus the levels of vitamin K within the liver decrease. Reduced amounts of clotting factors VII, IX, X, and II are produced, and the clotting action of the blood is progressively impaired.
All of the actions of Coumadin® are due to the drugs inhibition of vitamin K. Thus ingestion or administration of vitamin K can reverse the effects of Coumadin®. In fact, clinical overdosage with Coumadin® is corrected with vitamin K. Dietary intake of vitamin K does affect the metabolism of Coumadin®. This is one of the reasons that each patient seems to require a different dose of the drug to reach the target anticoagulation effect. Each person has different dietary intake of vitamin K, and also different liver function, different excretion of the drug, etc. Thus it is important for the physician to have a monitor of the Coumadin® effect on the patients clotting mechanism. Without a monitor, patients would frequently be overdosed or underdoses, with potentially hazardous consequences.
Monitoring of the Coumadin® effect is performed with a blood test. This test is known as the Prothrombin Time or P.T.. In recent years, the P.T. has been supplanted by the INR, or International Normalized Ratio. The INR is a more accurate way to calibrate the results of a prothrombin time test. It is important that you review the Pro-Time and INR information in The Learning Center and become familiar with the routine used to monitor this drugs effect.
Additional Coumadin Sections:
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