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Clinical Pharmacology
CLINICAL PHARMACOLOGY
COUMADIN and other coumarin anticoagulants act by inhibiting the synthesis of vitamin K dependent clotting factors, which include Factors II, VII, IX and X, and the anticoagulant proteins C and S. Half-lives of these clotting fac-tors are as follows: Factor II -60 hours, VII -4-6 hours, IX -24 hours, and X -48-72 hours. Text Continues Below
The half-lives of proteins C and S are approximately 8 hours and 30 hours, respectively. The resultant in vivo effect is a sequential depression of Factors VII, IX, X and II activities. Vitamin K is an essential cofactor for the post ribosomal synthesis of the vitamin K dependent clotting factors. The vitamin promotes the iosynthesis of -carboxyglutamic acid residues in the proteins which are essential for biological activity. Warfarin is thought to interfere with clotting factor synthesis by inhibition of the regeneration of vitamin K 1 epoxide. The degree of depression is dependent upon the dosage administered. Therapeutic doses of warfarin decrease the total amount of the active form of each vitamin K dependent clotting factor made by the liver by approximately 30% to 50%. An anticoagulation effect generally occurs within 24 hours after drug administration. However, peak anticoagulant effect may be delayed 72 to 96 hours. The duration of action of a single dose of racemic warfarin is 2 to 5 days. The effects of COUMADIN may become more pronounced as effects of daily maintenance doses overlap. Anticoagulants have no direct effect on an established thrombus, nor do they reverse ischemic tissue damage. However, once a thrombus has occurred, the goal of anticoagulant treatment is to prevent further extension of the formed clot and prevent secondary thromboembolic complications which may result in serious and possibly fatal sequelae. Page: 1 | 2 | 3 | 4 | 5 | Next >>
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