Warfarin

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  • Coumarin derivatives
    • include dicumarol, warfarin sodium, and phenprocoumon.
    • warfarin has the best bioavailability and the least severe adverse effects.
    • Actions and pharmacologic properties
      • indirectly interfere with gamma-carboxylation of glutamate residues in clotting factors II (prothrombin), VII, IX, and X, which is coupled to the oxidation of vitamin K. by vitamin K epoxide reductase is directly inhibited by coumarin derivatives.
      • Clotting factors are still synthesized, but at reduced levels, and are undercarboxylated and have greatly reduced biologic activity;
      • clotting factors produced before coumarin therapy decline in concentration as a function of factor half-life
      • This causes a latency period of 36–48 hours before effects are seen.
      • It does not affect established thrombi.
    • Warfarin
      • administered orally
      • has 100% bioavailability
      • Highly teratogenic and fetotoxic,
      • Has  a t1/2 of 2.5 days
      • warfarin is extensively (99%) bound to plasma albumin
      • can displace many other drugs from this site.
    • Dicumarol
      • much less well absorbed
      • a t1/2 of approximately 2–10 days
      • increases the potential for bleeding episodes.
    • Therapeutic uses
      • treatment and prophylaxis of venous thrombosis and of pulmonary embolism.
      • Coumarin derivatives are also indicated to reduce thromboembolism in patients with mechanical heart valves.
      • Coumarin derivatives are also used to treat patients with atrial fibrillation, whose risk for a stroke is greatly increased.
    • Adverse effects
      • Bleeding is a common adverse effect with oral anticoagulants
      • prothrombin times should be frequently monitored.
      • Warfarin causes hemorrhagic infarction in the breast, intestine, and fatty tissues
      • it also readily crosses the placenta and can cause hemorrhage in the fetus
      • Warfarin causes defects in normal fetal bone formation
      • its teratogenic potential is high.
    • Drug interactions
      • Amiodarone and sulfinpyrazone inhibit metabolism of the more active warfarin stereoisomer and increase drug activity.
      • Aspirin and salicylates increase warfarin action by
          • inhibiting platelet function
          • displacement of warfarin from plasma-binding sites.
      • Antibiotics decrease microbial vitamin K production in the intestine.
      • Barbiturates and rifampin decrease warfarin effectiveness by inducing microsomal enzymes.
      • Oral contraceptives decrease warfarin effectiveness by increasing plasma clotting factors and decreasing antithrombin III.

Warfarin drug

Differences Between Heparin and Warfarin

Warfarin medical animation

WARFARIN

Warfarin Pharmacology

Vitamin K and Warfarin Correlation