Warfarin

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Warfarin (Coumadin) belongs to a group of medicines called anticoagulants. It is used to reduce the clotting ability of the blood.

Warfarin prevents and treats blood clots forming in the legs, lungs, brain and heart

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[edit] STRUCTURE

Warfarin.jpg

[edit] MECHANISM OF ACTION

Warfarin, is a synthetic derivative of coumarin that acts as a vitamin K antagonist.

Vitamin K antagonists produce their anticoagulant effect by inhibition of the vitamin K-epoxide-reductase, leading to the depletion of the reduced form of vitamin K (Vitamin KH2). As vitamin KH2 is a cofactor for the carboxylation of certain glutamic acid residues near the N-terminals of vitamin K-dependent coagulation factors (II, VII, IX, and X). this ultimately results in reduced cleavage of fibrinogen into fibrin and decreased coagulability of the blood.

Warfarin is not useful to dissolve already formed blood clots, but, it can keep existing clots from becoming larger.

Anticoagulation effect generally occurs within 24 hours after warfarin administration. However, peak anticoagulant effect may be delayed 72 to 96 hours. The duration of action of a single dose of warfarin is 2 to 5 day.

[edit] INDICATIONS

  • Prevention and treatment of venous thrombosis and pulmonary embolism
  • Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation and/or prosthetic heart valves replacement
  • Reduction in the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction

[edit] DOSAGE

[edit] CONTRAINDICATIONS

  • Pregnancy, except in women with mechanical heart valves. Warfarin may cause birth defects, miscarriage, or death of the unborn baby.
  • Hemorrhagic tendencies or blood dyscrasias
  • Recent or contemplated surgery of the central nervous system (CNS) or eye, or traumatic surgery resulting in large open surfaces
  • Bleeding tendencies associated with certain conditions
  • Threatened abortion, eclampsia, and preeclampsia
  • Unsupervised patients with potential high levels of non-compliance
  • Spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding
  • Hypersensitivity to warfarin or any component of the product
  • Major regional or lumbar block anesthesia
  • Malignant hypertension

[edit] WARNINGS AND PRECAUTIONS

  • Tissue necrosis: Necrosis or gangrene of skin (Death of skin tissue) or other tissues is a rare but serious complication resulting from treatment with warfarin. IT occurs more frequently shortly after commencing treatment in patients with a deficiency of protein C. In severe cases of necrosis, treatment through debridement or amputation of the affected tissue, limb, breast, or penis has been reported. Although various treatments have been attempted, no treatment for necrosis has been considered uniformly effective. Discontinue Warfarin therapy if necrosis occurs. Consider alternative drugs if continued anticoagulation therapy is necessary
  • Systemic atheroemboli and cholesterol microemboli: Some cases have progressed to necrosis or death. Discontinue Warfarin if such emboli occur.
  • Heparin-induced thrombocytopenia (HIT): Initial therapy with Warfarin in HIT has resulted in cases of amputation and death. Warfarin may be considered after platelet count has normalized.
  • Pregnant women with mechanical heart valves: Warfarin may cause fetal harm; however, the benefits may outweigh the risks

[edit] INTERACTIONS

  • Consult labeling of all concurrently used drugs for complete information about interactions with Warfarin or increased risks for bleeding.
  • Inhibitors and inducers of CYP2C9, 1A2, or 3A4: May alter warfarin exposure. Monitor INR closely when any such drug is used with Warfarin.
  • Drugs that increase bleeding risk: Closely monitor patients receiving any such drug (e.g., other anticoagulants, antiplatelet agents, nonsteroidal anti-inflammatory drugs, serotonin reuptake inhibitors).
  • Antibiotics and antifungals: Closely monitor INR when initiating or stopping an antibiotic or antifungal course of therapy.
  • Botanical (herbal) products: Some botanicals may cause bleeding events when taken alone (e.g., garlic and Ginkgo biloba) and may have anticoagulant, antiplatelet, and/or fibrinolytic properties. These

effects would be expected to be additive to the anticoagulant effects of Warfarin. Conversely, some botanicals may decrease the effects of Warfarin (e.g., co-enzyme Q10, St. John’s wort, ginseng). Some botanicals and foods can interact with Warfarin through CYP450 interactions (e.g., echinacea, grapefruit juice, ginkgo, goldenseal, St. John’s wort). Monitor the patient’s response with additional INR determinations when initiating or discontinuing any botanicals.

[edit] PREGNANCY AND LACTATION

Warfarin is contraindicated in pregnancy, it can cause major congenital malformations, fatal fetal hemorrhage, and an increased risk of spontaneous abortion and fetal mortality.

[edit] SIDE EFFECTS

Most common adverse reactions to Warfarin are fatal and nonfatal hemorrhage from any tissue or organ

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