ORAL ANTICOAGULANTS

WARFARIN

This compound was originally employed as a rodent poison. It is the most widely used coumarin anticoagulant and may be considered to be the drug of choice as an oral anticoagulant.

Mechanism of action

• The anticoagulant prevents reductive metabolism of the inactive vitamin K epoxide back to its active form

Pharmacokinetics:

• It is administered orally as sodium salt and has 100% bioavailability.

• The drug has slow onset of action, and long half-life in plasma (36hr) because 99% of the drug is bound to albumin.

Clinical uses

Prevention and treatment of deep vein thrombosis, treatment of atrial fibrillation with thrombus formation, prevention and treatment of pulmonary embolus, as part of the treatment of coronary occlusion and prevention of thrombus formation after value replacement

Side effects

Birth defect in pregnancy, hemorrhagic disease of newborn, hemorrhagic infarcts and cutaneous necrosis

Contraindications – similar to heparin and the drug should never be administered during pregnancy.

Drug interactions

• The effect of warfarin will be increased when it is used with the following drugs.

Cimitidine, dsulfiram, metronidazole, phenylbutazone, ASA and cephalosporin (3^rd generations)

• The effect of warfarin will be decreased when it is used with the following drugs.

Barbiturates, Cholestyramine, Rifampincin, Diuretics, vit K