WARFARIN

“COUMADIN”

1) Action

• Prothrombinopenic anticoagulant

2) Mechanism

• Coumarin drugs are vitamin K antagonists — they compete

• with vitamin K which they chemically resemble

• Vitamin K is utilised by the liver for the synthesis of:

• Prothrombin (II), Proconvertin (VII), Christmas factor (IX)

& Stuart factor (X)

3) Indications

• Prophylaxis & treatment of venous thrombosis & its extension

• Treatment of atrial fibrillation with embolisation

• Prophylaxis & treatment of pulmonary embolism

• Adjunct in treatment of coronary occlusion

• Prosthetic valves

• Dacron grafts [thoracic aorta]; pericardial patches

4) Effects on organs—side effects

5) Toxic effects/ precautions with administration

• Increased PT: amiodarone, aspirin, heparin, liver disease

• Decreased PT: vitamin K, diuretics, barbiturates

6) Contraindications

• Recent surgery

• Bleeding of GIT, cerebrovascular haemorrhage, cerebral & aortic aneurysms, pericarditis, subacute bacterial endocarditis

• Spinal puncture

• Gastric ulcer

• Eclampsia

• Lack of patient cooperation

• Pregnancy: teratogenic

7) Reversal, antagonism or antidote

• Excessive anticoagulant effect reversed by stopping warfarin, administering vitamin K (phytonadione) & FFP or factor IX concentrates

8) Loading dose, maintenance dose, frequency & method of administration

• Oral

• Monitored using PT & INR

9) Drug’s metabolism—Drug’s excretion—Half life (pharmacokinetics)

• 12 hour delay in action of warfarin

• Induces hypoprothrombinaemia in 36 - 72 hours

• Duration of action persists for 4 - 5 days

• 100% bioavailability

• 99% bound to plasma protein [& small volume of distribution]

• Long half life in plasma (2.5 days)

• Metabolites excreted in urine