NursingStudyHub

Warfarin 

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by

Liu
in

MECHANISM OF ACTION 

  • Coumarin anticoagulant; inhibits hepatic synthesis of vitamin K-dependent clotting factors (II, VII, IX, X) and co-factors (proteins C and S).
  • Thus the predominant action of warfarin is on the extrinsic pathway of the clotting cascade.

INDICATIONS 

  • DVT.
  • PE.
  • Prophylaxis of VTE in AF, rheumatic heart disease and in patients with prosthetic heart valves.

CAUTIONS AND CONTRA-INDICATIONS

  • Peptic ulceration.
  • Severe hypertension.
  • Pregnancy (due to teratogenicity).
  • Caution if recent surgery.

SIDE-EFFECTS 

  • Haemorrhage.
  • Hypersensitivity/rash.
  • Hepatic dysfunction.
  • Skin necrosis (due to thrombosis in the microvasculature of subcutaneous fat)

METABOLISM AND HALF-LIFE

  •  t½ is 37h; metabolised by the liver.

MONITORING 

  • Monitor INR (initially daily and then at progressively lengthening intervals when steady INR is achieved).

DRUG INTERACTIONS 
The anticoagulant effect of warfarin is increased by:-

  • Antibiotics (due to reduced vitamin K synthesis by gut flora)
  • Amiodarone and diuretics (displace warfarin from plasma proteins)
  • Cimetidine, fluconazole, alcohol (reduce the metabolism of warfarin)
  • Aspirin, clopidogrel, NSAIDs (due to impaired platelet function)
  • Also by advanced age, biliary disease, CCF, hyperthyroidism, cranberry juice and intermittent alcohol binges.

The anticoagulant effect of warfarin is reduced by

  • Antiepileptic agents, rifampicin, alcoholism (due to induction of hepatic enzymes) Oestrogens and OCP (increase the concentration of vitamin K-dependent clotting factors)
  • Also by hypothyroidism and nephrotic syndrome.

IMPORTANT POINTS

  • Effects proteins C and S precede anticoagulant effect thereby transiently increasing the risk of thrombosis; anticoagulation with heparin should, therefore, be used concomitantly for at least 5 days and until INR is within the target range for treatment of a thrombotic event.
  • Target INR depends on indication(e.g.2.0–3.0forVTEandAF;3.0–4.5 for prostheti cheart valves; 4.0–5.0 for high-risk heart valves).
  • Vitamin K may be used to reverse anticoagulation with warfarin; use should be limited to major bleeding or high INR in a patient with other risk factors for bleeding.
  • Prothrombin complex concentrate may so be used to reverse effects of warfarin in severe bleeding