Warfarin

Question 1

What is it used for?

Answer 1

PE / Proximal DVT - >3mos if temp risk factors, >6mos if permanent risk factors

Calf DVT - Minimum 6wks, same as PE

Recurrence of DVT - >6mos with temp risk factors, long-term if permanent risk factors

AF - long term

Artificial valves - long-term

Question 2

How does it work?

Answer 2

Vitamin K antagonist - can be taken orally (unlike heparins)

Efficacy measured using INR (internal normalised ratio) - comparison of pt’s clotting ability compared to the ‘average’ of the population

NB - patients on warfarin need to have individualised doses, and this means the treatment is both inconvenient and has a low margin of safety.

Question 3

Mechanism of action

Answer 3

Inhibits enzymatic reaction of Vit K to active form hydroquinone

By preventing the activation of vitamin K, warfarin reduces the production of factors II, VII, IX, and X

Question 4

Side effects

Answer 4

Haemorrhage

Teratogenicity

Necrosis of soft tissues

Question 5

Interactions with warfarin - disease

Answer 5

Liver disease - reduces number of clotting factors produced

High metabolic rate - e.g. thyrotoxicosis and fever - as these increase the rate at which clotting factors are degraded

Question 6

Interactions with warfarin - drugs

Answer 6

Drugs that inhibit hepatic metabolism - cimetidine, ciprofloxacin, chloramphenicol, metronidazole and amiodarone

Drugs that inhibit platelet function - aspirin and other NSAIDs

Drugs that displace warfarin from its binding site on albumin - e.g. NSAIDs as this will increase the concentration of warfarin in plasma

Drugs that inhibit the synthesis of vit K - cephalosporins

Question 7

O-DEVICES - drugs that inhibit cytochrome p450 and thus increase the effects of warfarin

Answer 7

O - Omeprazole
D - disulfiram
E - erythromycin
V - valproate
I - isoniazid
C - cimetidine + ciprofloxacin
E - Ethanol (acutely)
S - sulphonamides