Warfarin

Question 1

What is warfarin?

Answer 1

anticoagulant drug initially marketed as a pesticide

Question 2

What class of compounds does warfarin belong to?

Answer 2

anticoagulants and antithrombotics

Question 3

What are examples of other drugs in the same class as warfarin?

Answer 3

• clopidogrel
• tirofiban
• anagrelide
• bivalirudin
• apsirin
• enoxaparin
• heparin

Question 4

What is warfarin indicated for?

Answer 4

• prevention and treatment of venous thrombosis and pulmonary embolism
• prevention of stroke following MI in patients with increased embolic risk
• Prevention of TE in atrial fibrillation and in patients with prosthetic heart valves

Question 5

What is the role of warfarin in therapy?

Answer 5

first line oral anticoagulant (but not for patients with a prosthetic at risk of VTE)

Dose adjusted according to INR

Question 6

What is the mechanism of warfarin?

Answer 6

inhibits Vit. K reductase, depleting the reduced form of vitamin K which is an essential cofactor for gamma carboxylation to form coagulation factors 2, 7, 9 and 10 and anticoagulant proteins C and S

Question 7

What are the relevant PD/PK parameters of warfarin?

Answer 7

-warfarin is a racemic mixture of 2 active isomers

PK:
rapidly absorbed following oral admin with considerable interindividual variations 
also absorbed percutaneously
99% bound to proteins, primarily albumin
metabolised 2C9 and 1A1, 1A3 and 3A4

metabolites excreted in urine

half life of 37-89 hours (r warfarin) and 21-43 hours (s warfarin)

Question 8

What are the precautions with warfarin use?

Answer 8

conditions in which bleeding risk is increased e.g. history og GI bleeds, peptic ulcers, recent surgery, recent ischaemic stroke, threatened abortion etc.

hepatic impairment
renal impairment
pregnancy class D

Question 9

What are the adverse effects with warfarin use?

Answer 9

haemorrhage
nausea, vomiting, diarrhoea

jaundice, hepaitc dysfunctio, pancreatitis, pyrexia, alopecial, purpura rash, purple toes, skin necrosis

Question 10

What are the contraindications with warfarin use?

Answer 10

• haemorrhagic stroke
• significant bleeding or bleeding risk
• avoid use within 48 hours postpartum

Question 11

What are the drug interactions with warfarin?

Answer 11

St John’s wort , carbamazepine, colesyramine, can reduce anticoagulant effects of warfarin

Amiodarone, cimetidine, high doses of salicylate (4g or more)increases warfarin effect

Question 12

What are the alarm bells associated with warfarin use?

Answer 12

monitor PT and INR ever y1-2 days initially, then 1-4 weeks when dosage is stable

adhere strictly to prescribed dose
avoid alcohol, salicylates (including topical analgesics), large amounts of green leafy vegetables, cranberry or grapefruit juice.

Avoid drastic dietary changes, and dairy products fortified with vitamin K.

Notify doctor immediately of illness (diarrhoea, infection, fever,) pain, swelling, unusual bleeding or bruising, dark brown or red urine, red or tar black stools.