Warfarin and Heparin

Question 1

What is the mechanism of action of warfarin?

Answer 1

It prevents recycling of vitamin K and therefore prevents gamma carboxylation of vitamin k dependent clotting factors so they are no longer able to bind phospholipids via the gla domain

Question 2

How do you reverse the action of warfarin?

Answer 2

Give vitamin K

Question 3

What is the mechanism of action of heparin?

Answer 3

A polysaccharide of repeating sugars which bind and enhance the action of antithrombin
Does this by trapping the thrombin against the AT
It also increases the release of TFPI from Gags

Question 4

What are the side effects of warfarin aside from bleeding?

Answer 4

SKin necrosis
Chondrodysplasia punctata in utero
Purple toe syndrome

Question 5

What are the side effects of heparin?

Answer 5

Bleeding
heparin induced thrombocytopaenia
Hyperkalaemia/osteoporosis and alopecia

Question 6

What are the tests used to monitor warfarin? What are the values?

Answer 6

INR
Target 2-3 for patients after their first VTE, AF, cardiomyopathy and valvular heart disease
Target 3-4.5 for recurrent VTE, valvular heart disease and other thrombophilias

Question 7

What are the tests used to monitor heparin? What are the values?

Answer 7

APTT - ratio of 2.0

LMWH gives a more predictable response than UFH

Question 8

What are the pharmacokinetics of warfarin?

Answer 8

Highly water soluble
Rapidly absorbed from GI tract 
high bioavailability
Maximum blood conc about 90 min after oral admin
halflife of 36-42 hrs
Most is protien bound and ineffective
metabolised by P450