Prophylaxis and Treatment of Thrombosis: Oral Anticoagulants

Question 1

Warfarin (coumadin)

Answer 1

Vitamin K antagonist (actually is Vit K analog)
Inhibits gamma-carboxylation of glutamic acid (required for FII, VII, IX, and X)
Blocks synthesis of vitamine K in liver by inhibiting epoxide reductase
These factors will be present in the blood, just inactive

Question 2

Warfarin Duration

Answer 2

Long half life due to being highly protein bound

Long onset

Question 3

Warfarin Metabolism

Answer 3

Metabolized in the liver

Very narrow therapeutic index

Question 4

Warfarin Monitoring

Answer 4

PT/INR is used to monitor
Blocks extrinsic pathway
1.5 x PT from baseline is therapeutic

Question 5

Warfarin Drug Interactions

Answer 5

Causing vitamin K deficiency
Displacing warfarin from albumin
Decreasing clotting-factor syntthesis
Suppressing or competing for microsomal enzymes
Having antiplatelet aggregating properties
Antibiotics: decreasing normal flora of gut and decreasing baseline vit K
NEVER GIVE TO PREGNANT WOMEN

Question 6

Coumadin induced necrosis

Answer 6

Pts with impairment of protein C (anticoagulant)
Protein C synthesis also requires gamma-carboxylation of glutamic acid)
If protein C levels fall too rapidly this can lead to clotting (in the skin) leading to necrosis

Question 7

Treatment of Warfarin Toxicity

Answer 7

Replacement of the 4 factors
Infusion with whole fresh blood or frozen plasma
Recombinant Factor VIIa
Vitamin K

Question 8

Vitamin K

Answer 8

Essential to teh attachment of a calcium binding functional group to prothrombin protein (in the presence of gamma-carboxyglutamic acid)
Required for synthesis of factors II, VII, IX, and X

Question 9

New Oral Anticoagulants

Answer 9

Anti-Xa agents (rivaroxaban and apixiban)
Antithrombin agents (Dabigatran)
Don’t have to be monitored like warfarin
All cleared renally (whereas warfarin is liver)