Heparin Anticoagulants II Flashcards
What are the main uses of the oral anticoagulants?
Prophylactic use: Prevention of thrombotic disorders
Therapeutic use: Treatment of established thrombus
What is the main oral anticoagulant?
Warfarin
What are the targets for warfarin action?
Factor II, VII, IX and X
What is the MOA of the coumarins (oral anticoagulants)?
All agents depress the formation of functional forms of factors II (prothrombin), VII, IX and X by inhibiting the ๐-carboxylation of glutamic acid in these proteins which is essential for Ca+2 binding.
How does warfarin inhibit the ๐-carboxylation of glutamic acid?
Inhibits the action of Vitamin K reductase
What is the onset of action of warfarin like?
Slow as it has an effect on the liver with enzyme synthesis
What is the function of Vitamin K?
It is essential for the attachment of Ca2+ binding group to prothrombin and for the synthesis of Factor II/VII/IX/X
What is the oral absorption of warfarin?
All are well absorbed orally
What is the half life of warfarin like?
Long T1/2 of the oral anticoagulants, due to binding to plasma albumin - warfarin is 97% bound
What pathway does warfarin inhibit?
Extrinsic Pathway
What is the therapeutic target with warfarin dosing?
1.5 times the prolongation of the normal bleed time
What is used to monitor warfarin dosing?
PT/INR
What are some factors that can affect warfarin dosing?
- ๔ฐNutrition - too many green leafy vegetables will increase Vitamin K
- Anemia
๔ฐ- Liver disease - will decrease production of clotting proteins so warfarin will have increased activity
๔ฐ- Biliary obstruction ๔ฐ - Drugs
How can drugs cause warfarin potentiation?
a. by causing vitamin K deficiency.
b. by displacing warfarin from protein binding sites.
c. by decreasing clotting-factor synthesis.
How can drugs inhibit the action of warfarin?
a. by decreasing warfarin absorption.
b. by enhancing warfarin metabolism.
What are some SE of warfarin?
- Bleeding, coumadin induced necrosis
- Ecchymosis/purpura/hematuria
- Has interaction with several medications which results in bleeding due to potentiating the effect of warfarin
- Bone malformations in the fetus
What is warfarin overdose treated with?
A. Replacement of 4 factors. Infusion of whole fresh blood or frozen plasma.
B. Recombinant Factor VIIa
C. Vitamin K
What are the new oral anticoagulants?
Rivaroxaban
Apixaban
Edoxaban
Dabigatran
What are the Xa inhibitors of the new oral anticoagulants?
Rivaroxaban
Apixaban
Edoxaban
What are the antithrombin inhibitors of the new oral anticoagulants?
Dabigatran
What is the main route of administration of warfarin?
Oral
What is the site of action of heparin?
Blood
What is the site of action of warfarin?
Liver
What is the onset of action of heparin and warfarin like?
Heparin has a rapid onset and warfarin has a slow onset
What is the MOA of heparin?
Activates AT, which inhibits FXa and thrombin
What is the MOA of warfarin?
Impairs the synthesis of factors II, VII, IX and X (vit. K antagonist
How is the effect of heparin reversed?
Protamine sulfate
How is the effect of warfarin reversed?
IV vitamin K and fresh frozen plasma
Does heparin cross the placenta?
No
MOA of Vitamin K
Cofactor in the synthesis of functional forms of factors II, VII, IX and X
Indications for Vitamin K
Hypoprothrombine mia, intestinal disorders and gastrectomy, reverses the effects of warfarin
SE of Vitamin K
Hemolysis
Rivaroxaban and Apixaban MOA
Inhibits factor Xa
Rivaroxaban and Apixaban Indications
Stroke prevention in patients with AF
Rivaroxaban also approved for prophylaxis and treatment of DVT
Rivaroxaban and Apixaban SE
Bleeding and liver toxicity
Dabigatran MOA
Inhibits thrombin
Dabigatran Indications
Stroke prevention in patients with AF
Dabigatran SE
Bleeding and liver toxicity
