Oral Anticoagulants

Question 1

The most commonly used Vitamin K antagonist is?

Answer 1

Warfarin (Coumadin)

Question 2

Warfarin

MOA

Answer 2

Suppress functional forms of factors 2, 7, 9, 10. Prevents carboxylation of glutamic acid in these proteins by blocking the epoxide reductase enzyme in the liver

Question 3

Why is carboxylation of coagulation factors important? Which factors require gamma-carboxylation for activation?

Answer 3

Factors 2, 7, 9, 10

Carboxylation is essential for Ca2+ binding

Question 4

Warfarin

Onset of Action

Answer 4

Very long onset of action. Typically heparin is given in emergency situations and warfarin is for long term use

Question 5

Warfarin

Absorption

Answer 5

Very well absorbed orally

Question 6

Warfarin

Does it have a short or long half life and why?

Answer 6

Long half life (36 hrs) due to high protein binding to plasma albumin

Question 7

Warfarin

Metabolism

Answer 7

Activated by enzymes in the hepatic ER. Varies greatly from patient to patient

Question 8

Which secondary hemostasis pathway does warfarin effect most? What test can be used to assess the effects of warfarin?

Answer 8

Extrinsic pathway (though decreasing functionality of 2, 7, 9, 10)

PT/INR (prothrombin time/international normalized ratio) used to assess anticoagulant effects of warfarin

Question 9

Therapeutic Range of Warfarin

Answer 9

1.5x baseline PT/INR is considered therapeutic

Question 10

Warfarin Drug Interactions

How do other drugs cause warfarin potentiation?

Answer 10

• Cause a vitamin K deficiency
• Decrease clotting factor synthesis
• Suppression or competition for microsomal enzymes

Question 11

Warfarin Drug Interactions

How do other drugs inhibit the anticoagulant effects of warfarin?

Answer 11

Decrease warfarin absorption

Enhance warfarin metabolism

Question 12

Warfarin

Toxicity

Answer 12

Hypoprothrombinemia
Ecchymoses, purpura, hematuria, hemorrhage

Coumadin induced necrosis due to warfarin causing impaired functionality of protein C

Fetal malformation

Question 13

Who should never receive warfarin?

Answer 13

Pregnant women. All oral anticoagulants can cross the placental barrier and cause fetal malformation

Question 14

What could you give a patient who has overdosed on warfarin?

Answer 14

• Fresh frozen plasma will replace factors 2, 7, 9, 10

- Vitamin K via IV will reverse warfarin’s effects

Question 15

Vitamin K

Function

Answer 15

Essential for attaching a Ca2+ binding functional group (y-carboxyglutamic acid) to prothrombin.

Required for synthesis of clotting factors 2, 7, 9, 10

Question 16

Vitamin K Therapeutic Use

Answer 16

Drug induced hypoprothrombinemia

Used in hypoprothrombinemias of newborns

Question 17

Vitamin K Toxicity

Answer 17

Pretty non-toxic. May cause hemolysis in some infants or individuals sensitive to primaquine

Question 18

List the Anti Xa agents

Answer 18

Rivaroxaban
Apixiban
Edoxaban

Question 19

List the Anti thrombin agents

Answer 19

Dabigatran

Question 20

Features of the new oral anticoagulant drugs

Answer 20

You do not have to monitor these drugs! (Unfortunately, there are no tests to monitor their efficacy).

Often have fixed, once daily dosing

All cleared by the renal system

Have a shorter half life than warfarin

Question 21

Who should never receive dabigatran?

Answer 21

Someone with severe renal impairment. Dabigatran has 100% renal clearance