Anticoagulants - vit K inhibitors

Question 1

Anticoagulants - 3 groups

Answer 1

Vitamin K antagonists.
Drugs that potentiate antithrombin III (AT-III).
Direct thrombin inhibitors

Question 2

Vitamin K antagonists - 1 drug

Answer 2

Warfarin

Question 3

Warfarin - classification

Answer 3

Vitamin K antagonist, coumarin compound.

Question 4

Warfarin - MOA

Answer 4

Inhibit the reduction of oxidized vit K, which blocks posttranslational carboxylation of factors II (prothrombin), VII, IX and X, and these factors cannot be synthesized.
Also inhibits proteins C and S (may cause transient procoagulant effect).

Question 5

Protein C and S - function

Answer 5

Endogenous anticoagulants that inactivate factors V and VIII and promote fibrinolysis.

Question 6

Warfarin - contraindications

Answer 6

Pregnancy (crosses placenta and may cause fetal warfarin syndrome - fetal hemorrhage and birth defects).
Starting/discontinuing other drugs: must be evaluated by physician because of interactions.

Question 7

Warfarin - onset of action

Answer 7

Delayed 3-5 days because of the time it takes to deplete the pool of circulating clotting factors.

Question 8

How should chronic treatment for thromboembolic disorders be started?

Answer 8

Low-molecular-weight heparin and warfarin. When warfarin has started working, heparin is discontinued.

Question 9

Adverse effets of warfarin

Answer 9

Bleeding (pts should report hematuria and ecchymoses)

Question 10

Fetal warfarin syndrome - symptoms

Answer 10

Chondrodysplasia puncta, malformation of ears & eyes, mental retardation, nasal hypoplasia, optic atrophy, skeletal deformities, hemorrhage)

Question 11

Why does warfarin cause fetal deformities?

Answer 11

Antagonizes vit K-dependent maturation of bone proteins.

Question 12

Interactions of warfarin (direct increasers of prothrombin time, inducing CYP enzymes, and inhibit absorption)

Answer 12

Direct reduction of prothrombin levels: High dose of salicylates. Some 3rd generation cephalosporins.
Induce CYP enzymes: rifampin and barbiturates.
Inhibit absorption: Cholestyramine

Question 13

Interactions of warfarin (drugs that inhibit CYP enzymes)

Answer 13

Amiodarone, cimetidine, erythromycin, fluconazole, gemfibrozil, isoniazid, metronidazole, sulfinpyrazone.

Question 14

Treatment of warfarin-associated hemorrhage

Answer 14

Withdraw/reduce dose of warfarin. Phytonadione (vitamin K1) - direct antagonism of warfarin.
Severe: (INR>20) fresh plasma or factor IX concentrate

Question 15

Warfarin - indications

Answer 15

Long-term treatments. DVT, AF, artificial heart valve. MI with heparin.

Question 16

How to measure the effect of warfarin?

Answer 16

PT (1.3-1.5 times control PT)

INR (observedPT/controlPT): 2-3 (3-4.5 mechanical prosthetic valves and recurrent embolization)