module 9 warfarin

Question 1

Anticoagulant drug classes

Answer 1

warfarin
unfactionated heparin
low molecular weight heparin
selective factor Xa inhibitors 
direction thrombin inhibitors

Question 2

intrinsic and extrinsic pathway meet at

Answer 2

activation of factor X

Question 3

Vitamin K is needed for synthesis of which coagulation factors

Answer 3

Factors II, VII, IX, X

Protein C and S (natural anticoag)

Question 4

Warfarin mechanism of action

Answer 4

Vitamin K antagonist:
acts on the carboxylation pathway by inhibiting the regeneration of active vitamin K.
- epoxide reductase enzyme complex

Question 5

warfarin uses

Answer 5

prevents further extension of formed clots
prevents secondary thromboembolic complications
- no direct effect on established thrombus
- no reversal of ischemic tissue damage

Question 6

warfarin onset

Answer 6

24 hours

Question 7

warfarin peak

Answer 7

72-96 hours

Question 8

warfarin duration of single dose

Answer 8

2-5 days

Question 9

Warfarin drug effects parallel half life of factors and proteins

Answer 9

Factor II: 60 hrs
VII: 4-6 hours
IX: 24 hours
X: 48 hours
Protein C: 8 hours 
Protein S: 30 hours

Question 10

Warfarin pharmacokinetics

Answer 10

mixture of R- and S- enantiomers (mirror images)
S: 2-5x anticoag activity
- - metabolized by CYP2C9: dec. warfarin clearance
R: metabolized by CYP pathways: longer half-life
99% albumin bound (low albumin -> inc. free drug)

Question 11

drugs that enhance warfarin’s anticoag effect

Answer 11

• chloral hydrate: displace warfarin from albumin
• amiodarone, clopidogrel, “-zole”: dec. warfarin metabolisms by inhibiting P450 enzymes
• broad- spectrum abx: dec. gut bacteria-> dec. availability of Vitamin K in GI tract
• anabolic steroids: inhibit synthesis and inc. degradation of coag factors.

Question 12

Drugs that dec. warfarin’s anticoag effect

Answer 12

• cholestyramine: inhibits warfarin absorption in GI
• barbiturates, carbamazepine, phenytoin, rifampin: accelerate warfarin metabolism by inducing P450 enzymes
• vitamin K (reduced): bypasses warfarin’s inhibition of epoxide reductase

Question 13

food interactions with warfarin

Answer 13

vitamin K-rich:

• green, leafy veggies
• beef or pork liver
• many fruits, veggies, legumes

Question 14

Warfarin AE

Answer 14

bleeding
- severe hemorrhage: administer FFP which contains coag factors
- vit. K
Skin necrosis
- microvascular thrombosis via inhibition of C and S
- bridge with heparin
Purple toe syndrome
- breakage of small cholesterol deposits into feet
Osteoporosis
- dec. dietary intake of vit K. / inhibition of vit. K

Question 15

Warfarin use

Answer 15

completion of anticoag initiated with heparin

prevention of thrombus

Question 16

Warfarin monitoring

Answer 16

goal INR: 2-3.5
Narrow TI
drug interactions
toxicity risk

Question 17

warfarin reversal agents

Answer 17

Vitamin K
prothrombin complex
recombinant factor VIIa