Warfarin Flashcards

0
Q

What vitamin is required for synthesis of key coagulation factors?

A

VITAMIN K

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1
Q

What does warfarin do?

A

It affects the SYNTHESIS OF coagulation factors

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2
Q

What coagulation factors are dependent on vitamin K for synthesis?

A
Prothrombin
Factor VII
Factor IX
Factor X
Protein C
Protein S
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3
Q

Why is carboxylation of the terminal glutamate on coagulation factors important?

A

it is key to Ca2+ binding and increases activity of coagulation factors

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4
Q

What helps with carboxylation of coagulation factors?

A

Vitamin K (reduced form of vitamin K is required)

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5
Q

What does Vitamin K Quinone Reductase do?

A

converts the intermediate form of Vit K that we get in our diet to the reduced form of it K (this is NOT affected by warfarin)

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6
Q

What does Vitamin K Epoxide Reductase do?

A

it converts oxidized vitamin K to the reduced form (IS affected by warfarin)

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7
Q

What is the onset of action for warfarin?

A

8-12 h

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8
Q

What is the peak action for warfarin?

A

4-5 days

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9
Q

True/False? Warfarin is typically given orally as a K+ salt

A

false (Na+ salt)

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10
Q

Warfarin is nearly ____ % BA

A

100%

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11
Q

What % is warfarin protein bound?

A

99%

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12
Q

S-warfarin is metabolized by. . .

A

CYP2C9

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13
Q

R-warfarin is metabolized by. . .

A

CYP1A1, 1A2 AND 3A4

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14
Q

What is the half-life of warfarin?

A

25-60 h with an avg of 40 h

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15
Q

Adverse effects of Warfarin:

A

BLEEDING
Crosses the placenta*
Rare: Skin necrosis due to thrombosis related to altered synthesis of protein C and S

17
Q

What would you use in a pregnant woman who needs an anticoagulant?

18
Q

Why does warfarin have a drug interaction with BAS?

A

BAS binds to warfarin and prevents absorption which decreases warfarin’s effect

19
Q

Why does warfarin have a drug interaction with aspirin and sulfonamides?

A

Protein binding: increase warfarin effects because drug x binds to albumin instead of warfarin

20
Q

Why does warfarin have a drug interaction with fluconazole, metronidazole, amiodarone and bactrim?

A
Inhibitors of CYP1A2, 2C9, 3A4 (increase effect of warfarin)
o Fluconazole (2C9, 3A4)
o metronidazole (2C9)
o amiodarone (2C9, 3A4)
o bactrim (2C9, 3A4)
21
Q

Why does warfarin have a drug interaction with Phenobarbital,
Rifampin, and phenytoin?

A

They are Inducers of CYP1A2, 2C9 or 3A4.

22
Q

Why does warfarin have a drug interaction with Heparin, Ibuprofen and aspirin?

A

They are agents that affect platelet/clotting factor function (increases risk of bleeding)

23
Q

Why does warfarin interact with antibiotics?

A

Antibiotics decrease vit K, increases warfarin effect

24
Q

Why does warfarin interact with pts who have hypothyroidism?

A

Hypothyroidism (decreases protein breakdown, decreases warfarin effect)

25
Why does warfarin interact with pts who have hyperthyroidism?
Hyperthyroidism (increases protein breakdown, increases warfarin effect
26
Why does warfarin interact with pts who have diarrhea?
Diarrhea (impacts gut flora and affects absorption of vitamin K so warfarin effect increases)
27
Why does warfarin interact with pts who have liver dysfunction?
Liver dysfunction (decreases CYP function, increases warfarin effect)
28
Which CYP2C9 enzyme is the normal "wild type? A. CYP2C9*1 B. CYP2C9*2 C. CYP2C9*3
A
29
Which CYP2C9 enzyme has low activity and is a slow metabolizer? A. CYP2C9*1 B. CYP2C9*2 C. CYP2C9*3
B, C
30
What measures the activity of clotting factors and time to clot?
Prothrombin Time (PT)
31
What is a normal PT?
11-13.5 sec
32
What compares the pt's PT to a control PT and accounts for variability in thromboplastin sensitivity?
INR
33
ISI
international sensitivity index
34
What does a high INR mean?
High INR = blood is too thin → increased risk of bleeding
35
What does a low INR mean?
Low INR = blood is too thick → increased risk of clotting
36
What is the target INR for pts on warfarin?
2-3
37
What are the limitations of warfarin?
* Food and drug interactions * Genetic variation in metabolism * Narrow therapeutic window * Slow onset of action