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PharmSci > Warfarin > Flashcards

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?

A

heparin

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
Q

Why does warfarin interact with pts who have hyperthyroidism?

A

Hyperthyroidism (increases protein breakdown, increases warfarin effect

26
Q

Why does warfarin interact with pts who have diarrhea?

A

Diarrhea (impacts gut flora and affects absorption of vitamin K so warfarin effect increases)

27
Q

Why does warfarin interact with pts who have liver dysfunction?

A

Liver dysfunction (decreases CYP function, increases warfarin effect)

28
Q

Which CYP2C9 enzyme is the normal “wild type?
A. CYP2C91
B. CYP2C92
C. CYP2C9*3

A

A

29
Q

Which CYP2C9 enzyme has low activity and is a slow metabolizer?
A. CYP2C91
B. CYP2C92
C. CYP2C9*3

A

B, C

30
Q

What measures the activity of clotting factors and time to clot?

A

Prothrombin Time (PT)

31
Q

What is a normal PT?

A

11-13.5 sec

32
Q

What compares the pt’s PT to a control PT and accounts for variability in thromboplastin sensitivity?

A

INR

33
Q

ISI

A

international sensitivity index

34
Q

What does a high INR mean?

A

High INR = blood is too thin → increased risk of bleeding

35
Q

What does a low INR mean?

A

Low INR = blood is too thick → increased risk of clotting

36
Q

What is the target INR for pts on warfarin?

A

2-3

37
Q

What are the limitations of warfarin?

A
  • Food and drug interactions
  • Genetic variation in metabolism
  • Narrow therapeutic window
  • Slow onset of action

PharmSci (12 decks)

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