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PT 1 > L32 Heparin Anticoagulants II > Flashcards

L32 Heparin Anticoagulants II Flashcards

1
Q

Broadly, which coagulation factors does heparin affect?

A

2a, 9a, 10a, 11a, 12a

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2
Q

Broadly, which coagulation factors does warfarin affect?

A

2, 7, 9, 10

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3
Q

Warfarin is an analogue and antagonist of ___.

A

Vitamin K

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4
Q

What is the MOA of warfarin?

A

Depression of the formation of functional forms of factors 2, 7, 9, 10; this occurs via inhibition of the carboxylation of glutamic acid in these proteins which is essential for calcium binding; this occurs via inhibition of vitamin K formation via inhibition of vitamin K reductase/epoxide reductase

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5
Q

Warfarin works in the ___, where coagulation factors are produced.

A

Liver

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6
Q

What does a mutation in VKORC1 gene cause?

A

Lack of epoxide reductase

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7
Q

Reduced/active vitamin K is used to convert the decarboxy form of ___ into the gamma carboxy form.

A

Prothrombin

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8
Q

What is used to measure the extrinsic coagulation factors?

A

PT INR

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9
Q

What is the order of reduction of Vitamin K dependent factors after warfarin administration?

A

7, 9, 10, 2

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10
Q

As the coagulation factors decrease, the INR starts to ___.

A

Increase

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11
Q

What is the 1st day of dosing for warfarin? The second day?

A

1st day: 5-10 mg/d

2nd day: 5-7 mg/d

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12
Q

How is warfarin administered?

A

Orally only

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13
Q

Describe the half life of warfarin.

A

Long (~36 hours) due to binding to plasma albumin (~99%)

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14
Q

How is warfarin metabolized?

A

Hydroxylated to inactive compounds by the hepatic ER

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15
Q

What is used to monitor the anticoagulant effects of warfarin?

A

Prothrombin time (PT/INR)

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16
Q

What is considered therapeutic for warfarin?

A

A 1.5 time prolongation of the PT from the baseline

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17
Q

Reagent based variations have been noted in PT. To obtain uniform degrees of anticoagulation, the concentp of INR has been introduced to adjust the level of anticoagulant in a given patient. INR = ?

A

(PT of patient/PT of mean normal control) x ISI

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18
Q

What are 5 factors that affect the dose of oral anticoagulants?

A
  1. Nutrition (diet high in vitamin K leads to a need for higher dose)
  2. Anemia (need a higher dose due to dilution effect)
  3. Liver disease
  4. Biliary obstruction (less absorption, lower effect)
  5. Drugs (increase or decrease effect)
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19
Q

What are important drug interactions that cause potentiation?

A
  1. Drugs that cause vitamin K deficiency (antibiotics)
  2. Drugs that displace warfarin from protein binding sites
  3. Drugs that decrease clotting-factor synthesis
  4. Drugs that suppress or compete for microsomal enzymes
  5. Drugs that have antiplatelet aggregating properties
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20
Q

What are important drug interactions that cause inhibition of anticoagulant action?

A
  1. Decreased warfarin absorption

2. Enhanced warfarin metabolism

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21
Q

What is the principal toxicity of warfarin?

A

Hypoprothrombinemia (ecchymosis, purpura, hematuria, hemorrhage)

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22
Q

Are oral anticoagulants contraindicated in pregnancy?

A

Yes

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23
Q

Warfarin also produces necrosis - how?

A

Impairment of the functionality of protein C, which requires gamma-carboxylation of glutamic acid for functionality (lack of functional protein C decreases anticoagulant effect)

24
Q

How is oral anticoagulant overdose treated?

A
  1. Replacement of the 4 factors with infusion of whole fresh blood or frozen plasma
  2. Recombinant factor 7a
  3. Vitamin K
25
Q

Compare and contrast heparin and warfarin vis a vis structure.

A

H: large acidic polymer
W: small lipid-soluble molecule

26
Q

Compare and contrast heparin and warfarin vis a vis route of administration.

A

H: IV, SC
W: Oral

27
Q

Compare and contrast heparin and warfarin vis a vis site of action.

A

H: Blood
W: Liver

28
Q

Compare and contrast heparin and warfarin vis a vis onset of action.

A

H: rapid (seconds)
W: slow, limited by half-lives of normal clotting factors

29
Q

Compare and contrast heparin and warfarin vis a vis MOA.

A

H: activates AT, which inhibits FXa and thrombin
W: impairs synthesis of 2, 7, 9, and 10

30
Q

Compare and contrast heparin and warfarin vis a vis duration of action.

A

H: acute (hours)
W: chronic (days)

31
Q

Compare and contrast heparin and warfarin vis a vis inhibition of coagulation in vitro.

A

H: yes
W: n

32
Q

Compare and contrast heparin and warfarin vis a vis treatment of acute overdose

A

H: protamine sulfate
W: IV vitamin K and fresh frozen plasma

33
Q

Compare and contrast heparin and warfarin vis a vis monitoring.

A

H: APTT
W: PT/INR

34
Q

Compare and contrast heparin and warfarin vis a vis crossing of the placenta.

A

H: No
W: Yes

35
Q

What is a naturally occurring fat soluble vitamin found in green vegetables and synthesized by gut flora?

36
Q

What is the function of vitamin K?

A

Required for the synthesis of factors 2, 7, 9, and 10; essential to the attachment of a calcium binding functional group to prothrombin protein

37
Q

What is the therapeutic use of vitamin K?

A

Drug induced hypoprothrombinemia antidote, intestinal disorders and surgery, and hypoprothrombinemia of newborns

38
Q

What are the toxicities of vitamin K?

A

Non-toxic; high doses sometimes cause hemolysis in infants

39
Q

What are the new oral anti-10a agents?

A

Rivaroxaban, Apixaban, Edoxaban, Betrixaban

40
Q

What is the antidote to the anti-10a agents?

A

There isn’t one as of right now

41
Q

What is the new oral anti-thrombin agent?

A

Dabigatran

42
Q

What is the antidote to dabigatran?

A

Idarucizumab

43
Q

What is the MOA of warfarin?

A

Competitive antagonist of vitamin K; suppresses the synthesis of 2, 7, 9, and 10 by blocking enzyme epoxide reductase in the liver

44
Q

What is the MOA of vitamin K?

A

Cofactor in the synthesis of 2, 7, 9, and 10

45
Q

What is the MOA of the oral anti-10a drugs?

A

Inhibits factor 10a

46
Q

What is the MOA of dabigatran?

A

Inhibits thrombin

47
Q

How are the oral anticoagulants monitored?

A

Warfarin: PT/INR

All others: not required

48
Q

What are the indications of warfarin?

A

Prolonged treatment of DVT and AFib

49
Q

What are the indications of Vitamin K?

A

Hypoprothrombinemia, intestinal disorders and gastrectomy, reverse warfarin effects

50
Q

What are the indications of the oral anti-10a’s?

A

Stroke prevention in patients with AF (all); prophylaxis of DVt (R, A, B); acute coronary syndrome (R)

51
Q

What are the indications of dabigatran?

A

Stroke prevention in patients with AFib

52
Q

What are the side effects of warfarin?

A

Bleeding, coumadin-induced necrosis; interacts with several medications that can potentiate/inhibit effects; crosses placental barrier and causes birth defects

53
Q

What are the side effects of Vitamin K?

54
Q

What are the side effects of oral anti-10a drugs?

A

Bleeding, liver toxicity (R, A, E)

55
Q

What are the side effects of dabigatran?

A

Bleeding, liver toxicity; cleared by kidney and could be problematic in patients with abnormal kidney function

PT 1 (34 decks)

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