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E.4 Anticoagulant Overview Flashcards

1
Q

These drugs inhibit at least one step of the coagulation cascade, prolonging the time it takes for a clot to form.

A

Anticoagulants.

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2
Q

What are the three steps leading to activation of the coagulation cascade.

A
  1. Platelet Activation
  2. Platelet Adhesion
  3. Platelet Aggregation.
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3
Q

Vascular injury leads to platelet activation which leads to activation of Factor ____, which then leads to activation of Factor ___ responsible for converting pro-thrombin to thrombin.

A

1) Factor VIIa
2) Factor Xa

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4
Q

Surface activation is responsible for upregulating the coagulation pathway. This starts with the activation of factor ____, which then activates factor ____, which then activates factor ____, leading to activation of factor Xa.

A

1) XIIa
2) XIa
3) IXa

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5
Q

_____ is responsible for converting pro-thrombin to thrombin.

A

Factor Xa

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6
Q

______ is responsible for converting fibrinogen to a fibrin clot.

A

Thrombin.

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7
Q

What are the two indications for anticoagulants?

A

1) Atrial Fibrillation
2) Venous Thromboembolism (VTE)

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8
Q

All anticoagulants significantly increase a patients risk of ______.

A

Bleeding.

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9
Q

What are the 4 DOACs currently on the market.

A
  1. Apixaban
  2. Rivaroxaban
  3. Edoxaban
  4. Dabigatran.
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10
Q

When is warfarin still indicated? (3 situations)

A
  1. Valvular Atrial Fibrillation
  2. Mechanical Heart Valves
  3. Some hypercoagulable states.
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11
Q

______ potentiates anti thrombin. This leads to decreased transformation of prothrombin to thrombin. (Note this does not directly inhibit factor Xa)

A

Heparin

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12
Q

How is heparin administered?

A

SQ (For prophylaxis)
IV (Treatment)

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13
Q

Heparin Half-Life

A

1-2 hours

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14
Q

When would heparin require a dose adjustment.

A

Higher body weights.

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15
Q

Goal Anti-Xa level with heparin treatment.

A

0.3-0.7 units/mL

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16
Q

______ potentiates antithrombin resulting in decreased transformation of prothrombin to thrombin. However, this also inactivates factor Xa.

A

Low Molecular Weight Heparin

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17
Q

How is low molecular weight heparin administered?

A

SQ (rarely IV)

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18
Q

What is the dose for low molecular weight heparin?

A

1 mg/kg Q12H

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19
Q

Enoxaparin half-life

A

12 hours

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20
Q

When should enoxaparin require dose adjustments.

A

1) CrCL <30ml/min
2) BMI 40+ kg/m^2

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21
Q

______ inhibits vitamin K this leads to a reduction of factors II, VII, IX and X. It also leads to a decrease in protein C and S by blocking carboxylation.

A

Warfarin

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22
Q

Warfarin blocks the synthesis of what coagulation factors?

A

II, VII, IX, X.

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23
Q

Warfarin Half-Life

A

20-60 hours (VARIES)

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24
Q

When might warfarin need to be dose adjusted?

A

High body weight.

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25
Q

Warfarin Drug Interactions

A

CYP1A2,, CYP2C19, CYP2C9 (MAJOR), CYP3A4

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26
Q

Warfarin Efficacy Monitoring

A

INR (Goal: 2-3)

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27
Q

The following are limitations to what drug?

~Frequent INR monitoring
~Bridging Requirements
~Peri-procedural anticoagulation
~DDI
~Drug Food Interactions

A

Warfarin

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28
Q

Why does warfarin require bridging with enoxaparin upon initiation?

A

It takes about 5 days to work. (In fact there is an increased risk of bleeding for a few days.)

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29
Q

Which Anticoagulant would have a significant interaction with each of the following drugs:

~Amiodarone
~Macrolide Antibiotics
~Azole Antifungals
~Sulfa Antibiotics
~Rifampin

A

Warfarin

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30
Q

Warfarin Starting Dose

A

5 mg QD for 3 days.

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31
Q

Warfarin Starting dose for those who are expected to be more sensitive to warfarin.

A

2.5 mg QD for 3 days.

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32
Q

Who would be expected to be more sensitive to warfarin?

A

1) Frail/Elderly
2) Liver Disease
3) Kidney Disease
4) Heart Failure
5) Acute Illness
6) Receiving medication that decreases warfarin metabolism

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33
Q

Eliquis Generic Name

A

Apixaban

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34
Q

Eliquis Mechanism

A

Direct Factor Xa inhibitor

35
Q

Eliquis Dosing (AFIB and VTE)

A

Afib: 5 mg twice daily

VTE: 10 mg twice daily x 1 week, then 5 mg twice daily.

36
Q

Eliquis Half-Life

37
Q

When should Eliquis dose be adjusted to 2.5 mg twice daily rather than 5 mg twice daily.

A

Only in Afib if the patient meets two of following criteria.

1) SCr 1.5+
2) Weight <60 kg
3) Age >80 years

38
Q

Which DOAC is preferred in ESRD or dialysis?

39
Q

Which CYP is Eliquis a major substrate for?

40
Q

Xarelto Generic Name

A

Rivaroxaban

41
Q

Xarelto Mechanism

A

Factor Xa Inhibitor

42
Q

Xarelto Dosing (Afib and VTE)

A

Afib: 20 mg QD
VTE: 15 mg BID x21 days, then 20 mg QD.

43
Q

Xarelto half-life

A

5-9 hours.

44
Q

When should Xarelto be dose adjusted.

A

CrCl 15-50: 15 mg QD

45
Q

Xarelto should be discontinued at a CrCl below _____.

46
Q

Xarelto is a major substrate of which CYP.

47
Q

_____ should be taken with food at doses >10 mg.

48
Q

Savaysa Generic Name

49
Q

Savaysa Mechanism

A

Factor Xa Inhibitor

50
Q

Savaysa Dose (Afib and VTE)

A

Afib: 60 mg QD

VTE: After 5 days parenteral—>

> 60 kg-> 60 mg QD
<60 Kg -> 30 mg QD

51
Q

Savaysa Half-Life

A

10-14 hours.

52
Q

_____ should only be used in patients with a CrCL between 15-95 ml/min

53
Q

When should savaysa be dose adjusted?

A

1) Weight (review)
2) Afib w/ CrCl 15-50 ml/min = 30 mg QD.

54
Q

Fondaparinux Brand Name

55
Q

Fondaparinux Mechanism

A

Factor Xa Inhibitor

56
Q

Fondaparinux Route of Administration

57
Q

Fondaparinux half-life

A

17-21 hours.

58
Q

When should Fondaparinux not be used?

A

1) CrCl <30 ml/min
2) <50 kg

59
Q

This anticoagulant does not contain pork and is a useful substitute for select patients wishing to avoid heparin products.

A

Fondaparinux.

60
Q

Pradaxa generic

A

Dabigatran

61
Q

Only GENERIC doac

A

Dabigatran

62
Q

Dabigatran mechanism

A

Direct Thrombin Inhibitor

63
Q

Dabigatran Dosing

A

Afib: 150 mg Twice Daily
VTE: 150 mg Twice Daily (after 5 days parenteral)

64
Q

Dabigatran Half-Life

A

12-17 hour.

65
Q

When should Dabigatran be dose adjusted in Afib?

A

CrCl 15-29 ml/min = 75 mg twice daily
Avoid < 15 mL/Min

66
Q

When should dabigatran be avoided in VTE?

A

CrCl <30 ml/min

67
Q

_____ has poor outcomes in those >120 kg or BMI >40 kg/m^2

A

Dabigatran

68
Q

____ is rarely used due to increased GI bleeds compared to warfarin.

A

Dabigatran.

69
Q

What are the two parenteral direct thrombin inhibitors?

A

1) Argatroban
2) Bivalirudin

70
Q

Argatroban Mechanism

A

Parenteral Direct Thrombin Inhibitor

71
Q

Argatroban Administration

A

Continous IV infusion

72
Q

Which has a faster onset Argatroban or Bivalirudin?

A

Bivalirudin

73
Q

Which can be dialyzed; Argatroban or Bivalirudin?

A

Bivalirudin.

74
Q

Argatroban metabolism

A

Hepatobiliary (85%)

75
Q

Bivalirudin Metabolism

A

85% proteolytic elimination.

76
Q

Argatroban andBivalirudin will increase ____

A

INR. (Complicates the switch to warfarin.)

77
Q

Warfarin Specific Reversal Agent

78
Q

Warfarin non-specific reversal agents.

A

1) Fresh Frozen Plasma
2) Prothrombin Complex Concentrate

79
Q

Factor Xa Inhibitor Specific Reversal Agent

A

Andexanet Alfa (Andexxa)

80
Q

Factor Xa Inhibitor Non-Specific Reversal Agent

A

Prothrombin Complex Concentrate

81
Q

Dabigatran Specific Reversal Agent

A

Idarucizumab (Praxbind)

82
Q

Dabigatran Non-specific reversal agent

A

Activated Prothrombin Complex Concentrate

83
Q

Heparin and Enoxaparin Reversal Agent

A

Protamine.

CRT (16 decks)

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