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IPC CARDIOLOGY 2 JEN > Pharmacology, PKPD, and Genomics of Anticoagulants > Flashcards

Pharmacology, PKPD, and Genomics of Anticoagulants Flashcards

1
Q

What are anticoagulants?

A

Drugs that inhibit at least one step of secondary hemostasis, prolonging the time it takes to form a clot

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2
Q

Prevention of anticoags?

A

Prevent clots from forming (prophylaxis)

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3
Q

Prophylaxis uses _____ doses

A

LOW

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4
Q

Treatment of anticoags?

A

1) Afib
2) VTE
3) Some valvular disease
4) Some hypercoagulable states

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5
Q

Treatment uses ______ doses

A

FULL

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6
Q

____ anticoagulants significantly ______ a patients risk of bleeding

A

ALL, INCREASE

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7
Q

Which are the parenteral anticoagulants?

A

Heparin, LMWH, Fondaparinux, Bivalirudin, Argatroban

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8
Q

Which are the oral anticoagulants?

A

Warfarin, Apixaban, Rivaroxaban, Edoxaban, Dabigatran

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9
Q

Which drugs are the DOACs?

A

Apixaban, Rivaroxaban, Edoxaban, Dabigatran

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10
Q

When is Warfarin still indicated?

A

Afib w/ history of moderate/severe rheumatic mitral stenosis
Mechanical heart valves
Some hypercoagulable states

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11
Q

MOA of heparin?

A

Potentiates antithrombin (AT) –> decreased transformation form prothrombin –> thrombin

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12
Q

Binding to AT increases heparins catalytic activity to ____ fold

A

1000

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13
Q

Route heparin

A

SQ (prophylaxis)
IV (treatment)

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14
Q

Half life heparin

A

1-2 hours (IV)

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15
Q

Monitoring Heparin: Efficacy

A

Anti-Xa levels or aPTT (1.5-2.5 x baseline) STANDARD

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16
Q

Monitoring Heparin: Goal

A

Anti-Xa: 0.3-0.7 units/mL (aPTT will be dependent on lab)

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17
Q

Monitoring Heparin: Safety

A

Hemoglobin, hematocrit, platelets, BLEEDING!

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18
Q

Heparin is typically used in a _____ setting

A

Hospital
Heparin is rarely used in outpatient!

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19
Q

Drugs that are LMWH

A

Enoxaparin (Lovenox)
Dalteparin (Fragmin)

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20
Q

LMWH MOA?

A

Potentiates antithrombin –> decreases transformation from prothrombin –> thrombin AND
inactivates factor Xa

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21
Q

LMWH Route?

A

SQ (rarely IV)

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22
Q

Dose LMWH?

A

1 mg/kg Q12H

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23
Q

Half life LMWH

A

12 hours

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24
Q

Renal CL requirements LMWH

A

CrCl < 30mL/min

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25
Q

Body Weight Considerations LMWH

A

May need to adjust doses with BMI > 40 kg/m2

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26
Q

Monitoring: Efficacy LMWH

A

Anti-Xa monitoring in obese patients, patients with renal dysfunction, pregnant patients
*Pregnant patients have a different Vd needing to monitor

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27
Q

Monitoring: Safety LMWH

A

Hemoglobin, hematocrit, platelets, BLEEDING, serum creatinine (bc of renal dose adjustments)

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28
Q

LMWH are commonly used in ______ setting

A

Hospital
Can be given outpatient

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29
Q

LMWH is a shorter chain fraction of heparin =

A

less effect on thrombin, increase effect on factor X

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30
Q

Brand name Warfarin

A

Coumadin

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31
Q

Warfarin MOA

A

Vitamin K antagonist –> reduction in the hepatic synthesis of factors II, VII, IX, and X as well as protein C and S by blocking carboxylation

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32
Q

Warfarin Route

A

Oral

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33
Q

Half life Warfarin

A

20-60 days variable

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34
Q

Body Weight considerations Warfarin?

A

higher bws may require higher doses, no specific way

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35
Q

Warfarin Drug Interactions: MINOR
CYPs

A

CYP1A2, CYP2C19, CYP3A4

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36
Q

Warfarin Drug Interactions: MAJOR
CYPs

A

CYP2C9

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37
Q

Monitoring Warfarin: Efficacy

A

INR for therapeutic level (usually 2-3)
Lab testing

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38
Q

Monitoring Warfarin: Safety

A

Hemoglobin, hematocrit, platelets, BLEEDING

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39
Q

Warfarin is ______ in pregnancy

A

Teratogenic

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40
Q

Warfarin decreases ______ of new clotting factors

A

SYNTHESIS
(for Warfarin to work, currently active clotting factors need to wash out)

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41
Q

Warfarin also decreases _______ of natural anticoagulants proteins ____ and ______

A

SYNTHESIS
C, S

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42
Q

Half life of Factor II

A

60 hours
the LONGEST…. multiple days

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43
Q

Half life of Factor VII

A

6 hours

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44
Q

Half life of Factor IX

A

24 hours

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45
Q

Half life of Factor X

A

40 hours

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46
Q

Half life of Protein C

A

10 hours

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47
Q

Half life of Protein S

A

42 hours

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48
Q

What are Warfarin limitations?

A

Frequent INR Monitoring
Bridging Requirements
Peri-procedural anticoagulation
DDI
Drug-Food interactions

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49
Q

Why do we need to overlap with a parenteral anticoagulant?

A

Protein C quickly depletes = transient
PROTHROMBOTIC STATE
Factor II takes multiple days to wash out

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50
Q

What is an INR test?

A

created specifically for Warfarin used an inverse ratio of prothrombin time which determines how long it takes for a clot to form
Made regular at all labs, all places have the same INR goals and numbers

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51
Q

Standard Dosing Warfarin: Initial Dose

A

5 mg daily for 3 days

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52
Q

Standard Dosing Warfarin: INR < 1.5

A

7.5 to 10 mg daily for 2 to 3 days

53
Q

Standard Dosing Warfarin: INR 1.5 to 1.9

A

5 mg daily for 2 to 3 days

54
Q

Standard Dosing Warfarin: INR 2 to 3

A

2.5 mg daily for 2 to 3 days

55
Q

Standard Dosing Warfarin: INR 3.1 to 4

A

1.25 mg daily for 2 to3 days

56
Q

Standard Dosing Warfarin: INR > 4

A

Hold until INR > 3

57
Q

Patients more sensitive to Warfarin…

A

Frail, elderly, or undernourished; liver disease, kidney disease, heart failure, or acute illness; or are receiving a medication that decreases Warfarin metabolism

58
Q

Reduced Dosing Warfarin for sensitive patients: Initial Dose

A

2.5 mg daily for 2 to 3 days

59
Q

Reduced Dosing Warfarin for sensitive patients: INR < 1.5

A

5 to 7.5 mg daily for 2 to 3 days

60
Q

Reduced Dosing Warfarin for sensitive patients: INR 1.5 to 1.9

A

2.5 mg daily for 2 to 3 days

61
Q

Reduced Dosing Warfarin for sensitive patients: INR 2 to 3

A

1.25 mg daily for 2 to 3 days

62
Q

Reduced Dosing Warfarin for sensitive patients: INR 3.1 to 4

A

0.5 mg daily for 2 to 3 days

63
Q

Reduced Dosing Warfarin for sensitive patients: INR > 4

A

Hold until INR > 3

64
Q

Maintenance Adjustment for Subtherapeutic INR Suggested adjustment: INR < 1.5

A
  • Increase weekly maintenance dose by 10% to 20%
  • Consider a one-time supplemental dose: 1.5-2 times the daily dose
65
Q

Maintenance Adjustment for Subtherapeutic INR Suggested adjustment: INR 1.5 to 1.7

A
  • Increase weekly maintenance dose by 5% to 15%
  • Consider a one-time supplemental dose: 1.5 to 2 times the daily dose
66
Q

Maintenance Adjustment for Subtherapeutic INR Suggested adjustment: INR 1.8 to 1.9

A
  • No dosage adjustment may be necessary if the last 2 INRs were in range
  • If adjustment needed, increase weekly maintenance dose by 5% to 10%
  • Consider a one-time supplemental dose: 1.5-2 times the daily dose
67
Q

Maintenance Adjustment for Subtherapeutic INR Suggested adjustment: INR 3.1 to 3.2

A
  • No dosage adjustment may be necessary if the last 2 INRs were in range
  • If dosage adjustment needed, decrease weekly maintenance dose by 5% to 10%
68
Q

Maintenance Adjustment for Subtherapeutic INR Suggested adjustment: INR 3.3 to 3.4

A
  • Decrease weekly maintenance dose by 5% to 10%
69
Q

Maintenance Adjustment for Subtherapeutic INR Suggested adjustment: INR 3.5 to 3.9

A
  • Consider holding 1 dose
  • Decrease weekly maintenance dose by 5% to 15%
70
Q

Maintenance Adjustment for Subtherapeutic INR Suggested adjustment: INR >4 but <10 no bleeding

A
  • Hold until INR below upper limit of therapeutic range
  • Decrease weekly maintenance dose by 5% to 20%
  • If patient considered to be at significant risk for bleeding, consider oral vitamin K
70
Q

Maintenance Adjustment for Subtherapeutic INR Suggested adjustment: INR > 10 and no bleeding

A
  • Hold until INR below upper limit of therapeutic range
  • Administer vitamin K orally
  • Decrease weekly maintenance dose by 5% to 20%
71
Q

For the INR 1.5 - 1.9 if the factor causing subtherapeutic INR is transient consider…

A

Resumption of prior maintenance dose following a one-time SUPPLEMENTAL dose

72
Q

For the INR 3.1 - 10 if the factor causing subtherapeutic INR is transient consider…

A

Resumption of prior maintenance dose following a one-time HELD dose

73
Q

Warfarin has a _______ therapeutic index

74
Q

Warfarin doses necessary to attain an INR goal of ______ vary from __ - ___ mg per day

75
Q

The major genes influencing the response to Warfarin are….

A

CYP2C9 and VKORC1
Minor: CYP4F2

76
Q

Apixaban Brand Name

77
Q

Apixaban MOA

A

Factor Xa inhibitor

78
Q

Apixaban Dose

A

Afib: 5 mg daily
VTE: 10 mg BID x 1 week, then 5 mg BID

79
Q

Apixaban Half life

80
Q

Apixaban Renal Adjustments

A

Afib: adjust dose to 2.5 mg daily if 2/3 criteria are met
SCr > 1.5, Weight < 60 kg, Age > 80 years old

81
Q

Apixaban BW considerations

A

May require a dose adjustment if < 60 kg (as above)
It is okay in those > 120 kg or BMI > 40kg/m2

82
Q

Apixaban DDIs… a major substrate of…

A

CYP3A4 and PgP

83
Q

Apixaban Monitoring

A

Monitor hemoglobin, hematocrit, platelets, serum creatinine

84
Q

Apixaban Pearls

A

The best DOAC in patients with poor renal function/ESRD dialysis

85
Q

Rivaroxaban Brand name

86
Q

Rivaroxaban Dose

A

Afib: 20 mg daily
VTE: 15 mg BID x 21 days then 20 mg daily

87
Q

Rivaroxaban Half life

88
Q

Rivaroxaban renal adjustments

A

Afib: dose adjust CCI 15-50 mL/min : 15 mg daily
Afib/VTE: Avoid use CCI < 15mL/min

89
Q

Rivaroxaban BW considerations

A

Okay in those > 120 kg or BMI > 40kg/m2

90
Q

Rivaroxaban DDIs: Major substrate of…

A

CYP3A4 and PgP

91
Q

Rivaroxaban monitoring

A

Monitor hemoglobin, hematocrit, platelets, serum creatinine

92
Q

Rivaroxaban Pearls

A

Doses > 10 mg should be given WITH FOOD

93
Q

Edoxaban Brand name

94
Q

Edoxaban MOA

A

Factor Xa inhibitor

95
Q

Edoxaban Dose

A

Afib: 60 mg daily
VTE (after 5 days parenteral):
> 60 kg- 60 mg daily
< 60 kg- 30 mg daily

96
Q

Edoxaban Half life

A

10-14 hours

97
Q

Edoxaban renal adjustments

A

Only use in patients with CrCl 15-95 mL/min
Afib/VTE: 15-50 mL/min: 30 mg daily

98
Q

Edoxaban BW considerations

A

VTE dosing varies pending weight > or < 60 kg
NOT well studied in those > 120 kg or BMI > 40 kg/m2

99
Q

Edoxaban Monitoring

A

Monitor hemoglobin, hematocrit, platelets, serum creatinine

100
Q

Edoxaban Pearls

A

Rarely used

101
Q

Fondaparinux Brand name

102
Q

Fondaparinux MOA

A

Factor Xa Inhibitor (via antithrombin)

103
Q

Fondaparinux route of administration

104
Q

Fondaparinux half life

A

17-21 hours

105
Q

Fondaparinux renal adjustments

A

Avoid use CrCl < 30 mL/min

106
Q

Fondaparinux BW considerations

A

Avoid weight < 50 kg

107
Q

Fondaparinux DDIs

108
Q

Fondaparinux Monitoring

A

Monitor hemoglobin, hematocrit, platelets, serum creatinine

109
Q

Fondaparinux Pearls

A

Does contain pork, can be used for select patients wishing to avoid

110
Q

Dabigatran Brand name

111
Q

Dabigatran Dose

A

Afib: 150 mg BID
VTE: (after 5 days parenteral): 150 mg BID

112
Q

Dabigatran half life

A

12-17 hours

113
Q

Dabigatran renal adjustments

A

Afib: CrCl 15-29 mL/min: 75 mg BID, avoid < 15 mL/min
VTE: avoid use CCI < 30mL/min

114
Q

Dabigatran BW considerations

A

Poor outcomes in those > 120 kg or BMI > 40 kg/m2

115
Q

Dabigatran DDIs

116
Q

Dabigatran Monitoring

A

Monitor hemoglobin, hematocrit, platelets, serum creatinine

117
Q

Dabigatran Pearls

A

Rarely used due to increased risk of GI bleeds compared to warfarin
The only generic DOAC

118
Q

MOA for both Argatroban and Bivalirudin

A

Direct thrombin inhibitor

119
Q

Route of Administration for both Argatroban and Bivalirudin

A

Continuous IV Infusion

120
Q

Half life Argatroban

A

39-51 minutes

121
Q

Half life Bivalirudin

A

10-24 minutes

122
Q

Argatroban renal adjustment

A

15% renal elimination, will likely need lower infusion rates
NOT dialyzable

123
Q

Bivalirudin renal adjustment

A

15% renal elimination, requires initial infusion rate decrease
DIALYZABLE

124
Q

Argatroban monitoring

A

Monitor hemoglobin, hematocrit, platelets, serum creatinine

125
Q

Bivalirudin monitoring

A

Monitor hemoglobin, hematocrit, platelets, serum creatinine

126
Q

Argatroban pearls

A

85% HEPATOBILIARY (liver) elimination
Will elevate INR

127
Q

Bivalirudin pearls

A

85% PROTEOLYTIC elimination
Will elevate INR

IPC CARDIOLOGY 2 JEN (6 decks)

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