Pharmacology, PKPD, and Genomics of Anticoagulants Flashcards
(128 cards)
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
2
Q
Prevention of anticoags?
A
Prevent clots from forming (prophylaxis)
3
Q
Prophylaxis uses _____ doses
A
LOW
4
Q
Treatment of anticoags?
A
1) Afib
2) VTE
3) Some valvular disease
4) Some hypercoagulable states
5
Q
Treatment uses ______ doses
A
FULL
6
Q
____ anticoagulants significantly ______ a patients risk of bleeding
A
ALL, INCREASE
7
Q
Which are the parenteral anticoagulants?
A
Heparin, LMWH, Fondaparinux, Bivalirudin, Argatroban
8
Q
Which are the oral anticoagulants?
A
Warfarin, Apixaban, Rivaroxaban, Edoxaban, Dabigatran
9
Q
Which drugs are the DOACs?
A
Apixaban, Rivaroxaban, Edoxaban, Dabigatran
10
Q
When is Warfarin still indicated?
A
Afib w/ history of moderate/severe rheumatic mitral stenosis
Mechanical heart valves
Some hypercoagulable states
11
Q
MOA of heparin?
A
Potentiates antithrombin (AT) –> decreased transformation form prothrombin –> thrombin
12
Q
Binding to AT increases heparins catalytic activity to ____ fold
A
1000
13
Q
Route heparin
A
SQ (prophylaxis)
IV (treatment)
14
Q
Half life heparin
A
1-2 hours (IV)
15
Q
Monitoring Heparin: Efficacy
A
Anti-Xa levels or aPTT (1.5-2.5 x baseline) STANDARD
16
Q
Monitoring Heparin: Goal
A
Anti-Xa: 0.3-0.7 units/mL (aPTT will be dependent on lab)
17
Q
Monitoring Heparin: Safety
A
Hemoglobin, hematocrit, platelets, BLEEDING!
18
Q
Heparin is typically used in a _____ setting
A
Hospital
Heparin is rarely used in outpatient!
19
Q
Drugs that are LMWH
A
Enoxaparin (Lovenox)
Dalteparin (Fragmin)
20
Q
LMWH MOA?
A
Potentiates antithrombin –> decreases transformation from prothrombin –> thrombin AND
inactivates factor Xa
21
Q
LMWH Route?
A
SQ (rarely IV)
22
Q
Dose LMWH?
A
1 mg/kg Q12H
23
Q
Half life LMWH
A
12 hours
24
Q
Renal CL requirements LMWH
A
CrCl < 30mL/min
25
Body Weight Considerations LMWH
May need to adjust doses with BMI > 40 kg/m2
26
Monitoring: Efficacy LMWH
Anti-Xa monitoring in obese patients, patients with renal dysfunction, pregnant patients
*Pregnant patients have a different Vd needing to monitor
27
Monitoring: Safety LMWH
Hemoglobin, hematocrit, platelets, BLEEDING, serum creatinine (bc of renal dose adjustments)
28
LMWH are commonly used in ______ setting
Hospital
Can be given outpatient
29
LMWH is a shorter chain fraction of heparin =
less effect on thrombin, increase effect on factor X
30
Brand name Warfarin
Coumadin
31
Warfarin MOA
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
32
Warfarin Route
Oral
33
Half life Warfarin
20-60 days variable
34
Body Weight considerations Warfarin?
higher bws may require higher doses, no specific way
35
Warfarin Drug Interactions: MINOR
CYPs
CYP1A2, CYP2C19, CYP3A4
36
Warfarin Drug Interactions: MAJOR
CYPs
CYP2C9
37
Monitoring Warfarin: Efficacy
INR for therapeutic level (usually 2-3)
Lab testing
38
Monitoring Warfarin: Safety
Hemoglobin, hematocrit, platelets, BLEEDING
39
Warfarin is ______ in pregnancy
Teratogenic
40
Warfarin decreases ______ of new clotting factors
SYNTHESIS
(for Warfarin to work, currently active clotting factors need to wash out)
41
Warfarin also decreases _______ of natural anticoagulants proteins ____ and ______
SYNTHESIS
C, S
42
Half life of Factor II
60 hours
the LONGEST.... multiple days
43
Half life of Factor VII
6 hours
44
Half life of Factor IX
24 hours
45
Half life of Factor X
40 hours
46
Half life of Protein C
10 hours
47
Half life of Protein S
42 hours
48
What are Warfarin limitations?
Frequent INR Monitoring
Bridging Requirements
Peri-procedural anticoagulation
DDI
Drug-Food interactions
49
Why do we need to overlap with a parenteral anticoagulant?
Protein C quickly depletes = transient
PROTHROMBOTIC STATE
Factor II takes multiple days to wash out
50
What is an INR test?
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
51
Standard Dosing Warfarin: Initial Dose
5 mg daily for 3 days
52
Standard Dosing Warfarin: INR < 1.5
7.5 to 10 mg daily for 2 to 3 days
53
Standard Dosing Warfarin: INR 1.5 to 1.9
5 mg daily for 2 to 3 days
54
Standard Dosing Warfarin: INR 2 to 3
2.5 mg daily for 2 to 3 days
55
Standard Dosing Warfarin: INR 3.1 to 4
1.25 mg daily for 2 to3 days
56
Standard Dosing Warfarin: INR > 4
Hold until INR > 3
57
Patients more sensitive to Warfarin...
Frail, elderly, or undernourished; liver disease, kidney disease, heart failure, or acute illness; or are receiving a medication that decreases Warfarin metabolism
58
Reduced Dosing Warfarin for sensitive patients: Initial Dose
2.5 mg daily for 2 to 3 days
59
Reduced Dosing Warfarin for sensitive patients: INR < 1.5
5 to 7.5 mg daily for 2 to 3 days
60
Reduced Dosing Warfarin for sensitive patients: INR 1.5 to 1.9
2.5 mg daily for 2 to 3 days
61
Reduced Dosing Warfarin for sensitive patients: INR 2 to 3
1.25 mg daily for 2 to 3 days
62
Reduced Dosing Warfarin for sensitive patients: INR 3.1 to 4
0.5 mg daily for 2 to 3 days
63
Reduced Dosing Warfarin for sensitive patients: INR > 4
Hold until INR > 3
64
Maintenance Adjustment for Subtherapeutic INR Suggested adjustment: INR < 1.5
* Increase weekly maintenance dose by 10% to 20%
* Consider a one-time supplemental dose: 1.5-2 times the daily dose
65
Maintenance Adjustment for Subtherapeutic INR Suggested adjustment: INR 1.5 to 1.7
* Increase weekly maintenance dose by 5% to 15%
* Consider a one-time supplemental dose: 1.5 to 2 times the daily dose
66
Maintenance Adjustment for Subtherapeutic INR Suggested adjustment: INR 1.8 to 1.9
* 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
Maintenance Adjustment for Subtherapeutic INR Suggested adjustment: INR 3.1 to 3.2
* 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
Maintenance Adjustment for Subtherapeutic INR Suggested adjustment: INR 3.3 to 3.4
* Decrease weekly maintenance dose by 5% to 10%
69
Maintenance Adjustment for Subtherapeutic INR Suggested adjustment: INR 3.5 to 3.9
* Consider holding 1 dose
* Decrease weekly maintenance dose by 5% to 15%
70
Maintenance Adjustment for Subtherapeutic INR Suggested adjustment: INR >4 but <10 no bleeding
* 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
Maintenance Adjustment for Subtherapeutic INR Suggested adjustment: INR > 10 and no bleeding
* Hold until INR below upper limit of therapeutic range
* Administer vitamin K orally
* Decrease weekly maintenance dose by 5% to 20%
71
For the INR 1.5 - 1.9 if the factor causing subtherapeutic INR is transient consider...
Resumption of prior maintenance dose following a one-time SUPPLEMENTAL dose
72
For the INR 3.1 - 10 if the factor causing subtherapeutic INR is transient consider...
Resumption of prior maintenance dose following a one-time HELD dose
73
Warfarin has a _______ therapeutic index
narrow
74
Warfarin doses necessary to attain an INR goal of ______ vary from __ - ___ mg per day
2-3
2.5
10
75
The major genes influencing the response to Warfarin are....
CYP2C9 and VKORC1
Minor: CYP4F2
76
Apixaban Brand Name
Eliquis
77
Apixaban MOA
Factor Xa inhibitor
78
Apixaban Dose
Afib: 5 mg daily
VTE: 10 mg BID x 1 week, then 5 mg BID
79
Apixaban Half life
12 hours
80
Apixaban Renal Adjustments
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
Apixaban BW considerations
May require a dose adjustment if < 60 kg (as above)
It is okay in those > 120 kg or BMI > 40kg/m2
82
Apixaban DDIs... a major substrate of...
CYP3A4 and PgP
83
Apixaban Monitoring
Monitor hemoglobin, hematocrit, platelets, serum creatinine
84
Apixaban Pearls
The best DOAC in patients with poor renal function/ESRD dialysis
85
Rivaroxaban Brand name
Xarelto
86
Rivaroxaban Dose
Afib: 20 mg daily
VTE: 15 mg BID x 21 days then 20 mg daily
87
Rivaroxaban Half life
5-9 hours
88
Rivaroxaban renal adjustments
Afib: dose adjust CCI 15-50 mL/min : 15 mg daily
Afib/VTE: Avoid use CCI < 15mL/min
89
Rivaroxaban BW considerations
Okay in those > 120 kg or BMI > 40kg/m2
90
Rivaroxaban DDIs: Major substrate of...
CYP3A4 and PgP
91
Rivaroxaban monitoring
Monitor hemoglobin, hematocrit, platelets, serum creatinine
92
Rivaroxaban Pearls
Doses > 10 mg should be given WITH FOOD
93
Edoxaban Brand name
Savaysa
94
Edoxaban MOA
Factor Xa inhibitor
95
Edoxaban Dose
Afib: 60 mg daily
VTE (after 5 days parenteral):
> 60 kg- 60 mg daily
< 60 kg- 30 mg daily
96
Edoxaban Half life
10-14 hours
97
Edoxaban renal adjustments
Only use in patients with CrCl 15-95 mL/min
Afib/VTE: 15-50 mL/min: 30 mg daily
98
Edoxaban BW considerations
VTE dosing varies pending weight > or < 60 kg
NOT well studied in those > 120 kg or BMI > 40 kg/m2
99
Edoxaban Monitoring
Monitor hemoglobin, hematocrit, platelets, serum creatinine
100
Edoxaban Pearls
Rarely used
101
Fondaparinux Brand name
Arixtra
102
Fondaparinux MOA
Factor Xa Inhibitor (via antithrombin)
103
Fondaparinux route of administration
SQ and IV
104
Fondaparinux half life
17-21 hours
105
Fondaparinux renal adjustments
Avoid use CrCl < 30 mL/min
106
Fondaparinux BW considerations
Avoid weight < 50 kg
107
Fondaparinux DDIs
NONE
108
Fondaparinux Monitoring
Monitor hemoglobin, hematocrit, platelets, serum creatinine
109
Fondaparinux Pearls
Does contain pork, can be used for select patients wishing to avoid
110
Dabigatran Brand name
Praxada
111
Dabigatran Dose
Afib: 150 mg BID
VTE: (after 5 days parenteral): 150 mg BID
112
Dabigatran half life
12-17 hours
113
Dabigatran renal adjustments
Afib: CrCl 15-29 mL/min: 75 mg BID, avoid < 15 mL/min
VTE: avoid use CCI < 30mL/min
114
Dabigatran BW considerations
Poor outcomes in those > 120 kg or BMI > 40 kg/m2
115
Dabigatran DDIs
NONE
116
Dabigatran Monitoring
Monitor hemoglobin, hematocrit, platelets, serum creatinine
117
Dabigatran Pearls
Rarely used due to increased risk of GI bleeds compared to warfarin
**The only generic DOAC**
118
MOA for both Argatroban and Bivalirudin
Direct thrombin inhibitor
119
Route of Administration for both Argatroban and Bivalirudin
Continuous IV Infusion
120
Half life Argatroban
39-51 minutes
121
Half life Bivalirudin
10-24 minutes
122
Argatroban renal adjustment
15% renal elimination, will likely need lower infusion rates
NOT dialyzable
123
Bivalirudin renal adjustment
15% renal elimination, requires initial infusion rate decrease
DIALYZABLE
124
Argatroban monitoring
Monitor hemoglobin, hematocrit, platelets, serum creatinine
125
Bivalirudin monitoring
Monitor hemoglobin, hematocrit, platelets, serum creatinine
126
Argatroban pearls
85% HEPATOBILIARY (liver) elimination
Will elevate INR
127
Bivalirudin pearls
85% PROTEOLYTIC elimination
Will elevate INR
