Exam 3: Anticoagulants & Antiplatelet Drugs Flashcards Preview

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Flashcards in Exam 3: Anticoagulants & Antiplatelet Drugs Deck (132):
1

Define hemostasis:

Cessation of bleeding from injured vessels

2

Mechanisms (3) of hemostasis:

Platelets
Clotting factors
Vasoconstriction

3

Steps (5) of hemostasis:

Vasoconstriction
Formation of plt plug
Activation of clotting cascade
Formation of fibrin clot
Clot retraction/lysis

4

Describe primary hemostasis:

Occurs immediately in response to vessel injury

Exposed subendothelial collagen attracts circulating platelets, which adhere and form plug

5

Primary hemostasis is promoted by:

Pro-coagulants:
von Willebrand factor
Clotting factor VIII
Adenosine diphosphate

6

Effect of primary hemostasis on vascular tone:

Causes localized vasoconstriction

7

Blood cell flow patterns in the vessel:

Platelets (heavier) flow along the edges of the vessels d/t radial dispersion

8

Activation of platelets causes (3):

Change in shape/formation of pseudopods
Release of thromboxane A2
Degranulation/release of biochemicals

9

Connecting agents in platelet aggregation:

Fibrinogen
vWF

10

Agents released in degranulation:

Serotonin + histamine
Thromboxane
ADP
Clotting factors Va, VIIIa, IXa
Platelet factor 4

11

Role of serotonin + histamine in clotting:

Vasoconstrictors

12

Role of thromboxane in clotting:

Vasoconstriction
Degranulation of adjacent platelets

13

Role of ADP in clotting:

Promotes Adherence and Degranulation of Platelets (A-D-P) by causing membranes to become sticky

Sticky ADP

14

Role of platelet factor 4 in clotting:

Heparin-neutralizing; enhances clot formation

15

Factor used in the intrinsic pathway:

XIIa

16

Factors used in the extrinsic pathway:

Tissue factor
Factor VIIa

17

Final common pathway of the coagulation cascade:

Factor Xa
Prothrombin (Factor II) --> Thrombin
Fibrinogen --> Fibrin

18

Describe secondary hemostasis:

Slower process (minutes to hours) that results in formation of fibrin clot (scab)

19

Describe a fibrin clot:

Meshwork of protein strands that stabilize the platelet plug and trap cells

20

At baseline, the coagulation/anticoagulation balance is:

Leaning more towards coagulation

21

Natural anticoagulants (5):

Prostacyclin (PCI2)
Antithrombin III
Hepatin
Protein C
Protein S

22

Events that happen when clot "retracts":

Fibrin strands shorten
Platelets use contractile proteins
Protein-free serum squeezed from cells

23

Clot lysis mediated by:

Plasmin

24

Role of plasmin:

To split fibrin and fibrinogen into fibrin degradation products (FDPs)

25

Five oral antiplatelets:

Aspirin
Ticlopidine
Clopidogrel (Plavix)
Prasugrel
Ticagrelor (Brilinta)

26

Three IV antiplatelets:

Abciximab
Eptifibatide
Tirofiban

27

MoA of aspirin:

COX inhibitor; irreversibly prevents the production of thromboxane A2

28

Indications for aspirin:

Prevention of recurrent ischemic events (MI, stroke, PAD)

29

Dosage of aspirin:

81-325mg qday

30

Precautions with aspirin:

Children (Reye's syndrome)
Pregnancy
Asthmatics (↑ leukotrienes and bronchoconstriction)

31

Cardiovascular drug interactions with aspirin:

Blunts effects of ACEIs, β-blockers, and diruetics

Prostaglandin inhibition blocks the vasodilatory effects

32

Tx of bleeding when on aspirin:

Plt transfusion

33

MoA of ticlopidine:

Blocks ADP receptor on platelet, inhibits fibrinogen binding

34

Indications for ticlopidine:

Prevention of recurrent ischemic events (esp. in ASA intolerance)

35

S/E of ticlopidine:

Neutropenia
Thrombotic thrombocytopenic purpura
GI upset
Teratogenesis

36

MoA of clopidogrel:

Irreversibly blocks ADP receptor on platelet and inhibits fibrinogen binding

37

Indications for clopidogrel:

Prevention of recurrent ischemic events: stroke, recent ACS, post-PCI

38

Clopidogrel vs. ASA for monotherapy:

Clopidogrel more effective but more costly

39

Dosage of clopidogrel:

Loading dose 300-600mg
Daily dose 75mg

40

Precautions with clopidogrel:

Metabolized by CYP2C19 - genetically poor metabolizers may need more
CYP450 inhibitor
Adjust dose for renal/hepatic
Use with other anticoags

41

Tx of bleeding on clopidogrel:

D/c drug
Plt transfusion

42

Class of drug for clopidogrel:

Thienopyridine

43

Class of drug for prasugrel:

Thienopyridine

44

Prasugrel vs. clopidogrel:

Prasugrel more effective but also more fatal bleeding events

Works in non-responders to clopidogrel

45

Dosing of prasugrel:

10mg qday

46

Precautions/contraindications with prasugrel:

Active bleeding

Previous stroke/TIA, underweight, elderly: consider 5mg/day instead

Do not use pre-cath!

47

MoA of ticagrelor:

Allosteric ADP antagonist

48

Ticagrelor vs. clopidogrel:

Ticagrelor has better death reduction post-MI than clopidogrel when it comes to vascular causes (MI/stroke)

Ticagrelor has higher rate of bleeding and higher rate fatal brain bleeding

49

Indications for ticagrelor:

Prevention of recurrent ischemic events after MI

50

Dosage for ticagrelor:

Loading: 180mg
90mg BID
Always given w/ ASA unless contraindicated

51

Precautions for ticagrelor:

Hepatic dysfunction
ASA > 100mg/day
5 days pre-op
Compliance (BID)

52

Contraindications for ticagrelor:

Active bleeding
Hx of intracranial hemorrhage

53

MoA of GPIIb/IIIa inhibitors:

Prevent fibrinogen binding to GPIIb/IIIa receptors by inhibiting them

54

Indications for GPIIb/IIIa inhibitors:

ACS
PCI (intra- and post-procedure)

55

Examples of GPIIb/IIIa inhibitors:

Abciximab
Eptifabatide (Integrillin)
Tirofiban

56

Indications and notables for abciximab:

Planned PCI
Most expensive, longest lasting

57

Dosing for eptifibatide:

If Cr is < 2: 2 mcg/kg/min up to 72 hrs
If Cr is > 2: 1 mcg/kg/min up to 72 hrs

58

Tx for bleeding on abciximab:

Plt transfusion

59

Tx for bleeding on eptifibatide and tirofiban:

D/c drug and wait/transfuse

60

Pre-op interruption of anti-platelet therapy:

7-10 days pre-op
Pts at high cardiac risk continue ASA, clopidogrel stop 5 days prior

61

Post-op resumption of anti-platelet therapy:

24 hrs/next AM post-op (as long as hemostasis was achieved)

62

MoA of heparin:

Activates antithrombin III, which increases inhibition of thrombin (IIa) and factor Xa by 1000x

63

Indications for heparin:

DVT prophylaxis/tx
PE tx
ACS
Warfarin bridge (or just contraindicated)

64

Dosing for heparin:

DVT: 5000 units q8hr (q12hr in neuro)
IV infusion - weight-based and titrated based on aPTT

65

Drawbacks of heparin:

Variable effect
Unable to inhibit clot-bound thrombin (cannot break down existing clots)

66

Tx of bleeding on heparin:

Stop the heparin - look for hidden sources
Reverse with protamine 1mg/100U heparin (or just give 50mg bolus)

67

Adverse effects of heparin:

Benign thrombocytopenia
HIT

68

Type I HIT:

Benign; less common
Mild drop in plts within 4 days of starting tx
Not progressive

69

Type II HIT:

Typical onset, following heparin exposure
Reduction in plts to < 150k or by 50%
5-14 days post-exposure

70

Incidence of HIT:

2-5%; surgical > medical > obstetric

71

Onset of HIT:

Typical: 5-14 days
Delayed (rare): 2-6 weeks
Rapid onset: 25%, from hours to days (usually with additional heparin exposure within last 100 days)

72

Types of HITT:

Venous (4x as common)
Arterial

73

Sequelae of venous HITT:

DVT
PE
Venous limb gangrene
Dural sinus thrombosis

74

Sequelae of arterial HITT:

Stroke
Limb ischemia/skin necrosis
MI
Mesenteric ischemia
Adrenal/renal/spinal artery infarcts

75

Mortality rate of HITT:

25-30% mortality
25% amputation rate

76

Lab testing for HIT (2):

ELISA - measures titer of IgG antibody to heparin (in-house)
C-serotonin release assay - detects plt activation (send-out test - confirmatory)

77

Tx of HIT:

Stop all thrombocytopenia-inducing drugs
Stop hepatin and start argatroban

78

MoA of enoxaparin:

Binds with antithrombin III and inhibits Xa

79

Indications of enoxaparin:

DVT prophylaxis
ACS
VTE tx

80

Dosage of enoxaparin:

DVT proph: 40mg q24h
THR/TKR: 30mg q12h
DVT tx: 1-1.5 mg/kg qday
ACS: 1 mg/kg qday

81

Lab monitoring for enoxaparin:

Not routinely monitored; anti-Xa levels if needed

82

Precautions for enoxaparin:

Pregnancy (monitor antiXa)
Obese (weight-based dosing)
Severe renal insufficiency (if CrCl < 30ml/min reduce dose 50%)
Avoid in spine surgury/epidural catheters

83

Tx of bleeding on enoxaparin:

Protamine reverses 60%

84

MoA of fondaparinux:

Synthetic Xa inhibitor; binds with antithrombin III to potentiate Xa inhibition 300x

*No* effect on IIa (thrombin)

85

Indications for fondaparinux:

ACS
DVT proph
DVT/PE tx

Very expensive!

86

Dosing of fondaparinux:

Proph: 7.5mg qday
VTE/>100kg: 10mg qday

87

Contraindications of fondaparinux:

CrCl < 30ml/min
Spinal anesthesia/lumbar puncture

88

Tx of bleeding on fondaparinux:

No reversal, FFP ineffective
D/c drug, supportive care

89

IV direct thrombin (IIa) inhibitors:

Hirudin
Lepirudin
Desirudin
Hirulog
Argatroban
Bivalirudin

90

Indications for direct IIa inhibitors:

HIT (Argatroban, Lepirudin)
PCI (Bivalirudin)

91

Special consideration with lepirudin and desirudin:

Can only use once d/t anaphylaxis risk

92

Tx of bleeding on direct IIa inhibitor:

Stop infusion
Factor VII/FFP/cryo

93

MoA of warfarin:

Interferes with the production of Vit K-dependent clotting factors (II, VII, IX, X)

Interferes with natural anticoagulants Protein C and Protein S

94

Indications for warfarin:

Prevention of DVT/Afib/heart valve thrombosis
Long-term VTE

95

Dosage of warfarin:

Start with 5-10mg/day
Base adjustments on PT/INR

96

Therapeutic INR goal for warfarin:

Normal: 2.0 - 3.0
High risk: 2.5 - 3.0

High risk = mechanical valves, prev. thrombus, anti-phospholipid syndrome

97

Initiation of warfarin:

Overlap with heparin/LWMH for 1-2 days

98

Duration of warfarin therapy:

3 months for uncomplicated DVT/PE

99

Toxicity from warfarin:

Bleeding
Birth defects
Cutaneous necrosis

100

Drugs that increase the effect of warfarin:

Amiodarone
Cimetidine
Acetaminophen
Phenylbutazone

101

Drugs that decrease the effect of warfarin:

Sucralfate
Cholestyramine
Spironolactone
Barbiturates
Foods containing Vit. K

102

Dosing adjustments for warfarin:

Subtherapeutic INR: same dose, recheck 1-2 weeks
Supratherapeutic INR: hold next dose, recheck within 1 week

103

Tx of bleeding on warfarin:

Vitamin K (oral/IV)
FFP

104

INR of FFP:

1.5

105

Pre-op hold time for warfarin:

Normal: 5 days
High-risk: bridge with heparin until 4-6 hrs pre-op

106

Post-op resumption of warfarin:

12-24 hours

107

MoA of dabigatran/Pradaxa:

Direct thrombin/IIa inhibitor

108

Indications for dabigatran/Pradaxa:

Prevention of stroke in non-valvular afib and tx of DVT/PE

109

Dosage of dabigatran/Pradaxa:

110 or 150mg BID
Lower dose for bleeding risk, elderly, renal impairment

110

Advantages of dabigatran/Pradaxa:

No monitoring
Predictable PK
Less diet/drug influence
Rapid time to peak (1hr)
Short t1/2 (12-14 hrs)

111

Disadvantages of dabigatran/Pradaxa:

High cost
BID dosing
No antidote - yet
No lab assay
No long-term data

112

MoA of rivaroxaban/Xarelto:

Direct factor Xa inhibitor

rivaro XA BAN

113

Indications for rivaroxaban/Xarelto:

Stroke/embolus prevention in non-valvular afib
DVT prevention post-knee/hip replacement
Tx of PE/DVT

114

Dosage of rivaroxaban/Xarelto:

20mg qday

115

Warfarin vs. rivaroxaban/Xarelto:

Rivaroxaban "non-inferior" to warfarin with less risk of fatal/intracranial bleeding

116

Advantages of rivaroxaban/Xarelto:

No monitoring needed
Predictable PK
Less diet/drug influence
Daily dosing

117

Time to peak action and half-life of rivaroxaban/Xarelto:

Peak: 2.5-4 hrs
t/12: 7-11 hrs

118

Disadvantages of rivaroxaban/Xarelto:

High cost
No antidote - yet
No lab assay
No long term data

119

MoA of apixaban/Eliquis:

Direct factor Xa inhibitor

api XA BAN

120

Indications for apixaban/Eliquis:

Stroke/emboli prevention in non-valvular afib
DVT prevention post-hip/knee replacement
Tx of DVT/PE

121

Dosage of apixaban/Eliquis:

5mg BID

122

ASA and warfarin vs. apixaban/Eliquis:

Apixaban clearly better than ASA for pts who cannot take warfarin

Apixaban superior to warfarin with less bleeding risk

123

Advantages of apixaban/Eliquis:

No routine monitoring
Predictable PK
Less diet/drug influence

124

Peak time and half-life of apixaban/Eliquis:

Time to peak: 3 hrs
t1/2: 12 hrs

125

Disadvantages of apixaban/Eliquis:

High cost
BID dosing
Reversed with expensive prothrombin complex concentrate
No lab assay
No long term data

126

MoA of fibrinolytics:

Plasminogen activators convert plasminogen to plasmin, which causes fibrinolysis

127

Fibrinolytic agents:

Streptokinase
Urokinase
tPA
Recombinant tPA
Tenecteplase/TNKase

128

Indications for fibrinolytics:

Acute STEMI
Acute stroke (within 6 hrs of symptom onset)
CVC declotting (urokinase)
PE (urokinase)

129

Dosing of recombinant tPA:

10 units over 2 min; repeat in 30 min

130

Dosing of TNKase

30-50 mg (weight based) single bolus over 5 sec

131

Absolute contraindications for fibrinolytics:

Previous hemorrhagic stroke
Ischemic stroke within 3 mo
Intracranial neoplasm
Active internal bleeding
Aortic dissection
Closed head/face trauma within 3 mo

132

Relative contradindications for fibrinolytics:

Uncontrolled severe HTN (BP > 180/110) at presentation or in hx
INR > 2.5 on anticoags
Bleeding d/o
Non-compressible vascular puncture
Recent trauma (2-4 wks) or surgery (< 3 weeks) or internal bleeding (2-4 wks)
PUD
Pregnancy
Streptokinase - allergy or prior exposure