anti-thrombotics, anti-coagulants, antiplatelets, and thrombolytics Flashcards
1
Q
thrombosis
A
when a clot blocks veins or arteries and can lead to many medical conditions
2
Q
clot in the brain
A
ischemic stroke/transient ischemic attack (TIA)
3
Q
clot in the lungs
A
pulmonary embolism (PE)
4
Q
clot in the appendages
A
DVT
5
Q
clot in coronary artery leading to myocardial death
A
heart attack
6
Q
hemostasis
A
physiologic process by which bleeding stops
7
Q
intrinsic pathway- contact activation pathway
A
turned on when blood makes contact with collagen after trauma to a blood vessel wall
8
Q
cascade starts with activation from factor XII to factor XIIa and proceeds until factor X is activated to factor Xa
A
intrinsic pathway- contact activation pathway
9
Q
extrinsic pathway- tissue factor pathways
A
turned on by trauma to the vascular wall-which triggers release of tissue factor (AKA thromboplastin)
10
Q
cascade starts with activation from factor VII to factor VIIa and proceeds until factor X is converted into factor Xa
A
extrinsic pathway-tissue factor pathway
11
Q
tissue plasminogen activator (tPA)
A
activates conversion from plasminogen to plasmin
found in endothelial cells-continuously released but increased when stimulation of certain endothelial cells
12
Q
antiplatelet drugs
A
primarily used to prevent arterial clots
13
Q
aspirin indications
A
ischemic stroke, TIAs, chronic stable angina, coronary stenting, acute myocardial infarction
14
Q
aspirin contraindications
A
use in children and teens with viral infection (Reye’s syndrome)
15
Q
aspirin ADRs
A
GI bleeds
hemorrhagic stoke
16
Q
aspirin metabolism/excretion
A
no renal or hepatic adjustments needed
17
Q
aspirin MOA
A
irreversible inhibitions of COX- decreases thromboxane A2 production thus reduces platelet activation
18
Q
clopidogrel
A
plavix
19
Q
Plavix indications
A
acute coronary syndrome (STEMI and NSTEMI), ischemic stroke, peripheral atherosclerotic disease
20
Q
Plavix US boxed warning
A
diminished effects in CYP 2C19 poor metabolizers
21
Q
Plavix MOA
A
irreversible blocks P2Y12 component of ADP receptors on the platelet surface- effects last the duration of the platelet’s life
22
Q
Plavix contraindications
A
active pathological bleeding (peptic ulcer, intracranial hemorrhage, etc.)
23
Q
Plavix ADRs
A
bleeding
24
Q
Plavix metabolism/excretion
A
no hepatic or renal dosage adjustment needed
must be metabolized by CYP2C19 into active drug
CYP2C19 is inhibited by PPIs
American College of Cardiology, American Heart Association, and American College of Gastroenterology issued a consensus document that PPIs may reduce the antiplatelet effects but not enough to diminish effects
25
prasugrel MOA
irreversibly blocks P2Y12 component of ADP receptors on platelet surface
26
prasugrel contraindications
active pathologic bleeding, prior TIA or stoke
27
prasugrel ADRs
bleeding
28
Prasugrel metabolism/excretion
no renal or hepatic adjustments needed
29
Prasugrel US Boxed Warning
Significant sometimes fatal bleeding – Avoid in patients with active pathological bleeding or a history of TIA or stroke
In patients 75 or older – use is generally not recommended – increased risk of fatal and intracranial bleeding – lacks additional benefit
Do not use in patients likely to need urgent coronary artery bypass graft (CABG) surgery – discontinue 7 days prior to surgery (most agents are 5)
Additional risk factors for bleeding – weight <60 kg, propensity to bleed or history of bleeding, concomitant medications that increase risk of bleeding (NSAIDs, warfarin, fibrinolytics)
Suspect bleeding in any patient who is hypotensive
If possible, manage bleeding without discontinuing prasugrel – discontinuing, particularly in the first few weeks post-acute coronary syndrome, increases the risk of a secondary event
30
Ticagrelor US Boxed Warnings
bleeding risk: avoid in patients with pathologic bleeding or history of intracranial hemorrhage
aspirin doses >100 mg daily reduce the effectiveness and should be avoided
31
Ticagrelor MOA
reversible P2Y12 inhibition
reduces platelet activation
32
Ticagrelor contraindications
active pathologic bleeding or history of intracranial hemorrhage
33
Ticagrelor ADRs
dyspnea
34
Ticagrelor metabolism/excretion
no hepatic or renal adjustments needed
35
Cangrelor MOA
reversible P2Y12 inhibition
reduces platelet activation
36
Cangrelor contraindications
significant active bleeding
37
Cangrelor ADRs
bleeding
38
Cangrelor metabolism/excretion
no renal or hepatic adjustment needed
39
vorapaxar MOA
PAR-1 antagonist
inhibits platelet aggregation
40
Vorapaxar contraindications
history of stroke, TIA, intracranial hemorrhage
active pathological bleeding
41
Vorapaxar ADRs
bleeding
42
Vorapaxar metabolism/excretion
no hepatic or renal adjustments needed
43
Glycoprotein IIB/IIIA inhibitors
Eptifibitide and Tirofiban
44
Eptifibitide and Tirofiban MOA
reversible blockade of Gp IIb/IIIa receptors on platelets and thereby inhibit the final step of aggregation
prevent aggregation stimulated by all factors including collagen, TXA2, ADP, thrombin, and PAF
45
Eptifibitide and Tirofiban contraindications
active abnormal bleeding within the previous 30 days or history of bleeding diathesis
history of stoke within 30 days or history of hemorrhagic stroke
major surgery within the preceding 6 weeks
46
Eptifibitide and Tirofiban ADRs
bleeding
47
Dipyridamole MOA
inhibits the uptake of adenosine into the platelets – prevents platelet activation/aggregation
48
Dipyridamole contraindications
Use in children and teens with viral infections (Reye’s Syndrome)
49
Dipyridamole ADRs
bleeding
GI disturbances
50
Dipyridamole metabolism/excretion
avoid use in severe liver and renal impairment
51
drugs for thromboembolic disorders
antiplatelets
anticoagulants
fibrinolytics
52
inhibit platelet activation
antiplatelets
53
decrease formation of thrombin
anticoagulants
54
promote breakdown of fibrin in thrombi
fibrinolytics
55
antiplatelet drugs
aspirin (NSAIDs)
P2Y12 antagonists/thienopyridines
protease-activated receptor-1 antagonist (PAR-1)
glycoprotein IIb/IIIa inhibitor
phosphodiesterase/adenosine deaminase inhibitor
56
anticoagulant drugs
vitamin K antagonist
antithrombin activators
direct thrombin inhibitors
direct factor Xa inhibitors
57
fibrinolytics
Alteplase
Tenecteplase
Retavase
58
warfarin
inhibits the synthesis of clotting factors
59
vitamin K antagonist
Warfarin
60
antithrombin activators
heparin, enoxaparin, fondaparinux
61
direct thrombin inhibitors
argatroban
bivalirudin
dabigitran
62
direct factor Xa inhibitors
apixaban
rivaroxaban
edoxaban
63
coumadin
warfarin
64
coumadin US boxed warnings
bleeding risk-monitor INR on all treated patients
65
coumadin indications
myocardial infarction, thromboembolic complications (PE, DVT, stroke, Afib, cardiac valve replacement)
66
coumadin MOA
vitamin K antagonist
inhibits synthesis of clotting factors II, VII, IX, and X and proteins C and S via inhibiting vitamin K epoxide reductase complex 1 (VKORC1) and decreasing activation of the factors
67
coumadin ADRs
bleeding
68
coumadin metabolism/excretion
adjusting dose in kidney function may need to happen- no robust guidelines
liver function plays a significant role in anticoagulant response-monitor INR closely
69
warfarin contraindications
hemorrhagic tendencies
recent or potential surgery on spine or eyes
malignant, uncontrolled hypertension
pericarditis or pericardial effusion
bacterial endocarditis
patients with high potential for non-compliance
pregnancy/breast feeding
70
vitamin K, phytonadione indications
hemorrhage prevention in newborns (intracranial)
warfarin antidote
71
vitamin K, phytonadione as a warfarin antidote
reverses hypoprothrombinemia and bleeding- perioperatively or in the case of severe bleeds
72
vitamin K, phytonadione MOA
required for synthesis of prothrombin and clotting factors VII, IX, and X- essential for coagulation cascade
73
vitamin K, phytonadione ADRs
essentially no storage- metabolism and secretion occur rapidly
74
vitamin K, phytonadione metabolism/excretion
no renal or hepatic adjustments needed
75
foods that interact with warfarin
vitamin K containing foods- decreased INR and effects- leafy greens, mayonnaise, others
foods that increase effects, alcohol, cranberries, cherries, grapefruit
76
warfarin drug interactions
sulfa-antibiotics
acetaminophen
carbamazepine, phenobarbital, rifampin
77
sulfa-antibiotics and warfarin interaction
sulfa-antibiotics displace warfarin on albumin
| significant bleeding risk (Bactrim)
78
acetaminophen and warfarin interactions
increase INR
79
carbamazepine, phenobarbital, rifampin and warfarin interactions
powerful inducers in CYP system-decrease warfarin effects
80
heparin indications
anticoagulation- prophylaxis and treatment of thromboembolic disorders, prevention of clotting in arterial and cardiac surgery, anticoagulation for blood transfusions, extracorporeal circulation and dialysis procedures
81
heparin MOA
potentiates the actin of antithrombin III, inactivating thrombin and factor Xa which prevents the conversion of fibrinogen to fibrin
82
heparin contraindications
severe thrombocytopenia (<100,000)
history of HIT
uncontrolled active bleeding
83
heparin ADRs
bleeding, thrombocytopenia
localized reactions in SubQ administration- bruising, irritation, hematoma
84
heparin metabolism/excretion
no renal or hepatic adjustments needed
85
aspirin routes
81 mg daily- maximal effects on platelet function
325 mg- indicated in initial treatment for an acute event
86
dipyridamole/aspirin routes
oral caps (not enough aspirin for primary prevention of MI)
87
vitamin K, phytonadione routes
oral tabs
| IV/IM
88
warfarin clinical pearls
in patients with new onset DVT/PA or other active clots, warfarin is started at the same time as parenteral anticoagulation (enoxaparin, heparin) and is continued for a minimum of 5 days AND until the INR >2.0 for 24 hrs
89
heparin routes/doses
IV (full-dose, treatment dose): algorithm based on following anti-Xa or activated partial thromboplastin time (aPTT) levels
bolus given if effect is needed immediately- active PE, STEMI
SubQ (prophylaxis): 5000 units q8h-q12h 7500 units q8h in morbidly obese
90
heparin induced thrombocytopenia (HIT)
potentially fatal immune-mediated disorder that results in rapid platelet count drops and potentially paradoxical increase in clotting
antibodies are developed against heparin-platelet complexes causing damage to the vascular endothelium- increases clotting and decreases platelets
91
protamine indications
heparin neutralization
92
protamine US boxed warnings
hypersensitivity reactions
93
protamine MOA
forms a stable salt with heparin and nullifies anticoagulant activity
94
protamine route
IV
95
protamine ADRs
bradycardia, flushing, hypotension
96
protamine metabolism/excretion
no renal or hepatic adjustments needed
97
enoxaparin
lovenox
low-molecular-weight heparin
98
Lovenox indications
acute coronary syndromes, DVTs/PEs, VTE prophylaxis
99
Lovenox US boxed warnings
spinal/epidural hematoma
100
Lovenox MOA
shortened derivative of heparin - has anti-Xa and antithrombin activity - has more Xa than thrombin inactivation
101
Lovenox contraindications
history of HIT
active major bleeding
102
Lovenox routes
subcutaneous
103
Lovenox ADRs
anemia
| hemorrhage
104
Lovenox metabolism/excretion
renal adjustments needed at CrCl <30 mL/min (40 mg daily --> 30 mg daily, 1 mg/kg q12h --> 1 mg/kg q24h)
avoid in severe renal impairment (CrCl <20 mL/min)
105
Lovenox subcutaneous dosin
full dose/treatment dose: 1 mg/kg q12h or 1.5 mg/kg q24h
prevention/prophylaxis: 40 mg q24h or 30 mg q12h
intermediate dosing: 60 mg q12h or 1 mg/kg q24h
106
Fondaparinux indications
DVT/PE treatment, VTE prophylaxis
does not promote HIT, although it can still lower platelets
can be used in patients with history of HIT but not in active HIT
107
Fondaparinux US boxed warnings
spinal/epidermal hematomas
108
Fondaparinux MOA
selective indirect inhibitions of factor Xa
no activity with thrombin
109
Fondaparinux contraindications
severe renal impairment (CrCl <30 mL/min), body weight <50 kg (prophylaxis), active major bleeding, bacterial endocarditis
110
Fondaparinux ADRs
anemia/bleeding
111
Fondaparinux metabolism/excretion
renal adjustments needed
| no hepatic adjustments needed
112
Argatroban indications
prophylaxis of treatment of thrombosis in patients with HIT or history of HIT
anticoagulant for PCI in patients with HIT or history of HIT
113
argatroban MOA
direct inhibition of thrombin
114
Argatroban contraindications
major bleeding
115
Argatroban ADRs
bleeding, hypotension
116
Argatroban metabolism/excretion
hepatic adjustments needed
no renal adjustments needed
dosed off of bilirubin and monitored with aPTT
117
Bivalirudin indications
anticoagulant used in patients undergoing primary PCI and PCI facilities
given in combo with aspirin and P2Y12 inhibitos
118
Bivalirudin MOA
direct thrombin inhibitor
119
Bivalirudin contraindications
active major bleeding
120
Bivalirudin ADRs
bleeding, hypotension
121
Bivalirudin metabolism/excretion
renal adjustments needed
| no hepatic adjustments
122
Dabigatran indications
DVT/PE treatment and prevention, Atrial fibrillation, VTE prophylaxis in total hip arthroplasty
123
Dabigatran US boxed warnings
Thrombotic Events – premature discontinuation increases risk of thrombotic events
Spinal/epidural hematoma
124
Dabigatran MOA
direct thrombin inhibitor
125
Dabigatran contraindications
active bleeding, patients with mechanical heart valves
126
Dabigatran ADRs
bleeding
| GI disturbances
127
Dabigatran metabolism/excretion
indication dependent- avoid use in DVT/PE for renal dysfunction, dose adjust for Afib
no hepatic adjustments needed
128
direct factor Xa inhibitors indications
Afib, VTE treatment and prophylaxis, VTE prophylaxis in hip and knee arthroplasty
129
direct factor Xa inhibitors US boxed warnings
premature discontinuation increases risk of thrombotic events
spinal/epidural hematoma
130
direct factor Xa inhibitors contraindications
active bleeding
131
direct factor Xa inhibitors ADRs
bleeding
132
direct factor Xa inhibitors metabolism/excretion
renal adjustments needed-drug specific
133
rivaroxaban
xarelto
134
xarelto additional indications
stable coronary artery disease to reduce risk of CV events
peripheral artery disease to reduce risk of thrombotic events
VTE prophylaxis in acutely ill
135
Xarelto dosing
Afib: 20 mg with evening meal
VTE: 15 mg bid x 21 days then 20 mg daily with evening meal
CAD/PAD: 2.5 mg bid
136
Apixaban
eliquis
137
Eliquis dosing
Afib: 5 mg bid
VTE: 10 mg bid x 7 days, then 5 mg bid
138
Edoxaban dosin
Afib: 60 mg daily
VTE: 30-60 mg daily
139
Edoxaban use not recommended if
CrCl >95 mL/min
140
Thrombolytic (fibrinolytic)
given to remove thrombi that have already formed
used for acute myocardial infarctions, massive pulmonary embolism, acute ischemic stroke
141
three thrombolytic agents available
altepase
tenecteplase
retaplase
142
alteplase indications
acute ischemic stroke
pulmonary embolism
STEMI
143
alteplase MOA
initiates fibrinolysis by converting plasminogen to plasmin in a thrombus- dissolves the clot
144
alteplase ADRs
bleeding
145
Alteplase metabolism/excretion
no hepatic or renal adjustments needed
