Pharm Unit 2 - Anti-Thrombotics Flashcards
(149 cards)
1
Q
antiplatelets
A
prevent blood clot formation
2
Q
primary hemostasis
A
endothelial injury
adhesion
activation
aggregation
3
Q
endothelial injury
A
exposure of collagen and vWF inside vessel
4
Q
adhesion
A
circulating platelets bind to vWF and collagen
5
Q
activation
A
shape change of platelets
TXA2 release
granual release
GP IIb/IIIa conformation change
6
Q
do platelets have nucleus?
A
no
7
Q
TXA2 function
A
thromboxane recruits more platelets to the plug
expands the clot
8
Q
what is converted into TXA2
A
arachadonic acid –> TXA2
9
Q
what does granule release do
A
ADP
coagulation factors
10
Q
aggregation
A
fibrinogen cross linking between platelets’ surfaces
11
Q
anti-thombotic therapy goals
A
prevent thrombosis
without over promotion of bleeding
12
Q
main risk of antithrombotics
A
bleeding
increase risk of death 3-5x
13
Q
pt monitoring during antithrombotic therapy
A
Hgb drop
bloody stools
melena
hematuria
bruising
oozing from arterial/venous puncture
14
Q
antiplatelets drug types
A
aspirin
P2Y12 receptor antagonists
GP IIb/IIIa inhibitors
Vorapaxar
15
Q
aspirin mechanism
A
irreversibly inhibits COX-1
prevents conversion of arachidonic acid into thromboxane
- decr platelet formation
- decr vasoconstriction
16
Q
aspirin uses
A
prevention of DVT
prevention of ASCVD (secondary)
- MI
- angina
- stroke/TIA
- PAD
- CAD
antiypyretic
analgesic
prevention of colorectal cancer
17
Q
what is the fastest way to get aspirin into the body?
A
chew non-enteric coated
–20 mins
18
Q
duration of aspiring effects
A
lasts entire platelet lifespan
wears off once new plts are made
19
Q
aspiring SE
A
GI
bleeding
allergic rxns
incr hemorrhagic stroke in men
20
Q
aspiring drug interactions
A
NSAIDs will blunt aspirins effect
incr risk of serious GI complications
21
Q
ADP
A
binds to P2Y1
- incr Ca2+ == shape change
binds to P2Y12
- granule release
both paths activate GPIIb/IIIa, resulting in platelet aggregation
22
Q
which is the more dominant ADP biding site?
A
P2Y12
so drugs target P2Y12
23
Q
P2Y12 ADP inhibitor drugs
A
clopidogrel
prasugrel
ticagrelor
cangrelor
24
Q
what polymorphism impacts clopidogrel?
A
decr CYP2C19 function
loss of effectiveness of drug
25
clopidogrel and prasugrel bind
irreversibly to P2Y12 receptor
26
which is more potent: clapidogrel or prasugrel?
prasugrel has more potent plt inhibition w/faster onset
clopidogrel is a prodrug so must be metabolized to work == slower
27
if you inhibit CYP2C19 function, would you amplify or reduce clopidogrels anti-platelet effect?
reduce
clopidogrel requires CYP2C19 to convert into active form
28
clopidogrel indications
acute coronary syndrome
- typically DAPT w/aspirin
percutaneous coronary intervention
- prevents stent thrombosis
2ndary prevention in atherothrombotic disease
- CAD
- CVD
- PAD
29
what drug can replace aspiring in prevention of atherothrombotic disease?
clopidogrel
30
Prasugrel CI
<60 kg = half dose
Stroke or TIA history
>75 yrs old
cannot be used in CABG pts
31
Prasugrel indication
only pts w/PCI and stent implant
32
Ticagrelor and Cangrelor bind
reversibly to ADP P2Y12 receptor
33
Ticagrelor and Cangrelor are administered
IV only
Ticagrelor: 2x daily
Cangrelor: continous IV
34
Ticagrelor is metabolized by
CYP3A
35
Ticagrelor vs Clopidogrel
ticagrelor has:
faster onset
more potent platelet inhibition
36
What other receptor does Tacagrelor block?
ENT1
-- incr adenosine plasma levels
-- incr endothelium function
-- decr HR
37
Ticagrelor SE
dyspnea
-- P2Y12 incr neuronal signaling
-- incr conductivity of pulmomnary vagal C-fibers
-- incr sensation of dyspnea
38
cangrelor bleeding rates compared to clopidogrel
cangrelor has higher bleeding rates compared to clopidogrel
39
cangrelor SE
dyspnea
decr renal function (3.2%)
40
Cilostazol mechanism
PDE3 inhibitor
incr intraplatelet cAMP
decr Ca2+
plt inhibition
41
Cilostazol effects
platelet inhibition
inhibit vascular smooth muscle cell proliferation
improves peripheral BF
42
Cilostazol indications
PAD - claudication
PVD
stroke/TIA
post-PCI
43
Cliostazol CI
HF
44
most abundant receptor on platelates
Gp IIb/IIIa
80,000 copies/plt
45
GPIIb/IIIa inhibitor mechanism
binds to GPIIb/IIIa receptors
prevents formation of fibrinogen plt-plt crosslinks
46
GPIIb/IIIa inhibitor indications
PCI
unstable angina
47
GP IIb/IIIa inhibitors SE
bleeding
thrombocytopenia
48
GP IIb/IIIa drugs
abcimimab
eptifibatide
tirofiban
49
GP IIb/IIIa inhibitor CI
active internal bleeding
major surgeries
recent trauma
intracranial hemorrhage
bleeding disorders
severe hypertension
50
abciximab has a ____ % risk of thrombocytopenia
5% risk
1% severe risk
51
anticoagulants
prevent blood clots from forming by interfering with coagulation factors
52
hemostasis
stopping bleeding
53
primary hemostasis
formation of platelet plug
54
secondary hemostasis
coagulation
55
extrinsic pathway of secondary hemostasis
activated by tissue factor found outside the blood
56
intrinsic pathway of secondary hemostasis
factors required for activation are found in the blood
57
common pathway
activation of factor X
coagulation cascade
58
4 parental anticoagulants
unfractionated heparin
low molecular weight heparin
synthetic pentasaccharides
direct thrombin inhibitors
59
parenteral anticoagulatns indications
DVT
PE
initial management of ACS
60
clotting times
measure the time it takes plasma to clot when various substances are added
61
prothrombin time (PT)
assesses extrinsic pathway of coagulation
INR
62
activated clotting time (ACT)
measures time of clot formation via the intrinsic coagulation pathway
63
high dose heparin monitoring uses
ACT
64
activated partial thromboplastin time (aPTT)
assess intrinsic pathway of coagulation
65
antifactor Xa assay
measures unbound Factor Xa level
assesses functional activity of anticoagulant
66
unfractionated heparin mechanism
binds to endothelium/plasma proteins
causes a confirmational change in antithrombin
inactivates clotting factor proteases (IIa, IXa, Xa)
67
which molecular weight heparin inhibits thrombin
High molecular weight heparin inhibits thrombin
68
heparin clinical uses
PE
DVT
clot prevention in arterial/cardiac surgery
Afib w/embolization
ACS
MI
69
Low-molecular weight heparin mechanism
primarily inhibit Factor Xa
70
heparin SE
hemorrhage
heparin induced thrombocytopenia (HIT)
epidural/spinal hematoma
71
HIT
prothrombotic
72
Heparin monitoring
aPTT
anti-factor Xa plasma levels
ACT (high doses)
73
heparin aPTT
2-3x normal
74
heparin clearance
reticuloendothelial system
dose-dependent
- low = fast clearance
- high = long clearance
75
heparin reversal
protamine sulfate
76
protamine sulfate
highly basic (+ charge)
neutralizes heparin
better at HWMH than LWMH
77
Heparin Induced Thrombocytopenia
antibody mediated process
PF4-heparin antibody rxn
activated plts
decr plt count
incr thrombin production
incr clotting
78
occurence rate of HIT
5%
79
HIT ocurrence timeframe
4-10 days post-heparin dosing
80
LMWH drugs
enoxaparin
dalteparin
tinzaparin
81
LMWH
longer half life
more predictable
minimal need for monitoring
kidney clearance
decr HIT risk
partial reversal by protamine
82
Fondaparinux
synthetic indirect Factor Xa inhibitor
100% bioavailability
83
Fondaparinux mechanism
binds antithrombin
inactivation of factor Xa
84
Fondaparinux is dependent on
renal excretion
85
renal impairment (Fondaparinux clearancce rates)
mild: decr clearance 25%
mod: decr clearance 40%
sev: decr clearance 55%
86
Fondaparinux SE
thrombocytopenia
(2.9%)
severe (0.2%)
hemorrhage
epidural/spinal hematoma
87
does fondaparinux cause HIT?
no
88
LMWH/Fondaparinux CI
epidural indwelling catheter
NSAIDs
plt inhibitors
anticoagulants
traumatic epidurals/spinals
spinal deformity
spinal surgery
89
Direct Thrombin inhibitor mechanismn
directly bind and inhibit unbound and fibrin-bound thrombin
90
direct thrombin inhibitor drugs
bivalriduin
argatroban
91
bivalirudin metabolism/excretion
met: blood proteases
excr: urine (20%)
92
argatroban metabolism
hepatic
93
bivalirudin requires does adjustment for
renal impairment
CrCl<30
94
argatroban requires dose adjustment for
hepatic impairment
95
direct thrombin inhibitor monitoring
aPTT
ACT
96
argatroban does what to PT and INR
argatroban prolongs PT/INR
97
argatroban indications
HIT pts
98
bivalirudin indications
PCI (coronary angioplasty)
with or w/o HIT
99
direct thrombin inhibitor side effects
hemorrhage
100
oral anticoagulants
warfarin
dabigatran
direct Factor X inhbitors
-- apixaban
-- edoxaban
-- rivaroxaban
101
oral anticoagulants indications
DVT
PE
stroke prevention in afib pts
102
Warfarin mechanism
inhibits conversion of Vit K into its active form
results in incomplete clotting factors that are biologically inactive in coagulation
103
Active Vit K is needed for
the production of functional clotting factors:
II
VII
IX
X
and anticoagulant proteins:
C
S
104
what polymorphisms impact warfarin clearance and dosing?
CYP2C9
105
what polymorphisms impact warfarin anticoagulation response?
VKORC1
106
which polymorphisms have reduced enzyme activity with warfarin?
CYP2C9*2
CYP2C9*3
107
what polymorphism are associated with increased sensitivity to warfarin and lower dose requirements?
VKORC1
-- G3673A
-- -1639G>A
108
VKORC1 G/G warfarin dosing
46 mg/wk
109
VKORC1 G/A warfarin dosing
33 mg/wk
110
VKORC1 A/A warfarin dosing
21 mg/wk
111
when is the anticoagulant effect of warfarin observed?
after elimination of normal pre-formed clotting factors
~48-72 hrs post-administration
112
how do you recover from warfarin?
synthesize new normal clotting factors
113
which coagulation factor has the shortest half-life with warfarin?
shortest: F VII
FIX
FX
longest: FII
114
what is the length of time to maximal effect of warfarin on Factor II?
7 days
115
warfarin normal INR
2.0-3.0
116
warfarin starting dose
5mg daily
titrate to appropriate INR
117
warfarin SE
bleeding
skin necrosis (3-10 days)
thrombosis of microvasculature
protein C depletion
118
warfarin CI
pregnancy
119
warfarin reversal
Vit K (phytonadione)
120
clotting factor replacements to help warfarin reversal
fresh frozen plasma
prothrombin complex concentrate
recombinant factor VIIa
121
Direct oral anticoagulant drugs
dabigatran
rivaroxaban
apixaban
edoxaban
122
direct oral anticoagulants inhibit what factors?
Factor Xa
Factor IIa
123
Factor Xa inhibitors
rivaroxaban
apixaban
edoxaban
124
Factor IIa inhibitor
dabigatran
125
DOAC onset
rapid
126
DOAC dosing
fixed
127
Do you need to monitor DOACs?
no
128
dabigatran clearance
renal (80%)
129
which DOACs are metabolized by the liver?
rivaroxaban
apixaban (minor)
edoxaban (minimal)
130
dabigatran SE
dyspepsia
131
DOAC boxed warning
increased rate of stroke following discontinuation of DOACs
(incr risk of thrombotic events)
132
dagibatran antidote
idarucizumab
(monoclonal antibody)
133
DOAC antidote
decoy Factor Xa
--decr DOAC effect
134
DOAC indications
DVT
PE
VTE (hip/knee replacements)
stroke prevention in afib
135
Rivaroxaban inbdications
chronic CAD or PAD
-- combined w/aspirin to decr risk
136
thrombolytics
break up blood clots formed during hemostasis
restore blood flow
137
thrombolytics drugs
alteplase
reteplase
tenecteplase
streptokinase
138
which thrombolytics are derived from tPA
alteplase
reteplase
tenecteplase
139
streptokinase is derived from
beta hemolytic bacteria proteins
140
tPA derived-thrombolytics mechanism
bind to fibrin proteins
onverts plasminogen to plasmin
plasmin degrades fibrin mesh
141
streptokinase mechanism
binds to circulating or fibrin bound plasminogen
converts plasminogen to plasmin
plasmin degrades fibrin mesh
142
which thrombolytic is not selective to fibrin? what does that mean?
streptokinase
it impacts the entire body, not just fibrin
143
thrombolytics indications
short term emergent mgmt of thrombosis
STEMI
DVT
PE
acute ischemic stroke
acute peripheral arterial occlusion
144
thrombolytics SE
severe bleeding
intracranial hemorrhage
145
thrombolytics CI
active internal bleeding
close to major surgiers
after recent trauma
suspected aortic dissection
intracranial hemorrhage
bleeding disorders
severe hypertension
146
thrombotic (fibrinolytic) antidotes
aminocaproic acid
tranexamic acid
147
aminocaproic acid mechanism
blocks binding of plasminogen to fibrin
blocks conversion of plasminogen to plasmin
148
tranexamic Acid mechanism
forms reversible complex that displaces plasminogen from fibrin
inhibition of fibrinolysis
149
thrombotic (fibrinolytic) antidote indications
fibrinolytic bleeding
hemophilia
prevention of surgical blood loss
post-trauma hemorrhage
