Antiplatelets/coagulants (exam 2) Flashcards
(128 cards)
1
Q
When does endothelium injury occur?
A
Single layer of cells lining blood vessels is damaged
2
Q
Injured vessel wall exposes blood to ___ and ____.
A
collagen
von Willebrand’s Factor
3
Q
Neutrophils and macrophages in response to endothelium injury release
A
Platelet Activating Factor (PAF)
4
Q
Activated platelets secrete
A
ADP, serotonin, and TxA2
5
Q
Endothelium injury leads to
A
vasoconstriction then eventually a platelet plug which forms a clot
6
Q
Consequences of endothelium injury
A
inflammation
vascular changes
thrombosis
leukocyte adhesion
7
Q
Hemostasis
A
- Vessel constriction
- Primary hemostasis (formation of platelet plug)
- Secondary hemostasis (formation of clot)
- Stable clot formed
8
Q
Formation of platelet plug
A
Platelet adhesion –> platelet activation –> platelet aggregation
9
Q
Activation of a clotting cascade results in a _____
A
fibrin-containing clot
10
Q
Platelets
A
blood cells that help form clots to stop bleeding
11
Q
Adhesion
A
Process of spreading across surface of damaged blood vessel to stop bleeding
12
Q
No injury present, platelet aggregation is prevented by
A
separating blood from collagen
secreting NO and PGI2
enzyme CD39 breaks down ADP in blood
13
Q
platelet adhesion
A
circulating platelets attach to exposed vWF and collagen via glycoprotein receptors
14
Q
platelet activation
A
irreversible change in shape to increase surface area and secrete granules
15
Q
during platelet activation, ADP binds to _________ which increases _______________
A
P2Y12 receptors
platelet activation
16
Q
platelet aggregation
A
fibrinogen binds to GP IIb/IIIa receptors on platelets –> crosslinks them to form a platelet plug
17
Q
extrinsic pathway and factors involved
A
external trauma that causes blood to leave the circulatory system
factors 7 and 10
18
Q
intrinsic pathway and factors involved
A
activated by trauma inside the vascular system
factors 8-12
19
Q
the intrinsic and extrinsic pathways converge at _____________ which is also known as the _____________
A
factor X
common pathway
20
Q
factor V is a __________ for Factor X because it ________-
A
cofactor
fits into the notch on X
21
Q
activated factor X converts
A
prothrombin to thrombin
22
Q
thrombin cuts
A
fibrinogen into fibrin
23
Q
fibrin fibers form
A
clots
24
Q
fibrinolysis pathway
A
plasminogen activator (tPA) –> plasminogen to plasmin –> breaks down fibrin and dissolves the clot
25
arterial thrombus are formed under ___________ and is ___________. Also called a _____________
high pressure
platelet rich
white thrombi
26
venous thrombus are formed under ___________ and is ___________. Also called a _____________
low pressure
fibrin rich
red thrombi
27
antithrombin primarily inactivates
factors II and Xa
28
Protein S is a cofactor of
Protein C
29
Protein C inactivates
factors Va and VIIIa
30
tissue factor pathway inhibitor
inhibits the tissue factor to factor VIIa complex and inhibits factor Xa
31
Virchow's triad
endothelial injury
abnormal blood flow
hypercoagulability
32
endothelial injury
main influence on thrombus formation in the heart and the arterial circulation
33
endothelial injury is caused by
hypertension
hyperlipidemia
elevated blood glucose in DM
traumatic vascular injury
34
abnormal blood flow
state of turbulence and/or stasis
35
abnormal blood flow is caused by
hyperlipidemia
aneurysm
MI
cardiac arrythmia
immobility or paralysis
36
inherited (primary) hypercoaguability
Factor V lieden (resistence to anticoagulant effects of protein C)
Protein C or S deficiency
37
acquired (secondary) hyper coagulability
cancer
smoking
pregnancy
some medications (estrogen, heparin)
38
tissue plasminogen activators (tPAs) examples
altepase (activase)
reteplase (retavase)
tenecteplase (TNKase)
39
tissue plasminogen activators MOA
used to break down a clot that's already formed by increasing the conversion of plasminogen to plasmin
40
uses for fibrinolytics
STEMI
acute ischemic use (most common)
severe cases of VTE, PE, DVT
41
tissue plasminogen activator binds to ____________ and converts __________________________
fibrin
plasminogen to plasmin
42
fibrinolytics are given
intravenously
43
MW and half life of alteplase
5-10 min
70 kd
44
MW and half life of reteplase
15 mins
39 kd
45
MW and half life of tenecteplase
20 mins
75 kd
46
ADRs of fibrolytics
high risk of bleeding
47
older clots have more ________ cross linking and are harder to ____________
fibrin
break down
48
do not give fibrinolytics to patients who
have an increased risk of bleeding
49
fibrinolytics must be given ____________ for benefit to outweigh bleeding risk
soon after thrombotic event
50
antiplatelet medication examples
COX1 inhibitors
P2Y12 receptor antagonists
PDE inhibitors
GP IIa/IIIa receptor antagonists
51
COX1 inhibitor example
aspirin
52
P2Y12 receptor antagonists examples
Clopidogrel (Plavix)
Prasurgel (Effient)
Ticagrelor (Brilinta)
Cangrelor (Kengreal)
53
PDE inhibitors examples
Dipyridamole (Persantine)
Cilostazol (Pletal)
54
GP IIa/IIIa receptor antagonists examples
Abciximab (Reopro)
Eptifibatide (Integrilin)
Tirofiban (Aggrastat)
55
anti platelet medications are used for
prevention of heart attack/stroke
ACS, especially when a stent (PCI) is used
56
_____________ is recommended after stent therapy
Dual anti platelet therapy (aspirin and P2Y12 receptor antagonist)
57
which type of drugs are used more frequently in arterial thrombosis?
anti platelet drugs
58
aspirin decreases the synthesis of ______________ which decreases ___________ and causes __________
thromboxane 2
platelet activation
vasodilation
59
ADRs of aspirin
gastric bleeding
tinnitus and hearing lose (high doses)
Reye's syndrome in children
60
Aspirin should not be given in anyone ______________ during fever causing illness
under 19 years old
61
In ACS, it is recommended to chew __________________ for immediate effects
non-enteric coated aspirin
62
Emax for inactivation of platelet COX1 is achieved with ______________
higher doses of aspirin do not seem to __________________________
a daily aspirin dose of about 75mg
improve efficacy for platelet effects but increase risk of bleeding
63
what is given in the case of aspirin overdose?
sodium bicarbonate
64
clopidogrel and prasurgel are ________________
ticagrejor and cangrelor are _________________
irreversible inhibitors and prodrugs
reversible inhibitors
65
______________ is important in bio activation of clopidogrel
CYP2C19
66
ADRs of P2Y12 receptor antagonists
bleeding
ticagrejor can cause dyspnea
67
which P2Y12 receptor antagonist is available as IV only?
cangrelor
68
some _________________ inhibit CYP2C19 and may reduce the effectiveness of clopidogrel
PPIs
69
which P2Y12 receptor antagonist should not be used in patients with high bleeding risk due to higher rates of life threatening bleeding?
prasurgel
70
PDE inhibitors inhibit the PDE enzyme which increases _________________ which does what?
increases cAMP and cGMP
reduces platelet activation and causes vasodilation
71
ADRs of PDE inhibitors
bleed risk
headache
dizziness
diarrhea
72
Cilostazol is _________________ and is primarily used in ______________
selective for PDE3
PAD
73
Dipyridamole inhibits __________________ and is combined with aspirin for treatment of _______________
PDE3 and PDE5
secondary stroke prevention
74
GP IIa/IIIa receptor antagonists are all given by
IV route
75
ADRs of GP IIa/IIIa receptor antagonists
risk of bleeding
thrombocytopenia
76
GP IIa/IIIa receptor antagonists are used during
PCI in ACS
77
half life of GP IIa/IIIa receptor antagonists
eptifibatide (2.5 hrs) > tirofiban (2 hrs) > abciximab (mins)
78
PDE inhibitors examples
dipyridamole (persantine)
cilostazol (pletal)
79
GP IIa/IIIa receptor antagonists examples
Abciximab (reopro)
eptifibatide (integrilin)
tirofiban (aggrastat)
80
abciximab is a
monoclonal antibody drug
81
eptifibatide is a
peptide derived from rattlesnake venom
82
tirofiban is a
non peptide small molecule inhibitor
83
which drugs are used more frequently in venous thrombosis?
anticoagulants
84
what are anticoagulants used to treat?
treatment and prevention of VTE
prevent cardioembolic stroke in patients with atrial fibrillation
85
anti platelet medications target ______________ while anticoagulants target ___________
primary hemostasis (platelet plug)
secondary hemostasis (clotting cascade)
86
which anticoagulants are also known as direct oral anticoagulants?
dabigatran
all direct factor Xa inhibitors
87
vitamin K antagonist MOA
inhibits the enzyme vitamin K epoxide reductase which prevents the conversion if inactive vitamin K to active vitamin K
88
vitamin K is required for the
synthesis of clotting factors VII, IX, X and II
89
vitamin K epoxide reductase converts
vitamin K epoxide to vitamin K hydroquinone
90
onset of action of warfarin is _______ due to _______
slow
long half life of clotting factors
91
full anticoagulant effect of warfarin takes
5-7 days
92
ADRs of warfarin
risk of bleeding
increased risk of clotting during initial days of therapy
purple toe syndrome
93
what to monitor when taking a vitamin K antagonist
prothrombin time
INR (international normalized ratio)
94
prothrombin time is used to calculate
INR
95
drug interactions with vitamin K antagonists
2C9 inducers and inhibitors
1A2 and 3A4 inducers/inhibitors
96
"Fab Four" that inhibit warfarin metabolism and increase bleed risk
fluconazole
metronidazole
amiodarone
bactrim
97
metabolism of warfarin
2C9, 2C19, 1A2, 3A4
98
bioavailability of vitamin K antagonists is
almost 100%
99
reversal agent of warfarin
vitamin K
100
vitamin K antagonists requires intensive ___________ monitoring.
how to monitor?
INR
every 2-3 days to start, then every 3-4 weeks when stable
101
MOA of indirect inhibitors
bind to antithrombin and make antithrombin more efficient
inhibits activated factors Xa and thrombin (IIa)
102
heparin is a mix of
polysaccarhides
103
heparin is an endogenous substance found in
mast cells
104
how are indirect inhibitors given? why?
parenteral route (IV or SQ)
they would be digested if given orally
105
mean size of saccharide chains of heparin
various lengths -- 45 saccharide units
106
mean size of saccharide chains of LMW heparin
15 saccharide units
107
mean size of saccharide chains of fondaparinux
5 saccharide units
108
heparin inhibits ____________
LMWH inhibits ____________
fondaparinux inhibits _________
Xa and IIa equally
Xa>> IIa
Xa only
109
the shorter the molecules, the _________________ at enhancing binding of antithrombin to IIa
less efficient
110
ADRs of indirect inhibitors
risk of bleeding
heparin induced thrombocytopenia
hyperkalemia
increased risk of osteoporosis
111
heparin can bind to _______________ creating a complex that is recognized by the body's immune system as foreign
platelet-factor-4
112
reversal agent for heparin and LMWH
protamine sulfate
113
is there a reversal agent for fondaparinux?
no
114
heparin is monitored by
measuring the aPTT (activated partial thromboplastin time
115
is monitoring required for LMWH or fondaparinux?
no
116
Heparin is given _______ because it has a __________
IV
quick onset and short duration
117
what indirect inhibitors are drugs of choice in pregnancy and why?
heparin and LMWH
do not cross the placental barrier
118
direct thrombin inhibitors MOA
binds thrombin and inactivates it directly
119
oral direct thrombin inhibitors
dabigatran (Pradaxa)
120
parenteral direct thrombin inhibitors
argatroban (Acova)
bivalirudin (Angiomax)
121
dabigatran is given as a _______ which is converted to the active form by _________________
prodrug
plasma esterase enzymes
122
reversal agent for dabigatran
idarucizumab (Praxbind) - monoclonal antibody
123
direct factor Xa inhibitors examples
Rivaroxaban (Xarelto)
apixaban (eliquis)
edoxaban (savaysa)
betrixaban (Bevyxxa)
124
direct factor Xa inhibitors MOA
reversibly bind to factor Xa and directly inactivates it
125
do direct factor Xa inhibitors require monitoring?
No
126
direct factor Xa inhibitors are increasingly used in place of
warfarin
127
reversal agent for factor Xa inhibitors
andexanet alfa (AndexCa)
128
ADRs of direct factor Xa inhibitors
increased risk of bleeding
