Hematological Agents Flashcards
1
Q
What does serotonin do in the blood vessels?
A
vasoconstriction
2
Q
What is the stimulus to secrete endothelin-1?
A
thrombin
3
Q
Upon activation, the platelets secrete what three coagulation mediators?
A
ADP
Serotonin
TXA2
4
Q
What are the two receptors for ADP on platelets?
A
P2Y1 and P2Y12
5
Q
P2Y12 activation increases the concentration of what intracellular ion? Decreases the concentraion of what intracellular signaling molecule?
A
calcium
cAMP
6
Q
What is the function of factor XIII?
A
stabilize fibrin clots
7
Q
What two molecules does thrombomodulin bind?
A
thrombin and Protein C
8
Q
What protein binds to and activates Activated Protein C?
A
Protein S
9
Q
The association of which two coagulation factors are inhibited by TFPI?
A
three and seven
10
Q
What clotting factors are inhibited by Antithrombin III? Which two coagulation factors promarily?
A
two, seven, nine, ten, eleven, twelve
two and ten
11
Q
What molecule inhibits tPA?
A
Plasminogen Activator Inhibitor
12
Q
What does α2 anti-plasmin inhibit?
A
plasmin not yet bound to fibrin
13
Q
What is the broad definition of acute coronary syndrome?
A
any disease process that limits blood flow through the coronary arteries
14
Q
What does Dipyridamole do to cAMP levels? What does increased cAMP do to calcium levels?
A
increase
decrease Ca2+
15
Q
Would dipyradimole be a vasoconstrictor or vasodilator?
A
vasodilator
16
Q
What receptor do Clopidogrel antagonize?
A
P2Y12
17
Q
What specific CYP enzyme activates Dipyradimole?
A
CYP 2C19
18
Q
What is the MOA of Prasugrel?
A
irreversibly inhibits P2Y12
19
Q
Is the activity of Prasugrel affected by CYP2C19 polymorphisms?
A
no
20
Q
What is the MOA of Ticagrelor?
A
reversibly inhibits P2Y12
21
Q
Which P2Y12 inhibitor is not a prodrug?
A
Ticagrelor
22
Q
What is the MOA of Cangrelor?
A
reversible inhibitor of P2Y12
23
Q
What is the MOA of Abciximab?
A
GPIIb/IIIa inhibitor
24
Q
What is the MOA of Eptifibatide?
A
peptide that prevents fibrinogen from binding GPIIb/IIIa
25
What is the MOA of Tirofiban?
non-peptide inhibitor of GPIIb/IIIa
26
What is the inhibitor of the Protease Activated Receptor (PAR)?
Vorapaxar
27
What type of severe hemorrhage can too much anti-coagulation medication produce?
Cerebral hemorrhage
28
In what cell type of heparin normally found?
mast cells
29
What is the inhibitor of heparin?
Protamine sulfate
30
What is the name for LMW Heparin?
Enoxaparin
31
What clotting factor does LMWH heparin inhibit the most?
factor X
32
Which has better bioavailability after a subQ injection, LMWH or Heparin?
LMWH
33
Which has better half-life after a subQ injection, LMWH or Heparin?
LMWH
34
What binds to plasma proteins and endothelial cells less, LMWH or Heparin? What does this mean?
LWMH
more predictable response
35
What is notable about the clearance of LMWH?
clearance = dose dependent
36
Would a patient with low renal function be put on LWMH or heparin? Why?
unfractioned
LWMH heparin is cleared almost exclusively by the kidneys
37
What is the effect of protamine sulfate on LMWH?
partial reversal
38
What drug does Fondaparinux funtion similarly to?
LMWH
39
What clotting factor does fondaparinux primarily inhibit?
Factor ten
40
What are the effects of protamine sulfate on Fondaparinux?
no effects
41
What is the MOA of hirudin?
direct thrombin inhibitor
42
What is the MOA of lepirudin?
direct thrombin inhibitor
43
What is the MOA of bivalirudin?
1. inhibits thrombin
| 2. blocks thrombin binding site of fibrin
44
What is the MOA of argatroban?
direct thrombin inhibitor
45
What is the MOA of dabigatran?
direct thrombin inhibitor
46
How long does it take for the full anti-coagulant effects of warfarin to be reached?
3-5 days
47
Which cytochrome metabolizes warfarin?
CYP 2C9
48
What is another family of drugs that are metabolized by CYP2C9? What does this do to warfarin clearance?
statins
decrease
49
What OTC drug can increase warfarin clearance? How?
aspirin
competing for plasma proteins
50
What protein is though to be responsible for Warfarin Induced Necrosis?
protein C
51
What is the MOA of rivaroxaban?
direct factor Xa inhibitor
52
What is the MOA of apixoban?
direct Xa inhibitor
53
What are two fibrinolytic antagonsists?
aminocaproic acid
Tranexamic acid
54
Which CYP enzyme activates Clopidogrel?
CYP2C9
55
What are the four P2Y12 receptor antagonists?
clopidogrel
Prasugrel
Ticagrelor
Cangrelor
56
Which drug is more efficiently metabolized, clopidogrel or prasugrel?
Prasugrel
57
Is Ticagrelor reversible or irreversible?
reversible
58
What is the most notable side effect of vorapaxar?
life-threatening intracranial bleeding
59
What are the two mechanisms of heparin clearance?
1. liver/kidneys
| 2. absorbed by endothelial cells
60
What is a side-effect of long-term heparin use?
osteoporosis
61
Why cant LMWH inhibit thrombin?
molecule is not long enough to bring thrombin to ATIII
62
What two partners does LMWH bind to less than unfractionated heparin? What does this mean?
plasma proteins/endothelial cells
more predictable dose
63
What type of drug is fondaparinux?
synthetic factor ten inhibitor
64
What drug is lepirudin designed to replace? When?
Heparin
HIT
65
What are the five DTIs?
Hirudin
Lepirudin
Bivalirudin
Argatroban
Dabigatran
66
What two drugs is a bivalent inhibitor of thrombin? How did it get this name?
Lepirudin and Bivalirudin
binds active site of thrombin and fibrin binding site of thrombin
67
What is the advantage of DTIs over heparin?
DTIs can inhibit thrombin and thrombin bound to fibrin. h
heparins only inhibit free thrombin
68
Where does argatroban and dabigotran bind?
fibrin binding site of thrombin
69
What is the only DTI that can be administered orally?
Dabigotran
70
How long does it take for the anticoagulant effects of warfarin to take place?
3-5 days
71
Does warfarin have a high or low plasma protein binding ability?
high
72
What CYP enzyme metabolizes warfarin? Inactivate or activate warfarin?
CYP2C9
activate
73
What three drugs induce CYP2C9? What would this do to warfarin clearance?
rifampicin, carbamazepine, barbiturates
increase warfarin clearance
74
What does liver disease do to liver clearance?
decrease warfarin clearance
75
What does renal insufficiency do to warfarins effects? Why?
increased warfarin activity
loss of albumin means more warfarin is released per dose
76
What anticoagulant is a teratogen?
warfarin
77
What are the two direct factor Ten inhibitors?
Apixiban
Rivaroxaban
78
Apixiban/Rivaroxaban have a decreased risk of what compared to warfarin?
decreased intracranial bleeding risk
79
Where is urokinase made?
kidney
80
What does the active site of thrombin do?
cleaves fibrinogen into fibrin
81
What does the E1 site of thrombin do?
binds fibrinogen
82
Does heparin/antithrombin complex inhibit fibrin bound to thrombin?
no
83
Do elevated levels of cAMP inhibit or increase levels of intracellular Ca2+ in platelets?
inhibit
84
What drug is Dipyramidole often used in combination with?
Warfarin
85
Would dipyramidole by itself be a vasodilator or vasoconstrictor?
vasodilator
86
The activation of P2Y12 by ADP will result in the increase or decrease of cAMP levels?
decrease
87
Which P2Y12 antagonists are prodrugs?
Clopidogrel and Prasugrel
88
Which two P2Y12 antagonists are irreversible?
Clopidogrel and prasugrel
89
Which two P2Y12 antagonists are reversible?
Ticagrelor and Cangrelor
90
What enzyme activates clopidogrel?
CYP2C19
91
What drug should not be given in combination with clopidogrel? Why?
Omeprazole
Omeprazole inhibits CYP2C19 and would lead to inhibition of clopidogrel activation
92
When compared to clopidogrel, what do prasugrel and ticagrelor carry a higher risk of?
intracranial bleeding
93
Which drug is more affected by polymorphisms in CYP2C19, clopidogrel or prasugrel?
clopidogrel
94
What are the two side effects of all GpIIb/IIIa antagonists?
bleeding and thrombocytopenia
95
Of the three GpIIb/IIIa antagonists, which has the highest risk of thrombocytopenia?
Abciximab
96
Is HIT more common in unfractionated or fractionated heparin?
unfractionated
97
Is HIT more common in men or women?
women
98
Does HIT more often produce venous or arterial thrombosis?
venous
99
Which is used to monitor LMWH and fondaparinox use, PTT or Xa?
Xa
100
What are the two DTIs that bind both the active site and fibrin binding site of thrombin?
Lepirudin and bivalirudin
101
Which two DTIs only bind to the thrombin active site?
Argatroban and Dabigatran
102
What is the advantage of DTIs vs. heparin/antithrombin?
DTIs can bind to thrombin bound to fibrin
ATIII/heparin only bind soluble heparin
103
Would broad spectrum antibiotics increase or decrease INR? Why?
increase
destroy gut flora that synthesize vitamin K
104
Would NSAIDs increase or decrease INR? Why?
increase
interfere with primary hemostasis
105
Would SSRIs increase or decrease INR?
increase
106
Would statins increase or decrease INR?
increase
107
Would Rifampin increase or decrease INR? Why?
decrease
increase hepatic metabolism of warfarin
108
Would barbiturates increase or decrease INR? Why?
DEcrease
increase hepatic metabolism
109
Would diseases of the GI tract increase or decrease INR? Why?
INrease
can interfere with vitamin K absorption
110
Would renal disease increase or decrease INR?
increase
111
When is dabigatran contraindicated?
mechanical heart valves
112
What is the route of administration for apixaban and rivaroxaban?
oral
113
Are fibrinolytics used for non-STEMI? Why?
no
increased risk of intracranial bleeding
114
What is the MOA of aminocaproic acid and tranexamic acid?
prevent plasmin binding to fibrin
115
Does antithrombin have a higher affinity for thrombin or factor X?
ten
116
What two mechanisms ca be employed to reverse the effects of DTIs?
factor seven
prothrombinase complex
117
Alteplase must be used within how many hours of an MI?
12 hours
118
Can DTIs induce HIT?
no
