1
Q
What does an endothelial cell normally secrete to repel circulating thrombocytes? (Two things)
A
- Prostocyclin (PG12)
2. Nitrous oxide (NO)
2
Q
This proteolytic enzyme converts fibrinogen to fibrin:
A
Thrombin
3
Q
What are the three phases of clotting?
A
- Platelet Adhesion
- Platelet Activation
- Platelet Aggregation
4
Q
How do NO and PGI2 affect platelets?
A
They induce cAMP synthesis, which decreases intracellular Ca++ and INHIBITS GPIIb/IIIa activation
5
Q
Damaged endothelial cells expose what?
A
Von Willebrand factor (vWF) and collagen
6
Q
Name the top three chemical mediators secreted by adhered/activated platelets:
A
- ADP (Adenosine diphosphate)
- TXA2 (thromboxane A2)
- 5HT (Serotonin)
7
Q
What action does local 5HT released by activated platelets have in the area of the endothelial damage?
A
Vessel spasm, reducing blood loss
8
Q
Primary actions of TXA2?
A
- Stimulate activation and aggregation of platelets
2. Potent vasoconstrictor
9
Q
What is thrombin’s job?
A
To convert fibrinogen to fibrin
10
Q
What is the function of the GPIIb/IIIa receptors on thrombocytes?
A
Facilitate platelet-platelet interaction; fibrin bridge connects the GPIIb/IIIA receptors of one platelet to another
11
Q
This pathway is shorter, and measured by PT/INR:
A
Extrinsic pathway
12
Q
This pathway in longer, and measured by aPTT:
A
Intrinsic pathway
13
Q
Which pathway is vitamin K dependent? Extrinsic or intrinsic?
A
Extrinsic, because it starts with Factor VII (which is Vitamin K dependent)
14
Q
Name three natural anticoagulants:
A
- Protein C
- Protein S
- Anti-thrombin III
15
Q
Which pathway is prothrombin time (PT) used to monitor?
Which factor is involved?
What does that factor need in order to be synthesized?
A
Extrinsic pathway
Factor VII
Vitamin-K dependent
16
Q
Which factors are Vitamin K-dependent?
Which has the shortest life-span?
Which has the longest?
A
Factors II, VII, IX, X
Shortest: VII
Longest: II (thrombin)
17
Q
Which pathway does the aPTT test assess?
A
The intrinsic pathway
18
Q
What are the elements of Virchow’s Triad?
A
- Vascular wall injury
- Stasis
- Hypercoagulable state
19
Q
MOA for ASA?
A
IRREVERSIBLY inhibits COX-1 and 2
Stops conversion of AA to prostaglandin, leading to less TXA2
Leads to inhibition of platelet aggregation, decreased inflammation
20
Q
ASA dose range for prevention of cardiovascular events:
A
50mg to 160mg
21
Q
Top risk of ASA use:
A
GI bleeding
22
Q
Rare SE of ASA?
A
Reye’s Syndrome - swelling of the liver and brain (peds)
Avoid use of salicylates in children
23
Q
ASA pregnancy category?
A
C/D —> avoid in 3rd trimester
*APAP —> preferred for pregnancy
24
Q
Dipyrimadole MOA?
A
- Stimulates PGI2 synthesis
- Stimulates cAMP
- Inhibits platelet aggregation
25
Dipyrimadole use?
1. Combined with ASA to prevent CVA (ischemic)
| 2. Post-heart valve replacement thrombus prevention
26
Dipyrimadole SE’s?
Coronary steal phenomenon: unstable angina patients
Caution when used with anticoagulants
27
Aggrenox (ASA and Dipyridamole) - use?
Reduce risk of stroke in pt’s who have already experienced TIA or CVA
28
Aggrenox - CI’s?
Reye’s Syndrome
29
Cilostazol - MOA?
PDE3 inhibitor
Inhibits cAMP breakdown
Inhibits platelet aggregation
Vasodilatory in vascular smooth muscle
30
Cilostazol - use?
Intermittent claudication (muscle pain) symptom relief
31
Cilostazol - SE’s?
Cardiac (palpitation, tachyarryhthmias)
HA
Diarrhea
32
Cilostazol - CI’s?
BLACK BOX: HF
33
Vorapaxar - MOA?
PAR-1 antagonist
Inhibits thrombin-induced platelet aggregation
Does NOT inhibit platelet aggregation via ADP, vWF, etc
34
Vorapaxar - use?
Prevention of thrombotic events in pt’s with hx of MI or PAD
35
Vorapaxar - CI’s?
Not for use in ACS
Avoid use with strong CYP3A inhibitors or inducers
Avoid use with anticoagulants
36
Clopidogrel (Plavix) and Prasugrel (Effient) - MOA?
IRREVERSIBLY inhibits ADP from binding to P2Y12 receptor - leads to inhibition of GPIIb/IIIa expression (required for platelet aggregation)
37
Ticagrelor - MOA?
REVERSIBLY inhibits ADP from binding to P2Y12 receptor - leads to inhibition of GPIIb/IIIa expression (required for platelet aggregation)
38
Clopidogrel/Prasugrel - use?
Prevention of atherosclerotic events for pt’s with:
Recent stroke or MI, or PAD
Post-PCI patients
39
Ticagrelor - use?
ACS patients
40
Clopidogrel - active or prodrug?
Prodrug
41
Prasugrel- active or prodrug?
Prodrug
42
Ticagrelor - active or prodrug?
Active
43
Cangrelor - MOA?
Inhibits binding of ADP to P2Y12 receptor
44
Cangrelor - use?
Adjunct to PCI
45
Abciximab - MOA?
Monoclonal antibody GPIIb/IIIa receptor inhibitor
46
Abciximab - use?
Adjunct to PCI
47
Ebtifibatide - MOA?
GPIIb/IIIa receptor inhibitor - prevents binding of fibrin to GPIIb/IIIa, preventing platelet aggregation
48
Eptifibatide - use?
ACS, PCI
49
Tirofiban - MOA?
GPIIb/IIIa receptor inhibitor - prevents binding of fibrin to GPIIb/IIIa, preventing platelet aggregation
50
Tirofiban - use?
ACS, PCI
51
Eptifibatide and Tirofiban - considerations?
Renal insufficiency
52
Pharmacological management of unstable angina?
1. Antiplatelet (P2Y12, GP)
| 2. Anticoag (UFH, LMWH, etc)
53
Clinical use for anticoagulants?
Reduce existing thrombi expansion (STEMI, CVA, PE) and prevent formation of new thrombi (a-fib)
54
What does UFH complex with to accelerate anticoagulation in the body?
Antithrombin III
55
Which factor(s) does UFH bind to and inhibit?
IIa (thrombin)
| Xa
56
Onset of UFH?
Minutes
57
Adverse reactions UFH?
Heparin-Induced Thrombocytopenia with paradoxical embolization
58
Antidote for UFH?
Protamine sulfate
59
UFH - CI’s?
1. Hx of HIT
2. Hypersensitivity
3. Recent surgery (increased bleeding risk)
4. Intracranial hemorrhage
60
What laboratory test do we use to evaluate UFH response and adjust dosage (titrate to effect)?
Activated partial thromboplastin time(aPTT)
61
An aPTT of longer than ___ may indicate bleeding:
70 seconds
62
UFH - pregnancy category?
C (recommended for certain situations)
63
LMWH - MOA?
Similar to heparin - binds anti-thrombin III, but only inactivates Xa rather than IIa AND Xa
64
Which is more preferable in pregnancy - UFH or LMWH?
LMWH
65
Enoxaparin - uses?
1. DVT prophylaxis
2. Unstable angina
3. STEMI
66
Dalteparin - uses?
1. DVT prophylaxis
| 2. Preferred Rx for tx of recurrent VTE in cancer patients
67
Monitoring considerations for LMWH?
Not necessary to monitor aPTT, but LMWH does have a longer half-life than UFH
68
LMWH advantages over UFH?
1. No need to monitor aPTT
2. Less incidence of HIT
3. Longer T1/2
4. Pregnancy-safe
69
Protamine sulfate - CI’s?
Fish allergy
70
Fondaparinux - MOA?
Binds with anti-thrombin III, SELECTIVELY inhibiting Xa
71
Fondaparinux - use?
1. DVT prophylaxis
2. Acute DVT (w/ warfarin)
3. Acute PE (w/ warfarin)
72
Fondaparinux - black box warning?
Spinal/Epidural hematoma
73
Fondaparinux - AE?
Less likely to cause HIT, but still CI in pt’s with thrombocytopenia (<100K)
74
Warfarin - MOA?
Inhibits Vitamin K epoxide reductase (in the liver), reducing the available Vitamin K for cofactors II, VII, IX, and X, as well as Proteins C and S
75
Warfarin - uses?
1. DVT, PE, a-fib - treatment and prophylaxis
2. Post-MI / CVA
3. Protein C and S deficiency
76
What factor is “half-life” of warfarin actually based on?
The lifespan of the Vitamin K-dependent clotting factors and Protein C and S
First to die - VII (6 hours)
Last to die - II (3 days)
77
Warfarin monitoring?
PT (prothrombin time)
| INR (international normalized ratio)
78
Target INR for DVT prophylaxis?
2 to 3
79
Target INR for artificial valve thrombosis prevention?
2.5 to 3.5
80
Warfarin in pregnancy?
Category X
81
Warfarin AE?
Purple Toe syndrome (from cholesterol microembolization)
82
Foods that can disrupt target warfarin therapy?
Vitamin-K heavy foods (mostly dark, leafy-green veggies)
83
Actions to take if INR is above target but less than 4.5?
Skip a dose
84
Actions to take if INR is 4.5 to 10?
Skip 1 to 2 doses, monitor, lower dose
85
Actions to take if INR is >10?
Hold warfarin and give Vit-K
86
If major bleeding associated with Warfarin use is present?
PCC (prothrombin complex concentrate)
Or
FFP (fresh frozen plasma)
87
Phytonadione - MOA?
Fat soluble Vitamin K
88
Phytonadione - use?
Warfarin reversal agent
89
Bivalirudin - action and indication?
Direct thrombin inhibitor (factor IIa) // patients at risk for HIT
90
Bivalirudin - clearance?
Renal
91
Argatriban - MOA and use?
Direct thrombin inhibitor, used for treatment or prevention of HIT
92
Argatroban - clearance?
Liver
93
Dabigatran (Pradaxa) - MOA and use?
Direct thrombin inhibitor, DVT/PE/afib
94
Dabigatran (Pradaxa) - metabolized by?
P-glycoprotein
95
Dabigatran - pregnancy?
C
96
Dabigatran advantages over warfarin?
1. Monitoring not required
2. Lower risk of brain bleed
3. More effective at preventing CVA
97
Dabigatran disadvantages over warfarin?
1. Renal elimination
2. Risk for dyspepsia
3. Twice daily dosing
98
Idarucizumab (Praxbind) - MOA and use?
Monoclonal Ab fragment - binds dabigatran, neutralized anticoagulant effect
Reverses dabigatran effects
99
Suffix for direct oral factor Xa inhibitors?
-Ban (banning the factor Xa fox)
100
Oral direct Xa inhibitors - MOA?
Selectively blocks Xa, preventing conversion of prothrombin to thrombin
101
Major disadvantage for oral direct Xa inhibitors?
No antidote
102
Rivaroxaban and Apixaban - caution in which population?
Liver disease
103
Edoxaban - caution in which population?
Liver disease AND renal insufficiency
104
Which oral Xa direct inhibitor is best for pregnancy?
Apixaban
105
Fibrinolytics - MOA?
Activates conversion of plasminogen to plasmin that hydrolyzes (cleaves) fibrin
106
What classes are co-administered along with fibrinolytics?
Antiplatelet
| Antithrombotic
107
Examples of two thrombolytic enzymes?
Streptokinase
| Urokinase
108
Examples of tissue plasminogen activators?
Alteplase
Reteplase
Tenecteplase
109
Which TPA’s are only for STEMI?
Reteplase
| Tenecteplase
110
Absolute contraindications for fibrinolytics? (Pneumonic - BD-HINT)
1. Bleeding (any active bleeding)
2. Dissection (aortic)
3. Hemorrhagic CVA (ever)
4. Ischemic CVA (< 3 months ago)
5. Neoplasm (cranial)
6. Trauma (head/face < 3 months ago)
111
Criteria for “massive” PE?
1. SBP < 90 x15 minutes
2. Loss of palpable pulse
3. Requiring inotropic support
112
Alteplase - use?
CVA, STEMI, PE
113
Cryoprecipitate - what is it, what is it used for?
Plasma protein from whole blood, containing clotting factors, used to treat acute bleeding problems
114
Prothrombin Complex Concentrate (PCC) - what is it, what is it used for?
Blood coagulation factors, used to reverse effects of the “-bans” (Xa inhibitors) (bc there’s no actual antidote for the -ban’s)
115
Tranexamic Acid - MOA?
Displaces plasminogen from fibrin, resulting in inhibition of fibronolysis (promotes clotting)
116
Tranexamic Acid - AE?
Severe thrombotic events
117
Trsanexamic acid - elimination?
Renal
118
Tranexamic acid - caution with pt’s with...?
1. Hx thrombotic events
| 2. Renal dysfunction
119
What are three essential nutrients for bone marrow hematopoiesis?
1. Iron
2. Vitamin B12
3. Folic Acid
120
What percentage of orally administered iron actually gets absorbed?
25%
121
Antidote for iron overdose?
Deferoxamine - iron-chelating agent
122
What is required in the stomach for B12 absorption?
Intrinsic factor
123
Hepatic stores of Vit-B12 can last how long?
Up to 5 years
124
Folate, Folic Acid, Vitamin B9 - required for...?
DNA synthesis
125
Pt’s that may need folic acid:
1. Pregnancy
2. Alcoholics
3. Hemolytic Anemia
4. Dialysis
126
Leucovorin?
Folic acid antagonist (OD)
127
Where is eryhtropoietin produced?
Renal peritubular cells
128
Epoetin Alfa and Darbapoetin Alfa - MOA and use?
Increase the rate of proliferation and differentiation of erythroid precursor cells in the bone marrow
Used for anemia of chronic renal failure, chemotherapy-induced anemia
129
Filgrastim and Sargramostim - MOA and use?
Colony stimulating factors that cause the production, maturation, and activation of neutrophils
Chemotherapy, leukemia, stem cell transplant
Sophomore - Pharm test 3
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