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Anti-thrombotic Agents Flashcards

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1
Q

What are venous and arterial thrombi composed of?

A

Venous: mainly fibrin and RBC w/ little platelets

arterial: mainly platelets with little fibrin holding it together

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2
Q

What are the main uses of anticoagulant agents?

A
  1. Prevention and tx of venous thrombus
  2. prevention of cardioembolic events w/ Afib
  3. arterial thrombus additive w/ antiplatelet agents
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3
Q

What are the main uses of antiplatelet agents?

A
  1. prevention and tx of arterial thrombus (primary and secondary prevention of ACS)
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4
Q

What are the drugs of choice for primary and secondary ACS prevention

A

Primary: ASA (M over 45, F over 65)

Secondary (ie. recent Mi or ischemic stroke): ASA +/- clopidogrel (or clopidogrel if ASA intolerant)

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5
Q

What are the drugs of choice for UA/NSTEMI

A

ASA
+/- clopidogrel or prasugrel or ticagrelor
+/- UFH or LMWH or fondaprinux
+/- GPIIb/IIIa inhibitors

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6
Q

What are the drugs of choice for acute MI/STEMI

A

ASA
+ clopidogrel or prasugrel or ticagrelor
+ UFH or LMWH or fondaprinux
+/- GPIIb/IIIa inhibitors

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7
Q

What are the drugs of choice for PCI

A

ASA
+ clopidogrel or prasugrel or ticagrelor
+ UFH or LMWH or bivalirudin
+/- GPIIb/IIIa inhibitors

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8
Q

What are the drugs of choice for Afib

A

Warfarin or dabigatran or rivaroxaban or apixaban

ASA for low risk pts

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9
Q

What are the drugs of choice for VTE treatment

A

LMWH or UFH or fondaparinux + warfarin

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10
Q

What are the drugs of choice for VTE prevention for:

pts hosptialized, general surgery, and orthopedic surgery

A

Hospitalized/ general surgery: ow dose UFH or LMWH or fondaparinux

ortho surg: Fondaparinux or rivaroxaban or dabigatran or LMWH or warfarin

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11
Q

What is the drug of choice for PAD

A

ASA (clopidogrel if ASA intolerant)

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12
Q

In patients with acute coronary syndrome (ACS), aspirin

reduces the incidence of myocardial infarction (MI) by __%

A

15-25%

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13
Q 
A 70-year-old man taking clopidogrel for ACS has recently been diagnosed with erosive esophagitis and asks his physician which PPI he should take. Which of the following would be the most appropriate choice for this patient? 
A.  Esomeprazole 
B.  Lansoprazole 
C.  Omeprazole 
D.  Pantoprazole 
E.  Rabeprazole
A

B.  Lansoprazole
D.  Pantoprazole
E.  Rabeprazole

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14
Q 
The most common complication of  glycoprotein IIIa/IIb receptor antagonists is: 
A.  Bleeding at arterial access sites 
B.  Leukopenia 
C.  Intracranial hemorrhage 
D.  All of the above
A

A.  Bleeding at arterial access sites

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15
Q

Compared to unfractionated heparin (UFH), low-molecular weight heparin (LMWH):
A.  Is more likely to cause heparin-induced thrombocytopenia
B.  Has a more predictable anticoagulant response
C.  Is more completely neutralized by protamine
D.  May be safer in patients with renal impairment

A

B.  Has a more predictable anticoagulant response

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16
Q

Fondaparinux can be used for:

A
  1. Prophylaxis of deep vein thrombosis (DVT)
  2. Treatment of venous thromboembolism (VTE)
  3. UA/NSTEMI
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17
Q

A 55-year-old man with nonvalvular A-fib asks physician to recommend a treatment to reduce his risk of thromboembolic stroke. You could tell him that:
A.  Rivaroxaban is non-inferior to warfarin and does not require INR monitoring
B.  Apixaban is more effective than warfarin, but requires monitoring to keep the INR in the therapeutic range
C.  Dabigatran is more than warfarin and has an FDA approved antidote to reverse its anticoagulant effect
D.  All of the above

A

A.  Rivaroxaban is non-inferior to warfarin and does not require INR monitoring
C.  Dabigatran is more than warfarin and has an FDA approved antidote to reverse its anticoagulant effect

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18
Q 
Which of the following anticoagulants would be an appropriate choice for a patient with A-fib associated with a mechanical valve 
A.  Apixaban 
B.  Dabigatran 
C.  Rivaroxaban 
D.  Warfarin
A

D. warfarin

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19
Q

What drugs accelerates the conversion of plasminogen to plasmin?

A

*Tissue plasminogen activators (fibrinolytics)
Reteplase
Alteplase

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20
Q

If a patient undergoes a PCI with placement of a stent in a coronary blood vessel, she may be given eptifibatide. Which of the following most accurately describes the antithrombotic mechanism of eptifibatide?
A.  Activation of antithrombin III
B.  Block of posttranslational modification of clotting factors
C.  Inhibition of thromboxane production
D.  Irreversible inhibition of platelet ADP receptors
E.  Reversible inhibition of platelet GPIIb/IIIa receptors

A

E.  Reversible inhibition of platelet GPIIb/IIIa receptors

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21
Q

Describe the mechanism of blood coagulation:

A
  1. damage to vessel exposes collagen of subendothelium
  2. vessels constrict to reduce blood loss
  3. adhesion and aggregation of platelets to damaged endothelium
  4. activation of platelets causes release of aggregating substances for more platelet adhesion and aggregation creating a thrombus plug
  5. aggregated platelets provide surface for fibrin deposition and coagulation
  6. Blood flow returns to normal when fibrinolysis occurs and clot is digested by enzymes from plasma (plasmin)
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22
Q

Blood vessel constriction during the mechanism of blood coagulation is mediated by ___ released by___

A

Vasoactive substances released by platelets (5HT, TXA2)

*pro-aggregatory substanes that increase expression of GIIb/IIIa receptors

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23
Q

Adhesion of platelets to damaged endothelium. and Aggregate (with other platelets): Biochemical reaction involving ___ and ___ that activates platelets upon adhesion

A

collagen of endothelial wall and von Willebrand factor

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24
Q

Describe the coagulation cascade of the intrinsic and extrinsic pathways

A

Intrinsic TEN1021: surface contact–> 12–>11–> 9–> 10–> 2 (prothrombin)–> 1 (fibrinogen)
*In VIVO and formation of Xa w/in SECONDS

Extrinisic: Tissue factor–> 7–>10–>2–>1
*In VITRO and formation of Xa w/in MINUTES

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25
___ catalyzes prothrombin (II) --> thrombin (IIa) ___ catalyzes fibrinogen (I)--> fibrin (Ia)
Xa thrombin (IIa)
26
How do you monitor lab values for the extrinsic and intrinsic clotting pathways
Intrinsic: aPTT Extrinsic: PT/INR (1972 WEPT)
27
MOA of warfarin
1. inhibits liver synthesis of vitamin K dependent factors: 10, 9, 7, 2 (1972 WEPT) 2. inhibits synthesis of protein C 2= prothrombin *delayed onset (hrs-todays)
28
MOA of heparin/UFH
combines/binds w/ ATIII to inactivate IIa (thrombin) and Xa *prevents prothrombin to thrombin and fibrinogen to fibrin
29
MOA of LMWH/Fondaparinux | Enoxaparin/Dalteparin
combines/binds w/ ATIII to inactivate Xa *prevents fibrinogen to fibrin
30
MOA of dabigatran
directly inactivates IIa (thrombin) *prevents activity of thrombin
31
MOA of Rivaroxaban and Apixaban
Direly inactivates Xa
32
What anticoagulants can be administered PO
Warfarin, dabigatran, rivaroxaban, apixaban *dabigatran is a prodrug (the heparins are parental)
33
``` What the brand names of: Dabigatran Rivaroxaban Apixaban Enoxaparin ```
Dabigatran: Pradaxa Rivaroxaban: Xarelto Apixaban: Eliquis Enoxaparin: Lovenox
34
What anticoagulants are eliminated renal vs hepatic metabolism (CYP)
Renal: LMWH, Enoxaparin, dabigatran (BID) Hepatic: Warfarin, rivaroxaban, apixaban (BID) *best to use warfarin in renal impairment
35
What monitoring lab tests are needed for: 1. Heparin/UFH: 2. LMWH/Enoxaparin: 3. Warfarin: 4. Dabigatran 5. Rivaroxaban and Apixaban:
1. Heparin/UFH: aPTT (activated partial thromboplastin time) 2. LMWH/enoxaparin: NONE- action predictable 3. Warfarin: PT/INR 4. Dabigatran: no routine monitoring-- could use DDT to assess management of bleeding episode or ECT (expensive) 5. Rivaroxaban and Apixaban: no routine monitoring
36
Adverse side effects of Heparin/UFH
1. bleeding 2. thrombocytopenia 3. Osteoporosis w/ LT heparin use
37
Adverse side effects of LMWH/Enoxaparin
1. bleeding 2. thrombocytopenia (less than UFH) 3. Osteoporosis w/ LT heparin use
38
Adverse side effects of Warfarin
1. bleeding 2. skin necrosis 3. contraindicated in pregnancy 4. osteoporosis
39
Adverse side effects of Dabigatran
1. bleeding | 2. gastritis symptoms
40
Adverse side effects of Rivaroxaban
1. bleeding | 2. hard to reverse
41
What anti-coagulants are safe in pregnancy?
1. heparin/UFH 2. LMWH/Enoxaparin [D]-[R]-[A] are not studied yet and category C **WARFARIN IS NOT SAFE! (X)
42
__ increase the risk of bleeding with all anticoagulants
NSAIDs
43
DDI of warfarin
Increase effect w/: CYP450 inhibitors, Abx Decrease effect w/: CYP450 inducers, dietary Vit. K
44
DDI of [D]-[R]-[A]
Increase effect w/: P-glycoprotein inhibitors [R]: CYP3A4 inhibitors Decrease effect w/: P-glycoprotein inducers (rifampin, dronedarone)
45
DDI of haparin/UFH and LMWH
antiplatelet agents
46
OD treatment of haparin/UFH and LMWH
Protamine
47
OD treatment of wafarin
Phytonadione (Vit. K) -- FFP
48
OD treatment of dabigatran
Idarucizumab-- specific antidote for life threatening bleeding
49
OD treatment of rivaroxaban and apixaban
No specific antidote--> hemostatic measures: FFP, RBCs
50
Uses of haparin/UFH and LMWH
1. ACS 2. tx and prophylaxis of VTE +/- postop 3. prevent cerebral thrombosis in evolving stroke
51
Uses of Warfarin
1. Afib | 2. VTE prophylaxis w/ valvular heart dz or CKD
52
Uses of Dabigatran
1. Afib (FDA approved) | 2. VTE (non-FDA approved)
53
Uses of Rivaroxaban
1. Afib | 2. DVT-PE prevention after total hip or knee replacement
54
Uses of Apixaban
1. Afib
55
____ generally preferred over warfarin for nonvalvular A Fib
DOAC (direct oral anticoagulants) Ie. dabigatran, rivaroxaban, apixaban
56
___ and ___ reverse vasoconstriction and inhibit platelet aggregation
PGI2 (prostacyclin) and NO
57
Activated protein C with cofactor S inactivates __ and ___ which results in
Va and VIIIa diminishing rate of prothrombin and factor X activation
58
___ proteolyzes ___ and limits thrombosis
plasmin proteolyzes fibrin
59
the central process of fibrinolysis is activation of ____ by __
plasminogen to plasmin by tPA (tissue plasminogen activator)
60
Contraindications of heparin (UFH and LMWH)
1. hypersensitivity 2. active bleeding/ ulcerative GI lesions 3. hemophilia 4. thrombocytopenia 5. purpura 6. severe hypertension 7. bacterial endocarditis 8. Threaten abortion
61
Why is there a delay onset with warfarin
delayed as existing factors turn over (12-24 hrs)
62
What is the management when the INR with warfarin is: 1. Over therapeutic but less than 4.5 w/o bleeding: 2. INR 4.5-10 w/o bleeding: 3. over 10 w/o bleeding: 4. major bleeding:
1. Over therapeutic but less than 4.5 w/o bleeding: reduce or skip dose and monitor 2. INR 4.5-10 w/o bleeding: hold 1-2 doses, check, restart at lower dose once therapeutic 3. over 10 w/o bleeding: hold, administer Vit K po, resume at lower dose once therapeutic 4. major bleeding: hold, Vit K IV, PCC over FFP or recombinant factor VIIa
63
What are CYP450 inhibitors and what is there effect on Warfarin
increase warfarins effect: 1. Amiodarone 2. Cimetidine 3. Fluconazole 4. Fluoxetine 5. Metronidazole 6. Rosuvastatin
64
What are CYP450 inducers and what is there effect on Warfarin
decrease warfarins effect: 1. Barbiturates 2. Carbamazepine 3. Phenytoin 4. Rifampin 5. St. John's Wort 6. Cholestyramine 7. Colestipol * *Decrease absorption
65
Inhibitors of platelet thromboxane A2 synthesis
ASA
66
Antagonists of platelet ADP receptor (P2Y12)
1. Ticagrelor (Brilinta) 2. Clopidogrel (Plavix) 3. Prasugrel (Effient)
67
MOA of ASA
low dose (81mg) "selective" inhibition of platelet COX-1 (irreversible)
68
MOA of Ticagrelor, Clopidogrel, and Prasugrel (ADP antagonist)
inhibition of platelet ADP (P2Y12) receptor [C]-[P]: irreversible, prodrugs activated by CYP2C19 [T]- reversible
69
MOA of Dipyridamole (persantine)
inhibits phosphodiesterase in platelets--> increases cAMP--> increase PGI2 anti-aggregation effect
70
MOA of Abciximab, Eptifibatide, and Tirofiban (GIIb/IIIa inhibitors)
blocks platelet GIIb and IIIa receptor preventing fibrinogen binding and platelet aggregation [A]- monoclonal Ab [E]- cyclic peptide [T]- non-peptide
71
Inhibitors of platelet GIIb/IIIa receptors
1. Abciximab 2. Eptifibatide 3. Tirofiban
72
Describe the administration of the antiplatelet drugs (ASA, ADP antagonists, GIIb/IIIa inhibitors, dipyridamole)
1. ASA: PO, QD 2. [C]-[P]: PO, QD 3. [T]: BID 4. [A], [E], [T]: parenteral 5. D: PO
73
What antiplatelets are eliminated renally vs hepatic (ASA, ADP antagonists, GIIb/IIIa inhibitors, dipyridamole)
Renal: all GIIb/IIIa inhibitor and [C]- activated by CYP2C19 then renal and fecal excretion Hepatic: ASA, [P], [T], Dipyridamole
74
Adverse effects of ASA
1. Bleeding | 2. Gastric upset
75
Adverse effects of Clopidogrel
1. Bleeding 2. Dyspepsia 3. Gastritis 4. HA
76
Adverse effects of Ticagrelor
1. Bleeding 2. dyspnea 3. bradyarrhythmias
77
Adverse effects of Dipyridamole
1. Dizziness 2. HA 3. nausea 4. GI upset
78
Adverse effects of Abciximab, Eptifibatide, and Tirofiban (GIIb/IIIa inhibitors)
1. Bleeding
79
Compare the efficacy of Ticagrelor, Clopidogrel, and Prasugrel (ADP antagonist)
P-T>C *same pattern for bleeding risk
80
What pregnancy category are the antiplatelet drugs? | ASA, ADP antagonists, GIIb/IIIa inhibitors, dipyridamole
1. ASA: C/D (3rd) 2. [C]: B 3. [P]-[T]: C 4. Dipyridamole: B 5. [A]: C 6. [E]-[T]: B
81
DDI with ASA
1. increased bleeding risk w/ anti-coagulants
82
DDI with clopidogrel
1. PPIs may block activation of prodrug by CYP2C19 | * No DDI w/ [P] + PPIs
83
Uses of ASA
1. acute MI-unstable angina (ACS) | 2. PCI/ secondary prevention MI-stroke
84
Uses of Ticagrelor, Clopidogrel, and Prasugrel (ADP antagonist)
1. acute MI-unstable angina | 2. PCI
85
Uses of Dipyridamole
1. secondary prevention of MI-stroke
86
Uses of Abciximab, Eptifibatide, and Tirofiban (GIIb/IIIa inhibitors)
1. PCI
87
What are the drugs of choice for AMI/STEMI
ASA (chewed) + ADP antagonist
88
What are the drugs of choice for unstable angina/NSTEMI
ASA +/- ADP antagonist
89
What are the drugs of choice for PCI
ASA + ADP antagonist +/- GIIb/IIIa inhibitors
90
What are the drugs of choice for secondary prevention of MI
ASA (enteric coated) +/- dipyridamole
91
The risk of bleeding in patients receiving heparin is increased by aspirin because aspirin: A.  Inhibits heparin anticoagulant activity B.  Inhibits platelet function C.  Displaces heparin from plasma protein-binding sites D.  Inhibits prothrombin formation E.  Causes thrombocytopenia
B.  Inhibits platelet function
92
Examples of fibrinolytic drugs
1. Tissue plasminogen activators (alteplase, reteplase, tenecteplase) 2. Streptokinase 3. Urokinase
93
MOA of fibrinolytic drugs
rapid lysis of thrombi by increasing formation of plasmin from plasminogen --> generalized lytic state
94
Streptokinase activates _____ while tPA (and variants) activate ___ limiting induction of a systemic lytic state
both circulating (free) and fibrin-bound plasminogen bound plasminogen several hundredfold more rapidly than circulating plasminogen
95
Human tPA from recombinant DNA technology: tPA binds to fibrin and selectively activates bound plasminogen under physiological conditions (i.e., “clot-selective”, but therapeutic levels are 100 times higher)
Alteplase tPA
96
Newer, modified forms of tPA can be given as bolus and have prolonged duration of action.
Reteplase, Tenecteplase * Reteplase is less fibrin specific than tPA, while tenecteplase slightly more.
97
Reteplase is ___ fibrin specific than tPA, while tenecteplase slightly ___.
less more
98
Inactive by itself, but forms 1:1 complex with plasminogen (proactivator above), this complex then converts uncomplexed plasminogen to active plasmin. Generally results in systemic activation of plasmin.
Streptokinase *no longer used in US
99
Uses of fibrinolytic agents
1. AMI/PCI 2. DVT 3. Multiple PE
100
- Emergency treatment of coronary artery thrombosis; prompt use [within 2 hours] associated with better clinical outcomes - Further reduction in mortality with use of adjunctive drugs (beta-blockers, ACE inhibitors, aspirin)
fibrinolytic agents
101
Adverse effects of fibrinolytic agents
1. Hemorrhage (intracranial hemorrhage is most serious)
102
Fibrin-specificity: preferential activation of fibrin-bound vs circulating plasminogen
tPA over SK
103
What fibrinolytic agent has the highest risk of systemic bleeding and ICH risks
SK
104
Contraindications of fibrinolytic agents
1. Active PUD 2. underlying bleeding disorder 3. recent stroke 4. recovering from recent surgery

Pharmacology (31 decks)

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