Anti-thrombotic Agents Flashcards
What are venous and arterial thrombi composed of?
Venous: mainly fibrin and RBC w/ little platelets
arterial: mainly platelets with little fibrin holding it together
What are the main uses of anticoagulant agents?
- Prevention and tx of venous thrombus
- prevention of cardioembolic events w/ Afib
- arterial thrombus additive w/ antiplatelet agents
What are the main uses of antiplatelet agents?
- prevention and tx of arterial thrombus (primary and secondary prevention of ACS)
What are the drugs of choice for primary and secondary ACS prevention
Primary: ASA (M over 45, F over 65)
Secondary (ie. recent Mi or ischemic stroke): ASA +/- clopidogrel (or clopidogrel if ASA intolerant)
What are the drugs of choice for UA/NSTEMI
ASA
+/- clopidogrel or prasugrel or ticagrelor
+/- UFH or LMWH or fondaprinux
+/- GPIIb/IIIa inhibitors
What are the drugs of choice for acute MI/STEMI
ASA
+ clopidogrel or prasugrel or ticagrelor
+ UFH or LMWH or fondaprinux
+/- GPIIb/IIIa inhibitors
What are the drugs of choice for PCI
ASA
+ clopidogrel or prasugrel or ticagrelor
+ UFH or LMWH or bivalirudin
+/- GPIIb/IIIa inhibitors
What are the drugs of choice for Afib
Warfarin or dabigatran or rivaroxaban or apixaban
ASA for low risk pts
What are the drugs of choice for VTE treatment
LMWH or UFH or fondaparinux + warfarin
What are the drugs of choice for VTE prevention for:
pts hosptialized, general surgery, and orthopedic surgery
Hospitalized/ general surgery: ow dose UFH or LMWH or fondaparinux
ortho surg: Fondaparinux or rivaroxaban or dabigatran or LMWH or warfarin
What is the drug of choice for PAD
ASA (clopidogrel if ASA intolerant)
In patients with acute coronary syndrome (ACS), aspirin
reduces the incidence of myocardial infarction (MI) by __%
15-25%
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
B. Lansoprazole
D. Pantoprazole
E. Rabeprazole
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. Bleeding at arterial access sites
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
B. Has a more predictable anticoagulant response
Fondaparinux can be used for:
- Prophylaxis of deep vein thrombosis (DVT)
- Treatment of venous thromboembolism (VTE)
- UA/NSTEMI
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. 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
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
D. warfarin
What drugs accelerates the conversion of plasminogen to plasmin?
*Tissue plasminogen activators (fibrinolytics)
Reteplase
Alteplase
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
E. Reversible inhibition of platelet GPIIb/IIIa receptors
Describe the mechanism of blood coagulation:
- damage to vessel exposes collagen of subendothelium
- vessels constrict to reduce blood loss
- adhesion and aggregation of platelets to damaged endothelium
- activation of platelets causes release of aggregating substances for more platelet adhesion and aggregation creating a thrombus plug
- aggregated platelets provide surface for fibrin deposition and coagulation
- Blood flow returns to normal when fibrinolysis occurs and clot is digested by enzymes from plasma (plasmin)
Blood vessel constriction during the mechanism of blood coagulation is mediated by ___ released by___
Vasoactive substances released by platelets (5HT, TXA2)
*pro-aggregatory substanes that increase expression of GIIb/IIIa receptors
Adhesion of platelets to damaged endothelium. and Aggregate (with other platelets): Biochemical reaction involving ___ and ___ that activates platelets upon adhesion
collagen of endothelial wall and von Willebrand factor
Describe the coagulation cascade of the intrinsic and extrinsic pathways
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
___ catalyzes prothrombin (II) –> thrombin (IIa)
___ catalyzes fibrinogen (I)–> fibrin (Ia)
Xa
thrombin (IIa)
How do you monitor lab values for the extrinsic and intrinsic clotting pathways
Intrinsic: aPTT
Extrinsic: PT/INR (1972 WEPT)
MOA of warfarin
- inhibits liver synthesis of vitamin K dependent factors: 10, 9, 7, 2
(1972 WEPT) - inhibits synthesis of protein C
2= prothrombin
*delayed onset (hrs-todays)
MOA of heparin/UFH
combines/binds w/ ATIII to inactivate IIa (thrombin) and Xa
*prevents prothrombin to thrombin and fibrinogen to fibrin
MOA of LMWH/Fondaparinux
Enoxaparin/Dalteparin
combines/binds w/ ATIII to inactivate Xa
*prevents fibrinogen to fibrin
MOA of dabigatran
directly inactivates IIa (thrombin)
*prevents activity of thrombin
MOA of Rivaroxaban and Apixaban
Direly inactivates Xa
What anticoagulants can be administered PO
Warfarin, dabigatran, rivaroxaban, apixaban
*dabigatran is a prodrug
(the heparins are parental)
What the brand names of: Dabigatran Rivaroxaban Apixaban Enoxaparin
Dabigatran: Pradaxa
Rivaroxaban: Xarelto
Apixaban: Eliquis
Enoxaparin: Lovenox
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
What monitoring lab tests are needed for:
- Heparin/UFH:
- LMWH/Enoxaparin:
- Warfarin:
- Dabigatran
- Rivaroxaban and Apixaban:
- Heparin/UFH: aPTT (activated partial thromboplastin time)
- LMWH/enoxaparin: NONE- action predictable
- Warfarin: PT/INR
- Dabigatran: no routine monitoring– could use DDT to assess management of bleeding episode or ECT (expensive)
- Rivaroxaban and Apixaban: no routine monitoring
Adverse side effects of Heparin/UFH
- bleeding
- thrombocytopenia
- Osteoporosis w/ LT heparin use
Adverse side effects of LMWH/Enoxaparin
- bleeding
- thrombocytopenia (less than UFH)
- Osteoporosis w/ LT heparin use
Adverse side effects of Warfarin
- bleeding
- skin necrosis
- contraindicated in pregnancy
- osteoporosis
Adverse side effects of Dabigatran
- bleeding
2. gastritis symptoms
Adverse side effects of Rivaroxaban
- bleeding
2. hard to reverse
What anti-coagulants are safe in pregnancy?
- heparin/UFH
- LMWH/Enoxaparin
[D]-[R]-[A] are not studied yet and category C
**WARFARIN IS NOT SAFE! (X)