MCQ Quiz: Pharmacology of Antiplatelet Therapy

Platelets play a pivotal role in hemostasis and thrombosis. Antiplatelet therapy is a cornerstone in the prevention and management of arterial thrombotic disorders, including acute coronary syndromes, ischemic stroke, and peripheral artery disease. These agents interfere with various stages of platelet activation and aggregation. For PharmD students, a comprehensive understanding of the pharmacology of diverse antiplatelet drugs—their mechanisms of action, pharmacokinetic and pharmacodynamic profiles, clinical indications, adverse effects, and important drug interactions—is essential for ensuring optimal and safe patient care. This MCQ quiz will assess your knowledge of the pharmacological principles governing these critical medications.

1. Aspirin exerts its primary antiplatelet effect by irreversibly inhibiting which enzyme in platelets?

• A. Phosphodiesterase-3 (PDE3)
• B. Cyclooxygenase-1 (COX-1)
• C. Lipoxygenase
• D. P2Y12 ADP receptor

Answer: B. Cyclooxygenase-1 (COX-1)

2. The inhibition of COX-1 by aspirin leads to a decreased synthesis of which potent platelet activator and vasoconstrictor?

• A. Prostacyclin (PGI2)
• B. Thromboxane A2 (TXA2)
• C. Leukotriene B4
• D. Adenosine diphosphate (ADP)

Answer: B. Thromboxane A2 (TXA2)

3. Clopidogrel, prasugrel, and ticlopidine belong to which class of P2Y12 inhibitors?

• A. Direct-acting reversible inhibitors
• B. Thienopyridine prodrugs (irreversible inhibitors)
• C. Glycoprotein IIb/IIIa receptor antagonists
• D. Phosphodiesterase inhibitors

Answer: B. Thienopyridine prodrugs (irreversible inhibitors)

4. Clopidogrel requires metabolic activation to its active thiol metabolite, primarily through which cytochrome P450 enzyme?

• A. CYP3A4
• B. CYP1A2
• C. CYP2C19
• D. CYP2D6

Answer: C. CYP2C19

5. Which P2Y12 inhibitor is a direct-acting, orally administered, reversible antagonist of the P2Y12 receptor?

• A. Clopidogrel
• B. Prasugrel
• C. Ticagrelor
• D. Ticlopidine

Answer: C. Ticagrelor

6. Glycoprotein IIb/IIIa receptor inhibitors (e.g., abciximab, eptifibatide, tirofiban) exert their potent antiplatelet effect by:

• A. Preventing ADP binding to its receptor.
• B. Blocking the final common pathway of platelet aggregation by preventing fibrinogen from cross-linking platelets.
• C. Inhibiting thromboxane A2 synthesis.
• D. Increasing intracellular cAMP levels in platelets.

Answer: B. Blocking the final common pathway of platelet aggregation by preventing fibrinogen from cross-linking platelets.

7. Abciximab is a Glycoprotein IIb/IIIa inhibitor that is a:

• A. Synthetic peptide
• B. Non-peptide small molecule
• C. Monoclonal antibody Fab fragment
• D. Thienopyridine

Answer: C. Monoclonal antibody Fab fragment

8. Dipyridamole is an antiplatelet agent that is thought to work through multiple mechanisms, including:

• A. Irreversible COX-1 inhibition
• B. Inhibition of phosphodiesterase (increasing cAMP) and inhibition of adenosine uptake
• C. Direct P2Y12 receptor blockade
• D. Activation of Protein C

Answer: B. Inhibition of phosphodiesterase (increasing cAMP) and inhibition of adenosine uptake

9. Cilostazol is a phosphodiesterase-3 (PDE3) inhibitor primarily indicated for the management of:

• A. Acute coronary syndromes
• B. Prevention of stroke in atrial fibrillation
• C. Intermittent claudication in peripheral artery disease
• D. Deep vein thrombosis

Answer: C. Intermittent claudication in peripheral artery disease

10. Vorapaxar is an antiplatelet agent that acts by antagonizing which receptor on platelets?

• A. P2Y12 ADP receptor
• B. Thromboxane A2 receptor
• C. Protease-Activated Receptor-1 (PAR-1), the major thrombin receptor on platelets
• D. Glycoprotein Ib receptor

Answer: C. Protease-Activated Receptor-1 (PAR-1), the major thrombin receptor on platelets

11. Which of the following is a common and potentially serious adverse effect of aspirin therapy?

• A. Hyperkalemia
• B. Gastrointestinal ulceration and bleeding
• C. Thrombocytopenia
• D. QT prolongation

Answer: B. Gastrointestinal ulceration and bleeding

12. Prasugrel generally offers more potent and consistent P2Y12 inhibition than clopidogrel but carries a higher risk of:

• A. Dyspnea
• B. Bleeding, particularly in certain patient populations (e.g., history of stroke/TIA, low body weight, elderly)
• C. Neutropenia
• D. Liver injury

Answer: B. Bleeding, particularly in certain patient populations (e.g., history of stroke/TIA, low body weight, elderly)

13. A unique, non-bleeding side effect sometimes associated with ticagrelor is:

• A. Tinnitus
• B. Dyspnea (shortness of breath)
• C. Metallic taste
• D. Peripheral edema

Answer: B. Dyspnea (shortness of breath)

14. “Dual Antiplatelet Therapy” (DAPT) most commonly refers to the combination of aspirin and:

• A. Warfarin
• B. A P2Y12 inhibitor
• C. A Glycoprotein IIb/IIIa inhibitor
• D. Heparin

Answer: B. A P2Y12 inhibitor

15. The duration of effect of aspirin’s antiplatelet action persists for the lifespan of the platelet (7-10 days) because:

• A. Aspirin has a very long plasma half-life.
• B. It causes irreversible acetylation of COX-1, and platelets cannot synthesize new enzyme.
• C. Aspirin is recycled in the enterohepatic circulation.
• D. It forms a reversible complex with COX-1.

Answer: B. It causes irreversible acetylation of COX-1, and platelets cannot synthesize new enzyme.

16. Ticlopidine, an older thienopyridine, has largely been replaced by clopidogrel and newer agents due to a higher risk of severe hematological adverse effects, including:

• A. Hemolytic anemia
• B. Neutropenia/agranulocytosis and thrombotic thrombocytopenic purpura (TTP)
• C. Polycythemia
• D. Eosinophilia

Answer: B. Neutropenia/agranulocytosis and thrombotic thrombocytopenic purpura (TTP)

17. Cangrelor is an intravenous P2Y12 inhibitor with a rapid onset and offset of action. This makes it suitable for:

• A. Long-term outpatient management of stable IHD.
• B. Use during percutaneous coronary intervention (PCI) as a bridge or when rapid platelet inhibition is needed.
• C. Primary prevention in low-risk individuals.
• D. Reversing the effects of oral P2Y12 inhibitors.

Answer: B. Use during percutaneous coronary intervention (PCI) as a bridge or when rapid platelet inhibition is needed.

18. Eptifibatide and tirofiban are Glycoprotein IIb/IIIa inhibitors that are:

• A. Monoclonal antibodies
• B. Irreversible inhibitors
• C. Synthetic peptides or non-peptide mimetics that reversibly bind the receptor
• D. Orally active agents

Answer: C. Synthetic peptides or non-peptide mimetics that reversibly bind the receptor

19. The main therapeutic use of Glycoprotein IIb/IIIa inhibitors is in:

• A. Prophylaxis of deep vein thrombosis
• B. High-risk patients undergoing PCI or those with certain acute coronary syndromes
• C. Management of intermittent claudication
• D. Long-term secondary prevention after stroke

Answer: B. High-risk patients undergoing PCI or those with certain acute coronary syndromes

20. A significant pharmacogenetic consideration for clopidogrel involves polymorphisms in the CYP2C19 gene, where poor metabolizers may experience:

• A. Increased risk of bleeding due to enhanced activation
• B. Reduced conversion to the active metabolite, leading to diminished antiplatelet effect and higher risk of thrombotic events
• C. No change in clinical outcomes
• D. Increased incidence of dyspnea

Answer: B. Reduced conversion to the active metabolite, leading to diminished antiplatelet effect and higher risk of thrombotic events

21. Which of the following antiplatelet agents acts by inhibiting the uptake of adenosine by cells, thereby increasing local adenosine concentrations which can inhibit platelet function?

• A. Aspirin
• B. Clopidogrel
• C. Dipyridamole
• D. Abciximab

Answer: C. Dipyridamole

22. Cilostazol’s mechanism of action, inhibition of PDE3, leads to an increase in intracellular ________ in platelets, which inhibits platelet aggregation.

• A. Thromboxane A2
• B. Cyclic AMP (cAMP)
• C. Calcium
• D. ADP

Answer: B. Cyclic AMP (cAMP)

23. Vorapaxar is generally used in combination with aspirin and/or clopidogrel for secondary prevention in patients with a history of MI or PAD because:

• A. It is a potent vasodilator.
• B. It targets a distinct pathway of platelet activation (thrombin-mediated via PAR-1).
• C. It has intrinsic fibrinolytic activity.
• D. It reverses the effect of aspirin.

Answer: B. It targets a distinct pathway of platelet activation (thrombin-mediated via PAR-1).

24. A major limitation and risk associated with vorapaxar therapy is:

• A. Severe neutropenia
• B. Significant risk of bleeding, including intracranial hemorrhage, and it’s contraindicated in patients with a history of stroke/TIA.
• C. QT prolongation
• D. Development of drug tolerance

Answer: B. Significant risk of bleeding, including intracranial hemorrhage, and it’s contraindicated in patients with a history of stroke/TIA.

25. The loading dose regimen for P2Y12 inhibitors in ACS is crucial for:

• A. Minimizing gastrointestinal side effects
• B. Achieving rapid and effective platelet inhibition at the onset of treatment
• C. Slowly titrating to the maintenance dose over several days
• D. Assessing for allergic reactions before committing to long-term therapy

Answer: B. Achieving rapid and effective platelet inhibition at the onset of treatment

26. The “offset” of antiplatelet effect (time for platelet function to recover after discontinuation) is longest for which type of P2Y12 inhibitor?

• A. Reversible inhibitors like ticagrelor
• B. Irreversible inhibitors like clopidogrel and prasugrel
• C. Intravenous inhibitors like cangrelor
• D. All P2Y12 inhibitors have the same offset time

Answer: B. Irreversible inhibitors like clopidogrel and prasugrel (due to irreversible binding for the life of the platelet).

27. Which antiplatelet drug is contraindicated in patients with active pathological bleeding, such as peptic ulcer or intracranial hemorrhage?

• A. Only aspirin
• B. Only clopidogrel
• C. Only ticagrelor
• D. Virtually all antiplatelet agents

Answer: D. Virtually all antiplatelet agents

28. The combination of aspirin and extended-release dipyridamole is approved for:

• A. Management of acute MI
• B. Secondary prevention of ischemic stroke or TIA
• C. Treatment of intermittent claudication
• D. Prophylaxis of DVT

Answer: B. Secondary prevention of ischemic stroke or TIA

29. How does ticagrelor differ from clopidogrel in terms of metabolic activation?

• A. Ticagrelor is a prodrug requiring two-step hepatic activation.
• B. Ticagrelor is an orally active drug that does not require metabolic activation for its antiplatelet effect.
• C. Ticagrelor is activated by renal enzymes.
• D. Both are activated by the same CYP2C19 pathway.

Answer: B. Ticagrelor is an orally active drug that does not require metabolic activation for its antiplatelet effect.

30. The antiplatelet effect of aspirin at low doses (e.g., 81-325 mg daily) is primarily due to inhibition of COX-1 in:

• A. Endothelial cells, reducing prostacyclin synthesis
• B. Platelets, reducing thromboxane A2 synthesis
• C. Both platelets and endothelial cells equally
• D. Leukocytes, reducing inflammation

Answer: B. Platelets, reducing thromboxane A2 synthesis

31. Prasugrel’s metabolic activation is more efficient and less dependent on CYP2C19 polymorphisms compared to clopidogrel, generally leading to:

• A. Slower onset of action
• B. More predictable and potent antiplatelet response
• C. Lower risk of bleeding
• D. Reversible platelet inhibition

Answer: B. More predictable and potent antiplatelet response

32. A common strategy for managing patients on DAPT who require elective surgery with a high bleeding risk is to:

• A. Continue both agents without interruption.
• B. Temporarily discontinue one or both agents (balancing thrombotic vs. bleeding risk), often with specific timing recommendations based on the agent.
• C. Add a third antiplatelet agent for bridging.
• D. Reverse the antiplatelet effects with protamine sulfate.

Answer: B. Temporarily discontinue one or both agents (balancing thrombotic vs. bleeding risk), often with specific timing recommendations based on the agent.

33. Platelet function testing (e.g., VerifyNow) can be used to assess:

• A. The degree of anticoagulation by warfarin.
• B. The level of platelet inhibition in patients receiving antiplatelet therapy, particularly P2Y12 inhibitors.
• C. The risk of developing HIT.
• D. The concentration of fibrinogen in the blood.

Answer: B. The level of platelet inhibition in patients receiving antiplatelet therapy, particularly P2Y12 inhibitors.

34. Which Glycoprotein IIb/IIIa inhibitor has the longest duration of action and potential for prolonged platelet inhibition even after discontinuation due to its antibody nature?

• A. Eptifibatide
• B. Tirofiban
• C. Abciximab
• D. Aspirin

Answer: C. Abciximab

35. The primary advantage of using P2Y12 inhibitors over aspirin monotherapy in certain high-risk cardiovascular settings (e.g., post-ACS, post-stent) is:

• A. Lower cost
• B. Reduced incidence of GI bleeding
• C. Greater reduction in ischemic events when used in combination with aspirin (DAPT) or as an alternative if aspirin intolerant
• D. No risk of bleeding

Answer: C. Greater reduction in ischemic events when used in combination with aspirin (DAPT) or as an alternative if aspirin intolerant

36. What is the main mechanism by which cilostazol improves symptoms of intermittent claudication?

• A. By directly dissolving atherosclerotic plaques
• B. Through vasodilation and inhibition of platelet aggregation, improving blood flow to extremities
• C. By lowering LDL cholesterol
• D. By increasing blood viscosity

Answer: B. Through vasodilation and inhibition of platelet aggregation, improving blood flow to extremities