(4.5) ANTIPLATELET DRUGS (HARD QUIZ)
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Questions and Answers

Which of the following components play a role in platelet plug formation?

  • Antithrombin III
  • Protein C
  • Thrombin
  • PDE (correct)

    • What is the role of arachidonic acid in platelet activation?

  • Inhibits platelet aggregation
  • Precursor for TxA2 synthesis (correct)
  • Decreases intracellular calcium concentration
  • Stabilizes platelet membranes

    • Which of the following antiplatelet drugs primarily acts by inhibiting the P2Y12 receptor?

  • Aspirin
  • Glycoprotein IIb/IIIa inhibitors
  • Clopidogrel (correct)
  • Dabigatran

    • What is the inhibition mechanism of action for aspirin in antiplatelet therapy?

    <p>Irreversibly inhibits cyclooxygenase-1</p> Signup and view all the answers

    Which of the following best describes the function of glycoprotein IIb/IIIa on platelets?

    <p>Mediates platelet aggregation by binding to fibrinogen</p> Signup and view all the answers

    What is a significant adverse event associated with clopidogrel therapy?

    <p>Gastrointestinal bleeding</p> Signup and view all the answers

    Which metabolic pathway is clinically significant for the activation of clopidogrel?

    <p>P450 enzymatic pathway</p> Signup and view all the answers

    The structure of the active metabolite of clopidogrel is primarily derived from which substance?

    <p>Thiomethyl derivative</p> Signup and view all the answers

    Which of the following factors does NOT directly influence platelet activation?

    <p>Carbon dioxide levels</p> Signup and view all the answers

    Which antiplatelet agent works primarily by inhibiting the glycoprotein IIb/IIIa receptor?

    <p>Abciximab</p> Signup and view all the answers

    What is the primary abnormality associated with hemostasis?

    <p>Thrombosis</p> Signup and view all the answers

    Which type of thrombus is primarily associated with myocardial infarction?

    <p>Platelet-rich clots</p> Signup and view all the answers

    What are the three main steps in the formation of a hemostatic plug?

    <p>Adhesion, Granule Release, Aggregation &amp; Consolidation</p> Signup and view all the answers

    Which two molecular interactions are essential for platelet adhesion?

    <p>Von Willebrand Factor and Platelet Glycoprotein VI</p> Signup and view all the answers

    What role does von Willebrand Factor (vWF) play in hemostasis?

    <p>Facilitates platelet adhesion</p> Signup and view all the answers

    What is a characteristic feature of red thrombus?

    <p>Rich in fibrin</p> Signup and view all the answers

    Which condition is primarily linked with cardioembolic strokes?

    <p>Atrial fibrillation</p> Signup and view all the answers

    What is the effect of activated platelets on von Willebrand Factor?

    <p>Release of vWF</p> Signup and view all the answers

    Which thrombosis is associated with the risk of pulmonary embolism?

    <p>Deep vein thrombosis</p> Signup and view all the answers

    Which interaction is particularly important for platelet Glycoprotein VI?

    <p>Interaction with collagen</p> Signup and view all the answers

    What is the mechanism by which aspirin reduces platelet activation?

    <p>It inhibits the synthesis of thromboxane A2 by irreversibly acetylating COX-1.</p> Signup and view all the answers

    What is the primary role of phospholipase A2 (PLA2) in platelet activation?

    <p>To liberate arachidonic acid and activate glycoprotein IIb/IIIa</p> Signup and view all the answers

    Which antiplatelet drug is classified as an irreversible P2Y12 blocker?

    <p>Clopidogrel</p> Signup and view all the answers

    Which of the following best describes the action of vorapaxar?

    <p>It targets thrombin-mediated platelet activation through PAR-1.</p> Signup and view all the answers

    Which of the following antiplatelet agents irreversibly inhibits the ADP receptor?

    <p>Clopidogrel</p> Signup and view all the answers

    Which drugs act by blocking the final common pathway of platelet aggregation?

    <p>Abciximab and tirofiban</p> Signup and view all the answers

    What is the mechanism of action of aspirin in the context of antiplatelet therapy?

    <p>Decreasing thromboxane A2 production via acetylation of COX-1</p> Signup and view all the answers

    What unique property differentiates ticagrelor from other P2Y12 blockers?

    <p>It acts as a reversible inhibitor.</p> Signup and view all the answers

    What is a common adverse effect of P2Y12 receptor inhibitors?

    <p>Risk of treatment failure in CYP2C19 poor metabolizers</p> Signup and view all the answers

    Which dosage form is common for GPIIb/IIIa inhibitors like Abciximab?

    <p>Intravenous bolus followed by infusion</p> Signup and view all the answers

    Which receptor does ticlopidine specifically target to exert its antiplatelet effects?

    <p>P2Y12 ADP receptor</p> Signup and view all the answers

    What is the result of reduced thromboxane A2 release in the context of platelet activity?

    <p>Decreased platelet activation</p> Signup and view all the answers

    Cilostazol primarily functions by inhibiting which enzyme?

    <p>Phosphodiesterase-3 (PDE3)</p> Signup and view all the answers

    Which statement about thromboxane A2 is true?

    <p>It is produced from arachidonic acid via COX-1.</p> Signup and view all the answers

    Which drug is a reversible inhibitor of P2Y12?

    <p>Cangrelor</p> Signup and view all the answers

    What role does eptifibatide play in platelet aggregation?

    <p>It obstructs fibrinogen and vWF binding to glycoprotein IIb/IIIa.</p> Signup and view all the answers

    What happens during platelet degranulation?

    <p>Numerous chemical mediators, including Ca2+ and vWF, are released.</p> Signup and view all the answers

    Which of the following correctly describes the route of action for antiplatelet drugs like abciximab?

    <p>They inhibit glycoprotein IIb/IIIa receptor binding.</p> Signup and view all the answers

    Which medication is an active drug that mimics adenosine?

    <p>Ticagrelor</p> Signup and view all the answers

    What is the primary indication for using GPIIb/IIIa inhibitors during percutaneous coronary intervention (PCI)?

    <p>As an alternative to P2Y12 inhibitors.</p> Signup and view all the answers

    Study Notes

    Lecture #28: Antiplatelet Pharmacology

    • Presenter: Brian Skinner, PharmD, BCPS
    • Affiliation: Associate Professor of Internal Medicine, Marian University - College of Osteopathic Medicine
    • Course: BMS 551 Med Phys Pharm
    • Year: Fall 2024

    Objectives

    • Describe platelet plug formation, identifying the roles of: cAMP, Ca²⁺, vWF, PLA₂, arachidonic acid, TxA₂, ADP, PKC, PKA, PDE
    • Identify the roles of platelet glycoproteins Ib, IIb/IIIa, and VI in platelet plug formation
    • Identify the mechanism of action, dosage forms, adverse events, indications, and contraindications of highlighted antiplatelet drugs
    • Describe the clinically significant metabolic pathway for clopidogrel
    • Identify the structure of the active metabolite of clopidogrel
    • Diagram arachidonic acid pathway relating to PGE₂, TxA₂, and leukotriene synthesis
    • Recommend appropriate pharmacotherapeutic strategies for simplified patient cases

    Drug Overview

    • COX Inhibitors: Aspirin
    • P2Y₁₂ Receptors Blockers: Clopidogrel, Prasugrel, Ticlopidine, Ticagrelor, Cangrelor
    • GP IIb/IIIa Inhibitors: Abciximab, Eptifibatide, Tirofiban
    • Phosphodiesterase Inhibitors: Cilostazol, Dipyridamole

    Hemostasis and Thrombosis

    • Hemostasis: The process of stopping blood flow
    • Thrombosis: The most common abnormality of hemostasis
    • Types of clots:
      • Platelet-rich (white thrombus): Myocardial Infarction (MI), Transient Ischemic Attacks (TIAs)
      • Fibrin-rich (red thrombus): Peripheral Arterial Clots, Cardioembolic strokes, Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE)

    Formation of a Hemostatic Plug

    • Three main steps: Adhesion, Granule Release, Aggregation & Consolidation

    Platelet Adhesion

    • vWF secreted by activated platelets and exposed collagen
    • vWF binds to Glycoprotein Ib on activated platelets
    • Platelet Glycoprotein VI (GPVI) expressed on platelet surface interacts with collagen (GPVI:collagen interaction)

    Granule Release

    • Numerous chemical mediators released in response to platelet activation
    • ADP, epinephrine, collagen activate phospholipase A₂ (PLA₂)
    • Arachidonic acid converted into thromboxane A₂ by cyclooxygenase-1 (COX-1)
    • ADP, Ca²⁺, ATP, serotonin, vWF, and platelet factor 4 released during degranulation

    Aggregation & Consolidation

    • Increased cytosolic calcium and activation of thromboxane A₂ and the GPIIb/IIIa receptors lead to further platelet activation
    • Thrombin, thromboxane A₂, ADP, and other mediators increase Ca²⁺ levels.

    COX-1 Inhibitors (Aspirin)

    • Mechanism: Irreversible inhibition of COX-1 enzyme via acetylation
    • Indications: Secondary prophylaxis following MI or stroke, prevention of thrombotic events
    • Adverse Effects: GI bleeding & ulcer formation, increased risk of asthma exacerbations

    P2Y₁₂ ADP Receptor Inhibitors (Clopidogrel, Ticagrelor)

    • Mechanism: Clopidogrel is a prodrug activated by CYP2C19, irreversibly binding to and inactivating the ADP receptor; Ticagrelor reversibly binds to the ADP receptor mimicking adenosine
    • Indications: Secondary prophylaxis following MI or stroke, prevention of thrombotic events during PCI
    • Adverse Effects: Bleeding

    GPIIb/IIIa Inhibitors (Abciximab, Eptifibatide, Tirofiban)

    • Mechanism: Monoclonal antibodies that reversibly bind to and inactivate GPIIb/IIIa preventing fibrinogen interaction and platelet aggregation
    • Indications: Prevention of thrombotic events during PCI as an alternative to P2Y12 inhibitors
    • Adverse Effects: Bleeding

    Phosphodiesterase Inhibitors (Cilostazol)

    • Mechanism: Inhibition of phosphodiesterase-3 (PDE3) leading to increased cAMP catabolism
    • Indications: Intermittent claudication
    • Adverse Effects: Bleeding, headache (cerebral vasodilation), contraindicated for heart failure

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    Med Phys Pharm L28 Antiplatelet Pharmacology (student) PDF

    Description

    This quiz focuses on the key concepts of antiplatelet pharmacology covered in Lecture #28 of the BMS 551 course. Students will explore platelet plug formation, the mechanisms of various antiplatelet drugs, and clinical implications related to their use. Prepare to navigate through essential pathways and recommend pharmacotherapeutic strategies based on case studies.

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