Antiplatelets and Anticoagulants Overview
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Questions and Answers

What are the contraindications of Apixaban?

  • Conditions with significant risk of bleeding, gastrointestinal ulceration, malignant neoplasms with high risk of bleeding, and oesophageal varices (correct)
  • Anaemia and haemorrhage
  • Elderly patients with severe hypertension
  • All of the above

    • What is the mechanism of action of Heparin?

  • Inhibits the coagulation cascade by activating anti-thrombin 3 (ATIII) (correct)
  • Activates clotting factors IX, Xa, XI and XII
  • Inhibits the production of platelets
  • Increases the risk of bleeding

    • What are the main differences between Heparin and Low Molecular Weight Heparin (LMWHs)?

  • LMWHs have more consistent activity and a longer duration of action than Heparin (correct)
  • Heparin is primarily used to treat deep vein thrombosis, while LMWHs are used to prevent stroke
  • Heparin is administered orally, while LMWHs are administered intravenously or subcutaneously
  • LMWHs have a shorter half-life than Heparin

    • Which of the following is NOT a type of Low Molecular Weight Heparin (LMWH)?

    <p>Warfarin (B)</p> Signup and view all the answers

    Which of the following drugs is a direct thrombin inhibitor used to prevent stroke and DVT?

    <p>Dabigatran etexilate (C)</p> Signup and view all the answers

    What is the significance of Heparin's short half-life?

    <p>Heparin requires frequent administration (C)</p> Signup and view all the answers

    What is the reversal agent for Apixaban, edoxaban and rivaroxaban?

    <p>Andexanet alfa (B)</p> Signup and view all the answers

    Which of the following drugs is a vitamin K antagonist?

    <p>Warfarin (A)</p> Signup and view all the answers

    Which of the following drugs is used to prevent venous thromboembolism (VTE) following surgery?

    <p>Apixaban (B)</p> Signup and view all the answers

    Which of the following drugs inhibits both factor Xa and thrombin?

    <p>Heparin (C)</p> Signup and view all the answers

    Which of the following is NOT a factor inhibited by Warfarin?

    <p>Factor XIIa (A)</p> Signup and view all the answers

    In the case of a proximal deep vein thrombosis (DVT) or pulmonary embolism (PE), which drug is the first-line treatment?

    <p>Apixaban (B)</p> Signup and view all the answers

    What is the mechanism of action of Rivaroxaban?

    <p>Inhibition of factor Xa (D)</p> Signup and view all the answers

    Flashcards

    Apixaban Side Effects

    Anaemia and haemorrhage are common side effects of Apixaban.

    Apixaban Contraindications

    Apixaban should be avoided in conditions like major bleeding risks and oesophageal varices.

    STOPP Criteria

    The STOPP criteria signal that Apixaban is inappropriate for elderly patients due to bleeding risk.

    Heparin Mechanism of Action

    Heparin inhibits the coagulation cascade by activating anti-thrombin 3 (ATIII).

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    Low Molecular Weight Heparin

    LMWHs inactivate factor Xa and thrombin while enhancing anti-thrombin III activity.

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    Anticoagulants

    Drugs that prevent thrombus formation by targeting clotting factors.

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    Antiplatelet drugs

    Medications that inhibit platelet aggregation, like Aspirin.

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    Fibrinolytic agents

    Drugs used to break down fibrin in clots, such as Alteplase.

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    Selective factor Xa inhibitors

    Anticoagulants like Apixaban that specifically inhibit factor Xa.

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    Dabigatran

    A direct thrombin inhibitor used to prevent clotting.

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    Heparin

    An anticoagulant that inhibits multiple coagulation factors, including thrombin.

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    Vitamin K antagonists

    Anticoagulants like Warfarin that inhibit vitamin K-dependent factors.

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    DOACs

    Direct-acting oral anticoagulants like Apixaban and Dabigatran.

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    Study Notes

    Antiplatelets and Anticoagulants

    • Drugs are used to prevent or reverse thrombus formation
    • Classified into 3 groups:
      • Anticoagulants:
        • Factor Xa inhibitors
        • Anti-thrombins
        • Heparin
        • Vitamin K antagonists
      • Anti-platelet drugs:
        • Aspirin: Inhibits COX-1 activity, inhibiting platelet aggregation
      • Fibrinolytic agents:
        • Alteplase: Breaks down fibrin

    Classes of Anticoagulants

    • Selective factor Xa inhibitors:
      • Apixaban
    • Direct thrombin inhibitors:
      • Dabigatran
    • Heparin and low molecular weight heparins
    • Vitamin K antagonists:
      • Warfarin

    Venous Thromboembolism

    • For confirmed proximal DVT or PE, use apixaban/rivaroxaban
    • If the above are contraindicated, use LMWHs, followed by dabigatran or edoxaban, or LMWHs with vitamin K antagonists (Warfarin) until INR is achieved or with vitamin K antagonist alone.
    • Use in patients undergoing surgery with thrombosis risk (thromboprophylaxis - NICE guidelines)

    Anti-coagulant cascade

    • Apixaban inhibits factor Xa
    • Dabigatran inhibits factor 2a (thrombin)
    • Heparin inhibits XIIa, Xla, IXa, Xa, and thrombin
    • LMWH inhibits Xa
    • Warfarin inhibits VIIa, Xa, IXa, and thrombin

    Direct-acting oral anticoagulants (DOACs)

    • Dabigatran etexilate: Reversible thrombin inhibitor (Idarucizumab is a reversal agent)
    • Apixaban, edoxaban, and rivaroxaban: Reversible activated factor X (Xa) inhibitors (Andexanet alfa reversal agent prevents thrombin generation)
    • Used to prevent strokes and secondary prevention of DVT or PE, and venous thromboembolism following surgery
    • Other use for Apixaban/Rivaroxaban to prevent arterial thrombosis, stroke and myocardial infarction.

    Contraindications and side-effects of Apixaban

    • Side effects: Anaemia and haemorrhage
    • Contraindicated in conditions with significant risk of bleeding (gastrointestinal ulceration, malignant neoplasms with high bleeding risk, oesophageal varices)
    • Not appropriate for elderly patients (STOPP criteria, significant risk of bleeding e.g. severe hypertension)

    What is the pharmacodynamics of Heparin?

    • Heparin is a family of sulphated mucopolysaccharides (long sugar chains) found in mast cell secretory granules
    • Can range in molecular weight from 3,000 to 30,000 Daltons
    • Mechanism of action: Activates antithrombin 3 (ATIII), inhibiting the coagulation cascade
    • ATIII is a natural inhibitor of thrombin and clotting factors IX, Xa, XI

    Low Molecular Weight Heparin (LMWH's)

    • Dalteparin sodium, Enoxaparin sodium, and Tinzaparin sodium
    • Fragments of synthetic heparin with consistent activity.
    • Inactivate factor Xa, thrombin, and activate antithrombin III.
    • Immediate onset, given intravenously or subcutaneously. Heparin has shorter half-life (low/high doses) than LMWHs.
    • Heparin-induced thrombocytopenia is less common with LMWHs.

    Warfarin

    • Vitamin K antagonist; inhibits activation of vitamin K-dependent clotting factors (II, VII, IX, X)
    • Requires administration with INR monitoring due to its narrow therapeutic window.
    • Absorbed rapidly from the GI tract, peaks in 0.5-4 hours.
    • Metabolic termination by CYP450 enzymes (CYP2C9, 2C19, 3A4)
    • Excreted in urine and faeces.
    • Side Effects: Haemorrhage or skin necrosis.

    Antiplatelet drugs

    • Platelets form the initial haemostatic plug for vascular injury, and their inhibition is essential
    • Aspirin irreversibly binds to COX-1, inhibiting TXA2 synthesis; lasts for the entire platelet lifecycle.
    • Used to prevent arterial thrombosis like transient ischemic attack (TIA), stroke, and myocardial infarction.
    • Other antiplatelet drugs include: Ticlopidine, Clopidogrel, and Prasugrel to inhibit ADP-mediated aggregation.

    Fibrinolytic/Thrombolytic drugs

    • Streptokinase and alteplase are thrombolytic and fibrinolytic drugs; potentiate fibrinolytic system by converting plasminogen to plasmin.
    • Plasmin breaks down fibrin, dissolving clots. 
    • Given intravenously, immediate effect, short half-lives (<10-90 minutes); major hazard is bleeding (dissolving normal clots).
    • Used for clot-related issues like restoring catheter function/shunts, and occlusion of blood vessels/hollow organs.

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    Description

    This quiz covers the essential aspects of antiplatelet and anticoagulant drugs, including their classifications, mechanisms, and usage in treating conditions like venous thromboembolism. Test your knowledge on the different types of anticoagulants, their specific indications, and the role of antiplatelet agents in thrombus prevention.

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