2.13 Pharmacology of Anticoagulants

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xangxelax
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2.13 Pharmacology of Anticoagulants
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2014-01-18 09:42:20
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  1. What is the mechanism of action for heparin?
    • Antithrombin binds to and inactivates ACTIVATED clotting factors: XIIa, XIa, IXa, XA, and IIA (Thrombin)
    • Binds to antithrombin and speeds up these reactions
    • Increases activity of antithrombin 3 of 1000X
    • Inactivate, activating clotting factors
  2. What is the mechanism of action for warfarin?
    • Inhibits Vitamin K Oxide (epoxide) Reductase
    • Means decreased levels of Active Vitamin K
    • Means decreased levels of Vitamin K Dependent Clotting Factors II, VII, IX, X (also anticoagulant proteins C & S)
    • No effect on already synthesized clotting factors; so therapeutic effects not seen until these factors are depleted
    • 3-4 days until effect is seen
  3. What are the main adverse effects from heparin?
    • Bleeding
    • HIT (Heparin-induced thrombocytopenia) - Heparin binds to platelet factor 4. And body makes antibodies for it. Which binds to platelets.
    • 1. Removed by the spleen and drops platelet count. Outcome is Thrombocytopenia
    • 2. Platelet is activated and stimulates blood clotting. Outcome is Thrombosis
    • Cause of HIT is having a thromboembolic event
  4. What are the main adverse effects from warfarin?
    Warfarin Skin Necrosis - caused by depletion of Protein C by Warfarin
  5. What is the time to steady-state anticoagulant effects during a heparin IV infusion?
    6 Hours
  6. What is the time to steady-state anticoagulant effects during a oral warfarin regimen?
    6 Days
  7. How does warfarin have a pro-coagulant effect early in therapy?
    Decreases level of Protein C (Anticoagulant)
  8. What are the lab tests used to monitor and adjust doses for heparin?
    • UFH
    • Activated partial thromboplastin time (aPTT or PTT)
    • Anti-Factor Xa levels
  9. What are the lab tests used to monitor and adjust doses for warfarin?
    • Prothrombin Time (ProTime or PT) - measured in seconds
    • INR = International Normalized Ration
    • ISI = International Sensitivity Inde
  10. How do you reverse anticoagulation from heparin?
    Protamine
  11. How do you reverse anticoagulation from warfarin?
    • Targets:
    • 1. Vit K Dependent Clotting Factor (acts faster) - FFP (Fresh Frozen Plasma), NovoSeven (Recombinant Factor VIIa), PCC (Prothrombin Complex Concentrate)
    • 2. Active Vit K - Phytonadione
  12. Which anticoagulant is injectable?
    Heparin
  13. Which anticoagulant is orally taken?
    Warfarin
  14. What is the MOA of Fondaparinux?
    • Inactivates 10a
    • Fondaparinux = Heparin with 5 saccharides
  15. How many saccharides does Heparin need to bind to both thrombin and antithrombin?
    18 saccharides
  16. What is the MOA of Low Molecular Weight Heparin?
    • Primarily Xa reactions
    • Some IIa (Thrombin)
  17. Is Heparin or Warfarin safe to give during pregnancy?
    • Heparin is safe
    • Larger molecules so can't cross placenta
  18. What should you check during heparin therapy?
    Patient platelet count
  19. What is the treatment approach for deep vein thrombosis and/or pulmonary embolism?
    • IV infusion heparin immediately
    • Add oral warfarin
    • Stop heparin once therapeutic warfarin effect attained
    • Outpatient warfarin therapy
  20. Why do you sometimes give Heparin and Warfarin at the same time?
    • Warfarin has a slow onset
    • Warfarin initially drops level of Protein C; so give Heparin until Factors 2, 10 are depleted

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