Therapeutics - IP anticoagulation 1

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kyleannkelsey
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260922
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Therapeutics - IP anticoagulation 1
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2014-02-09 11:19:33
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Therapeutics IP anticoagulation
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Therapeutics - IP anticoagulation 1
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Therapeutics - IP anticoagulation 1
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  1. What types of anticoagulants are classified as “Direct” and do not require plasma co-factors for activity?
    Thrombin inactivating (Bivalirudin, Agatroban and Dabigatran) and Factor-Xa inactivating (Rivaroxaban and Apixaban)
  2. What anticoagulants are classified as “Indirect” acting and require plasma co-factors for activity?
    • Heparin
    • LMWHs (enoxaparin, tinazaparin and daltaparin)
    • Fondaparinux
  3. What are the pharmacodynamic and kinetic properties of Bivalirudin (Angiomax)?
    • Anti-thrombotic
    • Forms reversible/transient complex w/Thrombin
    • t1/2: 20-30 min
    • adjust dose for <30 CrCl
  4. What are the pharmacodynamic and kinetic properties of Argatroban?
    • Anti-Thrombotic
    • Non-covalent reversible complex with Thrombin
    • t1/2: 45 min
    • CYP3A4 metabolized
    • Incr. t1/2 in hepatic failure
  5. What are the pharmacodynamic and kinetic properties of Dabigatran (Pradaxa)?
    • Oral prodrug
    • Reversible binding to factor IIa
    • Oral/unaffected by food
    • F = 3-7%
    • PgP
    • t1/2: 12-17 hours ( 15-34h in renal impaired)
    • Cmax occurs at 1-6h
    • low protein binding/dialyzable
  6. What are the pharmacodynamic and kinetic properties of Rivaroxaban (Xarelto)?
    • Direct Xa inhibitor
    • F= 80%, take w/ food
    • can crush tabs
    • Cmax at 3h
    • metabolized by CYP3A4/5, CYP2J2 and Pgp
    • High protein binding
    • t1/2: 5-9h (elderly 11-19h)
  7. What are the pharmacodynamic and kinetic properties of Apixaban (Eliquis)?
    • Binds clotted or free Xa
    • F= 66%, w or w/o food
    • CYP3A4/PgP metabolized
    • Cmax at 3-4 hours
    • high protein binding
    • t1/2: 12h
  8. What types of anticoagulants are classified as “Direct” and do not require plasma co-factors for activity?
    Thrombin inactivating (Bivalirudin, Agatroban and Dabigatran) and Factor-Xa inactivating (Rivaroxaban and Apixaban)
  9. What anticoagulants are classified as “Indirect” acting and require plasma co-factors for activity?
    • Heparin
    • LMWHs (enoxaparin, tinazaparin and daltaparin)
    • Fondaparinux
  10. What are the pharmacodynamic and kinetic properties of Bivalirudin (Angiomax)?
    • Anti-thrombotic
    • Forms reversible/transient complex w/Thrombin
    • t1/2: 20-30 min
    • adjust dose for <30 CrCl
  11. What are the pharmacodynamic and kinetic properties of Argatroban?
    • Anti-Thrombotic
    • Non-covalent reversible complex with Thrombin
    • t1/2: 45 min
    • CYP3A4 metabolized
    • Incr. t1/2 in hepatic failure
  12. What are the pharmacodynamic and kinetic properties of Dabigatran (Pradaxa)?
    • Oral prodrug
    • Reversible binding to factor IIa
    • Oral/unaffected by food
    • F = 3-7%
    • PgP
    • t1/2: 12-17 hours ( 15-34h in renal impaired)
    • Cmax occurs at 1-6h
    • low protein binding/dialyzable
  13. What are the pharmacodynamic and kinetic properties of Rivaroxaban (Xarelto)?
    • Direct Xa inhibitor
    • F= 80%, take w/ food
    • can crush tabs
    • Cmax at 3h
    • metabolized by CYP3A4/5, CYP2J2 and Pgp
    • High protein binding
    • t1/2: 5-9h (elderly 11-19h)
  14. What are the pharmacodynamic and kinetic properties of Apixaban (Eliquis)?
    • Binds clotted or free Xa
    • F= 66%, w or w/o food
    • CYP3A4/PgP metabolized
    • Cmax at 3-4 hours
    • high protein binding
    • t1/2: 12h
  15. LMWH’s require monitoring under what circumstances?
    • Pregnancy, CrCl <30 mL/min
    • Obesity
    • <50 kg
    • tinzaparin and <30 CrCl
  16. What monitoring is required for Unfractionated Heparin?
    • aPPT q6h
    • Actual s differs between Institutions/reagents/coagulometer
    • Ideal: 0.3-0.7 U/mL of anti-Xa
  17. What is aPPT?
    Activated partial prothromin time
  18. When would you draw for an Anti-Xa assay for LMWHs and what results are ideal?
    • 4 hours after admin
    • BID 0.6-1 U/mL
    • QD: 1-2 U/mL
  19. Which does not require monitoring: Unfractionated heparin, LMWH or Fondaparinux?
    LMWH and Fondaparinux
  20. Which drug is it recommended that you don't monitor: Unfractionated heparin, LMWH or Fondaparinux?
    Fondaparinux
  21. How can you reverse the Anticoagulative effects of Unfractionated Heparin?
    • Protamine Sulfate
    • slow (10 min) IV infusion of 1mg for every 100U heparin given over last 2-3h
    • Slow admin = reduced bradycardi and hypotension
  22. When should you pretreat a patient with Corticosteroids or Antihistamines for 30 minutes prior to Protamine sulfate infusion?
    • If they have previously had:
    • Vasectomy
    • insulin with protaminw sulfate
    • fish allergy
  23. How can you reverse the Anticoagulative effects of LMWH?
    • If given w/in past 8h:
    • 1 mg per 100U LMWH (max 50mg)
    • if given more than 8h ago or bleeding continues give 0.5 mg/100U LMWH
  24. How can you reverse the Anticoagulative effects of Fondaparinux?
    Theory: Recombinant Factor 7a (pricey)
  25. Which Anticoagulants cannot be reversed using Protamine sulfate?
    • Fondaparinux
    • Rivaroxban
    • Apixaban
    • Dabigatrin
  26. How can you reverse the Anticoagulative effects of Rivaroxaban/Apixaban?
    • W/in a few hours of injection: can give Activated charcoal
    • Recombinant factor 7a (Theory)
  27. Are Rivaroxaban/Apixaban dialyzable?
    No
  28. How can you reverse the Anticoagulative effects of Dabigatrin?
    • Dialyzable
    • w/in a few hours of injection: can give Activated charcoal
    • Recombinant 7a (Theory)
    • RBC transfusion
    • Plasma
    • Surgical hemostasis
  29. What are the risk factors for HIT?
    • Bovine UFH>Porcine UFH>LMWH
    • Female>Male
    • Treatment>Prophylaxis>Flush
    • Post-surgical>Prophylactic.Pregnancy
    • 14d>7d>1d
  30. How does HIT present?
    • 30-50% (150,000) decreases in platelets 5-14d after beginning heparin
    • 3-5% have Hit after UFH is stopped
    • 25% thrombotic episode before HIT
    • injection site lesion
    • anaphylaxis after bolus
  31. What should you do if a patient develops HIT?
    Stop Heparin and give: Argatroban (1st choice), Fondaparinux (off label) or Bivalirudin
  32. How do you confirm a diagnosis of Hit?
    • C-serotonin assay
    • HIPA assay
    • Heparin PF-4 ELISA assay
  33. What is the dose you would give of Fondaparinux for prevention of VTE?
    10 mg PO QD starting 6-10h AFTER surgery
  34. What is the dose you would give of Fondaparinux for treatment of VTE?
    • 15 mg PO BID w/ food for 21 days
    • followed by:
    • 20 mg PO BID w/ food for remainder of treatment

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