Therapeutics - Transplant 2

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kyleannkelsey
ID:
300296
Filename:
Therapeutics - Transplant 2
Updated:
2015-04-08 18:14:26
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Therapeutics Transplant
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Therapeutics - Transplant
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  1. What is the MOA of Cyclosporine?
    • Reversible inhibition of T helper cells activation and proliferation by inhibition of IL-2
    • Minimal inhibition of B cells, No inhibition of macrophages and neutrophils
  2. T cell inhibition by cyclosporine is dependent on what factors?
    Time and Dose
  3. What place in therapy is Cyclosporine used?
    • Not used for acute rejection
    • Maintenance therapy only
  4. What are the pharmacokinetics of Sandimmune (cyclosporine) specifically?
    • Lipophilic – oil in water
    • Bile needed for absorption
    • F is variable
    • Food delays absorption
  5. What are the pharmacokinetics of Neoral (cyclosporine) specifically?
    • F = consistent
    • Bile and food DO NOT effect absorption
    • Cmax is higher and earlier than with Sandimmune
  6. What are the pharmacokinetics of Cyclosporine (generally)?
    • Highly lipid soluble = accumulates in skin, organs and fat
    • Vd = 3-5L (large)
    • Use IBW or AdjBW
    • Highly protein bound
    • Enterohepatic recycling
    • Use whole blood assays to measure drug levels
    • CYP3A4 & pgp metabolism (>30 metabolites)
    • Age effects metabolism
  7. What are the dosing/admin concerns for Cyclosporine?
    • IV: 2-6 mg/kg QD over 2-6 hrs
    • IV:PO = 1:3
    • Use glass or non-PVC bag (to avoid carcinogenic thiolate esters)
    • Use Nitroglycerin tubing to prevent binding
    • Sandimmune = 5-15 mg/kg divided BID PO
    • Neoral or Gengraf = 2-10mg/kg divided BID PO
  8. How should you instruct a patient to use Cyclosporine Oral (Sandimmune or Neoral)?
    • Mix in beverage of choice (bad taste)
    • Use glass cup
    • Opened bottle is good for 2 months
    • Take same time each day
    • Avoid exposure to hot or cold
    • Refill 1 week before out
    • Take an extra bottle when traveling
  9. What monitoring should be performed for Cyclosporine?
    • Trough = 100-400 ng/mL, higher at first, lower with time, goals vary by transplant type
    • Daily levels right after first dose and while titrating
  10. How does Tacrolimus (FK506) compare to Cyclosporine (CsA)?
    • Similar immunosuppression
    • Better studied in liver transplant
    • 100 more potent than CsA (= lower dose)
  11. What are the pharmacokinetics of Tacrolimus (FK506)?
    • F = erratic
    • NO bile required for absorption
    • Highly lipophilic
    • 99% protein bound
    • CYP3A4 metabolism
  12. What are the dosing/admin concerns for Tacrolimus (FK506)?
    • IV = 0.03-0.1 mg/kg QD continuous
    • Oral = 1-20 mg PO QD, start 0.1 mg/kg/D
    • Mix in glass or non-PVC
    • Use IBW or AdjBW for oral dosing
    • 0.5, 1 and 5 mg capsules
    • IV:PO = 1:3
    • Prograf = BID
    • Astragraf XL = QD
  13. What should you monitor for Tacrolimus (FK506)?
    • 5-20 ng/mL
    • Higher conc at first then lower
    • Draw QD or 3x week during initiation and titration
  14. What are the AE of Tacrolimus (FK506)?
    • Nephrotoxicity
    • Hepatotoxicity
    • CNS: tremor, paresthesia, seizures, mental status changes
  15. How does Tacrolimus AEs compare to Cyclosporine?
    • Nephrotoxicity = similar
    • Hepatotoxicity = Cholestasis similar to CsA
    • CNS = higher incidence than CsA
  16. What are the signs that nephrotoxicity is induced by a Calcineurin Inhibitor?
    • > 6 weeks postop
    • No fever
    • Graft is non-tender
    • Adequate urine output
    • Gradual rise in SCr
  17. What are the signs that Nephrotoxicity is due to an acute graft rejection?
    • <4 weeks postop
    • Fever
    • Graft tenderness
    • Decreased urine output
    • Rapid rise in SCr
  18. How should HTN caused by a Calcineurin inhibitor be treated?
    • CCB
    • AVOID: ACEI or ARB
  19. Is Tacrolimus (FK506) or Cyclosporine (CsA) more likely to cause HTN?
    CsA
  20. Is Tacrolimus (FK506) or Cyclosporine (CsA) more likely to cause HYPERglycemia?
    • FK
    • May require insulin thereafter

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