DA4 Immunomodulation Part 1 UNFINISHED

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  1. The 3 types of drugs used to modulate the immune response are...
    • Immunosuppressants
    • Immunostimulators
    • Tolerance inducers
  2. What class of immunosuppressive drugs works by inhibiting gene expression?
  3. What 3 immunosuppressants are cytotoxic agents?
    • azathioprine
    • methotrexate
    • MPA (mycophenolic acid)
  4. What 3 agents are specific lymphocyte-signaling inhibitors?
    • CsA (cyclosporine A)
    • Tacrolimus
    • mTOR inhibitors (sirolimus, everolimus)
  5. What 3 classes of agents are immunosuppressive by their cytokine inhibition?
    • TNF-alpha inhibitors
    • IL-12 inhibitors
    • IL-1 inhibitors
  6. T/F Suppression of the immune system after organ transplant is specific and treatment lasts 2-4 weeks, also increases risks of infection and cancer
    F is nonspecific, lifelong treatment
  7. GC-receptor complexes ­ increase ______ expression, thereby curtailing activation of ____, which ­ increases apoptosis of
    activated cells
    • IkB
    • NFkB
  8. Which is not downregulated by glucocorticoids?
    IL-1, IL-2, IL-3, IL-4, IL-6, TNFalpha
  9. Decreased expression of ____ by glucocorticoids results in decreased proliferation and activation of T cells.
  10. glucocorticoids are used to block first-dose _____ ______ caused by treatment with muromonab-CD3
    cytokine storm
  11. What are some toxicities of glucocorticoids?
    • hyperglycemia (diabetogenic)
    • hypertension
    • risk of infection
    • osteopenia
    • growth retardation
  12. combination of glucocorticoids and ______ allows for reduced doses of steroids
  13. Azathioprine, a purine antimetabolite, is cleaved to _____ after nucleophile exposure, then converted to _____ by HGPRT, which inhibits IMPDH. It may also be converted to ______ which can cause DNA strand breaks
    • 6-MP
    • T-IMP
    • 6-TGMP
  14. How is azathioprine and 6-MP metabolized
    oxidation or methylation in the liver and/or erythrocytes
  15. What are some toxicities associated with azathioprine?
    • leukopenia
    • increased infections
    • hepatoxicity
  16. What are the uses for azathioprine
    • organ transplant rejection prevention
    • severe RA
  17. What is the MOA for methotrexate
    • DHFR inhibitor
    • Neu adhesion inhibitor
    • causes apoptosis of activated CD4 and CD8
  18. Azathiprione dose must be decreased while used concurrently with ______ because of an interaction
  19. What is the MOA of mycophenolate mofetil (MMF)?
    hydrolyzed to active drug mycophenolic acid (MPA), inhibits IMPDH (type 2), which inhibits guanosine formation, then inhibiting B and T lymphocyte proliferation
  20. T/F Plasma concentrations of MPA and MPAG are decreased in patients on MMF with renal insufficiency
    F -- increased
  21. What is MMFs therapeutic use
    prophylaxis of transplant rejection
  22. What are some toxicities associated with MMF
    • GI/hematologic toxicities
    • increased infections (sepsis from cytomegalovirus)
    • Viral infections when combined with tacrolimus (polyoma nephritis)
  23. _____ delays elimination of MMF by impairing the conversion of MPA to MPAG. This may enhance GI toxicity.
  24. These 2 antivirals compete with MPAG for tubular secretion, resulting in increased concentrations of both, especially in those with renal insufficiency
    acyclovir and ganciclovir
  25. What is the MOA for cyclosporine A?
    binds cyclophilin which blocks calcineurin, which blocks dephosphorylation of NFAT, blocking expression of IL-2 and T-cell growth
  26. What is the MOA for tacrolimus
    binds FKBP-12 which blocks calcineurin, which blocks dephosphorylation of NFAT, blocking expression of IL-2 and T-cell growth
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DA4 Immunomodulation Part 1 UNFINISHED
2012-04-07 14:47:05

Drug action 4 lecture from 3-12-12 Immunomodulation Part 1
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