1. What is azathioprine?
    • Old immunomodulator
    • High toxicities prevent long-term use
  2. What is Cyclosporine?
    • Calcineurin Inhibitor
    • Inhibit IL-2 --> CD4 & CD8 T-cells
    • High affinity to cyclophilin
  3. What's the metabolism of Cyclosporine?
    Hepatic CYP3A4 metabolism
  4. What's the therapeutic uses/toxicity of Cyclosporine?
    • Uses: transplants, autoimmune disorders
    • Toxicities: Nephro, neuro, Acute Tubular Necrosis, Lymphomas
  5. What is Calcineurin?
    Dephosphorylation of NFAT --> IL-2 activation
  6. What's the difference between acute/chronic toxicities of cyclosporin A?
    • Acute - reversable
    • Chronic - irreversible
  7. What's the absorption of Cyclosporin A?
    • Oral; different for various people (measure!!)
  8. What's Tacrolimus?
    • Potent Calcineurin Inhibitor
    • less nephrotoxicity
  9. What's the MoA of tacrolimus?
    Binding to FKBP-12 --> calcineurin inhibition
  10. What are metabolisl considerations of tacrolimus?
    Shorter half-life than cyclosporine; 2x daily
  11. What's the clinical use of tacrolimus?
    • Prophylaxis after transplans
    • Graft rejection Tx
  12. What is sirolimus?
    Cell Proliferation Inhibitor
  13. What's the MoA of sirolimus?
    • Bind to FKBP-12 --> inhibit mTOR
    • Lack of response to growth stimulator signals
  14. What are uses for sirolimus?
    • Prevent acute regection
    • prevent neointimal proliferation following stent placement in coronary arteries
  15. What's mycophenolate mofetil?
    • Prodrug
    • Inhibitor of inosine monophosphate dehydrogenase
    • Prevent de novo purine biosynthesis
  16. What are clinical uses for mycophenolate mofetil?
    Renal & heart transplants
  17. What are daclizumab & basiliximab
    • Monoclonal Abs
    • Bind to a-chain at IL-2 receptor
  18. What toxicity is associated with basiliximab?
  19. What's Muromonab?
    • Monoclonal Ab
    • Block ε chain of T cell CD3
  20. What's the use of Muromonab?
    Reverse rejection of heart, liver, kidney rejection
  21. What's MoA of abatacept?
    • Bind to CD80 & CD86
    • Prevent CD28 T-Cell activation
  22. What's the MoA of leflunomide?
    Inhibition of dihydroorotate -> pyrimidine biosynthesis
  23. What's the clinical use of leflunomide?
    Active RA
  24. What are toxicities of leflunomide?
    Diarrhea, nausea, hepatotoxicity
  25. What's the clinical use of Thalidomide?
    erythema nodosum leprosum
  26. What are toxicities of thalidomide?
    • Peripheral neuropathy
  27. What's the MoA of infliximab?
    • Ab against TNFa
    • Chron's, UC, RA, Psoriasis
  28. What are toxicities of infliximab?
    Increased infection (TB, HBV reactivation)
  29. What's the MoA of etanercept?
    Recombinant TNF receptor to soak up free TNF
  30. What are uses of etanercept?
    RA, ankylosing spondylitis, psoriasis
  31. What are toxicities of etanercept?
    Demyelinating diseases
  32. What's the MoA of natalizumab?
    • Ab against antibody against α4β1-integrin
    • Inhibit lymphocyte migration
  33. What's the use of natalizumab?
    Crohn's, MS
  34. What's an associated risk from Natalizumab?
    JC virus induced PML
  35. What's the MoA of Azathiprine?
    • Purine analog used to interupt de novo purine synthesis
    • Combination therapy of RA --> leukopenia
  36. What's the MOA of Fingolimod?
    • Block migration of lymphocytes from LN
    • Tx: MS
  37. What's the MoA of glatiramer?
    • Mix of AAs similar to myelin basic protein
    • Tx: MS
  38. What's the MoA of Lymphocyte Immune Globulin?
    • Ab to T-cell surface antigens
    • Block cell surface receptors
    • Direct cytotoxicity
  39. What's the MoA of Immune globulin?
    Human IgG to replace Abs in immune deficiencies
  40. What's the MoA of Anakinura?
    • IL-1 receptor antagonist
    • Tx: RA
    • SE: bacterial infection
  41. What's the Use of IFN-b?
  42. What's epoetin alfa?
    • EPO analogue
    • Stimulate RBC synthesis in anemic pts
  43. What's darbepoetin alfa?
    EPO analogue with longer half life
  44. What's the risk with EPO analogues?
    • Cancer - stimulate tumor cell proliferation
    • Renal Failure - CVA
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