Antiproliferatives/antimetabolites

• azathioprine
  

  • has been used for longer than the other antiproliferative agents—40, 50 years

  • mercaptopurine analog; inhibits purine synthesis and decreases cell proliferation

  • formerly used in conjunction with prednisone for solid organ transplants; also used for rheumatoid arthritis

  • no longer a first-line drug for organ transplants

  • major side effect = bone marrow suppression (white cells > red cells > platelets)

• Mycophenolate mofetil
  

  • newer drug; is a prodrug

  • metabolized to mycophenolic acid, the active drug

  • inhibits inosine monophosphate dehydrogenase, part of guanine nucleotide synthesis

  • in B and T cells, there is no salvage pathway for guanine nucleotides. this is why mcophenolate mofetil is relatively selective as an immunosuppressive

  • decreases lymphocyte proliferation

  • used to prevent organ transplant rejection in conjunction with glucocorticoids and calcineurin inhibitors

  • cardinal side effects: diarrhea, bone marrow suppression

• Sirolimus

  • isolated from a handful of dirt from Easter Island

  • binds to FKBP-12; blocks mTOR (mammalian target of rapamycin), a kinase that promotes the cell cycle

  • this blocks the effects of IL-2

  • so you can use it in conjunction with calcineurin inhibitors as a double-whammy against lymphocytes

  • also, spares the side effects of calcineurin inhibitors, including nephrotoxicity

  • cardinal side effect = bone marrow suppression

Category: Medical Subject Notes , Pathology Notes