1 / 5

Immunosuppression (IS) 1954 – 2005

Immunosuppression (IS) 1954 – 2005. Malononitrilamides (FK778). Everolimus (RAD). Sirolimus (SRL). Mycophenolate mofetil (MMF). Leflunomide. Tacrolimus (Tac). FTY720. Cyclosporine A (CsA). Azathioprine (Aza). Steroids. OKT 3. CTLA4Ig. Campath1H. monoclonal antibodies.

galvin
Download Presentation

Immunosuppression (IS) 1954 – 2005

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Immunosuppression (IS) 1954 – 2005 Malononitrilamides (FK778) Everolimus (RAD) Sirolimus (SRL) Mycophenolate mofetil (MMF) Leflunomide Tacrolimus (Tac) FTY720 Cyclosporine A (CsA) Azathioprine (Aza) Steroids OKT 3 CTLA4Ig Campath1H monoclonal antibodies polyclonal antibodies TBI - radiation 1950 1960 1970 1980 1990 2000 2010

  2. Targets of different IS drugs Co-stimulatorySignal AntigenicSignal APC IL-2 receptor TCR DaclizumabBasiliximab m-TOR (SRL/ EVL) Ca2+ T-cell De novopurine synthesis CNIs IL-2 AZA P ActivatedCalcineurin MMF S G1 NFAT CellCycle Steroid NFAT M G2 + IL-2 gene promotor

  3. MMF - Mechanism of action • MMF selectively and reversibly inhibits IMPDH (B- and T-lymphocytes); it’s not incorporated into DNA • AZA blocks proliferation of all rapidly dividing cells in a non-selective way and is incorporated into DNA (mutagenic), explaining the adverse effects and limiting the doses needed for accurate immunosuppression

  4. MMF - Mechanism of action Inhibition of de novo purine synthesis dGTP DNA De novo pathway RNA dGDP IMPDH GTP GMP IMP PRPP Glycoprotein synthesis HGPRTase MPA MMF Salvage pathway Guanine

  5. MMF - Mechanism of action Dependence on de novo synthesis Dependence on major salvage pathway Erythroid precursors intestinal epithelial cells Promonocytes Lymphocytes Neurons

More Related