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Immunosuppressants

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Sirolimus (Rapamycin)

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Summary

Sirolimus, also known as Rapamycin, is an immunosuppressant drug used to prevent transplant rejection and treat certain autoimmune conditions. Sirolimus binds FK506-binding protein (FKBP) to form a complex that goes on to inhibit mTOR. Blocking mTOR inhibits the growth and proliferation of T- and B-cells, which gives rise to immunosuppression. Clinically, sirolimus is part of the renal transplant regimen, since it is less nephrotoxic than other immunosuppressants. Notable side effects include hyperlipidemia, bone marrow suppression, and diabetes (hyperglycemia).

Key Points

  • Sirolimus (Rapamycin)
    • Immunosuppressant drug
      • Used in transplant rejection prophylaxis, drug-eluting stents (DES), lymphangioleiomyomatosis 
    • Mechanism
      • Inhibits mTOR by complexing with FK506-binding protein (FKBP)
        • mTOR stands for mammalian Target Of Rapamycin
      • Blocks proliferation of all lymphocytes (e.g. T cells, B cells)
        • mTOR involved in cell cycle and proliferation of lymphocytes
    • Adverse Effects
      • Bone marrow suppression (myelosuppression)
        • may result in pancytopenia (anemia, thrombocytopenia, leukopenia)
        • mTOR signaling involved in proliferation of marrow stem cells
      • Diabetes (hyperglycemia)
      • Hyperlipidemia
      • Note: not nephrotoxic (contrast vs. Cyclosporine and Tacrolimus)
        • Important because often used in renal transplant patients