Immunosuppressant Drugs Flashcards
Why are immunosuppressant drugs used?
Used to treat autoimmunity and prevent transplant rejection.
How does Prednisolone work?
Causes sequester of immune cells in the spleen and bone marrow, prevent PMN adherence, inhibit chemotaxis, interferes with antigen processing, and inhibits activation of NFkB.
What drug is Metabolized into 6-Mercaptopurine?
Azathioprine
How does Azathioprine work as a cytotoxic agent?
Can be used at low dose to prevent immune response killing the proliferating immune cells or can be used as a high dose to kill cancer cells.
What is the mechanism of action of Azathioprine?
Converted to 6-Mercaptopurine, inhibits purine biosynthesis by inhibiting both De Novo and Salvage pathway. Prevents production of GMP and AMP.
What is a major side effect of Azathioprine?
There is a certain percent of the population that have a deficiency breaking down 6MP, which causes excessive inhibition and major bone marrow suppression.
What is the mechanism of Cyclophosphamide and for what is it primarily used?
Alkylating agent that covalently bonds to DNA preventing transcription. Most prominent effect on B-cells, so is used to suppress humoral immunity/prevent antibody production.
What drug inhibits Dihydrofolate Reductase and the production of thymine for DNA?
Methotrexate
What drug inhibits IMP Dehydrogenase and selectively inhibits lymphocytes?
Mycophenolate Mofetil, 2nd generation. Lymphocytes don’t have salvage pathway, so they are selectively inhibited.
What is the pathway of action for Cyclosporin?
Binds to Cyclophilin, which then inhibits Calcineurin from activating NFAT transciption factor (produces IL2 for proliferation) Used to treat rejection of transplant. Nephrotoxicity big side effect.
What drug has the same mechanism as Cyclosporin, but is more potent and less toxic?
Tacrolimus. Binds FK BP-12 that inhibits Calcineurin.
What drug specifically inhibits T-cell Proliferation?
Sirolimus. Binds to TK BP-12, which binds mTOR inhibiting progression of the cell cycle downstream of IL-2.
