Drugs and the Immune System Flashcards
Two pro-inflammatory mediators that corticosteroids inhibit
IL-1 and IFNg
What does azathioprine do?
It is a prodrug which inhibits purine and DNA synthesis
What is cyclophosphamide used to treat, what are toxic side effects, and how does it work?
Treats SLE, Wegners Granulomatosis, and Autoimmune Hemolytic anemia. Toxicity is pancytopenia, hemorrhagic cystitis. Alkylates and cross-links DNA, interfering with DNA synthesis.
Toxic effects of mycophenolate mofetil (MMF)
Leukopenia, GI disturbances, CMV infections
Four drugs that produce generalized immunosuppression
Corticosteroids, azathioprine, cyclophosphamide, and MMF
Three drugs that produce selective inhibition of lymphocytes
Cyclosporine, Tacrolimus, Sirolimus
How does cyclosporine work?
Binds cyclophilin and thus inhibits activation of calcineurin, which activates NFAT, leading to T-cell activation (and IL-2 production). Thus, cyclosporine inhibits T-cell activation
What is cyclosporin used to treat and what are the toxic effects?
Used in transplant pts to prevent rejection, also autoimmune diseases. Can cause nephrotoxicity, neurotoxicity, hyperlipidemia, and hypertension (also metabolized by CYP 3A4, so has drug-drugs)
How does tacrolimus work?
Binds FK binding protein (FKBP), preventing calcineurin activation, which activates NFAT, leading to T-cell activation (and IL-2 production) . Thus, tacrolimus inhibits T-cell activation
What is tacrolimus used to treat and what are its toxic effects?
Used to avoid transplant rejection, also autoimmune diseases. Nephrotoxicity, neurotoxicity, hypertension, hyperglycemia, diabetes (esp with steroids). Also metabolized by CYP 3A4, so has drug-drug interactions
How does Sirolimus work?
Binds FK binding protein (FKBP), like tacrolimus, but this complex inhibits mTOR (which regulates cell cycle in T cells)
What is sirolimus used to treat and what are its toxic effects?
Used with tacrolimus or cyclosporine to prevent graft rejection. Associated with increases in cholesterol and triglycerides. Also metabolized by CYP 3A4, so may have drug-drug ints
Two toxicities from antibody treatments
HAMA reaction and serum sickness (depends on source and type of Abs)
ATG and ALG and what they do?
Antithymocyte and Antilymphocyte globulin, bind to T cells
What are ATG and ALG used for and what are their toxic effects?
Organ transplantation, graft rejection. Toxicities are serum sickness and glomerulonephritis (Type III hypersensitivity rxns)