Immunosuppressive Drugs Flashcards
IL-12
acts on Th1 to release IFN-gamma, IL-2, TNF for pro-inflammatory mediators
IL-4
acts on Th2 cells to release IL-4 for autoantibody production
IL-6
acts on Th17 to release IL-17, IL-21, TNF for pro-inflammatory/regulatory factors
sirolimus mechanism
binds FKBP which inhibits mTOR, inhibiting protein synthesis, cell proliferation, growth factor receptors
mycophenolate mechanism
inhibits IMPDH to prevent purine synthesis
NF-AT effector genes
cytokines; IL-2, IL-6
NF-KB effector genes
receptors; IL-2, IL-12
STAT effector genes
other proteins; MHC antigens, adhesion molecules, etc.
cyclosporin/tacrolimus mechanism
inhibit FKBP/calcineurin pathway which prevents NFAT from allowing T cell proliferation and inhibits IL-2 production
induction therapy
pre-operative infusion of antibodies against T-cell antigens to inhibit function and deplete T cell numbers; valuable for delayed graft function
monoclonal antibodies for induction therapy
bind to IL-2 receptor
daclizumab, basiliximab
bind to IL-2 receptor (CD25) and inhibit signaling and decrease T cell numbers; induction therapy
alemtuzumab
bind to T-cell antigen CD52 for T cell depletion; induction therapy
major side effects of antibodies used in induction therapy
anaphylaxis and infections, anti-monoclonal antibodies, cytokine release syndrome
maintenance therapy
glucocorticoids + calcineurin inhibitors + mycophenolate or glucocorticoids + sirolimus + mycophenolate
glucocorticoids
affect cell proliferation and lymphocyte recirculation, reduce Ig levels, affect chemotaxis via IkB
glucorticoid side effects
moon face, adrenal suppression, hyperglycemia, ulcers, fluid retention, increased infections, weight gain, emotional stuff, osteoporosis
cyclosporin/tacrolimus side effects
nephrotoxicity, hypertension, hepatotoxicity, neurotoxicity, GI effects, behavioral disturbances
mycophenolate side effects
metabolic disturbances, leukopenia, infection; higher incidence of reaction in hep C transplants
azathioprine
better for hepatitis C transplants; blocks purine synthesis
azathioprine side effects
bone marrow suppression, leukopenia, thrombocytopenia, GI/liver toxicity, nausea, infections
sirolimus
best at inhibiting secondary immune response by inhibiting response to IL-2 and growth factors
sirolimus side effects
hyperlipidemia, thrombocytopenia, bone marrow depression, anemia, infection
methotrexate mechanism
inhibits dihydrofolate reductase and cell proliferation
