Immunomodulators Flashcards
Glucocorticoids: MOA
Activates the glucocorticoid receptor transcription factor Modifies expression of cytokine and other immunoregulatory genes Suppresses active immune responses
Glucocorticoids: Indications
Immunosuppression To Prevent graft rejection To prevent GvHD Treatment of Cytokine-release Syndrome Treatment of a wide variety of autoimmune and inflammatory diseases
Glucocorticoids: adv.
Many Adverse effects Hyperglycemia Hypertension Hyperlipidemia Obesity Diabetes Poor wound healing Mania & Psychosis Inc. Risk infections
How to discontinue GC’s
Glucocorticoid dose must be gradually reduced to minimize adverse effects
Azathioprine: MOA
Prodrug Converted to 6-MP by HGPRT Inhibits de novo purine synthesis Incorporated into DNA & causes SSB base mispairing, leading to apoptosis Inhibits CD28 co-stimulation
Indications for azathioprine, mycophenolate
mofetil, and calcineurin inhibitors
Immunosuppression To Prevent graft rejection To prevent GvHD Treatment of autoimmune diseases
Azathioprine: adverse effects
Leukopenia/thrombocytopenia
Hepatotoxicity
Inc. Risk infections and malignancy
Notable interactions for azathioprine
Interacts with anti-gout drugs (Allopurinol &; Febuxostat), leading to Azathioprine toxicity, because inhibiting xanthine oxidase leads to increased levels of 6-mercaptopurine as well
Mycophenolate Mofetil: MOA
Prodrug
Converted to mycophenolic acid
Inhibits inosine monophosphate
dehydrogenase II (IMPDH2
- selectively expressed in lymphocytes, leading to Inhibition of purine nucleotide synthesis
- no salvage pathway in lymphocytes
Mycophenolate Mofetil: adv effects
Leukopenia/anemia
Teratogenic for both male and female
Inc. Risk infections, malignancy
***RARE- Risk of Progressive multifocal leukoencepalopathy (PML), a fatal viral disease caused by reactivation of JC virus
Mycophenolate Mofetil: counterindications
Men and women who wish to become parents
Calcineurin inhibitors: tacrolimus and cyclosporine, MOA
Cyclosporin and tacrolimus bind
cyclophilin and FKBP, respectively
to form inhibitory complexes
Cyclophilin/cyclosporin and
FKBP/tacrolimis complexes inhibit the
calcium-regulated phosphatase, calcineurin
Inhibition of calcineurin inhibits the activation
of the NFAT transcription factor, which is involved
in regulating the expression of IL-2 and multiple
other immunoregulatory genes
Potently inhibit the T cell immune response by
inhibiting Signal 1
Calcineurin inhibitors: adverse effects
Nephrotoxicity****
Hypertension***
Calcineurin inhibitors: Interactions
Metabolized by CYP3A4
3A4 inhibitors inc. risk of toxicity
3A4 inducers inc. risk of risk graft rejection
mTor inhibitors: sirolimus, everolimus, MOA
Drugs form complex with FBKP
FKBP/drug complexs inhibits:
IL-2 mediated activation of mTor kinase
(T cell signal 2)
IL-2 stimulated protein synthesis,
Cell proliferation and survival