Immunosuppressant Drugs Flashcards
What are the 4 main classes of immunosuppressants?
T cell suppressants
Antibody reagents
Cytotoxic drugs
Glucocorticoids
What are the 2 common pathways in T-cell inactivation for immunosuppression?
Protein kinase C –> AP1 –> cell nucleus
Calcineurin –> NFAT
What is the key signaling pathway for gene transcription in the T-cell model?
NFAT + AP1 leads to gene transcription.
Both factors must be present.
What 2 immunosuppressant drugs:
prevent the activation of NFAT
acts on calcineurin
Cyclosporine A
Tacrolimus (FK506)
What are significant side effects of calcineurin inhibitors such as Cyclosporine A, Tacrolimus? (3)
HTN
renal dysfunction
gingival hyperplasia
What is the new drug approach to immunosuppression?
NFAT inhibition w/out affect calcineurin activity to minimize side effects.
What new immunosuppressant drug:
mTOR inhibitor (mammalian target of r) blocks cytokine signaling in CD8
Sirolimus (rapamycin)
What drugs target calcineurin which affect the NFAT molecule?
Cyclophiline A
Tacrolimus
What drugs work on the immunophilin FKBP12?
Tacrolimus (FK506)
Sirolimus (Rapamycin)
What drug targets mTOR and affects p70s6 kinase?
Sirolimus (Rapamycin)
What antibody reagent:
depletes T-helper cells
used before organ transplant
kills cells at CD3 site
is a mouse monoclonal antibody
Muromonab CD3
What antibody reagent:
blocks cytokine signaling
is a genetically engineered reagent
is a humanized anti-IL2R antibody
Daclizumab (Zenapax)
What antibody reagent:
human IgG globulin
blocks formation of maternal antibody against Rh+ fetus
used in Rh- female during pregnancy and after birth to prevent hemolytic disease of the newborn
RhoGAM
What class of drugs:
used at lower doses than in cancer therapy
interfere with nucleic acid metabolism
prevent clonal expansion of T and B cells
cytotoxic drugs
What drug:
inhibits inosine monophosphate dehydrogenase (IMPDH)
Mycophenolate mofetil (MMF)
What drug:
Pro-drug: active metabolite is mycophenolic acid (MPA)
Mycophenolate mofetil (MMF)
What drug:
lymphocytes rely on de novo (from the beginning) pathway to greater extent than other cell types
Mycophenolate mofetil (MMF)
What drug:
prevents clonal expansion of immune cells
Mycophenolate mofetil (MMF)
What drug:
affects lymphocyte trafficking (anti- adhesion)
inhibit T cell proliferation
inhibit function of macrophages and lymphocytes
Glucocorticoids: Prednisone
Does prednisone inhibit the expression of cytokines?
Yes
What do glucocorticoids stimulate the production of?
IKB, NF-KB
What are the primary mechanisms of immunosuppressant drugs? (5)
1= Antigen recognition
2= T cell depletion
3= T cell activation
4= Cytokines (synthesis, signaling)
5= Proliferation
