Immunosuppressants Flashcards
Calcineurin
converts NFAT-P to NFAT –> transcribes inflammatory cytokine genes (IL-2)
NF-KB
stimulates production of inflammatory cytokine genes
IL-2R
Activates mTOR –> proliferation of genes
IMP dehydrogenase
Used to make purine nucleotides –> De novo purine synthesis –> DNA replication
PRPP amidotransferase
Used to make purine nucleotides –> De novo purine synthesis –> DNA replication
Cyclosporine (cyclophilin)
Inhibits calcineurin; bind cyclophilin
Blocks T-cell activation by inhibiting IL-2 transcription
Tacrolimus (FK506)
Inhibits calcineurin; binds FK506/FKBP
Blocks T cell activation by also preventing transcription of IL-2 (like cyclosporin)
Sirolimus
mTOR inhibitor
Prevents response to IL-2 (cell growth/ gene proliferation)
Daclizumab, basiliximab
monoclonal antibody that blocks IL-2 receptor
Azathioprine
Antimetabolite precursor of 6-MP
Inhibits PRPP amidotransferase; thereby blocking purine synthesis
Mycophenolate mofetil
Reversibly inhibits IMP dehydrogenase; preventing purine synthesis of B and T cells
Corticosteroids
Inhibit NF-KB; suppresses transcription of many cytokines (suppresses both B and T cells)
Induces apoptosis in T lymphocytes
All of these immunosuppressant drugs are used for:
Transplant rejection prophylaxis
Cyclosporine- unique uses
prophylaxis, psoriasis, (RA- normally use etanercept –> mab against TNF-alpha)
KIDNEY transplant rejection prophylaxis drugs (3)
Sirolimus (Rapamycin) and daclizumab, basiliximab
Azathioprine
Used for RA, Crohn, glomerulonephritis, and other autoimmune conditions
Mycophenolate mofetil
Used for lupus nephritis
Corticosteroids
Autoimmune and inflammatory disorders
Cyclosporine vs. Tacrolimus- toxicity
Both are NEPHROTOXIC, neurotoxic
Only cyclosporine causes gingival hyperplasia and hirsuitism
Sirolimus- toxicity
Pan”SIR”topenia (pancytopenia)
Not nephrotoxic
