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What is azathioprine?
- Old immunomodulator
- High toxicities prevent long-term use
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What is Cyclosporine?
- Calcineurin Inhibitor
- Inhibit IL-2 --> CD4 & CD8 T-cells
- High affinity to cyclophilin
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What's the metabolism of Cyclosporine?
Hepatic CYP3A4 metabolism
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What's the therapeutic uses/toxicity of Cyclosporine?
- Uses: transplants, autoimmune disorders
- Toxicities: Nephro, neuro, Acute Tubular Necrosis, Lymphomas
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What is Calcineurin?
Dephosphorylation of NFAT --> IL-2 activation
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What's the difference between acute/chronic toxicities of cyclosporin A?
- Acute - reversable
- Chronic - irreversible
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What's the absorption of Cyclosporin A?
- Oral; different for various people (measure!!)
- NARROW THERAPEUTIC RANGE
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What's Tacrolimus?
- Potent Calcineurin Inhibitor
- less nephrotoxicity
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What's the MoA of tacrolimus?
Binding to FKBP-12 --> calcineurin inhibition
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What are metabolisl considerations of tacrolimus?
Shorter half-life than cyclosporine; 2x daily
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What's the clinical use of tacrolimus?
- Prophylaxis after transplans
- Graft rejection Tx
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What is sirolimus?
Cell Proliferation Inhibitor
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What's the MoA of sirolimus?
- Bind to FKBP-12 --> inhibit mTOR
- Lack of response to growth stimulator signals
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What are uses for sirolimus?
- Prevent acute regection
- prevent neointimal proliferation following stent placement in coronary arteries
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What's mycophenolate mofetil?
- Prodrug
- Inhibitor of inosine monophosphate dehydrogenase
- Prevent de novo purine biosynthesis
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What are clinical uses for mycophenolate mofetil?
Renal & heart transplants
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What are daclizumab & basiliximab
- Monoclonal Abs
- Bind to a-chain at IL-2 receptor
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What toxicity is associated with basiliximab?
Hypersensitivity
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What's Muromonab?
- Monoclonal Ab
- Block ε chain of T cell CD3
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What's the use of Muromonab?
Reverse rejection of heart, liver, kidney rejection
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What's MoA of abatacept?
- Bind to CD80 & CD86
- Prevent CD28 T-Cell activation
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What's the MoA of leflunomide?
Inhibition of dihydroorotate -> pyrimidine biosynthesis
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What's the clinical use of leflunomide?
Active RA
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What are toxicities of leflunomide?
Diarrhea, nausea, hepatotoxicity
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What's the clinical use of Thalidomide?
erythema nodosum leprosum
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What are toxicities of thalidomide?
- Peripheral neuropathy
- TERATOGENICITY
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What's the MoA of infliximab?
- Ab against TNFa
- Chron's, UC, RA, Psoriasis
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What are toxicities of infliximab?
Increased infection (TB, HBV reactivation)
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What's the MoA of etanercept?
Recombinant TNF receptor to soak up free TNF
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What are uses of etanercept?
RA, ankylosing spondylitis, psoriasis
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What are toxicities of etanercept?
Demyelinating diseases
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What's the MoA of natalizumab?
- Ab against antibody against α4β1-integrin
- Inhibit lymphocyte migration
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What's the use of natalizumab?
Crohn's, MS
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What's an associated risk from Natalizumab?
JC virus induced PML
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What's the MoA of Azathiprine?
- Purine analog used to interupt de novo purine synthesis
- Combination therapy of RA --> leukopenia
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What's the MOA of Fingolimod?
Use?
- Block migration of lymphocytes from LN
- Tx: MS
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What's the MoA of glatiramer?
Use?
- Mix of AAs similar to myelin basic protein
- Tx: MS
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What's the MoA of Lymphocyte Immune Globulin?
- Ab to T-cell surface antigens
- Block cell surface receptors
- Direct cytotoxicity
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What's the MoA of Immune globulin?
Human IgG to replace Abs in immune deficiencies
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What's the MoA of Anakinura?
Use?
SE?
- IL-1 receptor antagonist
- Tx: RA
- SE: bacterial infection
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What's the Use of IFN-b?
MS
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What's epoetin alfa?
- EPO analogue
- Stimulate RBC synthesis in anemic pts
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What's darbepoetin alfa?
EPO analogue with longer half life
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What's the risk with EPO analogues?
- Cancer - stimulate tumor cell proliferation
- Renal Failure - CVA
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