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