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Immunosuppressant: Cyclosporin
- Mechanism: binds to cyclophilins, the complex blocks the differnetiation and acitivation of T cells by inhibiting calcieurin (phosphatase) = preventing production of IL-2 & its receptor
- Clinical use: suppresses organ rejection after transplantation; selected automimmune disorders
- Toxocity: predisposes pts to viral infections and lymphoma; nephrotoxic (preventable w/ mannitol diuresis), gingival overgrowth
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Immunosuppressant: Tacrolimus (FK506)
- Mechanism: binds to F-K binding proteins = inhibits calcineurin = prevents secretion of IL-2 and other cytokines
- Clinical use: potent immunosuppresive in organ transplants
- Toxicity: significant - nephrotoxicity, peripheral neuropathy, htn, pleural effusion, hyperglycemia
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Immunosuppressant: Azithroprine
- Mechanism: antimetabolite precursor of 6-mercaptopurine that inferferes w/ metabolism and synthesis of nucleic acids. Toxic to proliferating lymphocytes
- Clinical use: kidney transplantation, autoimmune disorders (glomerulonephritis, hemolytic anemia)
- Toxocity: bone marrow suppression. Active metabolite mercaptopurine is metabolized by xanthine oxidase thus increased toxicity by allopurinol
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Immunosuppressant: Monoclonal Antibody: Muromonab-CD3 (OKT3)
- Mechanism: monoclonal antibody that binds to CD3 (epislon chain) on surface of T cells = blocks cellular interaction with CD3 protein responsible for T cell signal transduction
- Clinical use: immunosuppression after kidney transplant
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Immunosuppressant: Monoclonal Antibody: Abciximab
- Mechanism: binds to glycoprotein receptor IIb/IIIa on activated platelets, prevening aggregation
- Clinical use: Acute coronary syndoromes, angioplasty
- Toxicity: bleeding, thrombocytopenia
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Immunosuppressant: Monoclonal Antibody: Infliximab
- Mechanism: monoclonal antibody to TNF, proinflammatory cytokines
- Clinical use: Crohns, RA
- Toxicity: respiratory function (including reactivation of latent TB) fever, hypotension
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dImmunosuppressant: Monoclonal Antiboty: Trastuzumab (herceptin)
- Mechanism: aginst HER-2 (erb-B2), helps kill breast cncer cells that overexpress HER-2, possibly thru antibody-dependent cytotoxicity
- Clinical use: met breast cancer
- Toxocity: cardiotoxicity
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Immunosuppressant: Monoclonal Antibody: Daclizumab
Mechanism: high affinity for the IL-2 receptor on activated T cells
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Immunosuppressant: Sirolimus (rapamycin)
- Mechanism: binds to mTOR = inhibits Tcell proliferation in response to IL-2
- Clinical use: immunosuppression after kidney transplantation in combo w/ cyclosporin and corticosteroids
- Toxicity: hyperlipidemia, thrombocytopenia, leukopenia
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Immunosuppressant: Mycophenolate mofetil
Mechanism: inhibits de novo guanine synthesis and blocks lymphocyte production
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Recombinant Cytokines & Uses
- Aldesleukin (IL2): RCC, met melanoma
- EPO: anemias (especially in renal failure)
- Filgrastin (granulocyte colony-stimulating factor): bone marrow recovery
- Sargramostim (granulocyte-macrophage colony-stimulating factor): bone marrow recovery
- Alpha-Interferon: Hep B, Hep C, Kapsoi's sarcoma, leukemias, mlaignant melanoma
- B-interferon: MS
- Gamma-interferon: Chronic granulomatous disease
- Oprelvel=kin (IL-11): thrombocytopenia
- Thrombopoietin: thrombocytopenia
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