Miscellaneous Pharm

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Miscellaneous Pharm
2011-04-04 10:23:04

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  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. Immunosuppressant: Monoclonal Antibody: Daclizumab
    Mechanism: high affinity for the IL-2 receptor on activated T cells
  9. 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
  10. Immunosuppressant: Mycophenolate mofetil
    Mechanism: inhibits de novo guanine synthesis and blocks lymphocyte production
  11. 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