Immunopharmacology - Chapter 55

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205241
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Immunopharmacology - Chapter 55
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2013-03-06 00:59:21
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Immunopharmacology Immune Pharmacology
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Immunopharmacology - Chapter 55 review
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  1. What effect do corticosteroids have on
    prostaglandins, leukotrienes, cytokines.
    Decreased synthesis
  2. How does continuous use of corticosteroids lower immunity?
    • - Inhibition of proliferation of T lymphocytes (Decreased cellular immunity),
    • - Continuous therapy lowers levels of IgG by increased catabolism of this class of
    • immunoglobulins
  3. CORTICOSTEROIDS - Clinical uses
    • Addison’s disease,
    • Asthma,
    • Arthritis,
    • cancer chemotherapy,
    • organ transplantation
  4. CORTICOSTEROIDS - Toxicity:
    • - Adrenal suppression,
    •  - growth inhibition,
    •  - muscle wasting,
    •  - osteoporosis,
    •  - salt retention,
    •  - diabetogenesis,
    •  - psychosis
  5. CYCLOSPORINE - MOA
    • Fat-soluble peptide antibiotic which blocks the antigen receptor-induced differentiation of T cells.
    • Binds to cyclophyllin and inhibits calcineurin
    • Inhibits production of IL2, IL3, and IFNγ.
  6. CYCLOSPORINE - Clinical use
    • immunosuppressant in organ transplantation,
    • in management of new-onset diabetes,
    • and may have a role in the management of asthma
  7. CYCLOSPORINE - Toxicity
    • renal,
    • hyperglycemia,
    • osteoporosis,
    • increased hair growth (in women),
    • transient liver dysfunction,
    • limb paresthesia,
    • distal tremor,
    • hallucinations,
    • seizures
  8. TACROLIMUS
    • - Immunosuppressant macrolide antibiotic,
    •  - Binds to FK-binding protein (FKBP),
    •  - Inhibits calcineurin which is necessary for activation of a T cell-specific transcription factor. 

    –More potent than cyclosporine
  9. TACROLIMUS
    Used in liver and kidney transplant recipients
  10. TACROLIMUS - Toxicity
    • renal,
    • hyperglycemia,
    • osteoporosis,
    • increased hair growth (in women),
    • transient liver dysfunction,
    • limb paresthesia,
    • distal tremor,
    • hallucinations,
    • seizures
  11. SIROLIMUS - MOA
    - Binds to immunophyllins and blocks the response of T cells to cytokines.

     - Potent inhibitor of B cell proliferation and immunoglobulin production
  12. SIROLIMUS - Clinical use
    Used alone or in combination with cyclosporine for heart and kidney transplant
  13. SIROLIMUS - Toxicity
    • hyperlipidemia, 
    • hematopoietic cell toxicity
  14. What is the name of the medicine that has a $1000 dollar reward for naming a newborn after this medicine?
    MYCOPHENOLATE MOFETIL
  15. MYCOPHENOLATE MOFETIL - MOA
    • - Inhibits a series of T and B cell responses.
    •  - Its action depends on its ability to inhibit the de novo pathway of purine synthesis by inhibition of inosine monophosphate dehydrogenase. 

    –Lymphocytes are particularly sensitive because they lack the enzymes needed for the alternative salvage pathway for purine synthesis
  16. MYCOPHENOLATE MOFETIL - Clinical use
    Has been used successfully as the sole agent in kidney, liver, and heart transplants.

    •  - In kidney transplants it has been used with low dose cyclosporine to reduce the incidence of cyclosporine-induced
    • nephrotoxicity
  17. MYCOPHENOLATE MOFETIL - Toxicity
    • GI distress,
    • Myelosuppression
  18. THALIDOMIDE - MOA
    Sedative drug that suppresses TNF production. 
  19. THALIDOMIDE - Clinical use
    • Leprosy,
    • SLE,
    • Wasting syndrome in AIDS,
    • multiple myeloma
  20. What drug was pulled from the market due to birth defects known as Phocomelia?
    THALIDOMIDE
  21. AZATHIOPRINE - MOA
    • - Prodrug of mercaptopurine which is a purine antimetabolite. 
    • – It is cytotoxic in the early phase of lymphoid cell production and has a greater effect on T than B cells. 

    • –Immunosuppression results from
    • interference with nucleic acid metabolism at steps that are required for the wave of lymphoid proliferation which follows antigenic stimulation
  22. AZATHIOPRINE - Clinical use
    • SLE,
    • RA,
    • Kidney transplants,
  23. AZATHIOPRINE - Toxicity
    Bone marrow suppression, when given with allopurinol the dose must be reduced by 75%
  24. CYCLOPHOSPHAMIDE - MOA
    • Transformed by liver enzymes into an alkylating agent
    • –It is the most potent of the immunosuppressant drugs. 
    • –Has greater effect on B than T cells.
  25. CYCLOPHOSPHAMIDE - Clinical use
    • hemolytic anemia,
    • antibody-induce red cell aplasia,
    • bone marrow transplants,
  26. CYCLOPHOSPHAMIDE - Toxicity
    hemorrhagic cystitis
  27. LEFLUNOMIDE - MOA
    • Prodrug of an inhibitor of pyrimidine synthesis
    • It arrests lymphocytes in the G1 phase of the cell cycle
  28. LEFLUNOMIDE - Clinical use
    RA
  29. LEFLUNOMIDE - Toxicity:
    • Alopecia,
    • rash,
    • and diarrhea
  30. LYMPHOCYTE IMMUNE GLOBULIN (LIG) - MOA
    • AKA antithymocyte globulin (ATG) produced in horses by immunization against human thymus cells. 
    • Binds to T cells and initiates their destruction by serum complement. 
    • Selectively blocks cellular immunity rather than antibody formation.
  31. LYMPHOCYTE IMMUNE GLOBULIN (LIG)

    Clinical Use?
    • Prior to bone marrow transplant of
    • suppress graft-vs-host reaction.

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