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34 Cards in this Set
- Front
- Back
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What are the prototype immunomodulators?
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CSF
Cyclosporine Cyclophosphamide Daclizumab Glucocorticoids Interferon-alpha Mycophenolate mofetil Sirolimus |
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Immunosuppressive agents are used to treat what conditions?
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Transplants
Tissue grafts Autoimmune disease |
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What is the mechanism of glucocorticoids?
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Transient clearing of lymphocytes from circulation.
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There are 6 factors that contribute to the anti-inflammatory effect of glucocorticoids. What are they?
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1. Decreases TNF-a production
2. Decreases tPA 3. Increases lipocortin, which inhibits phospholipase A2 4. Decreases the effect of macrophage inhibitory factor 5. Decreases PAF 6. Decreases IL-1 production |
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What are the two major glucocorticoids used as immunomodulators?
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prednisone
prednisolone |
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What are the adverse effects of long term glucocorticoid use?
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Ulcers
Hyperglycemia Osteoporosis Edema Hypokalemia Cushings syndrome |
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What drug is a structural analog of 6-mercaptopurine?
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Azathioprine
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What is the mechanism of azathioprine?
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Liver activated to 6-mercaptopurine causeing feedback inhibition of purine synthesis, blocking DNA replication.
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What is azathioprine used for?
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As a cytotoxic agent against proliferating cells
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Why is use of azathioprine limited? What drug replaced it?
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Mycophenolate mofetil replaced it because of its toxicity and adverse effects.
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What is the effect of cyclophosphamide?
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Inhibition of humoral and cellular immunity, esp B cells
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What immunomodulatory use does cyclophosphamide have?
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Used with glucocorticoids to treat autoimmune disease
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Why is cyclophosphamide not used in transplants and grafts?
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No consistent effect on T cells
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What is the mechanism of cyclosporine?
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Inhibits T cell proliferation. Binds cyclophilin, then the complex blocks calcineurin and calcium dependent phosphoprotein phosphatase.
Inhibition of calcineurin prevents the dephosphorylation of NFAT, which regulates expression of IL-2,3,4, GM-CSF, and TNF-a |
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What is the intracellular receptor for tacrolimus? The function of tacrolimus is similar to what other drug?
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FKBP12, function is similar to cyclosporine
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What are cyclosporine and tacrolimus used to treat?
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Used for transplants
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What are the adverse effects of cyclosporine?
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nephrotoxicity
hepatotoxicity |
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What considerations must be made in reference to the metabolism of cyclosporin?
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p450 metabolized, so watch out for other drugs that are also p450 metabolized (rifampin, ketoconazole, cimetidine, etc)
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What is the mechanism of sirolimus?
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Blocks cytokine signal transduction. Binds FKBP12 and inhibits mTOR, an enzyme for cell cycling. Also inhibits translation which decreases the production of cytokines.
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What other drugs can be combined with sirolimus?
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cyclosporine and corticosteroids
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What do sirolimus do (generally)?
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Blocks T cell activation
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What is the mechanism of mycophenolate mofetil?
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Block de novo purine synthesis causing a decrease in T and B cell proliferation
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What is mycophenolate mofetil used for?
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transplants of solid organs
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What drug are used for solid organ transplants?
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cyclosporine/tacrolimus and mycophenolate mofetil
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What is the mechanism of bacillus calmette-guerin?
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attenuated strain of mycobacterium bovis that activates NK cells to build immunity.
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What is BCG used for?
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Stimulation of immune response in cancer pts
Used against bladder cancer Immunization against TB |
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What is a LAK and how is it made?
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NK cells are isolated from the patient and treated with IL-2 forming Lymphokine activated killer cells (LAKs).
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IL-2/LAK have been used to treat what diseases?
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Melanoma
Renal cell carcinoma |
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Why is beta-interferon used?
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activates phagocytes and has antiproliferative and antiviral effects
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What disease is beta-interferon used to treat?
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MS
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What disease is gamma-interferon used for?
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granulomatous diseases
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What drugs can be used to stimulate bone marrow growth?
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GM-CSF
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Why was thalidomide withdrawn from the market?
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teratogenic effects during pregnancy
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What is the mechanism of thalidomide?
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Inhibits angiogenesis and is anti-inflammatory and immunomodulatory effects.
Inhibits: TNFa, phagocytosis, IL-10, adhesion molecules Enhances T cell immunity |
