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16 Cards in this Set
- Front
- Back
What enzyme converts Prednisone to Prednisolone?
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11-beta-hydroxysteroid dehydrogenase
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What is the MOA of Prednisone/Prednisolone?
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1. Leukocytopenia
2. Reduced size and lymphoid content of the lymph nodes & spleen 3. Interferes w/ function of Macrophages/Monocytes 4. Prevents activation of helper T cells 5. Prevents proliferation of T & B cells 6. Suppresses the production of Ab by B cells 7. Interferes w/ the function of helper T cells 8. Interference with lymphokine synthesis |
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The Leukocytopenia caused by Prednisone leads to what changes in the numbers of circulating Lymphocytes, Monocytes, Eosinophils, Basophils, and Neutrophils?
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All cells are decreased in number except Neutrophils
Increased circulating cells due to release of mature cells from bone marrow & decreased movement from blood into vascular tissue |
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Corticosteroids interfere with the function of Macrophages/Monocytes by blocking the expression of the genes for _______ & _______.
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IL-1: activates Th0 helper T-cells
IL-6: activates Th2 helper cells, B-cells, plasma cells |
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Corticosteroids interfere with the function of helper T cells by blocking the expression of the genes for: ????
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IL-2 : T-cell proliferation; further activation of IL-2 production from the Th0 cell secreting IL-2
IL-4: stimulates the proliferation of B-cells and the development of Ab-secreting plasma cells TNF-beta: activates macrophages, NK cells, and CTLs IFN-gamma: (same as TNF-beta) |
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What are the net effects of Corticosteroids on helper T cell function?
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1. No activation of Th1 & Th2 helper T cells
2. No activation of CTLs 3. No synthesis of TNFbeta & IFNy by helper T cells 4. Reverses the increased expression of MHC II proteins & adhesion molecules by allograft cells |
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Corticosteroid inhibit the expression of what Lymphokines?
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IL-1, 2, 4, 6
IFN-y TNF |
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What is the MOA of Cyclosporine?
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1. Blocks helper T-cell activation
2. Prevents clonal expansion of T cells and B cells 3. Prevents activation of CTLs |
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Cyclosporine prevents the transcription of the genes for ?
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IL-2
TNF-beta IFN-y IL-2 receptors (on T-cell surface) |
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What enzyme dephosphorylates cytosolic NFATC in activated T-cells?
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Calcineurin
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What is the function of dephosphorylated NFATC?
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Migrates to the nucleus where it activates the genes which code for IL-2, IL-2 receptors, TNF-beta, IFN-y
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How does Cyclosporine interfere with signal transduction mechanism that culminates in txn of genes for IL-2, IL-2 receptors, TNFbeta, and IFN-y?
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Cyclosporine binds to a cytoplasmic protein called Cyclophilin and the Cyclosporine-Cyclophilin complex inhibits the enzymatic activity of Calcineurin
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What is the MOA of Tacrolimus?
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Binds to the cytosolic protein FKBP of helper T cells
Tacrolimus-FKBP complex inhibits Calcineurin and thus prevents the production of IL-2, IL-2 receptors, IFN-y by helper T-cells |
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What is the MOA of Mycophenolate?
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Inhibits Inosine Monophosphate Dehydrogenase, an enzyme critical in the de novo synthesis of Guanine by T & B lymphocytes
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Why does Mycophenolic acid act specifically on Lymphocytes?
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These cells, unlike others derived from the bone marrow, lack HGPRT and thus have no alternate pathway for purine biosynthesis
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What is the MOA of Muromonab-CD3 (OKT-3)?
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Antibody directed against the CD3 complex of helper T-cells and CTLs
Binding of OKT3 to the CD3 complex blocks the binding of the foreign antigen presented by the APC; helper T-cell cannot be activated Deactivation of the CD3 complex causes the T-cell receptor antigen recognition site to undergo endocytosis T-cells become inactive and are removed from the circulation by the reticuloendothelial system |