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39 Cards in this Set
- Front
- Back
- 3rd side (hint)
Site of action of glucocorticoids
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Glucocorticoid response elements in DNA (regulate gene transcription)
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Site of action of Muromondab-CD3
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T-cell receptor comlex (blocks antigen recognition)
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Site of action of Cyclosporine
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Calcineurin (inhibits phosphatase activity)
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Site of action of Tacrolimus
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Calcineurin (inhibits phosphatase activity)
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Site of Action of Azathioprine
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DNA (false nucleotide incorporation)
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Site of action of Mycophenolate Mofetil
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Inosine monophosphate DH (inhibits activity)
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Site of action of Daclizumab and Basiliximab
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IL-2 receptor (block IL-2-mediated T-cell activation)
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Site of action of Sirolimus
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Protein kinase involved in cell-cycle progression (mTOR) (inhibits activity)
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Azathioprine, methotrexate, cyclophosphamide, rapamycin, corticosteroids, mycophenolic acid function
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interferes with proliferation and differentiation
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ATG, OKT3, anti-CD4, cyclosporine and tacrolimus function
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interferes with expression of IL-2 and other cytokines, then proliferation and differentiation
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Corticosteroids function
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interferes with stimulation of IL-1, then expression of IL-2 and other cytokines, then proliferation and differentiation
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Rh (D) immune globuline function
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interferes with antigen recognition, then stimulation of IL-1, then expression of IL-2 and other cytokines, then proliferation and differentiation
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Examples of corticosteroids. Differences.
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Prednisone
Methylprednisolone Dexamethosone Prednisone carbonyl reduced to (-OH) with added (-CH3). Dexamethasone displaced (-CH3) and added (-F) |
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MOA of glucocorticoid receptor (GR)
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glucocorticoid steroid enter cells and interact with the GR to change the GR conformation, induce GR nuclear translocation, and activate gene transcription. S and GR separate from HSP70 and HSP90 and enter nucleus.
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Corticosteroids (effect on lymphocytes) (4)
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1. Reduce the number of circulating lymphocytes
2. Suppress proliferation of lymphocytes. 3. Decrease thymic mass. 4. Interfere with cell cycle of lymphocytes. |
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Corticosteroids (effect on inflammatory response) (4)
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1. Reduce the phagocytic and cytotoxic ability of macrophages and neutrophils.
2. Reduce chemotaxis. 3. Reduce macrophage production of IL-1 4. Synthesize lipocortins (annexins) - inhibit PLA2 - PAF, PGs, and LTs |
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Corticosteroids (other effects) (3)
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1. Diminish expression of MHC Class II molecules in APCs
2. Stabilize lysosomal membranes 3. Diminish levels of inducible form of COX-II |
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Corticosteroids (major adverse effects) (7)
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1. Infections
2. Salt and water retention (hypertension, edema, electrolyte disturbances 3. peptic ulcer 4. adrenal suppression 5. hyperglycemia 6. steroid psychosis 7. Long term AEs: (Cushingoid changes, osteoporosis, cataracts, glaucoma) |
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Cyclosporine (characteristics)
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fat soluble cyclic polypeptide of 11 aa's
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SandImmune (non-modified)
Neoral and Gengral (modified lipid ME) |
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Cyclosporine MOA
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binds to specific immunophilin (cyclophilin) which interferes with gene transcription of IL-2 and INF-gamma
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Cyclosporine (effects) (2)
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1. inhibits activation and proliferation of immunocompetent celss, esp. TH1 cells
2. inhibits gene transcription of cytokines (IL-2, IL-3, INF-gamma) |
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What metabolizes cyclosporine?
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CYP3A enzymes
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Also CYP3A-metabolized are:
HIV protease inhibitors, anticonvulsants, azole antifungals, macrolides, grapefruit juice, etc... |
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Cyclosporine (indications) (4)
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1. allogeneic transplants (kidney, liver, heart)
2. RA 3. psoriasis 4. "dry eye syndrome" (Restasis) |
Unlabeled:
1. autoimmune and graft-vs.-host dz's 2. aplastic anemia 3. resistant leukemia |
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Cyclosporine (major AE's) (8) (3)
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1. infections
2. cancer 3. nephrotoxicity 4. HTN 5. hepatic toxicity 6. anaphylactic rxn's 7. hyperglycemia 8. hyperliidemia |
Similar to Corticosteroids:
1. infections 2. hypertension 3. hyperglycemia |
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Tacrolimus (characteristics)
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1. macrolide
2. terminal t 1/2 about 12 hrs in liver transplant pt.'s and 21 hrs for normal pt. |
Prograf
Protopic |
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Tacrolimus (MOA)
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binds to a specific immunophilin -> decrease transcription for IL-2 and INF-gamma
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FK binding protein-12 (FKBP-12) - immunophilin
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What metabolizes Tacrolimus?
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CYP3A enzymes
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Tacrolimus (indications) (2) (3)
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1. rejection prophylaxis of allogenic liver, kidney, and heart transplants
2. atopic dermatitis (Protopic) |
unlabeled:
1.autoimmune and graft-vs.-host dz's (GVHD) 2. RA 3. Crohn's dz |
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Tacrolimus (major AEs) (6) (4)
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1. infections
2. cancer 3. nephrotoxicity 4. hyperkalemia 5. hyperglycemia 6. neurotoxicity (tremor, HA, seizures, coma, delirium) |
Similarities
1. infections (CCs) 2. cancer (cyclosporine) 3. nephrotoxicity (cyclosporine) 4. hyperglycemia |
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Pimecrolimus (characterisitics) (4)
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1. macrolide immunosuppressant
2. don't use in immunocompromised pt.'s 3. after 6 weeks, reexamine 4. apply thin layer BID |
Elidel
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Pimecrolimus (MOA)
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binds with FKBP-12 and inhibit calcineurin activity
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Sirolimus (characteristics)
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macrolide immunosuppressant
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Rapamune
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Pimecrolimus (actions) (2)
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1. prevents mast cell degranulation
2. block transcription of IL-2 and IFN-gamma |
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Sirolimus (MOA) (5)
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1. binds to FKBP-12
2. NO effect on calcineurin 3. inhibit mTOR (key regulatory kinase) 4. inhibit G1 to S phase of T-cell proliferation 5. blocks lymphocyte activation and proliferaiton *after* IL-2 |
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Sirolimus (indications) (2) (1)
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1. renal transplants (conjunction w/ glucocoritcoids)
2. coronary stents (Cypher) |
unlabeled:
1. psoriasis |
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What metabolizes sirolimus? (1) (2)
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CYP3A enzymes
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Same as:
1. cyclosporine 2. tacrolimus |
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Sirolimus (major AEs) (12) (4)
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1. infections
2. hepatic artery thrombosis, graft loss, excess mortality (liver) 3. bronchial anastomotic dehiscence (lungs) 4. cancer 5. nephrotoxicity 6. cholesterol and TGs rise 7. anemia 8. leukopenia 9. thrombocytopenia 10. hypokalemia 11. fever 12. diarrhea |
Similarities:
1. infections 2. cancer 3. nephrotoxicity 4. hypokalemia |
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Everolimus (characteristics) (1) (2)
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1. macrolide immunosuppressant
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1. Novartis (Xience and Afinitor)
2. Macolides: tacrolimus, pimecrolimus, sirolimus |
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Everolimus (MOA) (2)
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1, binds to FKBP (like tacrolimus)
2. inhibits mTOR (like sirolimus) |
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