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18 Cards in this Set
- Front
- Back
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1. List 3 general uses of immunosuppressants.
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a. Organ transplantation
b. Treatment of autoimmune disorders c. Prevention of Rh hemolytic disease of the newborn |
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2. List examples of immunosuppressant drugs.
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a. Glucocorticoids
b. Calcineurin inhibitors c. Proliferation signal inhibitors d. Mycophenolate mofetil e. Thalidomide f. Cytotoxic drugs g. Antibodies (and fusion proteins) |
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what is the commmon metabolism path of cyclosporine, tacrolimus and sirolimus
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CYP3A
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what is the MOA of cyclosporine
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i. Binds the intracellular protein cyclophilin. The complex inhibits calcineurin, a phosphatase that regulates NFAT (nuclear factor of activated T cells), the transcription factor that induces IL-2 transcription. The phosphorylated form of NFAT is sequestered in the cytoplasm and cannot enter the nuclease. The phosphatase action of calcineurin removes the phosphate and allows NFAT to enter the cytoplasm. Inhibition of calcineurin blocks NFAT signaling and inhibits the transcription of the IL-2 gene.
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what are the adverse effects of cyclosporin?
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1. Renal dysfunction, hypertension, neurotoxicity, hirsutism (increased hair on women, esp. on face and chest), gingival hyperplasia, hepatotoxicity, hyperkalemia, hyperglycemia, increased risk of infections and malignancies.
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what is the MOA of tacrolimus
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i. Binds FK-binding protein and the complex inhibits calcineurin same downstream effects as cyclosporine.
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what are the adverse effects of tacrolimus
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1. Renal, hypertension, neurotoxicity, hyperglycemia, hyperkalemia, GI problems, increased risk of infections and malignancies.
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what is the MOA of sirolimus
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i. Binds FK-binding protein 12 and the complex inhibits mTOR (mammalian target of rapamycin), a kinase involved in T cell proliferation.
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what is the adverse effects of sirolimus
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1. Hyperlipidemia, myelosuppression, pneumonitis
2. Increased risk of infections and malignancy |
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what drugs can increase and decrease cyclosporine blood concentration
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CYP3A inducers will decrease its concentration
CYP3A inhibitors will increase it inducers:Phenobarbital, phenytoin, carbamazepine, rifampin i. St. John’s wort inhibitors:Calcium-channel blockers, ketoconazole (other antifungals), erythromycin (other abx), methylprednisolone |
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whats the MOAof mycophenolate mofetil
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a. Mycophenolate mofetil is a prodrug that is converted to the active metabolite mycophenolic acid, which inhibits the de novo pathway of guanine nucleotide synthesis by inhibiting the enzyme inosine monophosphate dehydrogenase.
i. Interestingly, lymphocytes are more dependent on the de novo pathway of nucleotide synthesis than the salvage pathway. Therefore, inhibition of the de novo pathway confers some selectivity for lymphocytes and potentially spares nucleotide synthesis in other types of cells. |
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what are the adverse effects of mycophenolate mofetil
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i. GI, neutropenia, increased risk of infections and malignancies, teratogenic effects
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what is thalidomide approved for use in
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multiple myeloma and erythema nodosum leprosum
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what are the adverse effects of thalidomide
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i. Severe human teratogenicity
1. There is an elaborate restricted distribution program called System for Thalidomide Education and Prescribing Safety or “STEPS.” ii. Peripheral neuropathy iii. Use in multiple myeloma results in an increased risk of venous thromboembolic events |
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what are two cytoxic drugs used as immunosuppressants
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a. Azathioprine: prodrug for mercaptopurine, which inhibits purine synthesis and is incorporated into DNA and RNA.
b. Cyclophosphamide: alkylating agent |
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8. Cite examples of antibodies (or fusion proteins) used as immunosuppressants.
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a. Antithymocyte globulin
b. Rh(D) immune globulin c. Muromonab-CD3 d. Basiliximab e. Daclizumab |
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9. List 3 general uses of “immunomodulation therapy.”
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a. Immunodeficiency
b. Chronic infections c. Cancer |
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10. List 2 types of cytokines used in “immunomodulation therapy.”
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a. Interferons
b. Interleukin-2 |
