Term
| Three clinical indications for immunosuppressive therapy |
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Definition
Organ transplant
Prevention of Rh hemolytic disease in newborns
Autoimmune dz |
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Term
| 4 classes of immunosuppressive drugs |
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Definition
1. Adrenocortical steroids
2.Cyclosporine A and tacrolimus
3. Cytotoxic drugs
4. Antibody |
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Term
| Cortisol is what class of drug? |
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Definition
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Term
| cortisone is what class of drug? |
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Definition
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Term
| fludrocortisone is what class of drug? |
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Definition
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|
Term
| prednisone is what class of drug? |
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Definition
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Term
| prednisolone is what class of drug? |
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Definition
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Term
| 6a-methylprednisolone is what class of drug? |
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Definition
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|
Term
| triamcinolone is what class of drug? |
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Definition
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|
Term
| betamethasone is what class of drug? |
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Definition
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|
Term
| dexamethasone is what class of drug? |
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Definition
|
|
Term
| What are the calcinurin inhibitors? |
|
Definition
| cyclosporine A and Tacrolimus (FK506) |
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|
Term
| cyclosporine A is what class of drug? |
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Definition
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|
Term
| Tacrolimus is what class of drug? |
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Definition
|
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Term
| Sirolimus (rapamycin) is what class of drug? |
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Definition
| antiproliferative cytotoxic drug |
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|
Term
| methotrexate is what class of drug? |
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Definition
|
|
Term
| cyclophosphamide is what class of drug? |
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Definition
|
|
Term
| mycophenolate mofetil is what class of drug? |
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Definition
|
|
Term
| Azathioprine is what class of drug? |
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Definition
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|
Term
| What are some monoclonal Ab useful in immunosuppressive thearpy? |
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Definition
| Anti-CD3, anti-IL-2R, Anti-TNFa |
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Term
| Antithymocyte globulin is what class of drug? |
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Definition
|
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Term
| The immune system has a stimulatory or inhibitory impact on HPA axis? |
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Definition
| stimulatory! (just think...need cortisol in stressful situations) |
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|
Term
| Two classes of corticosteroids: |
|
Definition
| minearlcorticoid, glucocorticoid |
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Term
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Definition
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Term
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Definition
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Term
| Mechanism of action: glucocorticoids |
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Definition
| suppression of cytokines at gene level achieved through activation of the glucocorticoid receptor |
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|
Term
| Cortisol's effect on carbs and protein metabolism |
|
Definition
gluconeogenesis (want more glucose!)
inhibit glycolytic pathways |
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|
Term
| Cortisol's effect on lipid metabolism |
|
Definition
redistributes fat to face, neck, supraclavicular area, loss of fat from periphery
promote lipolysis |
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|
Term
| Cortisol's effect on skeletal muscle |
|
Definition
requrie for nl function
protein breakdown |
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|
Term
| Cortisol's effect on cardio |
|
Definition
| potentiate B-adrenergic effects (HT via inc HR and inc vasoconstriction) |
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|
Term
|
Definition
| increase awareness, effect behavior and mood |
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|
Term
| Cortisol's effect on immune system |
|
Definition
suppress numbers of circulating lymphocytes, eosinophils, monocytes, and basophils
Inhibit cytokine synthesis (so less proliferation and response) |
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|
Term
| Cortisol's effect on enzymes |
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Definition
| inhibits phospholipase A2 -> reduces PG and LT production -> anti-inflammatory |
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|
Term
| Which corticosteroid has modest mineralcorticoid activity compared to cortisol (125X more) |
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Definition
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|
Term
| Which two corticosteroids have the highest potency and longest duration of action? (25x cortisol potency) |
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Definition
| betamethasone, dexamethasone |
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Term
| Drugs of choice in adrenal cortical insufficiency? |
|
Definition
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|
Term
| Drugs of choice in Addisons disease, salk losing adrenogenital syndrome, adrenal insufficiency |
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Definition
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|
Term
| Drugs of choice in glucocorticoid effects of adrenal insufficiency and immunosuppression |
|
Definition
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|
Term
| Drugs of choice in glucocorticoid only - anti-inflammatory/immunosuppression |
|
Definition
6a-methylprednisolone
triamcinolone
betamethasone
dexamethasone |
|
|
Term
| What is the imoprtance of 11-B-hydroxysteroid dehydrongenase in cortisol v. aldosterone activity? |
|
Definition
| This enzyme is expressed only in tissues containing the mineralcorticoid receptor and inactivates glucocorticoids such as cortisol |
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|
Term
| Side effects: glucocorticoids |
|
Definition
|
|
Term
| side effects: glucocorticoid |
|
Definition
| HT, hyperglycemia, infection, peptic ulcer, myopathy, cataracts, osteoporosis (inhibiting osteoblast activity, inhibit calcium absorption, and increase PTH), behavioral changes (nervousness, insomnia, mood swings, suicidal tendencies) |
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|
Term
| Two main differences between tacroliums and cyclosporine |
|
Definition
| tacrolimus is 100x more potent and has 11-21 hr half life vs. the 6 hr half life of cyclosporine |
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|
Term
| Side effects: cyclosporin A |
|
Definition
| nephrotoxicity (due to vasoconstriction and thrombotic angiography) and predisposition to viral infections and lymphoma due to decreased T cells differentiation and activation |
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|
Term
| Cyclosporine blocks ____ & ___ of __ cells by inhibiting _____ thus preventing production of _____ and its receptor |
|
Definition
| differentiation and activation of T cells; calcineurin, prevents production of IL2 and its receptor |
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|
Term
| tacrolimus binds to the ___ protein and inhibitions secretion of _____ and other cytokines |
|
Definition
| FK binding, inhibits secretion of IL2 |
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|
Term
| common mechanism of action in cytotoxic drugs |
|
Definition
| prevention of clonal expansion of both B and T lymphocytes |
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|
Term
| Azathioprine is an antimetabolite precursors of _________ that intereferes with ________. |
|
Definition
| 6-mercaptopurine, intereferes with metabolism and synthesis of nucleic acids |
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|
Term
| route of admin: azathioprine |
|
Definition
|
|
Term
| side effects: azathioprine |
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Definition
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|
Term
| Mycophenolate mofetil inhibits ______ synthesis and blocks _____ production |
|
Definition
| de novo guanine synthesis; lymphocyte |
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|
Term
| Which cytotoxic agent is more functionally selective for immune system than other actively dividing cells (so less side effects) and why? |
|
Definition
| mycophenolate mofetil - b/c it only affects de novo purine biosynthesis which T and B cells are more dependant upon. Other dividing cells are more dependent on purine salvage pathways |
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|
Term
| route of admin: mycophenolate mofetil |
|
Definition
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|
Term
| Mechanism of action: cyclophosphamide |
|
Definition
| an akylating agent that makes the DNA structure inseparable |
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|
Term
| Which cyotoxic agent is primarily used to suppress humoral immunity such as in bone marrow patients? (why?) |
|
Definition
| cyclophosphamide b/c as it akylates it affects profliferating cells more and especially B cells (They can't seem to recover as quickly as T cells) |
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|
Term
| Mechanism of action: methotrexate |
|
Definition
| inhibition of DNA synthesis by inhibiting dihydrofolate reductase |
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|
Term
| Sirolimus binds to _____ thereby inhibiting ______ in response to IL-2 |
|
Definition
| mTOR; T cell proliferation in response to IL2 |
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|
Term
| metabolism and excretion: sirolimus |
|
Definition
| metabolized in liver and ninety percent of metabolites in feces |
|
|
Term
|
Definition
| hyperlipidemia, thrombocytopenia, leukopenia |
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|
Term
| Where does antithymocyte globulin come from? |
|
Definition
| purified gamma gobulin from serum of rabbits immunized with human monocytes |
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|
Term
| Mechanism of action: antithymocyte globulin |
|
Definition
| deplete circulating lymphocytes and block lymphocyte function; cytotoxic Abs that bind to various CDs, HLA I & II |
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|
Term
| Mechanism of action: anti-cd3 |
|
Definition
| depletion and extravasation of majority of T cells from bloodstream and peripheral LN and spleen; bind to epsilon chain of CD3 (part of Tcell receptor complex) involved in Ag recognition, cell signaling, and proliferation |
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Term
|
Definition
| increased serum levels of cytokines (TNFa, IL2, IL6) "cytokine release syndrome" |
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|
Term
| Mechanism of action: Anti-IL2R |
|
Definition
| binding to IL2R on activated T cells thus preventing the cyotkine from binding (no proliferation cytokine production) |
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|
Term
| What are the Anti-TNFa antibodies? |
|
Definition
| Infliximab, adalimumab, etanercept (not monoclonal) |
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|
Term
| What monoclonal Ab is used to treat rheumatoid arthrisis? |
|
Definition
| infliximab, adalimumab, etanercept (TNF-a Abs) - RA is characterized by elevated TNFa |
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Term
|
Definition
| NEPHROTOXIC, peripheral neuropathy, hypertension, pleural effusion, hyperglycemia |
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|
Term
| that active metabolite of azathioprine is metabolized by ______ ______ thus toxic effects may be increased by ______ |
|
Definition
| xanthine oxidase; allopurinol |
|
|
Term
| Muromonab is a monoclonal Ab that binds ___ of __ cells thereby blocking ______ |
|
Definition
| CD3 of T cells, signal transduction |
|
|
Term
|
Definition
| cytokine release syndrome, hypersensitivity reaction |
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|
Term
| Daclizumab is a monoclonal Ab for the _____ on T cell's |
|
Definition
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|
Term
| what recombinant cytokine can be used for RCC and metastatic melanoma |
|
Definition
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|
Term
| what recombinant cytokine can be used for Anemias |
|
Definition
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|
Term
| what recombinant cytokine can be used for Bone marrow recovery |
|
Definition
| filgrastim (G-CSF) and sargramostim (GM-CSF) |
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|
Term
| what recombinant cytokine can be used for hep B and C, Kaposi's sarcoma, leukemias, malignant melanoma |
|
Definition
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|
Term
| what recombinant cytokine can be used for multiple sclerosis |
|
Definition
|
|
Term
| what recombinant cytokine can be used for chronic granulomatous disease? |
|
Definition
|
|
Term
| what recombinant cytokine can be used for thrombocytopenia |
|
Definition
| oprelvekin (IL-11) and thrombopoietin |
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|
Term
| Which immunosuppresant (Cyclosporine, tacrolimus, murmonab, sirolimus, azathiorprine, mycophenolate mofetil, daclizumab) is responsible for neprotoxicity, peripheral neuropathy, HT, pleural effusion, and hyperglycemia |
|
Definition
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|
Term
| Which immunosuppresant (Cyclosporine, tacrolimus, murmonab, sirolimus, azathiorprine, mycophenolate mofetil, daclizumab) is responsible for BM suppression and whose toxic effects are increased by allopurinol? |
|
Definition
|
|
Term
| Which immunosuppresant (Cyclosporine, tacrolimus, murmonab, sirolimus, azathiorprine, mycophenolate mofetil, daclizumab) is responsible for cytokine release syndrome and hypersensitivity reaction |
|
Definition
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|
Term
| Which immunosuppresant (Cyclosporine, tacrolimus, murmonab, sirolimus, azathiorprine, mycophenolate mofetil, daclizumab) is responsible for hyperlipidemia, thrombocytopenia, leukopenia |
|
Definition
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