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Immunosuppressants
| Question | Answer |
|---|---|
| Complications of immunosuppressive therapy ? | * Suppression of immune system .... (lead to infections such as CMV) |
| Major classes of immunosuppressive agent classes ? | * Glucocorticoids -- Calcineurin inhibitors -- Cytotoxic agents -- Biologics |
| Glucocorticoids = ? | * Prednisone -- methylprednisolone -- dexamethasone |
| Gluco. Uses ? | * Prevent rejection - best if given at time of transplant ..... * high doses treat Acute Rejection phases ..... * helps supress/lower GVHD |
| Gluco. MOA ? | * Inhibits innate and acquired immunity by inhibiting T cell proliferation and inhibits IL-2 production (which increase T-cells) |
| Gluco. SEs ? | * Steroid Man |
| Calcineurin inhibitors (antibiotics)= ? | * Cyclosporine and Tacrolimus |
| Cyclosporine use ? | * prophylaxis only - not effective in ongoing rejection |
| Cyclosporine MOA ? | * Binds to cyclophilin --> Cyclosporin-cyclophilin complex binds calcineurin --> prevents IL-2 from being activated (no T-cells) .... * Prevents transcription factors from being made to activate IL-2 |
| Cyclosporine pharmokinetics ? | * Narrow TI ….. Need enough dose to prevent rejection, but have to monitor as to not get toxicity |
| Cyclosporine SEs ? | * typical stuff and weird ones --> hirsutism and gingival bleeding ..... * Highly Nephrotoxic (give to prevent rejection, yet it is damaging to an organ you are trying to help) .... * Hyperkalemia - due to decreased K excretion |
| Tacrolimus MOA and SEs ? | * Similar MoA and Use as cyclosporine except binds FKBP rather than cyclophilin.... * No side effects like cyclosporine |
| Antiproliferative Agent - Sirolimus use and MOA ? | * USE: prophylaxis (usually in combo) - + calcineurin inhibitor + glucocorticoid ...... * Binds to FKBP like tacrolimus but Does NOT block IL-2 production, the Sirolimus-FKBP complex binds to mTOR which blocks kinases needed for genes binds mTOR |
| MOA basics ? | * Interrupts T-cell activation downstream of IL-2 receptor --> Inhibits proliferation bc stops cell proliferation at G1-S phase |
| Sirolimus SEs ? | * hyperlipidemia and myelosuppression --> (thrombocytopenia, anemia, leukopenia) |
| Antiproliferative - Azathioprine uses ? | * Prodrug converted to mercaptopurine..... * Primary cytotoxic agent used for immunosuppression to prevent and maintain transplant.... * CAN use in ongoing Rejection |
| Azathioprine MOA ? | * the active metabolite (6-MP) Interferes with purine nucleotide de novo synthesis --> inhibits DNA synthesis ..... acts just like the anti-cancer antimetab purine drugs by (-) TMP/IMP synthesis needed for G and A synthesis |
| Azathioprine pharmokinetics ? | * Metabolized (cleared) by the enzyme xanthine oxidase..... * So Azathioprine dose reduction required when allopurinol is being used |
| Azathioprine SEs ? | * bone marrow suppression -- leukopenia (most common) |
| Immunosupressant - Mycophenolate mofetil MOA and USE? | * Selective, noncompetitive inhibitor of IMPDH --> Stops IMP from being made --> no pureines made ..... * Used w/ glucocorticoid + calcineurin inhibitor --- Has mostly replaced azathioprine for maintenance immunosuppression |
| Methotrexate use ? | * Used extensively to treat GVHD and Rheumatoid arthritis |
| Immunosuppressive Antibodies purpose ? | * lower/impair T-Cells, while keeping humoral immunity intact |
| Immunosuppressive Antibody ALG when to use ? | * is a Polyclonal anti-lymphocyte .... * Major use in kidney transplants after transplant .... * |
| ATG ? | * Polyclonal anti-thymocyte also.... *Used during acute rejection episodes...... * also be used in immunosuppression like ALG |
| ALG & ATG summary ? | * Used to treat donor BM prior to transplantation to destroy T cells to avoid GVHD |
| ALG AND ATG SEs ? | * allergic type reactions from body recognizing foreign particles and mounting a response to them |
| Muromonab-CD3 (OKT3) MOA? | * Directed against CD3 on surface of human thymocytes & mature T-cells ......... * Shuts down activation of T-cell proliferation |
| Muromonab-CD3 (OKT3) uses and SEs ? | * USES: - Treat acute rejection episodes in combination with other drugs --- Deplete donor BM of T-cells prior to BM transplant ...... * not really used anymore bc SEs...... * SEs: fever, chills,and Cytokine Storm ... * body can develop ABs to it also |
| Daclizumab & Basiliximab MOA ? | * Monoclonal antibodies to part of IL-2 receptor (CD25) … IL-2 antagonist ...... * prevents IL-2 from binding to lymphocytes...... ---- * Daclizumab – humanized IgG1 ---- Basiliximab – chimeric mouse-human IgG1 |
| Daclizumab & Basiliximab use ? | * Can use long term ..... * Primarily used for prophylaxis against acute rejection of renal transplants in combination with cyclosporine and corticosteroids |
| For a renal graft rejection, what Treatment (frequency of use) is most commonly used ? | * High dose corticosteroid pulse (76%) - 1st line therapy in most centers ...... * Anti T-cell antibody therapy -- Thymoglobulin (ALG AND ATG)(28%) |
| GVHD Prophylaxis ? | * Methotrexate + cyclosporine and deplete T-Cells |
Created by:
thamrick800
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