Created by Kate Parvey
over 7 years ago
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Question | Answer |
WHAT ARE THE PHASES OF IMMUNOSUPPRESSION IN TRANSPLANTATION? | 1) INDUCTION - time to achieve therapeutic levels decreases risk of acute allograft rejection 2) MAINTENANCE - required for life of allograft 3) RESCUE - treatment of acute rejection |
NAME THE 3 IMMUNOSUPPRSSANTS COVERED IN CLASS | CALCINEURIN INHIBITORS 1) Cyclosporine (Neoral, Gengraf) 2) Tacrolimus (Prograf) 3) Mycophenolate (Cellcept, Myfortic) |
HOW DO CALCINEURIN INHIBITORS WORK? | Suppress production of Interleukin-2 (IL-2) - IL-2 is req for T cell proliferation * backbone of anti-rejection therapy - liver, kidney, lung, heart, pancreas, small bowel, bone marrow etc |
CYCLOSPORIN (Sandiumme, Neoral, Gengraf) Uses & MOA | For; Antirejection therapy of organs Rheumatological disease Severe psoriasis MOA: Calcineurin Inhibitor: Suppress production of interleukin- 2 (IL-2) which is required for T cell proliferation Cyclosporin must first bind to cyclophilin to activate |
CYCLOSPORIN Adverse Effects | AE: Nephrotoxicity (avoid using with NSAIDS) Hypertension Hyperlipidemia Gingival hyperplasia Infection Tremor Hepatotoxicity Lymphomas |
CYCLOSPORIN Drug Interactions | Metabolized by CYP 3A4= drug interactions Decreased Cyclosporin levels: phenytoin, phenobarbital, carbmazepine, rifempin, terbenafine, trimethoprim/ sulamethoxole Increased Cyclosporin levels- ketoconazole, erythomycin, amphoteracin B, grapefruit juice |
CYCLOSPORIN Monitoring | Ongoing evaluation and intervention - Evaluate therapeutic effects - Dosage adjustments Initial dose given 4-14hr before surgery then titrated to 3-10 mg/kg/day (following levels) Target concentration: 100-300ng/mL |
TACROLIMUS (Prograf, FK506) Uses & MOA | For: Antirejection therapy Immunosuppressant to prevent the rejection of organ in allograft transplant MOA: Calcineurin Inhibitor: Suppress production of interleukin- 2 (IL-2) which is required for T cell proliferation Tacrolimus: must first bind to intracellular protein (FKBP- 12) to inhibit calcineurin Tacrolimus: must first bind to intracellular protein (FKBP- 12) to inhibit calcineurin |
TACROLIMUS (Prograf, FK506) Adverse Effects | Nephrotoxicity (avoid using with NSAIDS) Risk of infection Neurotoxicity- headache, tremor, insomnia GI: N/V, diarrhea Hyperglycemia Hypertension Infection Lymphoma |
TACROLIMUS (Prograf, FK506) Drug Interactions | Metabolized by CYP 3A4= drug interactions Decreased cyclosporin levels: phenytoin, phenobarbital, carbmazepine, rifempin, terbenafine, trimethoprim/ sulamethoxole Increased cyclosporin levels- ketoconazole, erythomycin, amphoteracin B, grapefruit juice |
TACROLIMUS (Prograf, FK506) Monitoring | Ongoing evaluation and intervention - Evaluate therapeutic effects - Dosage adjustments Target concentration 4-14 ng/mL |
MACROPHENOLATE (Cellcept, Myfortic) Uses & MOA | Immunosuppressant MOA: Rapidly converted in body to mycophenolic acid (MPA) - Inhibits inosine monophophate dehydrogenase (enzyme key to purine synthesis) - Inhibits proliferstion of B & T nucleocytes - Metabolized in liver to inactive metabolite |
MYCOPHENOLATE Adverse Effects | AE: GI symptoms: diarrhea, vomiting, abdominal pain Bone marrow suppression: leukopenia, thrombocytopenia, anemia Infection, lymphomas, teratogenic |
MYCOPHENOLATE Drug Interactions | Drug Interactions: Decreased absorption with magnesium and aluminum and cholestyramine |
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