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CALCINEURINE
INHIBITORS
Cyclosporine
| Representative Examples: | Cyclosporine (Sandimmune®, Neoral®, Gengraf®), Tacrolimus (Prograf®, FK506) |
| Clinical Use: | Calcineurine Inhibitors are used in maintenance immunosuppression. |
| General Mechanism: | The mechanisms of Calcineurine Inhibitors converge at the inhibition of the calcineurin. This inhibition ultimately inhibits the production and secretion of IL-2. The interaction between IL-2 and the IL-2 Receptor is crucial in the activation and differentiation of B and T cells. Therefore, halting the rejection process at this step is highly effective at combating rejection. |
Cyclosporine
| Pharmacological Mechanism: | Cyclosporine is a small fungal cyclic peptide that is used to prevent allograft rejection. Cyclosporine works by binding a protein found in the cytosol: cyclophilin. This complex inhibits calcineurin. The rest of the mechanism is outlined above. Cyclosporine is a highly effective immunsuppressant. In fact, cyclosporine is generally hailed as the cornerstone of immunosuppression. The clinical introduction of Cyclosporine significantly increased graft survival and significantly reduced the occurrence of acute rejection in patients. |
| Side Effects: | Side effects observed
with cyclosporine use include:
|
| Representative Dose/Route: |
Cyclosporine is available in form of emulsions and micro-emulsions. Maintenance doses consist of orally administered cyclosporine, normally 5-10 mg/kg/day given in two doses. This is usually taken along with an antiproliferative agent and prednisone as part of an immunosuppression regimen. Intravenous solutions also exist, with only a third of the oral dose required for this form. |
Tacrolimus
| Pharmacological Mechanism: |
Tacrolimus is a microlide antibiotic that works in a mechanism similar to that of cyclosporine to prevent allograft rejection. Tacrolimus binds the cytosolic protein FKPB-121. This complex inhibits calcineurin in a manner parallel to cyclosporine. |
| Side Effects: | Side
effects observed with tacrolimus use include:
|
| Representative Dose/Route: | Tacrolimus is available in oral pills. A maintenance dose is usually 0.15-0.3 mg/kg/day given in two doses. There is also an intravenous form available, those dosing of which is usually 0.03 mg/kg intravenously for 24 hours. |
Corticosteriods Calcineurine Inhibitors Antiproliferative Agents Monoclonal Antibodies Polyclonal Antibodies
Other References
Side Effects Drug Efficacy