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Cyclosporine : A review article

Abstract

Cyclosporine is a immunosuppressive agent used in solid organ and bone marrow transplantation worldwide. Its discovery in 1972 was revolutionary in transplant medicine because of the need to suppress the immune system without affecting other cells substantially. The biochemical effect of calcineurin inhibitors, including cyclosporine and tacrolimus, is the inhibition of T-cell activation through various mechanisms. Even though cyclosporine was considered less cytotoxic, some adverse effects were revealed later. Nephrotoxicity is a well known adverse effect, probably induced by the vasoconstrictive effect of cyclosporine. In addition, this article describes cardiovascular, gastrointestinal and neurological adverse effects. Disturbances in blood glucose, lipids and electrolytes have also been reported. A narrow therapeutic range, in addition to interactions with Cyt-P450, makes careful monitoring of cyclosporine very important. Cyclosporine also have interactions with other drugs, such as calcium-inhibitors, carbamazepine and rifampine. The clinical use and efficacy have been described in transplantation of various solid organs as well as bone marrow transplantation. The results for cyclosporine and other immunosuppressive agents have been compared. As an example of cyclosporine-induced visual adverse effects, we also included a case report describing onset of visual adverse effects in a patient after 15 years of cyclosporine prophylaxis due to cardiac transplantation. These visual symptoms showed improvement on cessation of cyclosporine. Possible microangiopathic effects of cyclosporinehave been described, e.g. local endothelin-1 (ET-1) activity, effects on nitric oxide (NO), superoxides (O2-) and interactions on the sympathetic nervous system. Finally, future aspects and the new immunosuppressive agent known as the mTOR inhibitors have been discussed. Especially the need to use cyclosporine sparing regimens in the future has drawn much attention. Most importantly this is due to the nephrotoxic effect of cyclosporine

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