Cyclosporine: Immunosuppressive effects, entwined toxicity, and clinical modulations of an organ transplant drug

Abstract

The discovery and use of cyclosporine since its inception into the clinics in the ‘70s and up have played a crucial role in advancing transplant therapy, and containment of the immune-based rejections. The drug has improved the high rates of acute rejections and has supported early graft survival. However, the long-term survival of renal allografts is still less prevalent, and an in-depth analysis, as well as reported findings led us to believe that there is a chronic irreversible component to the drug, that is tackled through its metabolites, and that causes toxicity, which has led to new therapies, including monoclonal antibody-based medications. A recap of the immunosuppressive effects, and entwined toxicity of the drug, now relegated primarily to bone marrow early transplants, is being overviewed for the past protocols that were used to minimize, and avoid, or use this calcineurin inhibitor class of drug, cyclosporine, in combination with other drugs. The current review circumvents the cyclosporine's mechanism of action, pathophysiology, cytochrome roles, and other factors associated with acute and chronic toxicity developments. The review also attempts to find conclusive strategies reported in the recent studies to avoid its toxic side effects, and develop a safe-use strategy for the drug. Gastrointestinal decontamination, supporting the airway, monitoring for signs of respiratory insufficiency, monitoring for severe reactions, such as seizures, need for administration of oxygen, and avoiding the administration of drugs, that increase the blood levels of the cyclosporine, are beneficial interventions, when encountering cyclosporine toxicity cases. The constrained therapeutic outcomes have also led to redesign, and making use of combined formulations to reassess the pharmacokinetics of the drug.