Major immunosuppressive agents
Information about Major immunosuppressive agents
Solid organ transplantation has been made possible by the development of potent immunosuppressive agents which block cellular rejection adequately for survival of the transplanted organ and induction of at least partial tolerance.
History of Major immunosuppressive agents
The first regimens that were found to successfully prevent cellular rejection consisted of high doses of corticosteroids and an immunosuppressive antimetabolite such as azathioprine, 6-mercaptopurine or cyclophosphamide. These combinations allowed for the initial successes in renal, liver, lung and heart transplantation in the 1950s and 1960s. However, acute and chronic rejection as well as complications of high dose corticosteroid therapy remained major problems. The subsequent introduction of the calcineurin inhibitors, cyclosporine and tacrolimus in the 1980s placed organ transplantation on a solid basis, leading to its acceptance as the standard of care for end-stage kidney, liver, heart and lung disease. The further addition of the newer, more specific antiproliferative and immunosuppressive agents–mycophenolate mofetil (1995) and sirolimus (1999)–have further improved the management of patients after solid organ transplantation.
Liver safety of Major immunosuppressive agents
All of these agents are associated with mild liver test abnormalities that occur early during therapy or shortly after transplantation and that resolve rapidly with dose modification. While these potent immunosuppressive agents all have some degree of liver toxicity, clinically significant injury is rare and has invariably been mild and rapidly reversible with dose modification or switching to another agent. These agents are often used in patients with underlying liver disease or who are receiving multiple potentially hepatotoxic drugs, so that their role in causing hepatic injury is not always clear.
The following drugs used to prevent transplant rejection.