Immunosuppression is started soon after surgery. Transplant recipients are maintained on an immunosuppression regimen that includes 1-3 drugs. Generally, the drugs fall into 3 categories: steroids, antimetabolites, and other immunosuppressants.Several regimens can be used, including pretransplantation induction therapy and simple postoperative maintenance therapy; the choice of regimen depends on the training and experience of the transplantation center.
Cyclosporine is a cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease for various organs.
For children and adults, base dosing on ideal body weight. Maintaining appropriate levels of the drug in the bloodstream is crucial to the maintenance of the allograft. Foods can alter the level of the drug and time of administration. Medication must be taken at the same time every day.
Neoral is the capsular form of cyclosporine, available in 25- and 100-mg capsules. Sandimmune is the liquid form. GENGRAF is the branded generic form, available in 25- and 100-mg capsules.
Prednisone is an immunosuppressant used for the treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear (PMN) leukocyte activity. It is an oral steroid with approximately 5 times the potency of endogenous steroids. Minimal to no oral prednisone should be given for the first 21 days after transplantation unless rejection occurs.
Methylprednisolone is an immunosuppressant used to treat autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. It is the intravenous (IV) form of prednisone.
Tacrolimus suppresses humoral immunity (T-cell activity). It is a calcineurin inhibitor with 2-3 times the potency of cyclosporine. Tacrolimus can be used at lower doses than cyclosporine, but it has severe adverse effects, including renal dysfunction, diabetes, and pancreatitis. Levels are adjusted according to renal function, hepatic function, and adverse effects.
Mycophenolate mofetil inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thus inhibiting their proliferation. It inhibits antibody production.
Azathioprine antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. It may decrease proliferation of immune cells, which results in lower autoimmune activity. Antimetabolites are used to block the uptake of vital nutrients needed by the cells. As implied, these drugs affect not only the cells of the immune system but also other cells of the body. The potency of therapy is dose dependent. Azathioprine is not effective treatment for acute rejection episodes but remains an economical choice for long-term immunosuppression.
Sirolimus, also known as rapamycin, is a macrocyclic lactone produced by Streptomyces hygroscopicus. It is a potent immunosuppressant that inhibits T-cell activation and proliferation by a mechanism that is distinct from those of all other immunosuppressants. This inhibition suppresses cytokine-driven T-cell proliferation by inhibiting progression from the G1 phase to the S phase in the cell cycle.