Cyclosporine solid organ transplantation

Cyclosporine and tacrolimus have dramatically enhanced the success of solid organ transplantation. Nephrotoxicity, however, remains a major dose-limiting adverse effect of both drugs. " Early acute hemodynamically-mediated renal insufficiency and delayed chronic interstitial nephritis have been observed (see section on chronic interstitial nephritis later in this chapter). ... 

See Chap. 87 on solid organ transplantation for a discussion of drug interactions involving cyclosporine. 

Grieff M, Loertscher R, Shohaib SA, Stewart DJ. Cyclosporine-induced elevation in circulating endothelin-1 in patients with solid-organ transplants. Transplantation 1993 56 880-884. 

Clinical uses and pharmacokinetics Use of these immunosuppressants is a major factor in the success of solid organ transplantation. Cyclosporine is used in solid organ transplantation and in graft-versus-host syndrome in bone marrow transplants. Tacrolimus is used in liver and kidney transplant recipients and may be effective as rescue therapy in patients who fail standard therapy. Sirolimus is used alone or in combination with cyclosporine in kidney and heart transplantation. The agents, particularly cyclosporine, may also be effective in immune diseases, including rheumatoid arthritis, uveitis, psoriasis, asthma, and type 1 diabetes. 

Cyclosporine A (CsA) is an inhibitor of intracellular calcineurin, thereby inhibiting the production and release of interleukin-2 (IL-2) which subsequently limits clonal activation and expansion of T-lymphocytes. CsA is FDA-approved for the prevention of solid organ transplant rejection (kidney, liver) and keratoconjunctivitis sicca. Non-FDA labeled indications include, but are not limited to, the autoimmime diseases systemic lupus erythematosus rheumatoid arthritis myasthenia gravis. 

Immunosuppressants are drugs capable of suppressing immune responses. They are used to treat autoimmune disease, aUergy, multiple myeloma, and chronic nephritis, and in organ transplantation. For example, immunosuppressants that are used to provide maintenance immunosuppression in solid organ and bone marrow transplant patients include cyclosporine, everoHmus (Ever), mycophe-nolic acid (MPA), Siro, and Tac (Figure 33-13). 

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