Immunosuppressant Drugs Health Article

Definition

Immunosuppressant drugs, which are also called anti-rejection drugs, are used to prevent the body from rejecting a transplanted organ.

Purpose

When an organ, such as a liver, heart or kidney, is transplanted from one person (the donor) into another (the recipient), the immune system of the recipient triggers the same response against the new organ that it would have against any foreign material, setting off a chain of events that can damage the transplanted organ. This process is called rejection. It can occur rapidly (acute rejection), or over a long period of time (chronic rejection). Rejection can occur despite close matching of the donated organ and the transplant patient. Immunosuppressant drugs greatly decrease the risks of rejection, protecting the new organ and preserving its function. These drugs act by blocking the recipient's immune system so that it is less likely to react against the transplanted organ. A wide variety of drugs are available to achieve this aim but work in different ways to reduce the risk of rejection.

In addition to being used to prevent organ rejection, immunosuppressant drugs are also used to treat such severe skin disorders as psoriasis and such other diseases as rheumatoid arthritis, Crohn's disease (chronic inflammation of the digestive tract), and patchy hair loss (alopecia areata). Some of these conditions are termed "autoimmune" diseases, indicating that the immune system is reacting against the body itself.

Description

Immunosuppressant drugs can be classified according to their specific molecular mode of action. The four main categories of immunosuppressant drugs currently used in treating patients with transplanted organs are the following:

• Cyclosporins (Neoral, Sandimmune, SangCya). These drugs act by inhibiting T-cell activation, thus preventing T-cells from attacking the transplanted organ.
• Azathioprines (Imuran). These drugs disrupt the synthesis of DNA and RNA as well as the process of cell division.
• Monoclonal antibodies, including basiliximab (Simulect), daclizumab (Zenpax), and muromonab (Orthoclone OKT3). These drugs act by inhibiting the binding of interleukin-2, which in turn slows down the production of T-cells in the patient's immune system.
• Such corticosteroids as prednisolone (Deltasone, Orasone). These drugs suppress the inflammation associated with transplant rejection.

Most patients are prescribed a combination of drugs after their transplant, one from each of the above main groups; for example, they may be given a combination of cyclosporin, azathioprine, and prednisolone. Over a period of time, the doses of each drug and the number of drugs taken may be reduced as the risks of rejection decrease. Most transplant patients, however, will need to take at least one immunosuppressive medication for the rest of their lives.

Immunosuppressants can also be classified according to the specific organ that is transplanted:

• Basiliximab (Simulect) is also used in combination with such other drugs as cyclosporin and corticosteroids in kidney transplants.
• Daclizumab (Zenapax)is also used in combination with such other drugs as cyclosporin and corticosteroids in kidney transplants.
• Muromonab CD3 (Orthoclone OKT3) is used along with cyclosporin in kidney, liver and heart transplants.
• Tacrolimus (Prograf) is used in liver and kidney transplants. It is under study for bone marrow, heart, pancreas, pancreatic island cell, and small bowel transplantation

Some immunosuppressants are also used to treat a variety of autoimmune diseases:

• Azathioprine (Imuran) is used not only to prevent organ rejection in kidney transplants, but also in treatment of rheumatoid arthritis. It has been used to treat chronic ulcerative colitis, although it has proved to be of limited value for this use.
• Cyclosporin (Sandimmune, Neoral) is used in heart, liver, kidney, pancreas, bone marrow, and heart/lung transplantation. The Neoral form of cyclosporin has been used to treat psoriasis and rheumatoid arthritis. The drug has also been used to treat many other conditions, including multiple sclerosis, diabetes, and myasthenia gravis.
• Glatiramer acetate (Copaxone) is used in the treatment of relapsing-remitting multiple sclerosis. In one study, glatiramer reduced the frequency of multiple sclerosis attacks by 75% over a two-year period.
• Mycopehnolate (CellCept) is used along with cyclosporin in kidney, liver, and heart transplants. It has also been used to prevent the kidney problems associated with lupus erythematosus.
• Sirolimus (Rapamune) is used in combination with other drugs, including cyclosporin and corticosteroids, in kidney transplants. The drug is also used to treat patients with psoriasis.