IMMUNOSUPPRESSANT DRUGS

Immunosuppressant drugs
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.

Recommended dosage
Immunosuppressant drugs are available only with a physician’s prescription. They come in tablet, capsule, liquid, and injectable forms. The recommended dosage depends on the type and form of immunosuppressant drug and the purpose for which it is being used. Doses may be different for different patients. The prescribing physician or the pharmacist who filled the prescription will advise the patient on the correct dosage.

Patients who are taking immunosuppressant drugs should take them exactly as directed. They should never take smaller, larger, or more frequent doses of these medications. In addition, immunosuppressant drugs should never be taken for a longer period of time than directed. The physician will decide exactly how much of the medicine each patient needs. Blood tests are usually necessary to monitor the action of these drugs. Patients should always consult the prescribing physician before they stop taking an immunosuppressant drug.

Precautions
Patients who are taking immunosuppressant drugs should see their doctor on a regular basis. Periodic checkups will allow the physician to make sure the drug is working as it should and to monitor the patient for unwanted side effects. These drugs are very powerful and can cause such serious side effects as high blood pressure, kidney problems and liver disorders. Some side effects may not show up until years after the medicine was used. Anyone who has been advised to take immunosuppressant drugs should thoroughly discuss the risks and benefits of these medications with the prescribing physician.

Immunosuppressant drugs lower a person’s resistance to infection and can make infections harder to treat. The drugs can also increase the chance of uncontrolled bleeding. Anyone who has a serious infection or injury while taking immunosuppressant drugs should get prompt medical attention and should make sure that the treating physician knows that he or she is taking an immunosuppressant medication. The prescribing physician should be immediately informed if such signs of infection as fever or chills; cough or hoarseness; pain in the lower back or side; painful or difficult urination; bruising or bleeding; blood in the urine; bloody or black, tarry stools occur. Other ways of preventing infection and injury include washing the hands frequently, avoiding sports in which injuries may occur, and being careful when using knives, razors, fingernail clippers, or other sharp objects. Avoiding contact with people who have infections is also important.

In addition, people who are taking or have been taking immunosuppressant drugs should not have such immunizations as smallpox vaccinations without consulting their physician. Because their resistance to infection has been lowered, people taking these drugs might get the disease that the vaccine is designed to prevent. People taking immunosuppressant drugs should avoid contact with anyone who has had a recent dose of oral polio vaccine, as there is a chance that the virus used to make the vaccine could be passed on to them.

Immunosuppressant drugs may cause the gums to become tender and swollen or to bleed. If this happens, a physician or dentist should be notified. Regular brushing, flossing, cleaning, and gum massage may help prevent this problem. A dentist can provide advice on how to clean the teeth and mouth without causing injury.