McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 1 7  Immune modulators

T- and B- cell suppressors Several T- and B-cell immune suppressors are available for use. Of the numerous agents available, cyclosporin is the most commonly used immune suppressant. Addi- tional agents include abatacept ( Orencia ), azathioprine ( Imuran ), cyclosporin ( Sandimmun , Neoral ), glatiramer ( Copaxone ), mycophenolate ( CellCept ), pimecrolimus ( Elidel ), sirolimus ( Rapamune ) and tacrolimus ( Prograf ). Therapeutic actions and indications The exact mechanism of action of the T- and B-cell suppressors is not clearly understood. It has been shown that they block antibody production by B cells, inhibit suppressor and helper T cells, and modify the release of interleukins and of T-cell growth factor (see Figure 17.1). The T- and B-cell suppressors are indicated for the prevention and treatment of specific transplant rejec- tions. See Table 17.2 for usual indications of each agent. Pharmacokinetics Cyclosporin is well absorbed from the GI tract, reaching peak levels in 1 to 2 hours. It is extensively metabo- lised in the liver by the cytochrome P450 system and is primarily excreted in the bile. The half-life of the drug is about 19 hours for Sandimmun and 8.4 hours for Neoral. It is available as an oral solution that can be mixed with milk, chocolate milk or orange juice for ease of administration. Abatacept must be given as a 30-minute infusion every 2 to 4 weeks, depending on the person’s response. Peak levels are reached at the end of the infusion. Abatacept has a half-life of 12 to 23 days and usually reaches a steady state by 60 days of treat- ment. The drug is cleared from the body by the kidneys. Azathioprine is rapidly absorbed from the GI tract, reaching peak levels in 1 to 2 hours. This drug is catab- olised in the liver and red blood cells. Little is known about the pharmacokinetics of glati- ramer. Some of it is immediately hydrolysed on injection, some enters the lymph system and some may actually reach the systemic circulation. Mycophenolate is readily absorbed and immediately metabolised to its active metabolite. Most of the metab- olised drug is then excreted in the urine. Sirolimus is rapidly absorbed from the GI tract, reaching peak levels in 1 hour. It is extensively metabo- lised in the liver, partly by the cytochrome P450 system. The drug is then excreted primarily in the faeces. Tacrolimus (not available in New Zealand) is rapidly absorbed from the GI tract, reaching peak levels in 1.5 to 3.5 hours. It is extensively metabolised in the liver by the cytochrome P450 system and is excreted in the urine.

■■ Immune stimulants assist the immune system to fight specific pathogens or cancer cells; in doing so they cause flu-like symptoms (lethargy, muscle and joint aches and pains, anorexia, nausea). ■■ Interferons are used to treat various cancers and warts. ■■ Interleukins stimulate cellular immunity and inhibit tumour growth. IMMUNE SUPPRESSANTS Immune suppressants (Table 17.2) often are used in conjunction with corticosteroids, which block the inflammatory reaction and decrease initial damage to cells. They are especially beneficial in cases of organ transplantation and in the treatment of autoimmune diseases. The immune suppressants include T- and B-cell suppressors, an interleukin-receptor antagonist and monoclonal antibodies —antibodies produced by a single clone of B cells that react with specific antigens. ■ ■ Monitor for severe reactions, such as severe hypersensitivity reactions, and arrange to discontinue the drug immediately if they occur . ■ ■ Arrange for supportive care and comfort measures for flu-like symptoms (e.g. rest, environmental control, paracetamol) to help the person cope with the drug effects . Ensure that the person is well hydrated during therapy to prevent severe adverse effects . ■ ■ Instruct women in the use of barrier contraceptives to avoid pregnancy during therapy because of the potential for adverse effects on the fetus . ■ ■ Offer support and encouragement to deal with the diagnosis and the drug regimen . ■ ■ Provide teaching about measures to avoid adverse effects; warning signs of problems; and proper administration technique. Evaluation ■ ■ Monitor response to the drug (improvement in condition being treated). ■ ■ Monitor for adverse effects (flu-like symptoms, GI upset, CNS changes, bone marrow depression). ■ ■ Evaluate the effectiveness of the teaching plan (person can name drug, dosage, adverse effects to watch for, specific measures to avoid adverse effects). ■ ■ Monitor the effectiveness of comfort measures and compliance with the regimen. KEY POINTS