Immunosuppressant Drugs Chapter 48 Immunosuppressant Drugs Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Immune System The purpose of the immune system is to distinguish self from nonself and to protect the body from foreign material (antigens), including cancer Two types of immunity: humoral immunity, which is mediated by B lymphocytes, and cellular immunity, which is mediated by T lymphocytes Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Immune System (cont’d) Participates in anaphylactic reactions Responsible for rejection of kidney, liver, and heart transplants Can also sometimes attack itself, causing “autoimmune diseases” or immune-mediated diseases Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Immunosuppressants Drugs that decrease or prevent an immune response, thus suppressing the immune system Used to prevent or treat rejection of transplanted organs Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Immunosuppressants (cont’d) All suppress certain T-lymphocyte cell lines, thus preventing their involvement in the immune response Results in a pharmacologically immunocompromised state Mechanisms of action vary according to drug Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Immunosuppressants (cont’d) Major classes used to prevent organ rejection Glucocorticoids Calcineurin inhibitors Antimetabolites Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Immunosuppressants (cont’d) cyclosporine (Sandimmune) azathioprine (Imuran) muromonab-CD3 (Orthoclone) daclizumab (Zenapax) sirolimus (Rapamune) basiliximab (Simulect) glatiramer acetate (Copaxone) tacrolimus (Prograf) mycophenolate mofetil (CellCept) Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Immunosuppressants (cont’d) Indications vary from drug to drug Primarily indicated for the prevention of organ rejection Muromonab-CD3, mycophenolate, and tacrolimus are indicated for both prevention of rejection and treatment of organ rejection Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Classroom Response Question The nurse should question the prescriber regarding use of cyclosporine for the treatment of which disease? Arthritis Psoriasis Irritable bowel disease Multiple sclerosis Correct answer: D Rationale: Cyclosporine (Sandimmune, Neoral, Gengraf) is an immunosuppressant drug that is indicated for the prevention of organ rejection as well as the treatment of other immunologic disorders, such as various forms of arthritis, psoriasis, and irritable bowel disease. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Immunosuppressants (cont’d) azathioprine (Imuran) Prophylaxis of organ rejection concurrently with other immunosuppressant drugs, such as cyclosporine and corticosteroids Also used in the treatment of rheumatoid arthritis Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Immunosuppressants (cont’d) basiliximab (Simulect) and daclizumab (Zenapax) Monoclonal antibodies Used to prevent rejection of transplanted kidneys Generally used as part of a multidrug immunosuppressive regimen that includes cyclosporine and corticosteroids Have a tendency to cause the allergy-like reaction known as cytokine release syndrome Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Immunosuppressants (cont’d) cyclosporine (Sandimmune) Prevention of organ rejection May be used for other autoimmune disorders tacrolimus (Prograf) Used for the prevention of liver transplant rejection Others uses are unlabeled uses Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Classroom Response Question A patient who had a kidney transplant is receiving cyclosporine PO in maintenance doses. What action would decrease the potency of this drug? Taking it with orange juice Taking it with milk Using a Styrofoam container to administer the drug Mixing it with chocolate milk Correct answer: C Rationale: Cyclosporine should not be mixed in a Styrofoam container because the medication has been found to adhere to the inside wall of the cup or container. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Immunosuppressants (cont’d) glatiramer acetate (Copaxone) Works by blocking T-cell autoimmune activity against myelin protein, which reduces the frequency of the neuromuscular exacerbations associated with multiple sclerosis Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Immunosuppressants (cont’d) fingolimod (Gilenya) Failed as an antirejection drug Approved in 2010 for multiple sclerosis Only oral drug for relapsing forms of multiple sclerosis Significant adverse effects, including headache, hepatotoxicity, flulike symptoms, back pain, AV block, bradycardia, hypertension, and macular edema, may occur Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Immunosuppressants (cont’d) muromonab-CD3 (Orthoclone OKT3) Reversal and prevention of graft rejection Monoclonal antibody Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Immunosuppressants (cont’d) mycophenolate (CellCept) Indicated for the prevention of organ rejection as well as the treatment of organ rejection FDA black box warning for increased risk of congenital malformations and spontaneous abortions when used during pregnancy Common side effects include hypertension, hypotension, peripheral edema, tachycardia, pain, headache, hyperglycemia, hyperlipidemia, electrolyte disturbances, and others Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Immunosuppressants (cont’d) Adverse effects vary according to drugs and may be devastating All immunosuppressed patients have a heightened susceptibility to opportunistic infections Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Nursing Implications Perform a thorough assessment before administering these drugs Renal, liver, and cardiovascular function studies CNS baseline function Respiratory assessment Baseline vital signs Baseline laboratory studies, including hemoglobin, hematocrit, WBC, and platelet counts Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Nursing Implications (cont’d) Assess for contraindications, drug allergies, and drug interactions Monitor WBC counts throughout therapy; if the count drops below normal range, contact the prescriber Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Classroom Response Question Which potential problem is of most concern for the patient receiving immunosuppressant drugs? Orthostatic hypotension Increased susceptibility to infections Neurotoxicity Peripheral edema Correct answer: B Rationale: Neurotoxicity and edema may be a problem with some immunosuppressants (not orthostatic hypotension), but a heightened susceptibility to opportunistic infections is a major risk factor in immunosuppressed patients. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Nursing Implications (cont’d) Oral immunosuppressants should be taken with food to minimize GI upset Oral forms are used when possible to decrease the risk of infection that may occur with parenteral injections Note that there are several possible drug interactions Grapefruit juice also interacts with some of these drugs Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Nursing Implications (cont’d) Oral antifungal drugs are usually given with these drugs to treat oral candidiasis that may occur Assess the oral cavity often for white patches on the tongue, mucous membranes, and oral pharynx Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Nursing Implications (cont’d) Mix oral cyclosporine solution in a glass container Do not use Styrofoam containers because the drug adheres to the inside wall of the container Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Nursing Implications (cont’d) Follow guidelines for parenteral administration carefully Inform patients that lifelong therapy with immunosuppressants is indicated with organ transplantation Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Nursing Implications (cont’d) Patients taking immunosuppressants should be encouraged to take measures to reduce the risk of infection Avoiding crowds Avoiding people with colds or other infections Inform patients to immediately report fever, sore throat, chills, joint pain, fatigue, or other signs of a severe infection Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Nursing Implications (cont’d) Monitor for therapeutic responses Monitor for adverse effects and signs of drug toxicity Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Classroom Response Question A male patient who received a kidney transplant 6 months ago is taking cyclosporine. The patient tells the nurse that he has started to take several herbal preparations. Which does not pose a possible problem for the patient? St. John’s wort Ginkgo Cat’s claw Echinacea Correct answer: B Rationale: The potential for interactions between immunosuppressant drugs and herbal preparations should not be overlooked. For example, the enzyme-inducing properties of St. John’s wort have been demonstrated to reduce the therapeutic levels of cyclosporine and cause organ rejection. The immunostimulant properties of cat’s claw and echinacea may be similarly undesirable in transplant recipients, because they have effects that are opposite those of the immunosuppressants. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.