Immunosuppressant Drugs Chapter 48 Immunosuppressant Drugs Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. 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 © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. Immune System (Cont.) 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 © 2017, Elsevier Inc. All rights reserved.

A Simplified Depiction of the Complicated Immune System Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. Immunosuppressants Drugs that decrease or prevent an immune response, thus suppressing the immune system Used to prevent or treat rejection of transplanted organs Immunosuppressive therapy Uses: rheumatoid arthritis, systemic lupus erythematosus, Crohn’s disease, multiple sclerosis (MS), myasthenia gravis, psoriasis, and others Copyright © 2017, Elsevier Inc. All rights reserved.

Immunosuppressants (Cont.) 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 © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. Transplants Types: kidney, heart, liver, lung, pancreas, small bowel, bone marrow, and cornea transplantation Rejection: primary concern; occurs from an immune response targeted against the transplanted organ Immunosuppressants are used to inhibit the immune system and prevent organ rejection. Transplant patients are on immunosuppressant therapy for the duration of their lifetime. Cost of therapy can average more than $2500 per month. Copyright © 2017, Elsevier Inc. All rights reserved.

Immunosuppressants (Cont.) Major classes used to prevent organ rejection: Glucocorticoids: inhibit all stages of T-cell activation and are used for induction, maintenance immunosuppression, and acute rejection Calcineurin inhibitors: inhibit the phosphate required for interleukin 2 production Antimetabolites: inhibit cell proliferation Biologics: inhibit cytotoxic T killer cell function Copyright © 2017, Elsevier Inc. All rights reserved.

Immunosuppressants (Cont.) cyclosporine (Sandimmune) azathioprine (Imuran) muromonab-CD3 (Orthoclone) daclizumab (Zenapax) sirolimus (Rapamune) basiliximab (Simulect) glatiramer acetate (Copaxone) tacrolimus (Prograf) mycophenolate mofetil (CellCept) fingolimod (Gilenya), 2010 Copyright © 2017, Elsevier Inc. All rights reserved.

Immunosuppressants (Cont.) Therapeutic use varies 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 © 2017, Elsevier Inc. All rights reserved.

Audience Response System Question The nurse should question the prescriber regarding use of cyclosporine for the treatment of which disease? Arthritis Psoriasis Irritable bowel disease MS 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 © 2017, Elsevier Inc. All rights reserved.

Immunosuppressants (Cont.) Azathioprine (Imuran) Prophylaxis of organ rejection concurrently with other immunosuppressant drugs, such as cyclosporine and corticosteroids. Adverse effects: lymphoma and other malignancies as well as hepatosplenic T-cell lymphoma Copyright © 2017, Elsevier Inc. All rights reserved.

Immunosuppressants (Cont.) 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 © 2017, Elsevier Inc. All rights reserved.

Immunosuppressants (Cont.) Basiliximab (Simulect) and daclizumab (Zenapax) Cytokine release syndrome: can be severe and even involve anaphylaxis. Patients are often premedicated with corticosteroids (e.g., intravenous [IV] methylprednisolone) in an effort to avoid or alleviate this problem. Basiliximab: black-box warning-potential for lymphoproliferative disorders and opportunistic infections and severe hypersensitivity reactions, including anaphylaxis Copyright © 2017, Elsevier Inc. All rights reserved.

Audience Response Question The nurse notes an order for the patient to receive an IV dose of methylprednisolone prior to administration of basiliximab. The nurse understands the rationale for this therapy as: decrease pain at infusion site. enhanced suppression of immune system. prevention of fluid retention. prevention of cytokine release syndrome. Correct answer: D Rationale: Both basiliximab and daclizumab, both injectable dosage forms, are associated with an allergic-like reaction known as cytokine release syndrome. It may be severe and even involve anaphylaxis, so patients are usually premedicated with corticosteroids (e.g., IV methylprednisolone) to try to avoid or alleviate this problem. Copyright © 2017, Elsevier Inc. All rights reserved.

Immunosuppressants (Cont.) Cyclosporine (Sandimmune) Prevention of organ rejection May be used for other autoimmune disorders Several black box warnings: renal impairment (structural kidney damage), increased risk of serious and fatal infections, liver injury, seizures, encephalopathy, and skin cancer Copyright © 2017, Elsevier Inc. All rights reserved.

Audience Response System Question A patient who had a kidney transplant is receiving cyclosporine orally 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 © 2017, Elsevier Inc. All rights reserved.

Immunosuppressants (Cont.) Glatiramer acetate (Copaxone) Works by blocking T-cell autoimmune activity against myelin protein, which reduces the frequency of the neuromuscular exacerbations associated with MS Copyright © 2017, Elsevier Inc. All rights reserved.

Immunosuppressants (Cont.) Fingolimod (Gilenya) Failed as an antirejection drug Approved in 2010 for MS Only oral drug for relapsing forms of MS Significant adverse effects: headache, hepatotoxicity, flulike symptoms, back pain, atrioventricular block, bradycardia, hypertension, and macular edema Action: blocks T-cell autoimmune activity against myelin protein, which reduces the frequency of the neuromuscular exacerbations associated with MS Copyright © 2017, Elsevier Inc. All rights reserved.

Immunosuppressants (Cont.) Muromonab-CD3 (Orthoclone OKT3) Reversal and prevention of graft rejection Monoclonal antibody: differs from human antibodies in that it comes from mice Action: specifically targets the binding sites on the T cells that recognize foreign invaders, such as a transplanted organ Copyright © 2017, Elsevier Inc. All rights reserved.

Immunosuppressants (Cont.) Mycophenolate (CellCept) Indicated for the prevention of organ rejection as well as the treatment of organ rejection U.S. Food and Drug Administration black box warning for increased risk of congenital malformations and spontaneous abortions when used during pregnancy Common side effects: hypertension, hypotension, peripheral edema, tachycardia, pain, headache, hyperglycemia, hyperlipidemia, electrolyte disturbances, and others Copyright © 2017, Elsevier Inc. All rights reserved.

Immunosuppressants (Cont.) Adverse effects vary according to drugs and may be devastating. All immunosuppressed patients have a heightened susceptibility to opportunistic infections. Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. Nursing Implications Perform a thorough assessment before administering immunosuppressants: Renal, liver, and cardiovascular function studies Central nervous system baseline function Respiratory assessment Baseline vital signs Baseline laboratory studies, including hemoglobin, hematocrit, white blood cell (WBC) count, and platelet count Copyright © 2017, Elsevier Inc. All rights reserved.

Nursing Implications (Cont.) Assess for contraindications, drug allergies, and drug interactions. Monitor WBC counts throughout therapy; if the count drops below normal range, contact the prescriber. Copyright © 2017, Elsevier Inc. All rights reserved.

Audience Response System Question Which potential problem is of most concern for a 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 © 2017, Elsevier Inc. All rights reserved.

Nursing Implications (Cont.) Oral immunosuppressants should be taken with food to minimize gastrointestinal 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 © 2017, Elsevier Inc. All rights reserved.

Nursing Implications (Cont.) 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 © 2017, Elsevier Inc. All rights reserved.

Nursing Implications (Cont.) 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 © 2017, Elsevier Inc. All rights reserved.

Audience Response Question A patient is being discharged on cyclosporine therapy. Which statement by the patient indicates that more teaching is needed? “I will take the cyclosporine tablet with: water.” milk.” grapefruit juice.” apple juice.” Correct answer: C Rationale: Common drug interactions to assess for when patients take cyclosporin include estrogens, protease inhibitors, HMG-CoA reductase inhibitors, clarithromycin, phenytoin, phenobarbital, St. John’s wort, nonsteroidal antiinflammatory drugs, and grapefruit juice. Copyright © 2017, Elsevier Inc. All rights reserved.

Nursing Implications (Cont.) Follow guidelines for parenteral administration carefully. Inform patients that lifelong therapy with immunosuppressants is indicated with organ transplantation. Copyright © 2017, Elsevier Inc. All rights reserved.

Nursing Implications (Cont.) Patients taking immunosuppressants should be encouraged to take measures to reduce the risk of infection: Avoid crowds. Avoid 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 © 2017, Elsevier Inc. All rights reserved.

Nursing Implications (Cont.) Monitor for therapeutic responses. Monitor for adverse effects and signs of drug toxicity. Copyright © 2017, Elsevier Inc. All rights reserved.

Audience Response System 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 © 2017, Elsevier Inc. All rights reserved.