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614 PA R T IV / Pathophysiology and Management of Heart Disease

Table 25-5 ■ MAJOR ADVERSE SIDE EFFECTS OF IMMUNOSUPPRESSIVE AGENTS
AND CLINICAL MANIFESTATIONS (continued)
Drug Adverse Effects Clinical Manifestations
Rapammune Bone marrow suppression Anemia, thrombocytopenia
Hypercholesteremia Elevated serum cholesterol, elevated triglycerides
Hyperlipidemia Elevated serum lipid levels
Hypertension Elevated blood pressure
Lower extremity edema Swelling of lower extremites
Interstitial pneumonitis Crackles over lung fields, shortness of breath
Oral ulcerations Pain in and around mouth and lips

ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen.
From Urden, L. D., Stacy, K. M., & Lough, M. E. (Eds.). (2002). Critical care nursing: Diagnosis and management (4th ed., pp. 998–1001). St. Louis: Mosby; Micromedex Healthcare
Series: Micromedex, Inc. Breenwood Village, CO (edition expires 9/03). Available: http://hcs.mdx.com (accessed April 2003); Luikart, H. (2001). Pediatric transplantation: Man-
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agement issues. Journal of Pediatric Nursing, 16, 320–331.)
condition of their skin and be alert for lesions that do not heal nucleic acids in rapidly proliferating cells, such as the cells of the
well or that become infected. immune system. 86 Prevention of this cell proliferation can also
Fragile skin and bruising were reported to occur often or always impair other rapidly proliferating cells in the body and cause con-
in up to 60% of patients on corticosteroid and azathioprine proto- ditions such as leukopenia, thrombocytopenia, and anemia. It is
cols. Changed facial and bodily appearance was reported by 43%. important to monitor the patient’s white blood cell count closely
Poor vision, a problem associated with corticosteroid therapy, was and to titrate the dose of the drug accordingly.
“quite a bit” or “extremely” upsetting to 30% of patients. 83,85
Antilymphocyte Antibodies
Mycophenolate Mofetil. Mycophenolate mofetil (CellCept) Orthoclone OKT3. Orthoclone OKT3 is a monoclonal an-
is an immunosuppressive agent that inhibits the de novo pathway tibody that is targeted to remove T cells from circulation through
of purine synthesis in activated lymphocytes. Mycophenolate the formation of antigen–antibody complexes. 86 It can be used
mofetil works at a late stage in T-cell activation, in contrast to cy- initially after transplantation as an induction agent to eliminate
closporine and tacrolimus, which inhibit the earliest events. My- the T-cell response in the first 14 postoperative days, or can be
cophenolate mofetil has been shown to have activity against B used to treat a later rejection episode. Patients can acquire sensi-
cells; therefore, it may have a role in preventing graft atheroscle- tivity to the drug and form antibodies against the foreign protein.
rosis. 82 For that reason, usually only one 5-day course of the drug is given.
Multicenter trials have shown that mycophenolate mofetil is Adverse effects are caused by the massive lysis of T cells, resulting
an effective immunosuppressant, safe and well tolerated in kidney in general malaise, fever, and chills.
and heart transplant recipients. It is less myelosuppressive than
azathioprine, thereby avoiding the neutropenia and anemia, and Antithymocyte Preparations. Thymoglobulin is rabbit
less hepatotoxic as well. Its major side effects are gastrointestinal immune globulin and is an antithymocyte preparation that uses
disturbances. Nausea, vomiting, and diarrhea are the most fre- antibodies produced by animals in response to foreign human T
quently reported symptoms. These symptoms are usually self- cells. They are polyclonal preparations pooled from multiple ani-
limiting and dose dependent. 53 mals. These preparations are used as an induction therapy and to
treat severe rejection after standard antirejection therapy has
Sirolimus and Everolimus failed. Its possible mechanisms of action include T-cell clearance
Sirolimus. Sirolimus (Rapamune) and its derivative from the circulation and modulation of T-cell activation. The
everolimus (Certican, Rad) is an antibiotic and in a class of drugs course of therapy is typically 2 to 5 days. As with orthoclone
called mTOR (mammalian targets of rapamycin) inhibitors. OKT3, adverse effects are associated with the massive lysis of T
Sirolimus prevents cell cycle activation and T-cell proliferation. cells, causing fever and chills. 86 Although rare, patients can have
Sirolimus and its derivatives may be synergistic with the calcineu- anaphylactic reactions to the foreign animal protein.
ron inhibitors. These drugs are dosed orally once or twice daily.
Blood trough levels are measured for dose monitoring. Research Daclizumab and Basiliximab. Daclizumab and basilix-
studies suggest that rapamycin treatment may prevent or even re- imab are monoclonal antibodies used as induction agents. They
verse allograft vascular disease. 52 The common side effects of are hybrid, humanized interleukin-2 receptor antibodies. The ad-
sirolimus are increased levels of triglycerides, decrease in hemo- vantage of these agents is the minimal administration side effects
globin and platelet counts, tremors, peripheral edema, arthralgias, that other monoclonal have exhibited, and the apparent useful-
and the potential for slow wound healing. 51 ness in preventing early rejection. 51,52

Azathioprine. Azathioprine (Imuran) can be used as a main- Complications
tenance drug to prevent activation and proliferation of T cells in
response to the foreign antigen or the transplanted heart. It is an Hypertension
antimetabolite that interferes with purine synthesis. Purine syn- Hypertension is a long-term, ever-present complication that re-
thesis is necessary for antibody production and for synthesis of quires considerable attention. Hypertension is caused in large part