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KEY CONCEPTS

KEY CONCEPTS

  • Image not available. Generally patients receive a combination of two to four immunosuppressive drugs in order to minimize individual drug toxicities as well as block different aspects of the immune response.

  • Image not available. While the calcineurin inhibitors (CI) tacrolimus and cyclosporine, inhibitors of interleukin (IL)-2 and thus T-cell activation, are the backbone of immunosuppressive regimens, they are associated with serious adverse effects, primarily, nephrotoxicity, and neurotoxicity.

  • Image not available. Calcineurin inhibitor-induced nephrotoxicity is one of the most common adverse effects observed in renal and nonrenal transplant recipients. Therapeutic drug monitoring is used in an attempt to optimize the use of calcineurin inhibitors and prevent toxicity.

  • Image not available. Corticosteroids are a key component of most immunosuppressive strategies because they block the initial steps in allograft rejection. Their significant adverse effects have led to steroid-minimizing and steroid-free imunosuppressive protocols. Corticosteroids, however, remain first-line treatment for allograft rejection.

  • Image not available. Azathioprine and mycophenolic acid derivatives inhibit T-cell proliferation by altering purine synthesis. Bone marrow suppression is the most significant adverse effect associated with these agents.

  • Image not available. Sirolimus and everolimus inhibit the mTOR (mammalian target of rapamycin) receptor, which alters T-cell response to IL-2. The adverse effects associated with these agents include leukopenia, thrombocytopenia, anemia, and hyperlipidemia.

  • Image not available. Antibody preparations that target specific receptors on T cells are classified based on their ability to deplete lymphocyte counts. Most lymphocyte-depleting antibodies are associated with significant infusion-related reactions, where as nondepleting agents are generally better tolerated.

  • Image not available. Long-term allograft and patient survival is limited by chronic rejection, cardiovascular disease, infection, and long-term immunosuppressive complications such as malignancy.

Solid-organ transplantation provides a lifesaving treatment for patients with end-stage cardiac, kidney, liver, lung, and intestinal disease. Over 300 U.S. hospitals offer transplant services, and pharmacists are often an integral part of the transplant team.1 In 2009, over 250 pharmacists were members of the American College of Clinical Pharmacy’s Transplant Interest Group and more that 65% of responding centers reported a pharmacist on their transplant teams.2 The Centers for Medicare and Medicaid Services regulations require that transplant programs have a multidisciplinary team including individuals with experience in pharmacology. While the regulations do not specifically state that each center must have a pharmacist, a pharmacist could provide the desired expertise in transplant pharmacotherapy that the regulations mandate.1

Since 1980 over 630,000 transplants have been performed, with over half being kidney transplants. A recent analysis estimated that since 1987 over 2.27 million life years have been saved by transplantation, with an average of 4.3 years per patient.3 In 2014, 29,532 solid-organ transplants were performed and over half of these in were for patients over 50 years of age. Kidneys remain the most commonly transplanted organs; 11,570 from cadaveric donors and 5,536 from living donors in 2014. The next most frequently transplanted organ was the liver, with 6,449 from cadaveric donors and 280 from living donors. Heart and pancreas (or combined kidney–pancreas) transplants account for over 2,600 and 700 transplants, respectively while 1,900 lung transplants were ...

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