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PHARMACOTHERAPY PRINCIPLES AND PRACTICE CARE PLANS & CASES

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LEARNING OBJECTIVES

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LEARNING OBJECTIVES

Upon completion of the chapter, the reader will be able to:

  1. Describe the reasons for solid organ transplantation.

  2. Differentiate between the functions of cell-mediated and humoral immunity and how they relate to organ transplant.

  3. Describe the roles of antigen-presenting cells in initiating the immune response.

  4. Compare and contrast the types of rejection including hyperacute, acute, chronic, and humoral rejection.

  5. Define the terms “host–graft adaptation” and “tolerance,” paying close attention to their differences.

  6. Discuss the desired therapeutic outcomes and appropriate pharmacotherapy utilized to avoid allograft rejection.

  7. Compare and contrast currently available immunosuppressive agents in terms of mechanisms of action, adverse events, and drug–drug interactions.

  8. Develop a therapeutic drug-monitoring plan to assess effectiveness and adverse events of the immunosuppressive drugs.

  9. Design an appropriate therapeutic regimen for the management of immunosuppressive drug complications based on patient-specific information.

  10. Write appropriate patient education instructions and identify methods to improve patient adherence following transplantation.

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INTRODUCTION

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The earliest recorded attempts at organ transplant date back thousands of years.1 More than a few apocryphal descriptions exist from ancient Egypt, China, India, and Rome describing experimentation with transplantation. However, it was not until the early 1900s that French surgeon, Alexis Carrel, pioneered the art of surgical techniques for transplantation.1 Together with Charles Guthrie, Carrel experimented in artery and vein transplantation. Using revolutionary methods in anastomosis operations and suturing techniques, Carrel laid the groundwork for modern transplant surgery. He was one of the first to identify the dilemma of rejection, an issue that remained insurmountable for nearly half a century.1

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Prior to the work of Alexis Carrel, malnourishment was the prevailing theory regarding the mechanism of allograft rejection.1 However, in 1910, Carrel noted that tissue damage in the transplanted organ was likely caused by multiple, circulating biological factors. It was not until the late 1940s with the work of Peter Medawar that transplant immunology became more understood. Medawar was able to define the immunologic nature of rejection using skin allografts. In addition, George Snell observed that grafts shared between inbred animals were accepted but were rejected when transplanted between animals of different strains.1

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The seminal work by early transplant researchers eventually led to the concept of histocompatibility.1 Histocompatibility describes the process by which polymorphic genes encode cell membrane antigens that serve as targets for immune response, even within a species. Further research in transplant immunobiology led to a more accurate understanding of the alloimmune response.1

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Joseph Murray performed the first successful organ transplant in 1954.1 It was a kidney transplant between identical twins. This was a success in large part because no immunosuppression was necessary due to the fact that donor and recipient were genetically identical. Murray’s success laid the groundwork for modern-day transplantation.

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EPIDEMIOLOGY ...

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