RT Book, Section
A1 Johnson, Heather J.
A1 Schonder, Kristine S.
A2 DiPiro, Joseph T.
A2 Talbert, Robert L.
A2 Yee, Gary C.
A2 Matzke, Gary R.
A2 Wells, Barbara G.
A2 Posey, L. Michael
SR Print(0)
ID 1145201144
T1 Solid-Organ Transplantation
T2 Pharmacotherapy: A Pathophysiologic Approach, 10e
YR 2017
FD 2017
PB McGraw-Hill Education
PP New York, NY
SN 9781259587481
LK accesspharmacy.mhmedical.com/content.aspx?aid=1145201144
RD 2024/04/16
AB KEY  CONCEPTS  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.  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.  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.  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.  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.  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.  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.  Long-term  allograft  and  patient  survival  is  limited  by  chronic  rejection,  cardiovascular  disease,  infection,  and  long-term  immunosuppressive  complications  such  as  malignancy.