Transplantation II Immunosuppressive Drugs (!!!

)
2009 Mark Tuttle
Name Action Mechanism Side-effects Notes
Azathioprine
(AZA
Disrupt purine
synthesis, inhibiting
proliferation of
lymphocytes
Metabolite !thionsinic aci" is
a purine analogue#
$ncorporation causes
chromosome to break#
%ymphocytes lack the
sal&age path'ay so they
cannot 'ork aroun" this
! Does not inhi!it e"isting
sensitized T-cells (Tmemor# cells
! %eukopenia na" thrombocytopenia
! ($ "isturbances
! )e&er
! *epatoto+icity
! $ncrease" risk for infections an"
neoplasia
This "rug is first
metaboli,e" to !
mercaptupurine 'hich is
cleare" by Thiopurine
methyltransferase before it
can be incorporate" into
D-. in /90 of people# This
lea"s to se&ere re1ection
making it a shitty "rug
Steroids 2lock synthesis of
prostaglan"ins,
leukotrienes, cytokines,
3.), neutrophil
chemotactic factor,
eosinophil chemotactic
factor
$nhibits 45!%6 (%eukotrienes)
$nhibits 768!9
(3rostaglan"ins)
! $ncrease" fragility of capillary
&essels
! $ncrease" susceptibility to infectisn
! .&ascular necrosis
! 6steoporosis
! 6besity
! Diabetes
! (ro'th suppression in chil"ren
! *yperglycemia, hyperkalemia,
hypertension
:se" 'ith .,athioprine
ha&e pretty shitty outcomes
for ki"ney allograft sur&i&al
$#closporine
($sA
2lock s#nthesis of $%!
2, $)-!;, inhibiting
proliferation of
lymphocytes
2locks calcineurin in T7<
receptor signal casca"e
! Nephroto"icit#
! *ypertension
! -euroto+icity
! Diabetes
! =*irisuitism
! =(ynecomastia
! =(ingi&al hyperplasia
! =%o'ering of Mg
2>
=:ni?ue to 7yclosporine
Much better than .@. >
Ateroi"s, although it is
nephroto+ic
Tacrolimus
(%&'()
M#cophenolate
Mofetil (MM%
Disrupt purine
synthesis (guanine
only), inhibiting
proliferation of
lymphocytes
2locks $nosine
monophosphate
"ehy"rogenase ($M3D*)
'hich is part of *uanine
purine synthesis#
! No nephroto"icit#
! 2M to+icity (platelets "rop)
! Digesti&e "uct to+icity ("iarrhea)
2etter than .@. but .@. is
cheaper
Sirolimus (S+,
+apam#cin
2lock signal of $%!2
<eceptor, inhibiting
proliferation of
lymphocytes
2locks mT6< (mammalian
target of rapamycin)
! No nephroto"icit#
! No hepatoto"icit#
! Thrombocytopenia
! *ypercholesterolemia
mT6< has many acti&ities
in lymphocytes, inclu"ing
<2 phosphorylation,
ribosomal function