Transplantation

Created by

Mira W

Cards (26)

we use immunosuppressants for organ transplant
diffrent organ transplant uses diffrent immunospressant :
heart : tacrolimus,
kidney liver: steroids tacrolimus
HSCT: cyclosporine
know this
cyclosporine va changer AUC
tacrolimus va chnager concentration min
inhibiteur de la calcineurie : tacrolimus et cyclosporine (Csa inhibite CaN) et (FK506 inhibe CaN)
tacrolimus et cyclosporine substrat de Pgp et CYP3A4 et 3A5
pour atcro et cyclo CYP3A5 tres muté (*3) diminution de l'activité
CYP3A5 non fonctionnelle (*6,*7)
frequnece allelique CYP3A5 *3 very present in caucasien and asians and africans (but a little less)
CYP3A4 *22 very mutated and phenotype: diminution de activité
CYP3A4*22 present in caucasiens
CYP3A4*1B activité metabolique augmenter chez africains plus souvent
doses were determined with mutated ppl (so reduced activity for CYP3A5) so ppl who are not mutated need higher doses
POR helps CYP enzymes to oxidize
POR*28 mutation that reduces oxidoreduction id CYP enzymes
Pgp mutation (C3435T) = diminution activité duedenal
if Pgp is mutated : more Rx is absorbed and more concentration
for ppl with non mutated Pgp, we must increase dose bcuz it was decreased for mutated ppl )the studies and doses are done on them)
in the kidneys if Pgp is mutated, we have less clerance of drug and cause for nephrotoxixity
with tacrolimus, CYP3A5 *3 we have reduce metabolism (so Rx has to be decreased)
with tacrolimus CYP3A5 non mutated, we must increase dose because muatted dose not enough for them
with tacrolimus, if carrier of POR *28, we have less metabolism (so Rx accumulated in systemic system)
pour cyclosporine, CYP3A4*22 (diminution de activité) we will have accumulated drug in systeme so diminution de clairance CsA
it is important de genotype transplant organ like when we do renal transplant and the donor has polymorphism in Pgp (diminution activité TT) more at risk of nephotoxicity
tacrolimus is related to neurotoxicity due to mutation in CYP3A4