Drug

Gene] Lnzyme]
keceptor
Lnzyme] kecptor Act|v|ty] Descr|pt|on Drug Descr|pt|on
rob|em |f drug not
|nact|vated
urlneLhol
(MercapLopurlne / 6M)
1M1 (unA
muLaLlon ln
normal cells)
1M1 found ln all cells (LhroughouL
body) breakdown lnacLlvaLe
purlneLhol Lo avold LoxlclLy ln body
common chemoLherapy
drug (leukemla) LhaL
lnacLlvaLes unA
polymerase
cause LoxlclLy ln
body also klll
normal cells
1rasLuzumab (PercepLln)
PL82
(ampllcaLlon ln
Lumor cells only)
PL82 ls an overexpressed proLo
oncogene ln some 8C (30) causlng
unconLrollable cell prollferaLlon PL82
(cell membrane recepLor) only ln Lumor
cells
monoclonal anLlbody LhaL
lnLerferes wlLh PL82/neu
recepLor Cnly work lf
paLlenLs are PL82+
1herefore geneLlc LesL
requlred
n/A
A||e|es] Descr|pt|on Stat|st|cs
1M1*1 (wlldLype) *3A*3C *2
accounL for 93 decrease
enzyme acLlvlLy
10 Caucaslans Afrlcan Amer are
heLerozygous lnL enzyme acLlvlLy 03
are homozygous low or absenL 1M1
acLlvlLy 1M1 deflclency lnherlLed as
auLosomal recesslve LralL
PL82+ overexpresslong Lhe
Per2/neu proLeln can use
LrasLuzumab
n/A
hase Lnzyme] Gene Metabo||ze what drugs Stats ] Info M UM
l C?2u6 23 of drugs ln markeL
AnlLdepressanLs anLlpsychoLlcs
cardlovascular agenLs oplold
analgeslcs uebrlsoqulne (nonLoxlc
subsLraLe used Lo measure enzyme
acLlvlLy)
2 muLanL alleles (loss of
ucnLlon) 310 whlLe M8
10 conseq dec drug
clearance exaggeraLed
cllnlcal ouLcome slde
effecLs
dup or amp of funcLlonal
alleles 2 Swedlsh 30
LLhloplan M8 01
conseq req hlgh dose slde
effecLs lf Loxlc meLabollLes
loss of drug efflcacy due Lo
rapld meLabollsm
l C?2C9 warfarln (anLlcoagulanL) C?2C9
converLs Swarfarln Lo lnacLaLlve form
33 whlLe 33 whlLe 2 non
synonymous varlanLs
(mlssense muL) wlLhln
C?2C9 produce M *2 and
*3 mlssense muL become
M Conseq prolonged
bleedlng Llme lnc bleedlng
eplsodes
l C?2C19 proLon pump lnhlblLors (omeprazole)
anLlplaLeleL (clopldogrel prodrug)
anLldepressanL (amlLrlpLyllne) beLa
adrenerglc blockers
23 whlLe 2023
aslans
omeprazole (acLlve drug)
M noL effecLlve aL
meLabollzlng Lherefore
more effecLlve for M
ll uC11A1 caLalyze glucuronldaLlon rxn xenobloLlc
(lrlnoLecan (anLlcancer) and
eLoposlde) and endogenous cmpds
(esLrogens Lhyrold hormones) Lo
waLer soluble molecules for excreLlon
lrlnoLecan (prodrug/lnacLlve) +
carboxylesLerase (llver enzyme) Sn
28 (acLlve/Loxlc) uC11A1 lnacLlvaLes
Sn28 (acLlve Loxlc) Lhru
glucuronldaLlon for blllary excreLlon
lnLo Cl LracL
promoLer reglon and
exon 1 conLaln mosL
common polymorph
(lnserLlon of 1A (*28) and
nonsyn muL (*6) *28
common ln whlLe and
Afrlcan *6 almosL all ln
azn
reduce enzyme aclLlvLy
LoxlclLy
,
2 func allele 1 func 1
nonfunc 2 func muLanL
(dec acLlvlLy) wlde
range of M8 01 Lo 10
(100fold dlff) hlgh or
low end group may
need ad[usLmenL
C?2C19 meLaobllze
ls Lo lnacLlvaLe Lhe
drug Lherefore noL as
effecLlve ln LM
Drug Drug Descr|pt|on 1reat? A||e|e
Abacavlr (Zlagen) nucleoslde reverse LranscrlpLase
lnhlblLor
LreaL Plv PLA8*3701 develop hypersenslLlvlLy rxn
Codelne (prodrug) analgeslc properLles Lhru lLs converslon
Lo morphlne (Loxlc meLabollLe) by
C?2u6
analgeslc deflclenL ln C?2u6 enzyme acLlvlLy (310 whlLe)
1amoxlfen (nolvadex)
(prodrug)
esLrogenanLagonlsL Lherapy for L8+ 8C
paLlenLs AnLlprollferaLlve acLlvlLy ln
cancer cell
meLasLaLlc 8C C?2u6
Clopldogrel (lavlx)
(prodrug)
plaLeleL lnhlblLor anLlplaLeleL effecL
(lnhlblL bloL cloLs)
Cvu C?2C19 converLs clopldogrel Lo acLlve meLabollLe ls
dlmlnlsh anLlplaLeleL aclLlvLy/ suppress C?2C19 acLlvlLy
Warfarln (Coumadln)
(acLlve form)
anLlcoagulanL or geL rld of blood cloLs Lhromboembollc
dlsease (formaLlon of
blood cloL)
warfarln meLabllzed by C?2C9 warfarln lnhlblLs vkC8C1
(synLheslzes coagulaLlon facLors) lnhlblLlng vkC8C1
good b/c wanL Lo decrease cloLLlng lf slow meLabollsm
by C?2C9 ( loLs of warfarln ln blood) and reduced
coagulaLlon by vkC8C1 ( lnc rlsk of bleedlng 89 Azn
carry aL leasL 1 varlanL ln vkC8C1