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Acetaminophen

metabolism

Ahmad Izzuddin Mohd Rosli

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METABOLISM

Paacetamol is pimail! metabolized in the

li"e

#o a du$ to be eliminated %om the bod!& it isimpotant %o the du$ to be su'cientl! h!dophilic()u$ *ill be moe soluble in *ate so it is easie to

We willlook intothis!

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To do so& thee ae + phases o%du$ metabolism eactions

Wewilllookintothis!

adding or unmasking

a hydroxyl group

adding a large polar

group

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PHASE +, CON-./ATION

A. MAJOR PATHWAY

Cause con0u$ation o%sulphate $oup on theacetaminophen

Cause con0u$ation o%$lucuonide $oup onthe acetaminophen

lucuronide conjugate ulhate conjugate

"#$M$%AT$O%&onjugation result in increase

h'drohilicit'.(rug )ore solu*le in water and easil'

,%O% TO-$& ,%O% TO-$&

uridinediphosphoglucuronosyltransferase /01

Ente oubod!

con"etedto

21eli)inateddirectl' 3ia

urine

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PHA" 45 &O%J6GAT$O% ,M$%ORPATHWAYe1cessi"e amount o% acetaminophen in the li"e cansatuate the sulphation and $lucuonidation path*a!s

so the acetaminophen is pocessed thou$h anothepath*a!& the c!tochome P2345 s!stem

&'7208iso9')es resonsi*le +or

*iotrans+or)ation o+ )an' drugs3ia o:idation

21enter &YP720

s'ste)

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At theapeutic doses& NAP6I *illunde$o this path*a!& the nomal

path*a!

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TH"RAP"6T$& (O"5 %ORMA#PATHWAY NAP6I *ill beinacti"ated thou$h con0u$ation o%$lutathione

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At to1ic doses& NAP6I*ill unde$o this

path*a!

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AT TO-$& (O"

NAP6I

%AP;$ roduction increase!

NAP6I

NAP6I

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NAP6I/L.TATHIONE

%AP;$ roduction e:ceed the a)ount o+ glutathione roduced

Glutathione is not enough to inacti3ate the %AP;$

E1ceed7777777777777777777777777777777777

inacti"ate

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NAP6I /L.TATHIONE

e1ceed

inacti"ate

8 NAP6I poduction incease andcause depletion o% hepatic$lutathione

9 /lutathione bein$ used up

because ate $lutathioneutilised : ate $lutathione%omed

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AT TO-$& (O"

; $lutathionedepletion causethe eaction tomo"e to this

path*a!

NAP6I

< Reacti"e =uinone in NAP6I stuctue

hi$hl! succeptible to thiol nucleophilicattac> %om the li"e potein

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NAP6I

? Abundance o%to1ic NAP6I

cause

Hepatic necosis

Renal %ailue

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Heatic necrosis( to1ic in0u! to the li3er*ith sudden and pecipitous onset&

ma>ed ele"ations in seum aminotans%ease le"els& and eal! si$ns o%

heatic@o othe o$an d!s%unction o %ailue despite minimal o no 0aundice

-livertox.nih.gov/Phenotypes_ahn.html

Renal +ailure. kidne's%ail to ade=uatel! lte *aste poducts %om the blood(

N-acetyl cysteine - used to counteract acetaminophen and carbon monoxide

poisoning

adduct is a complex that forms when a chemical binds to a biological

molecule, such as DNA or protein.

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Than> !ou