Acetaminophen Flashcards
diagnostic clue of acetaminophin OD in an alchoholic patient
high levels of AST
how is acet eliminated
liver metabolism by conjugation by glucuronic acid or sulfate
small % oxidized into NAPQI (toxic metabolite)
NAC MOA
acts as a glutathione and sulfate precursor or substitute that binds to NAPQI causing modulation of cascade of inflammatory events
nonspecific antioxidant effects and mediation of microvascular tone = improved organ function
acet safety in pregnnacy and breast feeding
cross placenta and a very small amount into breast milk
likely fine
how does the half life of acet change in od
1-3 hr normally, increases to >12 hr in OD
toxic dose of acet
6-7g in adults
>140mg/kg in children
why can children handle higher doses of acet
lower p450 capacity in the liver so less gets converted to NAPQI
plasma levels we need to show OD
4 hr after exposure
levels >150ug/mL
how does acute hepatic toxicity work in OD
saturation of glucuronide and sulfate conjugation pathways shunts APAP into the p450 system forming NAPQI
glutathion becomes depletes build of NAPQI binds and arylates cell proteins causing cell death
inflammation after necrosis (cell death) causes impaired microcirculation and tissue hypoxia
how does acute renal toxicity occur in OD
renal P450 formation of NAPQI causes acute proximal renal tubular necrosis
clinical presentation in the first 24hr (phase 1)
no symptoms
non specific - nausea, vomiting, malaise
clinical presentation in 24-72hr (phase 2)
abd pain lver tenderness elevated AST and ALT elevated bilirubin metabolic acidosis hypoglycemia
clinical presentation in 72-96hr (phase 3)
hepatic encephalopathy continuing rise in PT coagulopathy fulminant hepatic failure acutee renal failure
clinical presentation in 4d-2weeks (phase 4 )
resolution of hepatic dysfunction if survive phase 3
device used to predict toxicity
nomogram
how to interpret the nomogram
look at the concentration 4hr after exposure
if >200ug/mL - probably hepatic toxicity
150-200 - possible
<150 - hepatic toxicity not expected
interventions for acet OD
gastric emptying AC NAC supportive care liver transplant
when is gastric emptying appropriate
very early presentation - <1 hr
large amount ingested
ingestion of sustained release
coingestion of agents that delay absorption
concerns with activated charcoal and NAC
when orally administed NAC will be absorbed by charcoal
when do we assume that GI absorption is complete in acet
4hrs
what is n-acetylcysteine
thiol containing agent which is deacetylated in the body to cysteine )precursor of glutathione
NAC dosing
iv NAC for 20hr
150mg/kg over 15hr
50mg/kg over 4hr
100mg/kg over 16hr
oral NAC issues
foul smelling and tasting
irritating for the stomach
administer with grapefruit juice or soda and antiemetics
problems with NAC iv admin
rapid admin can cause flushing, hypotension and bronchoconstriction - anaphylactoid
want to be sure there is liver toxicity before you administer
when should NAC be administed for effectiveness
within 8-10 hr s
is NAC safe for use in pregnancy
yes
how does chronic toxicity happen
daily consumption of supratherapeuic (4-6g/day) doses by alcoholic patients
chronic toxicity doses in children
60-150mg/kg/d for 2-8 days
overdose from pediatric formulation not really possible
chronic toxicity treatment
NAC if liver enzymes elevated or high risk patients (alcoholic, meds that increase metabolism)
risk factors for chronic toxicity
alcoholism
chronic treatment with anticonvulsants or isoniazid
fasting and malnutrition
why does alcohol intensify toxicity
induces hepatic enzymes producing the toxic metabolite
