Acetaminophen

Question 1

diagnostic clue of acetaminophin OD in an alchoholic patient

Answer 1

high levels of AST

Question 2

how is acet eliminated

Answer 2

liver metabolism by conjugation by glucuronic acid or sulfate
small % oxidized into NAPQI (toxic metabolite)

Question 3

NAC MOA

Answer 3

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

Question 4

acet safety in pregnnacy and breast feeding

Answer 4

cross placenta and a very small amount into breast milk

likely fine

Question 5

how does the half life of acet change in od

Answer 5

1-3 hr normally, increases to >12 hr in OD

Question 6

toxic dose of acet

Answer 6

6-7g in adults

>140mg/kg in children

Question 7

why can children handle higher doses of acet

Answer 7

lower p450 capacity in the liver so less gets converted to NAPQI

Question 8

plasma levels we need to show OD

Answer 8

4 hr after exposure

levels >150ug/mL

Question 9

how does acute hepatic toxicity work in OD

Answer 9

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

Question 10

how does acute renal toxicity occur in OD

Answer 10

renal P450 formation of NAPQI causes acute proximal renal tubular necrosis

Question 11

clinical presentation in the first 24hr (phase 1)

Answer 11

no symptoms

non specific - nausea, vomiting, malaise

Question 12

clinical presentation in 24-72hr (phase 2)

Answer 12

abd pain 
lver tenderness
elevated AST and ALT
elevated bilirubin
metabolic acidosis 
hypoglycemia

Question 13

clinical presentation in 72-96hr (phase 3)

Answer 13

hepatic encephalopathy
continuing rise in PT
coagulopathy
fulminant hepatic failure
acutee renal failure

Question 14

clinical presentation in 4d-2weeks (phase 4 )

Answer 14

resolution of hepatic dysfunction if survive phase 3

Question 15

device used to predict toxicity

Answer 15

nomogram

Question 16

how to interpret the nomogram

Answer 16

look at the concentration 4hr after exposure
if >200ug/mL - probably hepatic toxicity
150-200 - possible
<150 - hepatic toxicity not expected

Question 17

interventions for acet OD

Answer 17

gastric emptying 
AC
NAC
supportive care
liver transplant

Question 18

when is gastric emptying appropriate

Answer 18

very early presentation - <1 hr
large amount ingested
ingestion of sustained release
coingestion of agents that delay absorption

Question 19

concerns with activated charcoal and NAC

Answer 19

when orally administed NAC will be absorbed by charcoal

Question 20

when do we assume that GI absorption is complete in acet

Answer 20

4hrs

Question 21

what is n-acetylcysteine

Answer 21

thiol containing agent which is deacetylated in the body to cysteine )precursor of glutathione

Question 22

NAC dosing

Answer 22

iv NAC for 20hr
150mg/kg over 15hr
50mg/kg over 4hr
100mg/kg over 16hr

Question 23

oral NAC issues

Answer 23

foul smelling and tasting
irritating for the stomach
administer with grapefruit juice or soda and antiemetics

Question 24

problems with NAC iv admin

Answer 24

rapid admin can cause flushing, hypotension and bronchoconstriction - anaphylactoid
want to be sure there is liver toxicity before you administer

Question 25

when should NAC be administed for effectiveness

Answer 25

within 8-10 hr s

Question 26

is NAC safe for use in pregnancy

Answer 26

yes

Question 27

how does chronic toxicity happen

Answer 27

daily consumption of supratherapeuic (4-6g/day) doses by alcoholic patients

Question 28

chronic toxicity doses in children

Answer 28

60-150mg/kg/d for 2-8 days

overdose from pediatric formulation not really possible

Question 29

chronic toxicity treatment

Answer 29

NAC if liver enzymes elevated or high risk patients (alcoholic, meds that increase metabolism)

Question 30

risk factors for chronic toxicity

Answer 30

alcoholism
chronic treatment with anticonvulsants or isoniazid
fasting and malnutrition

Question 31

why does alcohol intensify toxicity

Answer 31

induces hepatic enzymes producing the toxic metabolite