3. Acetaminophin
Nsaid with potent anti pyretic, analgesic action
Unintentionally ingested by young children
Intentional overdose by adults
Inappropriately dosed in all ages
4. Acetaminophen toxicity
Results from the formation of a
HIGHLY REACTIVE INTERMEDIATE
METABOLITE
N-acetyl-p-benzoquinone imine (NAPQI)
5. NAPQI
In therapeutic use:
Small percentage of dose, 5% is metabolized
by hepatic cytochrome P450 enzyme to
NAPQI
Which is immediately conjugated with
glutathione
Form a nontoxic mercapturic acid conjugate
6. NAPQI
In overdose :
Glutathione stores are overwhelmed, and free
NAPQI is able to combine with hepatic
macromolecules to produce
HEPATOCELLULAR DAMAGE
7. Acute toxic dose of
acetaminophen
The single acute toxic dose >200mg /kg in
children
Supratherapeutic dose>75mg/kg/d can lead
to hepatic injury in some children,especially
in the setting of
Fever
Dehydration
Poor nutrition
Dec glutathione stores
9. Investigations
Serum APAP level should be measured 4hr
after reported time of ingestion
Level obtained <4hr after ingestion cannot be
used to estimate potential toxicity
Check levels 6-8 hours if it is co ingested with
other substance that slows GI motility ,
diphenhydramine
Other BLI lfts, rfts, coagulation prrofile
10. RUMACK –MATTHEW nomogram
foa acetaminophen poisoning
Any patient with serum acetamiophen level in
possible or probable hepatotoxicity range per
RM nomogram should be treated with
N-ACETYLCYSTEINE
11. N=acetylcysteine
Start NAC
If acetaminophen level is above the treatment
line on Rumack-matthew nomogram
If levels are low but LFTS dearrange
If level is > 10microg/ml even with normal lfts
12. Treatment
Initial treatment:
Basic life support (ABCs)
Decontamination with activated
charcaol(Within 1-2 hr of ingestion)
The antidote for acetaminophen is N-
acetylcysteine
MOA replenish hepatic glutathione stores
13. NAC
Most effective when initiated within 8 hr of
ingestion
NAC available both oral and iv
DOSE ]ORAL :140mgKG loading,followed by
70mgkg every 4hr for 17 doses
(MUCOMYST)
DOSE IV:150mg/kg iv over 1 hr, followed by
50mg kg over 4 hours, followed by 100mg/kg
over 16 hrs
14. What is next
A patient who is being on NAC , the following
lab test , lfts and rfts should be followed daily
Patients who develop hepatic failure in spite o
NAC therapy may be candidates for liver
transplant
15. King’’s college criteria
Are used to determine which patients should
be referred for consideration of liver transplant
1. Acidosis (Ph <7.3) after adequate fluid
resuscitation
2. Coagulopathy if Pt is more than 100 sec
3. Renal dysfunction (creatinine >3.4mg/dl
4. Hepatic encephalopathy grade 3/4
16. Prevention
Inform and educate parents and caregivers
proper dosing and danger associated with
misusing varioius formulations
Parents should always be given clear dose
and formulation instructions
Based on age and weight