1) 7 year old boy presented with nausea, vomiting, sweating, abdominal pain, and jaundice after accidentally ingesting an unknown syrup the previous night. Examination found hepatomegaly. He was diagnosed with paracetamol poisoning. 2) Paracetamol is metabolized in the liver. In overdose, glutathione stores are depleted allowing a toxic metabolite to bind to hepatocytes and cause liver damage. Paracetamol poisoning management includes gastric lavage, N-acetylcysteine as an antidote to prevent binding, and monitoring for liver transplantation.

1. Case-
7 year old boy came with his mother in casuality in midnight
with complains of Nausea,vomiting,excessive
sweating,malaise,pain in upper abdomen. On basis of history
patient has accidently taken full bottle of unknown syrup last
night. Examination findings- pain in right upper quadrant with
hepatomegaly and jaundice . Diagnosis was made of PCM
poisoning.

2. Paracetamol
Poisoning
By-
Dr. Ranjan Dubey
INTERN
Batch-2017-18

3. Introduction
• Paracetamol is also known as acetaminophen, n-acetyl-p-
aminophenol,4-hydroxyacetanilide.
• Physical appearance- exists as white odourless bitter tasting cystal or
crystalline powder
• Uses-
1) Antipyretics- in 1893 von mering introduced paracetamol into
pharmacotherapeutics. It is active metabolite of acenilide and
phenacetin
2) Analgesic

4. Mode of action
• Paracetamol rapidly and completely absorbed from gi tract
• Peak plasma levels are reached in 1hr
• Plasma half life is about 2hrs
• Absorption is delayed by high carbohydrate foods
• Protein binding for paracetamol is 20%
• Volume of distribution is 0.8 to 1l/kg
• Normally 90% of the drugs undergoes hepatic conjugation with
glucuronide and sulphuric acid to form inactive and harmless
metabolites

5. • 10% is oxidised to n-acetyl-p-benzo quinonines(NAPQI) which is
highly reactive intermediate
• NAPQI is capable of covalent binding and arylating critical cell
proteins inducing a series of events that result in cell death
• Normally glutathione detoxifies NAPQI to cysteine and
mercapturate conjugates which is secreted through urine
• In overdose situation glutathione stores become depleted and
NAPQI binds covalently with hepatocytes of liver causing
centrilobular hepatic necrosis
• Concomitant intake of drugs induces P450 enzymes can enhance
the chance of hepatoxicity

6. • Toxic features-
1) Acute poisoning- clinical manifestation of acetaminophen intoxication
are described in 4 stages
STAGE 1- (1/2 hrs to 24hrs)- anorexia,vomiting,sweating,malaise
STAGE 2-(24 hrs to 72hrs)-s symptom free stage,only right upper quadrate
pain,LFT is normal
STAGE 3-(72 to 96hrs) phase of peak
Hepatic necrosis sets in with conjugation defects.jaundice and encephalitis
nausea,vomiting reappears
 Elevated blood levels of liver enzymes(SGOT/ALT,SGPT/AST)
Increased total bilirubin and prolonged PT is seen
Decreased serum IL-6
Acute renal failure

7. STAGE 4( 4 days to 2 weeks) phase of recovery
If the patient survives the 3rd stage complete resolution of hepatic
damage is the rule. There is no reported cause of chronic hepatic
dysfunction from paracetamol
ADDITIONAL MANIFESTATION-
Hypotension and shock with hypothermia in absence of hepatic
dysfunction have been reported in acute paracetamol poisoning the
mechanism is unclear

8. 2) Chronic poisoning
This is common in alcoholics ,AIDS patients,T.B patients where
individuals has consumed large doses of paracetamol over period of
time for relief of chronic pain
This is also very common in children because of dose miscalculation
by parents it presents with low body
temperature,hepatomegaly,anorexia,vomiting
Fatal Dose- 20-25 grams
Children under the age of 10 years appears to be more resistant to the
toxic effects of paracetamol. It has been suggested that toxic dose of
5year old child is 187.5mg/kg
Fatal time- 3 days

9. Diagnosis
• Serum paracetamol levels should be measured after 4 hrs
• AST and ALT level-10,000 units/l within 72 to 96hrs
• Total bilirubin level- 4 mg/100 ml(which may be fatal)
• 150 mg/kg is the lowest acute dose of pcm capable of hepatotoxicity
• Diagnosis of hepatotoxicity is done by RUMACK MATTHEW
NOMOGRAM
• RUMACK MATTHEW NOMOGRAM is not useful in-
Poisoning with sustained release formulations
Chronic poisoning
Pcm ingested with anticholinergics or opiods

11. Management
1. Gastric lavage within 4hrs
2. ANTIDOTE-
a) N Aetaly cysteine (NAC) is the specific antidode and is used orally within
16hrs after ingestion. It is not effective if given after 24hrs of in gestion
Dose-140mg/kg f/b 70mg/kg every 4hrs for 17dose(18 doses)
MOA-
It prevents binding NAPQI to hepatocytes
Directly binds to NAPQI
Enhances synthesis of glutathione
Containdication of NAC
oComa,vomiting,hepatic failure,encephalopathy
oPretreatment with activated charcoal
 NAC can be administered orally of I/V

12. b)Methionine
I. Oral antidote
II. Glutathione precursor
III. Dose-2.5gm 4hrly interval upto 4 doses
c)Cysteamine
Kings college criteria for PCM poisoning are used for deciding referral
for liver transplantation
1. Acedimia ( serum pH<7.3)
2. Coagulopathy(INR>6)
3. Renal dysfunction( creatinine > 3.4mg/dl)
4. Grade III or IV hepatic encephalopathy

13. Medicolegal
importance
• Mostly suicidal rarely
accidental
• Organ donation after pcm
poisoning can be done
• Homicidal poisoning virtually
unknown because large dose
required

14. References
Parikh
Anil
Agarwal
K.s.n REDDY
OP ghai
Harrisons
principles
of medicine

15. Thank you