Paracetamol poisoning

ParacetamolParacetamol

• One of the most commonly used analgesics , hence overdoses are common .

• Trade names : panadole , fevadol , adol … ect• Widely used in both : over the counter and

prescription → analgesics and cold remedies . • Relatively narrow therapeutic index ( 2 tabs → safe )

while 20 tabs → toxic (lethal) .• Toxic effects potentiated by ethanol (Alcohol), eating

disorders, and enzyme inducing drugs.• Hepatotoxic dose : 140 mg/kg in children . And in

adults 6 gm ( 12 tab ) →liver necrosis. • Fatal dose = 10 – 15 gm ( 20 – 30 tablets ) • each tablet = 500mg .

Pathophysiology

PARACETAMOL

Microsomal oxidation (<5%)Conjugation (>95%)

Glucuronide & sulfate

NAPQI “toxic metabolite”

Mercapturic acid

“water soluble, excreted in urine”

GSH transferase (detoxification)

NAPQI = N-acetyl-P-benzoquinoneimine

PARACETAMOL

Conjugation (>95%)

Glucuronide & sulfate

NAPQI “toxic metabolite”

Mercapturic acid

“water soluble, excreted in urine”

Co

valent b

ind

ing

QI - protein

Mitochondrial collapse ATP depletion

ANTI-DOTE

-

+

Microsomal oxidation (<5%)

Pathophysiology

Pathophysiology

GSH transferase (detoxification)

Case 1

Name:Maryam Abdulla

Age: 24 yrs

Gender: female

PMH:

Dose not has any diseases

HPI:

Dose not have any problems

PE: well nourished female, scleral icterus was present nose & throat were HENTnormal but she was in apparent distress. Normal bowel sounds were heard in the abdominal examination. Liver spanned approximately 5 cm below the right costal margin & was mildly tender to palpation.

On admission to ER, chest X-ray examination, electrolytes, urinalysis & CBC were within normal limits.

All liver enzymes were raised.

CC: ingested approximately 25 tablets of Panadol (500 mg Paracetamol/tablet) during an argument with her husband.

S:

pain in the upper abdominal quadrant & vomited several times at home & once in the ER. she went to an emergency room 4 hours after the ingestion.

O:

scleral icterus was present she was in apparent distress. Liver spanned approximately 5 cm below the right costal margin & was mildly tender to palpation. All liver enzymes were raised.

A:

She suffer from paracetamol poisoning because she ingested 25 tab.

Goals of therapy:

• Stabilize vital signs

• Remove poisonous substance

• Psychological treatment

Principles of Management

• Stabilize vital signs• ABC

• Investigation for baselines

• Give the Antidotes

• Give anti-emetic

• Re-evaluate the patient

• Psychological assessment

Anti-emetic or emetic drug Anti-emetic or emetic drug ????

If the patient is presented to ER after 1-2 hours of ingestion of poisonous material, there is a rule of emetic drug, gastric lavage & activated charcoal in early management (i.e before completion of absorption).

BUT in our case, she went to ER after 4 hrs. so, emetic drug is contraindicated because it will interfere with administration of oral anti-dot.

In fact, we should manage vomiting to make administration of oral anti-dot possible by giving anti-emetic drug…!!

Prescription

Name: Maryam Abdulla Age: 24 yrs. Gender: female

Date: 4 – Dec - 2007

Dx: Paracetamol Poisoning

1) N-acetylcystine 10.5 g I.V in 200 mL 5% dextrose over 15 min stat.

2) N-acetylcystine 3.5 g I.V infusion in 500 mL over 4 hours after the 1st dose.

3) N-acetylcystine 7 g I.V infusion in 500 mL over 16 hours after the 2nd dose.

4) Metoclopromide 10 mg I.V over 1-2 min stat.

Refer to psychiatry clinicRefer to psychiatry clinicDoctor’s NameDoctor’s NameTelephone #Telephone #

We should admit the patient and monitor liver function daily and if PT>100sec consult hepatologist due to possibility of liver failure.

Case 2

Name :L.PAge:23 yoGender :femalePMH:Dose not have any chronic diseasesHPI:Pregnant for 32 wk , She is depressed and hopes

to end her pregnancy by ingesting acetaminophen.

PE:BP 100/70mmHg normalTemp(36.38) normalHR 100 beats/min normal

CC:Vomiting, She is depressed &hope to end her

pregnancy by ingestion acetaminophen.S:Ingestion of 50 tab acetaminophen 500mgWent to ED after 90 minVomiting (twice)O:Known A: She suffer from paracetamol poisoning because

she ingested more than 50 tab for treatment use of emetic drug or gastric lavage or activated charchol or antidote.

Goals of therapy:1-Managment often centers around symptomatic &

supportive care until the substance is cleared from the body.

2-Prevent complications.

3-Psychological assessment.

PrescriptionName: L.P Age: 23 yrs. Gender: female

Date: 4 – Nov - 2007

Dx: Paracetamol Poisoning

1) Activated charcoal 50 g should be mixed into a slurry with water.

2) Remove charcoal by lavage or wait 1-2 hr before starting acetylcysteine

3) Metoclopramide (anti-emetic) 30 min before oral dose of N-acetylcysteine.

4) Acetylcysteine (Mucomyst) 140mg/kg PO as first dose, dilute to a conc of 5% using a carbonated beverage or fruit juice to mask the sulfur order.

5) Then 70 mg/kg Q 4 hr after for 72 hr.

An obstetrics consultation was requested for evaluate L.P. pregnancy ( A sonogram was taken of the baby).

Refer to psychiatry clinicRefer to psychiatry clinic

Doctor’s NameDoctor’s NameTelephone #Telephone #

Outcome

• 36 hours after ingestion, her acetaminophen level was no longer detectable.

• Her depression seemed to lift once she saw her baby picture from the sonogram.

• Her liver function test showed a mild elevation in ALT & AST enzymes and her PT and total bilirubin values were normal.

• Six weeks later, she had a normal delivery of a healthy baby girl.

Prepare By :1- السعيد زهرة2- الحرز جمانة3- الشايب رقية

4- الجاسم فاطمة5- بوحليقة والء6- الهزاع حور

7- الشيماسي علياء8- االبيض مريم9- النمر سكينة

10- بوخمسين ثناء11- البقشي فاطمة