Paracetamol poisoning

Paracetamol 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” Covalent binding QI - protein Mitochondrial collapse ATP depletion ANTI-DOTE - + Microsomal oxidation (<5%) 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 ?? 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 AbdullaAge: 24 yrs. Gender: female Date: 4 – Dec 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 1 st dose. 3)N-acetylcystine 7 g I.V infusion in 500 mL over 16 hours after the 2 nd dose. 4)Metoclopromide 10 mg I.V over 1-2 min stat. Refer to psychiatry clinic Doctor’s Name 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.P Age:23 yo Gender :female PMH: Dose not have any chronic diseases HPI: Pregnant for 32 wk, She is depressed and hopes to end her pregnancy by ingesting acetaminophen. PE: BP 100/70mmHg normal Temp(36.38) normal HR 100 beats/min normal

CC: Vomiting, She is depressed &hope to end her pregnancy by ingestion acetaminophen. S: Ingestion of 50 tab acetaminophen 500mg Went to ED after 90 min Vomiting (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.

Prescription Name: L.P Age: 23 yrs. Gender: female Date: 4 – Nov 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 clinic Doctor’s Name 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-زهرة السعيد 2-جمانة الحرز 3-رقية الشايب 4-فاطمة الجاسم 5-ولاء بوحليقة 6-حور الهزاع 7-علياء الشيماسي 8-مريم الابيض 9-سكينة النمر 10-ثناء بوخمسين 11-فاطمة البقشي