Paracetamol Overdose

Paracetamol Overdose

Paracetamol/AcetaminophenN acetyl p aminophenol (APAP)

2Paracetamol/AcetaminophenUse: Anti-pyretic & analgesicTherapeutic dosage:

Neonate dosage:10 days: 15 mg/kg

Oral/IVRectalSTAT20mg/kg40mg/kgMaintenance (4-6 hourly)15mg/kgMax: 4g/d or 60mg/kg30mg/kgMax: 5g/dRisk Factors Of OverdoseChilds factor Paracetamol is reachable, mistaken for candyParents/caregivers/medical personnel factor mistaken dosage (over-dosage), increasing frequency of administration/repeated administration in less than 4 hoursRisk Factors Of OverdoseUse of P450 2E1 inducing drugs (phenobarbitone, carbamazepine)Induction of the P450 2E1 iso-enzyme leads to increased conversion of paracetamol to its toxic metabolite NAPQI.Malnourishment, fasting, acute or chronic illnessRecent significant fasting or illness, such as eating disorders (eg. Anorexia nervosa), or chronic illness such as HIV/AIDS may reduce intracellular glutathione levels increasing toxicity of NAPQIRisk Factors Of OverdoseChronic alcoholismAlcohol consumption at these levels may both induce iso-enzyme P450 2E1 and reduce intracellular glutathione storesGilberts syndrome, Crigler-Najjar syndromeIndividuals suffering these genetic defects may be at greater risk of paracetamol toxicity

Paracetamol OverdosePoisoning: >150mg/kg Fatality: >225mg/kgComplications: Hepatotoxicity, liver failure, renal failure, myocardial damage (rare)

Paracetamol Poisoning

Clinical ManifestationStage 1: Nausea, vomiting, aneroxia, diaphoresis, pale, ill, drowsyStage 2: Right upper quadrant pain (in case of hepatic injury)Stage 3: Jaundice, coagulation defect (bruising, bleeding), renal failure (oliguria), nausea, vomitingStage 4: Complete resolution if reversibleMetabolism N-acetylparabenzoquinoneimineAcetaminophen glutathione conjugate

Acetaminophen glucuronideUrine

AcetaminophenAcetaminophen sulfatePhenosulfotransferase

UDP-glucuronosyl-transferase50%40% 4 at 48h or INR >6 at 72hRenal impairment creatinine >200 mol/lHypoglycemiaMetabolic acidosis despite rehydrationHypotension despite fluid resuscitationEncephalopathyPrognosisGood prognosis: Younger children who accidentally ingest a single dose are less at risk for hepatotoxicityPoor prognosis: Older children who self-harm with overdoses and young children who ingest repeated overdosing may suffer severe morbidity and mortalityPreventionUse of child-resistant closures & packagingPrescription of smaller volumesEducating family of safe medication storage out-of-reach of children with child-resistant latch