Paracetamol poisoning

HideShow resource information
  • Created by: z
  • Created on: 17-03-16 18:16

Mechanism of toxicity

  • NAPQI, paracetamol metabolite, is severly hepatotoxic
    • N-acetyl-p-benzoquinonimine
      • generated by p450 enzymes
    • also causes paracetamol induced renal damage
      • generated by prostoglandin endoperoxide synthetase rather than p450
  • NAPQI is normally detoxified by interaction with glutathione (GSH) to form glutathione conjugate 
  • mechanisms of NAPQI induced hepatic injury include:
    • glutathione depletion
    • direct oxidising and arylating effects
1 of 5

Factors affecting hepatotoxicity I

  • dose ingested/absorbed
    • <75mg/kg = v unlikely 
    • >150 mg/kg = possible
      • dep largely on pt size- e.g. 15 x 500mg tablet in a 50kg pt = 150mg/kg = possible
  • plasma paracetamol conc
    • use graph
    • >100mg/L 4 hrs post ingestion = possible
    • >50mg/L 8 hrs post
  • single vs staggered dose
    • OD over 60 mins=staggered dose
    • treat all staggered ODs w/ acetylcysteine
2 of 5

Factors affecting hepatotoxicity II

  • time to antidote administration
    • glutathione precursors= IV acetylcysteine over 21 hours
      • bag 1: 150mg/kg in 200ml 5% glucose over 1 hour
      • bag 2 : 50mg/kg in 500ml 5% glucose over 4 hours
      • bag 3: 100mg/kg in 1000ml 5% glucose over 16 hours
    • acetylcysteine a/e: anaphylactoid features in 10-15%; flushing, urticuria, pruritus, bronchospasm, angio-oedema immdiately following admin- resolve by dicontinuing short time
    • histamine mediated thus give antihistamine if necessary
    • 8 hour rule
      • treat w/in 8 hrs of ingestion- not at risk of sig lievr damage
      • thus wait for plasma conc following single OD provided it will be w/in 8 hrs of ingestion before deciding on Rx
      • late presenters= >8 hrs
        • if Rx >15 hrs post-OD, less reliable
        • NB hard to work out if liver damage possible if not sure of exact time later
3 of 5

Clinical presentation

  • NB 24 hour rule: clinically significant hepatotoxicity is v unlikely if 24hrs after most recent P:
    • asymptomatic
    • no paracetamol detectable in plasma
    • normal ALT, normal INR
  • features at presentation:
    • day 1
      • asymptomatic
      • nausea, vomiting, abdo pain, anorexia, pallor
    • day 2 
      • may become asymptomatic
      • N&V
      • hepatic tenderness +/-generalised abdo pain, seltem mild jaundice
    • days 3-5 (severe poisoning)
      • jaundice, liver failure and encephalopathy
      • back pain + renal angle poisoning = renal failure
      • DIC +/- liver failure
      • cardiac arrythmias > arrest
4 of 5

Bloods and biomarkers

  • abnormal bloods in OD
    • AST/ALT v elevated
    • bilirubin elevated
    • PT/INR incr
    • glucose decr
    • phosphate decr
    • pH decr (metabolic acidosis)
    • decr clotting F II, V, VII
    • platelets decr
  • biomarkers in late presenters
    • PT/INR
    • creatinine
    • pH
    • presence of encephalopathy
    • age
5 of 5

Comments

No comments have yet been made

Similar Medicine resources:

See all Medicine resources »See all Therapeutics resources »