Makindo Medical Notes

⚠️ Be alert for acute anaphylactoid reactions during or shortly after IV administration of acetylcysteine — typically presenting with flushing, urticaria, wheeze, or hypotension. Slow or pause the infusion and restart cautiously once symptoms resolve. Always ensure resuscitation facilities and bronchodilators are available.

📘 About: Always check the BNF link here

• Acetylcysteine (N-acetylcysteine, NAC) replenishes hepatic glutathione stores depleted by toxic paracetamol metabolites (NAPQI).
• Prevents hepatic necrosis if given promptly after overdose — ideally within 8 hours of ingestion.
• Also used as a mucolytic and experimentally to reduce renal injury after contrast exposure.

🧬 Mechanism of Action

• Paracetamol is metabolised mainly by conjugation, but a small fraction is converted by CYP450 to N-acetyl-p-benzoquinone imine (NAPQI).
• NAPQI is detoxified by conjugation with glutathione; in overdose, glutathione is depleted, causing hepatic injury.
• Acetylcysteine replenishes glutathione and directly binds NAPQI, preventing hepatocellular necrosis.

🎯 Indications

• Paracetamol overdose:
  • Ingested >75 mg/kg (or >150 mg/kg if sustained-release formulation).
  • Plasma paracetamol concentration above the treatment line on the nomogram.
  • Staggered overdose (multiple doses over >1 h) or uncertain timing.
  • If presentation is close to or after 8 hours post-ingestion — treat immediately, do not wait for paracetamol level.
• Other indications (off-label):
  • Prevention of contrast-induced nephropathy (uncertain efficacy).
  • Mucolytic therapy — reduces sputum viscosity in chronic bronchitis and cystic fibrosis.

💉 Dosing for Paracetamol Overdose (Adults, max weight 110 kg)

• For adults >110 kg, calculate doses as if 110 kg to avoid overdose of NAC.
• Repeat Bag 3 if ALT or INR remains elevated or paracetamol level still detectable after 21 h course.

💥 Side Effects

• Anaphylactoid reaction — flushing, rash, bronchospasm, hypotension (not IgE-mediated; due to histamine release). → Pause infusion, treat with chlorphenamine ± hydrocortisone, and restart at slower rate.
• GI upset (especially with oral NAC).
• Bronchospasm — especially in asthmatic patients; give bronchodilator if needed.
• Hypotension, tachycardia, or nausea if infused too rapidly.

⚠️ Cautions

• Asthma — higher risk of bronchospasm; have salbutamol ready.
• Previous anaphylactoid reaction — may premedicate with chlorphenamine.
• Monitor for fluid overload in elderly or cardiac patients due to large infusion volumes.

📈 Monitoring

• Check baseline and post-treatment ALT, INR, creatinine.
• Observe for allergic symptoms during each bag change.
• In severe cases, continue NAC until transaminases stabilise and paracetamol undetectable.

🧠 Teaching Point

Acetylcysteine is one of the most effective antidotes in toxicology — capable of completely preventing liver failure if given within 8 hours of a paracetamol overdose. Its “anaphylactoid” reactions are rate-related, not allergic, and should rarely prevent therapy continuation. It exemplifies rational antidote design: restoring a critical intracellular antioxidant to neutralise a reactive toxic metabolite.

📚 References

• BNF: Acetylcysteine
• TOXBASE: Paracetamol poisoning
• NICE CKS: Paracetamol poisoning