Pharm 101: Paracetamol


Analgesic agent

  • Weak COX-1 and COX-2 inhibitor
  • No anti-inflammatory effects, no anti-platelet effects
  • Well absorbed from GIT
  • Bioavailability 80%
  • Peak plasma levels 30-60 mins
  • Lipid soluble
  • Low protein binding ~15-20%
  • Half-life 2-3 hours (increased in liver disease to > 6 hours)
  • First order kinetics
  • Hepatic metabolism to toxic and non-toxic products:
    • > 95% conjugated by glucuronidation and sulphation (transferase enzymes)
    • 5% undergoes metabolism via CYP 2E1 pathway (phase I hydroxylation reaction) to form toxic metabolite NAPQI (N-acetyl-p-benzoquinone imine)
    • NAPQI is irreversibly conjugated with sulfhydryl groups of glutathione
  • Renal excretion of conjugate, < 5% excreted unchanged
Clinical uses
  • Mild-moderate pain
  • Fever
Paracetamol toxicity
  • Therapeutic doses may occasionally cause a mild reversible increase in hepatic enzymes, but larger doses > 150-200mg/kg or > 10 g single ingestion in adults (whichever is less) can cause severe hepatotoxicity with centrilobular necrosis
  • Features of toxicity:
    • Nausea/vomiting
    • Abdominal pain
    • Hepatic failure
    • Renal failure (tubular necrosis)
    • HAGMA
    • Coma
  • For more details regarding pharmacology of paracetamol toxicity, see Pharm 101: N-Acetyl-Cysteine
Further reading
Pharm 101 700

Pharmacology 101

Top 200 drugs

MBBS CCPU (RCE, Biliary, DVT, E-FAST, AAA) Rob is an Emergency Medicine Advanced Trainee based in Melbourne, Australia. He has special interests in medical education, ECG interpretation, and the use of diagnostic and procedural ultrasound in the undifferentiated and unwell patient.

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