Pharm 101: Paracetamol

Class

Analgesic agent


Pharmacodynamics
  • Weak COX-1 and COX-2 inhibitor
  • No anti-inflammatory effects, no anti-platelet effects

Pharmacokinetics
  • 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

References

Pharm 101 700

Pharmacology 101

Top 200 drugs

MBBS (UWA) CCPU (RCE, Biliary, DVT, E-FAST, AAA) Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Editor-in-chief of the LITFL ECG Library. Twitter: @rob_buttner

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