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

• Buttner R. Pharm 101: N-Acetyl-Cysteine. LITFL

References

• Katzung BG. Basic and Clinical Pharmacology. 14e. 2018: 659