Everything you need to know about this Over the counter drug, PARACETAMOL

Uses of paracetamol

  • Paracetamol is a widely used analgesic for:
    • Headache
    • Mild migraine
    • Musculoskeletal pain
    • Dysmenorrhoea (menstrual pain)
  • Recommended as the first-choice analgesic in osteoarthritis
  • Acts as an antipyretic and is prescribed for fevers of any cause
  • Safe for use in children, with no risk of Reye’s syndrome
  • Paracetamol has negligible anti-inflammatory actions

Class of Drug

  • Analgesic drug
  • Antipyretic drug

Mode of Administration and Dosage of paracetamol

  • Available in tablet form (325 to 650 mg)
  • Intravenous administration: 15 mg/kg
  • Also available as a suppository

Mechanism of Action of paracetamol

  • Paracetamol exhibits central analgesic action similar to that of aspirin
  • It inhibits COX in the brain and is a poor inhibitor of prostaglandin synthesis in peripheral tissues
  • Once absorbed, it raises the pain threshold, acting as a temporary analgesic
  • Due to its inability to inhibit COX in the presence of peroxides (which are generated in sites of inflammation but not in the brain), paracetamol has poor anti-inflammatory effects. This explains its antipyretic and analgesic actions.

Metabolism of paracetamol

  • Oral acetaminophen has excellent bioavailability
  • Half-life of the drug is 2-3 hours
  • Approximately one-fourth of the drug is protein-bound in plasma
  • Peak plasma concentration occurs within 30 to 60 minutes after intake
  • Metabolized through conjugation with glucuronic acid, sulfate, and cysteine
  • 90-100% of the drug is excreted in urine within the first day after therapeutic dosage
  • A small portion of acetaminophen undergoes CYP-mediated N-hydroxylation to form toxic NAPQI

Toxicity of paracetamol

  • NAPQI, formed after CYP-mediated N-hydroxylation, is responsible for acetaminophen toxicity
  • Hepatotoxicity is the primary concern with acetaminophen overdose, known as acute paracetamol poisoning
  • Hepatotoxicity occurs in adults after ingesting 10 to 15 g (150–250 mg/kg)
  • In children, a dose greater than 150 mg/kg is hepatotoxic
  • A dose of 20-25 g can be potentially fatal
  • Initial symptoms of hepatotoxicity may reflect gastric distress
  • After 2-4 days, symptoms such as tender hepatomegaly, jaundice, coagulopathy, and renal impairment may develop
  • After 72 hours, hepatic encephalopathy and liver enzyme abnormalities occur
  • Severe liver damage and centrilobular necrosis are observed in patients
  • Severe liver damage occurs in 90% of patients with plasma acetaminophen concentrations greater than 300 µg/mL at 4 hours or 45 µg/mL at 15 hours post-ingestion
  • Activated charcoal, if administered within 4 hours of ingestion, can decrease acetaminophen absorption by 50-90%
  • N-acetylcysteine (NAC) is the most accepted antidote for paracetamol overdose, as it detoxifies NAPQI

Adverse Effects of paracetamol

  • Nausea
  • Rashes
  • Leukopenia (rare)

Contraindications of paracetamol

  • Contraindicated in patients with existing liver and kidney diseases
  • Contraindicated in premature infants weighing less than 2 kg due to the risk of hepatotoxicity

Additional Information

  • Paracetamol, dose for dose, is equally effective to aspirin for non-inflammatory conditions and is much safer than aspirin in terms of gastric irritation, ulceration, and bleeding
  • Patients contraindicated for aspirin may be prescribed paracetamol instead
  • Some paracetamol combinations include:
    • Paracetamol and Ibuprofen
    • Paracetamol and Aceclofenac
    • Paracetamol, Aspirin, and Caffeine
    • Paracetamol and Tramadol