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Research in practice
Paracetamol: pharmacology, prescribing and controversies
  1. Camilla Moriarty1,
  2. Will Carroll2
  1. 1Chelsea and Westminster Hospital, London, UK
  2. 2Academic Department of Paediatric, Respiratory Medicine, University Hospitals of the North Midlands, Stoke-on-Trent, UK
  1. Correspondence to Dr Will Carroll, Academic Department of Paediatric, Respiratory Medicine, University Hospitals of the North Midlands, Newcastle Road, Stoke-on-Trent ST4 6QG, UK; will.carroll{at}nhs.net

https://doi.org/10.1136/archdischild-2014-307287

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    Indications and mechanism of action

    Paracetamol (internationally known as acetaminophen) is the most common medicine encountered in paediatric practice. It is used widely by parents and health professionals and it has analgesic and antipyretic effects. Its short-term safety and efficacy are well established and it is readily available for purchase over the counter. Its mechanism of action is not fully understood but it is known to inhibit prostaglandin synthesis and is highly selective for cyclooxygenase enzymes in the central nervous system. It also has a weak anti-inflammatory action. An understanding of its pharmacology can significantly increase the apparent effectiveness and safety of this useful medicine.

    Oral paracetamol is used in children for mild-to-moderate pain and fever, including postimmunisation fever.1 It may also be given by intravenous infusion or per rectum when it is most commonly used for the short-term treatment of moderate pain, particularly after surgery, and for persistent fever. Unlike opioid analgesia, there is no dependence or tolerance seen with paracetamol, but there is a ceiling effect on analgesia and once this is achieved higher doses do not have an increased effectiveness. Its long-term use tends to deplete glutathione stores, which can enhance toxicity in overdose. Overdose may result in irreversible hepatotoxicity, which can be fatal.

    Pharmacology of paracetamol: an ABCD approach

    Absorption

    The pharmacokinetics of paracetamol in infants and children has been described in detail.2 Oral formulations have high bioavailability and around 80% of a dose is absorbed, mainly by passive diffusion. Rectal formulations have a reduced bioavailability compared with other routes and therefore require higher doses. Importantly, absorption through the gastric mucosa is negligible and therefore any process (or disease) that delays gastric emptying will slow down the absorption of an orally administered dose. The time to peak blood levels after oral administration of the drug in children (aged 6 months to 12 years) ranges from 0.5 to 1.8 h, …

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    Footnotes

    • Contributors CM and WC jointly prepared the review and contributed equally to the final version.

    • Competing interests None declared.

    • Provenance and peer review Commissioned; externally peer reviewed.