TY - JOUR T1 - Paracetamol: pharmacology, prescribing and controversies JF - Archives of disease in childhood - Education & practice edition JO - Arch Dis Child Educ Pract Ed SP - 331 LP - 334 DO - 10.1136/archdischild-2014-307287 VL - 101 IS - 6 AU - Camilla Moriarty AU - Will Carroll Y1 - 2016/12/01 UR - http://ep.bmj.com/content/101/6/331.abstract N2 - 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.AbsorptionThe 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, … ER -