Cold comfort for hot children.

Addy, D P

doi:10.1136/bmj.286.6372.1163

Cited by 13 publications

(3 citation statements)

References 20 publications

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“…Over all, paracetamol seems to cause fewer side effects than aspirin: it does not produce the incidence of gastrointestinal disturbances that aspirin does, it rarely produces hypersensitivity reactions, and it has not been implicated in Reye's syndrome. Both aspirin and paracetamol can potentially produce severe toxic reactions after acute overdosage and sometimes during long term treatment employing doses at the higher levels of the therapeutic range (Addy, 1983;Hollister, 1981). …”

Section: Side Effectsmentioning

confidence: 99%

Paracetamol and Phenacetin

Clissold¹

1986

Drugs

214

107

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Since their synthesis in the late l800s paracetamol (acetaminophen) and phenacetin have followed divergent pathways with regard to their popularity as mild analgesic/antipyretic drugs. Initially, paracetamol was discarded in favour of phenacetin because the latter drug was supposedly less toxic. Today the opposite is true. and paracetamol. along with aspirin. has become one of the two most popular 'over-the-counter' non-narcotic analgesic agents. This marked increase in the wide approval attained by paracetamol has been accompanied by the virtual commercial demise of phenacetin because of its role, albeit somewhat circumstantial. in causing analgesic nephropathy.Both paracetamol and phenacetin are effective mild analgesics, suitable for treating mild to moderate pain. and their actions are broadly comparable with those of aspirin and related salicylates. although they do not appear to possess significant anti-inflammatory activity. Since a major portion of a dose of phenacetin is rapidly metabolised to paracetamol. it seems possible that phenacetin owes some of its therapeutic activity to its main metabolite. paracetamol. whereas its most troublesome side effect (methaemoglobinaemia) is due to another metabolite. p-phenetidine. The mechanism of action of paracetamol is poorly defined. although it has been speculated that it may selectively inhibit prostaglandin production in the central nervous system. which would account for its analgesic/antipyretic properties. The lack of any significant influence on peripheral cyclooxygenase would explain the absence of anti-inflammatory activity.At therapeutic doses paracetamol is well tolerated and produces fewer side effects than aspirin. The most frequently reported adverse effect associated with paracetamol is hepatotoxicity. which occurs after acute overdosage (usually doses greater than 10 to 15g are needed) and. very rarely. during long term treatment with doses at the higher levels of the therapeutic range. Paracetamol damages the liver through the formation of a highly reactive metabolite which is normally inactivated by conjugation with glutathione. Overdoses of par aceta mol exhaust glutathione stores. thus allowing the accumulation of this toxic metabolite which covalently binds with vital cell elements and can result in liver necrosis. Glutathione precursors (notably intravenous N-acetylcysteine) have proved remarkably successful in treating paracetamol overdose, as long as treatment is initiated within 10 hours.Apart from pharmacokinetic drug interactions resulting from changes in gastric emptying rate. there have been very few reports of clinically important drug-drug interactions involving paracetamol or phenacetin.The pre-eminent position of paracetamol and aspirin as the non-narcotic analgesic agents of choice for mild to moderate pain is being seriously challenged by 'newer' nonsteroidal anti-inflammatory drugs. Some of these newer agents have been found to have significantly superior analgesic activity and. in some cases. longer durations of action.

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Section: Side Effectsmentioning

confidence: 99%

Paracetamol and Phenacetin

Clissold¹

1986

Drugs

214

107

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“…Contraindications and cautions are also added to the label from time to time when adverse effects become apparent. Examples include: restricting the use of aspirin to those over 16 years of age because of the risk of Reye's syndrome 111,112 adding a warning about the risk of an interaction of repeated doses of paracetamol with warfarin 113 In some cases a licence may be revoked if a serious adverse reaction is discovered 114 .…”

Section: Legislation After 1900mentioning

confidence: 99%

“…restricting the use of aspirin to those over 16 years of age because of the risk of Reye's syndrome 111 , 112…”

Section: Legislation After 1900mentioning

confidence: 99%

Medicines legislation and regulation in the United Kingdom 1500‐2020

Ferner

Aronson

2022

Brit J Clinical Pharma

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The initial purposes of regulation of medicines in England, and latterly in the United Kingdom, were principally to raise government revenue, to discourage murder by poisoning and to regulate the activities of pharmacists. It was only much later that regulators sought to ensure that medicines were of good quality, reasonably safe, and at least somewhat effective, and to curtail misuse of drugs. Here we survey the history of the regulation of medicines and poisons in England from the perspective of clinicians with an interest in therapeutics.

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Antipyresis and Fever

Styrt¹

1990

Arch Intern Med

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Cold comfort for hot children.

Cited by 13 publications

References 20 publications

Paracetamol and Phenacetin

Paracetamol and Phenacetin

Medicines legislation and regulation in the United Kingdom 1500‐2020

Antipyresis and Fever

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