The Editorial Executive Committee welcomes letters, which should be less than 250 words. Before a decision to publish is made, letters which refer to a published article may be sent to the author for a response. Any letter may be sent to an expert for comment. When letters are published, they are usually accompanied in the same issue by their responses or comments. The Committee screens out discourteous, inaccurate or libellous statements. The letters are sub-edited before publication. Authors are required to declare any conflicts of interest. The Committee's decision on publication is final.

Letter to the Editor

Editor, – The article on paediatric analgesia (Aust Prescr 2008;31:63-5) provides a valuable quick reference on the subject. There is an additional purported mechanism of action for paracetamol, which may have implications in the setting of polypharmacy, especially perioperatively, or associated with chemotherapy.

A serotonergic mechanism of action has been reported for paracetamol.1,2,3 The inhibition or obliteration of paracetamol-induced analgesia by 5-HT3 antagonists, commonly used as antiemetics perioperatively, may warrant consideration when prescribing paracetamol concurrently with drugs from this class. Ondansetron, perhaps the most likely drug from the class to be prescribed to a child, may be less likely to inhibit analgesia, particularly in comparison to tropisetron.4

Ian Cox
Department of Anaesthesia and Pain Management
Concord Hospital, Sydney

Author's comments

Dr Sean Beggs, author of the article, comments:

The lack of clarity about the mechanism of action for paracetamol is even greater than presented in the article (Aust Prescr 2008;31:63-5). Experimental studies have shown that the analgesic effect of paracetamol can be decreased with the administration of some 5-HT3 antagonists (tropisetron)1,4but not others (ondansetron)4, while some have been shown to have conflicting effects (granisetron).3,4This therefore raises the question of whether it is specifically a 5-HT3 antagonist effect, or if some drugs in the class are having this effect via another mechanism.4

Of importance, however, is the fact that the effects of any of the 5-HT3 antagonists on paracetamol's action have yet to be shown to be clinically significant. Given this and the fact that ondansetron is the 5-HT3 antagonist most likely to be used in children, it is difficult to argue that they should not be used in combination. Until clinical trials in children have been undertaken however some doubt remains.


  1. Pickering G, Esteve V, Loriot MA, Eschalier A, Dubray C. Acetaminophen reinforces descending inhibitory pain pathways. Clin Pharmacol Ther 2008;84:47-51.
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  3. Pickering G, Loriot MA, Libert F, Eschalier A, Beaune P, Dubray C. Analgesic effect of acetaminophen in humans: first evidence of a central serotonergic mechanism. Clin Pharmacol Ther 2006;79:371-8.
  4. Libert F, Bonnefont J, Bourinet E, Doucet E, Alloui A, Hamon M, et al. Acetaminophen: a central analgesic drug that involves a spinal tropisetron-sensitive, non-5-HT(3) receptor-mediated effect. Mol Pharmacol 2004;66:728-34.