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I was interested to read the letter by Dodd and Doyle 1 criticising routine paramedic use of cyclizine as an antiemetic for patients with chest pain. They sensibly highlight the BNF statement citing cyclizine’s side effects of palpitations and arrhythmias as cause for concern but they then go on to recommend ondansetron as the antiemetic of choice for patients with chest pain based on its lack of “serious” side effects.
Several reports have implicated ondansetron in causing not just arrhythmias2 but chest pain3,4 too. In fact, the BNF lists chest pain, arrhythmias, hypotension, and bradycardia under ondansetron’s side effects, while the packaging insert for ondansetron (Zofran) lists “chest pain with or without ST depression” among associations with its use. Angina is not specifically mentioned on the UK insert (because of lack of proof of a cause-effect relation) but has been on the insert for the US product since 1992. Furthermore, clinical trials have shown ECG changes after intravenous administration of ondansetron and other 5-HT3 receptor antagonists in healthy subjects.
The method by which 5-HT3 receptor antagonists might precipitate myocardial ischaemia and arrhythmias is not clear. It has been postulated that it results from inhibition of the Bezold-Jarisch reflex by 5-HT3 receptor block on vagal afferent fibres and a complex pattern of coronary vasoconstriction and vasodilatation mediated via various cardiac 5-HT receptors. Other authors have explained ECG changes on the basis of 5-HT3 antagonists ability to block cardiac sodium channels and their affinity for the potassium channel, which may delay repolarisation.
Overall, ondansetron has a better side effect profile than many antiemetics but it is the side effect of chest pain, specifically, that may cloud the clinical picture the most. It would seem prudent to exercise caution when using ondansetron in the treatment of suspected acute coronary syndromes.
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