Ondansetron (Zofran) and granisetron (Kytril) are potent antagonists of 5-HT3 receptors, which are found peripherally on vagal nerve terminals and centrally in the CTZ. During chemotherapy that induces vomiting, mucosal enterochromaffin cells in the GI tract release serotonin, which stimulates 5-HT3 receptors. This causes va-gal afferent discharge, inducing vomiting. In binding to 5-HT3 receptors, ondansetron and granisetron block serotonin stimulation, hence vomiting, after emetogenic stimuli such as cisplatin. Headache is the most frequently reported adverse effect of these medications.
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