From the Guidelines
Ondansetron works by blocking serotonin 5-HT3 receptors in the chemoreceptor trigger zone of the brain and in the gastrointestinal tract. The mechanism of action of ondansetron is based on its ability to selectively antagonize 5-HT3 receptors, which are involved in the vomiting reflex. When patients experience nausea and vomiting, particularly after chemotherapy, radiation, or surgery, serotonin is released from enterochromaffin cells in the small intestine, which then activates 5-HT3 receptors 1. By blocking these receptors, ondansetron prevents serotonin from binding and initiating the vomiting reflex.
Key Points
- Ondansetron is a 5-HT3 receptor antagonist
- It is effective in preventing acute nausea and vomiting
- The medication is typically administered at doses of 16-24 mg orally or 8-16 mg intravenously, as outlined in the NCCN guidelines 1
- Ondansetron may be less effective for delayed symptoms of nausea and vomiting
- Side effects can include headache, constipation, and rarely QT interval prolongation, so caution is needed in patients with cardiac conditions or electrolyte abnormalities.
Clinical Use
Ondansetron is often used in combination with other medications, such as dexamethasone, to prevent nausea and vomiting in patients undergoing chemotherapy 1. The NCCN guidelines provide recommendations for the use of ondansetron and other antiemetic medications in patients with cancer 1.
From the FDA Drug Label
Ondansetron is a selective 5-HT 3receptor antagonist. While its mechanism of action has not been fully characterized, ondansetron is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HT 3type are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema It is not certain whether ondansetron’s antiemetic action is mediated centrally, peripherally, or in both sites. However, cytotoxic chemotherapy appears to be associated with release of serotonin from the enterochromaffin cells of the small intestine. The released serotonin may stimulate the vagal afferents through the 5-HT 3receptors and initiate the vomiting reflex.
The mechanism of action of Ondansetron is as a selective 5-HT3 receptor antagonist. It is believed to work by blocking the action of serotonin at the 5-HT3 receptors, which are involved in initiating the vomiting reflex. The exact site of action (central, peripheral, or both) is not certain. 2
From the Research
Mechanism of Action of Ondansetron
- Ondansetron is a potent and highly selective 5-HT3 receptor antagonist that prevents emesis following chemotherapy by antagonising the action of 5-hydroxytryptamine (5-HT) at 5-HT3 receptors on vagal afferent neurons that innervate the gastrointestinal tract and 5-HT3 receptors in the central vomiting system 3.
- The mechanism of action of ondansetron involves blocking the initiation of the emetic reflex by preventing the activation of 5-HT3 receptors at two sites: centrally, in the area postrema and nucleus tractus solitarius, and peripherally, on vagus nerve terminals 4.
- Ondansetron's anti-emetic activity is thought to be due to its selective inhibition of 5-HT3 receptors, which are located in the chemoreceptor trigger zone and the gastrointestinal tract 5, 6, 7.
- The drug's ability to block 5-HT3 receptors in the area postrema and on vagus nerve terminals prevents the stimulation of vagal afferent nerves and the subsequent activation of the central vomiting system, thereby preventing emesis 3, 4.
Sites of Action
- Central: area postrema, nucleus tractus solitarius (NTS) 4
- Peripheral: vagus nerve terminals 4
- Chemoreceptor trigger zone in the area postrema 5, 7
- Gastrointestinal tract 3, 6, 7
Key Findings
- Ondansetron is a highly potent and selective antagonist at 5-HT3 receptors 3, 4.
- The drug's anti-emetic activity is very powerful in preventing nausea and vomiting induced by chemotherapy 7.
- Ondansetron has been shown to be effective in controlling nausea and vomiting in patients treated with cisplatin and other emetogenic chemotherapy agents 5, 6.