- Pharmacodynamics: – Ondansetron is a highly specific and selective serotonin 5-HT3 receptor antagonist, not shown to have activity at other known serotonin receptors and with low affinity for dopamine receptors. The serontonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema. The temporal relationship between the emetogenic action of emetogenic drugs and the release of serotonin, as well as the efficacy of antiemetic agents suggest that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting.
Mechanism of Action: – Ondansetron is a selective serotonin 5-HT3 receptor antagonist. The antiemetic activity of the drug is brought about through the inhibition of 5-HT3 receptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of 5-HT3 receptors in turn inhibits the visceral afferent stimulation of the vomiting center, likely indirectly at the level of the area postrema, as well as through direct inhibition of serotonin activity within the area postrema and the chemoreceptor trigger zone.
- Pharmacokinetics: –
- Absorption: – Ondansetron is well absorbed after oral administration and undergoes limited first-pass metabolism.
- Protein Binding: – 70%-76%
- Metabolism: – Hepatic
- Half-Life: – 5.7 hours
Indications: – For the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy, postoperation, and radiation. Also used for the treatment of postoperative nausea and vomiting.