5-HT3 receptor antagonists, such as dolasetron, granisetron (Kytril), ondansetron (Zofran), and palonosetron (Axoli), are crucial in managing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea. These drugs selectively block 5-HT3 receptors in the visceral vagal and spinal afferent nerves, chemoreceptor trigger zone, and the vomiting center. They have a rapid onset of action and can be given as a single dose before chemotherapy. Ondansetron and granisetron, in particular, can prevent emesis in 50% to 60% of patients treated with the chemotherapy drug cisplatin (Platinol).
The liver extensively metabolizes these drugs, with excretion primarily via urine. Ondansetron requires dosage adjustments for hepatic insufficiency. These drugs do not inhibit dopamine or muscarinic receptors and do not affect esophageal or gastric motility. These antagonists are also effective in treating hyperemesis of pregnancy and upper abdominal irradiation-induced nausea. However, they may cause adverse effects, including constipation, diarrhea, headache, and lightheadedness. All of these drugs are associated with QT prolongation, especially when combined with other drugs and anesthetics, which can lead to cardiac arrest. They are also associated with serotonin syndrome when combined with other serotonergic drugs. However, their efficacy may be enhanced in combination therapy with corticosteroids, NK1 receptor antagonists, and dopamine D2 antagonists.
Vomiting is a common side effect among individuals undergoing chemo and radiation therapy. In these patients, the damaged GI mucosa releases serotonin, which binds to receptors on vagal afferent nerves. This relays the signal towards the vomiting center, initiating vomiting reflex.
Also, the vomiting center and chemoreceptor trigger zone are rich in 5-HT3 receptors, making them key targets for treating chemotherapy-induced nausea and vomiting or CINV.
Several antagonist drugs, including dolasetron, granisetron, ondansetron, and palonosetron selectively block 5-HT3 receptors. These drugs are available as tablets, oral solutions, and intravenous formulations.
They act rapidly at the target site and effectively alleviate vomiting in patients undergoing chemotherapy and in postoperative and post-radiation cases.
Notably, palonosetron exhibits a higher affinity for 5-HT3 receptors and a longer half-life of 40 hours.
Common adverse effects include headache, dizziness, and constipation. Additionally, high doses of dolasetron prolong the QT interval, causing arrhythmias.
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