How 5-HT3 Antagonists Work
5-HT3 antagonists target the 5-HT3 subtype of serotonin receptors. Serotonin is a neurotransmitter found primarily in the gut and also in the central nervous system. When certain treatments or conditions cause the release of large amounts of serotonin from gut cells, it binds to 5-HT3 receptors on vagal nerves and in the brain, triggering the vomiting reflex. By blocking serotonin from binding, 5-HT3 antagonists suppress nausea and vomiting. These drugs are often identified by the suffix 'setron'.
A list of 5-HT3 antagonist medications
Several 5-HT3 antagonists are available with varying properties. Most are used as antiemetics, while some treat other conditions.
Common Anti-Emetic 5-HT3 Antagonists
- Ondansetron (Zofran®): An early 5-HT3 antagonist available in various forms and used for nausea and vomiting from chemotherapy, radiation, and surgery.
- Granisetron (Kytril®): A potent antagonist available in tablets, injection, and a patch.
- Dolasetron (Anzemet®): A prodrug converted in the liver. The injectable form is generally not recommended for chemotherapy-induced nausea and vomiting in adults due to QT prolongation risk.
- Palonosetron (Aloxi®): A second-generation antagonist with a longer half-life and higher binding affinity, effective for both acute and delayed chemotherapy-induced nausea and vomiting.
- Ramosetron: Available in some countries, known for its high affinity and long action, particularly for delayed nausea and vomiting.
5-HT3 Antagonists for Other Indications
- Alosetron (Lotronex®): Used for severe diarrhea-predominant IBS in women when other treatments fail. Its use is restricted due to risks like ischemic colitis.
How 5-HT3 Antagonists Are Used
These drugs primarily prevent and treat nausea and vomiting caused by serotonin release.
Chemotherapy-Induced Nausea and Vomiting (CINV)
They are standard treatment for CINV, especially with moderately to highly emetogenic chemotherapy. They are often given before chemotherapy and may be combined with other antiemetics for better efficacy.
Postoperative Nausea and Vomiting (PONV)
5-HT3 antagonists are commonly used to prevent PONV from anesthesia or surgery.
Radiation-Induced Nausea and Vomiting (RINV)
Similar to CINV, these drugs effectively manage RINV caused by damage to the gastrointestinal lining and serotonin release.
Side Effects and Precautions
Common side effects include headache, fatigue, dizziness, and constipation. Some drugs like ondansetron and dolasetron can cause QT prolongation, a heart rhythm issue, especially at high doses. Palonosetron does not cause significant QT prolongation. Caution is needed for patients with heart conditions or those taking other heart-affecting medications. There's also a potential risk of serotonin syndrome when used with other serotonergic drugs.
Comparison of 5-HT3 Antagonists
| Feature | Ondansetron | Granisetron | Palonosetron | Dolasetron | Alosetron |
|---|---|---|---|---|---|
| Generation | First | First | Second | First | First |
| Key Indication(s) | CINV, PONV, RINV | CINV, PONV, RINV | CINV (acute & delayed), PONV | PONV, CINV (Oral only) | Diarrhea-predominant IBS |
| Typical Half-Life | ~3-5 hours | ~5-8 hours | ~40 hours | ~7 hours (active metabolite) | Unknown / Varies |
| QT Prolongation Risk | Yes (dose-dependent) | Yes | No significant risk | Yes (higher risk) | No anti-emetic use, risk minimal |
| Routes | Oral, IV, ODT, Solution | Oral, IV, Patch | Oral, IV | Oral, IV (limited) | Oral |
Conclusion
5-HT3 antagonists, or "setrons," are vital for preventing and treating severe nausea and vomiting, particularly in cancer and surgical patients. They block 5-HT3 serotonin receptors, preventing the vomiting reflex. Various agents, from first-generation like ondansetron and granisetron to longer-acting palonosetron, allow for tailored treatment. While generally safe, potential side effects like headache, constipation, and QT prolongation with some drugs should be considered. {Link: NCBI https://www.ncbi.nlm.nih.gov/books/NBK548191/}
