Pharmacology · 5-HT3 receptor antagonists (setrons)
Ondansetron !
The most used setron: blocks serotonin 5-HT3 receptors to prevent vomiting after chemotherapy and surgery. Its key risk is a longer QT interval.
Updated 2026-11-01
The cryo-EM structure is the mouse 5-HT3A receptor with ondansetron in the serotonin-binding pocket between two subunits; the human receptor's pocket is closely similar.
Mechanism of action
Ondansetron is a selective antagonist of the 5-HT3 receptor, a serotonin-gated cation channel. After chemotherapy, radiotherapy or surgery, enterochromaffin cells in the gut release serotonin, which excites vagal afferent nerves through 5-HT3 receptors; the signal reaches the nucleus of the solitary tract and the area postrema and triggers vomiting. Ondansetron occupies the serotonin site and keeps the channel closed, at the periphery and in the brainstem. It does not block dopamine receptors and does not speed up the gut.
- Chemotherapy makes gut enterochromaffin cells release serotonin
- Serotonin opens 5-HT3 channels on vagal nerves and in the brainstem
- Ondansetron fills the serotonin pocket and keeps the channel shut
- The vomiting reflex is not triggered
Pharmacokinetics
- Absorption
- Given by mouth (tablets, orally disintegrating tablets, solution) or intravenously.
- Distribution
- About 70–76% bound to plasma proteins.
- Metabolism
- Extensive in the liver by several CYP enzymes, mainly CYP3A4 and CYP1A2; CYP2D6 plays a minor role.
- Elimination
- Mostly as metabolites in the urine; only about 5% leaves unchanged.
- Half-life
- About 4 hours in adults with cancer; longer in older adults and much longer in liver impairment.
Indications
- Prevention of nausea and vomiting from emetogenic cancer chemotherapy, usually with dexamethasone and, for highly emetogenic regimens, an NK1 antagonist.
- Prevention of post-operative nausea and vomiting.
- Nausea and vomiting from radiotherapy.
- Vomiting in children with acute gastroenteritis, to make oral rehydration possible (off-label use). Acute (viral) gastroenteritis →
Adverse effects
Common
- Headache
- Constipation
- Diarrhoea and fever
- Transient rise in liver enzymes
Contraindications
- Hypersensitivity to ondansetron
- Use with apomorphine (profound hypotension and loss of consciousness)
- Congenital long QT syndrome (avoided)
Key interactions
- Other QT-prolonging drugs (some antiarrhythmics, antipsychotics, macrolides, methadone)
- Additive QT prolongation and risk of torsades de pointes.
- SSRIs, SNRIs, MAO inhibitors, mirtazapine, fentanyl, lithium, tramadol, IV methylene blue
- Serotonin syndrome.
- Apomorphine
- Profound hypotension and loss of consciousness; the combination is contraindicated.
- Strong CYP3A4 inducers (phenytoin, carbamazepine, rifampicin)
- Faster clearance and lower ondansetron levels.
- Tramadol
- Weaker pain relief from tramadol in small trials.
What is monitored
- ECG in patients with low potassium or magnesium, heart failure, bradyarrhythmias or other QT-prolonging drugs
- Potassium and magnesium before and during treatment in those at risk
- Bowel sounds and abdominal distension after abdominal surgery
- Signs of serotonin syndrome when combined with serotonergic drugs
Administration and safety
- IV doses are infused at the rate set in the label; giving it faster raises the risk of chest pain from coronary spasm
- Not mixed with alkaline solutions, which can make it precipitate; it is diluted only in compatible fluids
- Orally disintegrating tablets dissolve on the tongue and are useful when the patient cannot swallow; some contain phenylalanine
- It does not stimulate the gut and does not replace nasogastric suction
Nursing care
- Check potassium, magnesium and any QT-prolonging drugs before the dose; a baseline ECG in high-risk patients
- Give it before the start of chemotherapy so that it acts before serotonin is released
- Ask about constipation and headache, the most common complaints
- Watch for agitation, tremor, sweating or fever if the patient also takes SSRIs, SNRIs or opioids such as fentanyl
- After abdominal surgery, watch bowel sounds and distension, because ondansetron can hide an ileus
Pregnancy and breastfeeding
Studies on birth defects, including oral clefts, give inconsistent results; it is used in pregnancy when the benefit outweighs the uncertain risk.
Test yourself
Think of the answer, then tap the question to see it.
Which cardiac effect of ondansetron is checked with an ECG in patients with low potassium or magnesium?
QT prolongation, which can lead to torsades de pointes; the effect is dose-dependent.
Which drug is contraindicated with ondansetron, and why?
Apomorphine: the combination has caused profound hypotension and loss of consciousness.
Why can ondansetron be dangerous after abdominal surgery even though it controls vomiting?
It does not move the gut and can mask a progressive ileus or gastric distension.
Which cells release the serotonin that ondansetron blocks after chemotherapy?
The enterochromaffin cells of the small-intestine mucosa.
Related drugs
Related conditions
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - ONDANSETRON injection (DailyMed (U.S. National Library of Medicine), 2026); Ondansetron: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Key points from the evidence | Management of vomiting in children and young people with gastroenteritis: ondansetron | Advice | NICE (National Institute for Health and Care Excellence (NICE), 2014); RCSB PDB - 6W1M: Cryo-EM structure of 5HT3A receptor in presence of Ondansetron (RCSB Protein Data Bank, 2026).
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Representative model, for educational purposes only.