Pharmacology
Ondansetron and 5-HT3 receptor antagonists in chemotherapy-induced vomiting
Ondansetron is a 5-HT3 receptor antagonist: it blocks one of the receptors that serotonin acts on, and is given to prevent chemotherapy-induced vomiting.
Remember
Match the cause to the receptor: chemotherapy makes the gut release large amounts of serotonin, the dominant trigger of acute chemotherapy-induced vomiting, and serotonin acts through 5-HT3 receptors, so a 5-HT3 antagonist such as ondansetron is the natural first choice.
Chemotherapy makes enterochromaffin cells (specialised serotonin-secreting cells in the lining of the gut) release large amounts of serotonin, also called 5-hydroxytryptamine or 5-HT. This is the dominant trigger of acute vomiting after chemotherapy.
The serotonin then stimulates 5-HT3 receptors at two linked sites. One is the vagal afferents (sensory fibres of the vagus nerve that carry signals from the gut up to the brainstem). The other is the chemoreceptor trigger zone (an area of the brainstem outside the blood-brain barrier, so it can sample the blood for drugs and toxins). Both routes switch on the vomiting centre in the medulla (the brainstem area that coordinates vomiting).
Ondansetron is a 5-HT3 receptor antagonist: it competes with serotonin for the receptor and blocks it without switching it on. Granisetron and palonosetron work in the same way, and all three names end in -setron. Ondansetron is first-line (the natural first choice) for preventing nausea and vomiting from radiotherapy; for acute symptoms from chemotherapy it is first-line, usually with dexamethasone (a steroid). With dexamethasone it is only moderately effective against delayed symptoms (from about 24 hours). It is also used for nausea and vomiting after operations.
Many antiemetics (drugs against nausea and vomiting) are grouped by the receptor they block. Aprepitant, an NK1 (neurokinin-1) antagonist, is added for highly emetogenic regimens (those most likely to cause vomiting), mainly to reduce delayed vomiting. Metoclopramide blocks dopamine D2 receptors. Cyclizine (an H1 antihistamine) and hyoscine (an antimuscarinic, which blocks acetylcholine at muscarinic receptors) suit motion sickness and vertigo, which come from the vestibular system (the balance organs and their brainstem nuclei).
Ondansetron's side effects are usually mild: constipation, headache and flushing. The main caveat is QT prolongation (a delay in the heart's electrical recovery between beats, seen on the ECG), which matters with other QT-prolonging drugs.
Key facts
- Drug class
- ondansetron, granisetron and palonosetron are 5-HT3 receptor antagonists, and all three names end in -setron.
- Sites of action
- 5-HT3 receptors sit on vagal afferents from the gut and also in the chemoreceptor trigger zone.
- Trigger
- chemotherapy makes enterochromaffin cells release serotonin, the dominant trigger of acute chemotherapy-induced vomiting.
- Main use
- first choice for preventing acute chemotherapy-induced nausea and vomiting (usually with dexamethasone) and for radiotherapy-induced nausea and vomiting, and also used for post-operative nausea and vomiting.
- Add-on
- aprepitant, an NK1 antagonist, is added for highly emetogenic regimens, mainly to reduce delayed vomiting.
- Side effects
- usually mild: constipation, headache and flushing.
- Caveat
- QT prolongation is the main caveat, so take care with other QT-prolonging drugs.
Exam traps
- Blocking dopamine D2 receptors with a prokinetic (gut-moving) effect is the action of metoclopramide, not ondansetron, which targets serotonin 5-HT3 receptors, does not hasten gastric emptying and has constipation among its recognised side effects.
- Blocking neurokinin-1 receptors is the action of aprepitant, which belongs to a separate drug class from ondansetron and is added to a 5-HT3 antagonist and dexamethasone for highly emetogenic chemotherapy, mainly to reduce delayed vomiting.
- Reducing inflammation around the chemoreceptor trigger zone is probably how dexamethasone, the steroid partner, works, whereas ondansetron blocks serotonin 5-HT3 receptors.
- Blocking muscarinic receptors is the action of hyoscine, the standard treatment for motion sickness, not of ondansetron, which blocks serotonin 5-HT3 receptors instead.
- Cyclizine is an H1 antihistamine, so it blocks histamine rather than serotonin receptors, even though it is often used for opioid-induced and post-operative nausea, which overlaps with ondansetron's uses.
Read the full notes
Tested in 14 SimpleMed+ questions
Practise it in Pharmacology, with the answer and a full explanation after every question.
Practise these questions