Show the model answerAttempt it first — that is what makes it stick
6 marks
Classification by mechanism
What earns the markscore answer
| Four core classes | Anticholinergic, antihistamine, 5-HT3, dopamine antagonist |
|---|---|
| For each | The receptor AND its site — central, peripheral or both |
| An example drug | Matched to the correct receptor |
| Additional classes | Propofol, dexamethasone, NK1 — credited, not the core |
| Class | Receptor | Site of action | Example |
|---|---|---|---|
| Dopamine antagonists | D2 | Central — CTZ | Metoclopramide, prochlorperazine, droperidol, domperidone |
| Serotonin antagonists | 5-HT3 | Peripheral (vagal afferents, gut) and central (CTZ) | Ondansetron |
| Antihistamines | H1 | Vomiting centre, vestibular nucleus, area postrema | Cyclizine |
| Anticholinergics | Muscarinic | Vestibular apparatus, near the CRTZ | Hyoscine |
Commonly lost: Confusing D1 with D2, H1 with H2, or serotonin with histamine lost marks — the example drug is then matched to the wrong receptor.
Commonly lost: Naloxone for opioid-induced nausea was not accepted as an antiemetic-drug answer.
Both the dopamine and serotonin antagonists act at both central and peripheral sites — a point the examiner specifically flagged as commonly missed. State it explicitly rather than naming the CTZ alone.
Working through the mechanism, not just the label, is what separates a passing answer from a full-marks one. Dopamine antagonists such as metoclopramide block D2 receptors at the CTZ, which sits in the area postrema outside the blood–brain barrier and is rich in D2 and 5-HT receptors — this is why a circulating drug or toxin can trigger vomiting through the CTZ without itself crossing into the brain. Serotonin antagonists such as ondansetron block 5-HT3 receptors at two separate points in the same reflex: peripherally, where serotonin released from gut enterochromaffin cells (by chemotherapy, radiotherapy, or surgical stimulation) activates vagal afferents, and centrally, at the CTZ itself — a single drug class covering both explains why 5-HT3 antagonists are effective against causes as different as CINV and PONV. Antihistamines such as cyclizine block H1 receptors in the vomiting centre, vestibular nucleus and area postrema, and typically carry a genuine anticholinergic action alongside the H1 blockade that contributes independently to their antiemetic effect. Anticholinergics such as hyoscine block muscarinic receptors in the vestibular apparatus, near the CRTZ — the pathway responsible for the well-known link between motion, vertigo and vomiting.
4 marks
Adverse effects
What earns the marksby class
| Name them specifically | Per class, not a general list of side effects |
|---|---|
| Link each to its receptor | The effect follows from what the drug blocks |
| Class | Adverse effects |
|---|---|
| Dopamine antagonists | Extrapyramidal reactions (oculogyric crisis, akathisia, dystonia), sedation, neuroleptic malignant syndrome, hyperprolactinaemia |
| Serotonin antagonists | Headache, flushing, constipation, QTc prolongation |
| Antihistamines | Sedation, dry mouth, blurred vision (anticholinergic overlap) |
| Anticholinergics | Dry mouth, sedation, mydriasis, central anticholinergic syndrome (hyoscine, atropine only) |
If this came up in the viva
Viva points
Why can the CTZ be triggered by a circulating drug or toxin that never crosses the blood–brain barrier?
Answer
Because the CTZ lies in the area postrema, on the floor of the fourth ventricle, functionally outside the blood–brain barrier. It is rich in dopamine (D2) and serotonin (5-HT) receptors, so a circulating agent can activate it directly without needing to cross the barrier at all.
Are 5-HT3 antagonists effective for motion sickness?
Answer
No. They are effective for chemotherapy- and radiotherapy-induced nausea and vomiting and for PONV, but not for nausea and vomiting caused by vestibular stimulation or by dopamine agonists — those causes need a drug acting on a different receptor.
Diphenhydramine, dimenhydrinate, cyclizine and promethazine are H1 antagonists. Why do they also have meaningful antimuscarinic effects?
Answer
These agents have significant anticholinergic activity alongside H1 blockade, concomitantly blocking muscarinic receptors in the vestibular system — part of their antiemetic effect comes from this second mechanism, not from H1 blockade alone.