Nine groups, one shared logic
— and the mark is in the site of the receptor, not just its name.

Commonly lostCommonly lost: “Antagonises the receptors in the vomiting centre” scored lower than naming the actual receptor and its site. Despite a 73.3% pass rate, fewer than 20% scored full marks — depth, not breadth, was the limiting factor.

Naming the receptor is only half of each row — the site is the other half, and it is what the examiner explicitly rewarded. The vestibular apparatus feeds into the CRTZ through muscarinic receptors, which is why hyoscine is effective for motion-related and vestibular causes of nausea that a 5-HT3 or D2 antagonist alone will not reliably cover. Histamine H1 receptors sit alongside the vomiting centre, vestibular nucleus and area postrema, and cyclizine’s antiemetic effect is not purely H1 blockade — a genuine anticholinergic action contributes as well, which is why cyclizine and hyoscine share some side effects despite acting through different primary receptors. Serotonin (5-HT3) receptors are the one class acting at two separate points in the same reflex arc: peripherally on vagal afferents activated by serotonin released from gut enterochromaffin cells, and centrally at the CTZ — a dual site of action worth stating explicitly, since a receptor named without its site earns partial credit at best. Dopamine (D2) receptors are concentrated at the CTZ specifically; of the five dopamine receptor subtypes described, D2 is the one relevant here, and metoclopramide’s antagonism of it is the mechanism shared with the whole dopamine-antagonist class covered later in this lesson.

Corticosteroids are the one class here with no single defined receptor — say that plainly rather than inventing a confident mechanism, then give the proposed explanations: central prostaglandin-synthesis inhibition, control of endorphin release, and an anti-inflammatory effect that may also reduce 5-HT release in the gut. NK1 antagonists block a G-protein-coupled receptor whose ligand, substance P, acts in the dorsal vagal complex — they are described as potentiating ondansetron and dexamethasone rather than replacing them, which is worth stating if the question allows discussion beyond simple classification. Cannabinoids act on the CB1 receptor both peripherally (suppressing gut motility) and centrally, in the nucleus of the solitary tract — effective for chemotherapy-induced nausea and vomiting, but not for PONV, a distinction worth naming rather than assuming. GABA-A agonism (midazolam) is proposed to act by decreasing dopamine synthesis and release within the CRTZ — an indirect route to the same D2 pathway the dopamine antagonists block directly. Propofol at sub-induction dose has an antiemetic effect that is genuinely independent of its use as an induction or maintenance agent, though the receptor basis for this is not established in the same terms as the other classes.

1. 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.

2. Ondansetron and droperidol are both used for PONV prophylaxis at similar efficacy. Why is ondansetron free of the extrapyramidal effects droperidol can cause?

   Answer

   Ondansetron is specific for the 5-HT3 receptor, with no meaningful activity at dopamine, histamine, adrenergic or cholinergic receptors. Droperidol acts as a dopamine (D2) antagonist, and it is D2 blockade that produces extrapyramidal effects — a receptor ondansetron does not touch.

3. Where do NK1 antagonists act, and on what ligand?

   Answer

   On the neurokinin-1 receptor, whose primary ligand is substance P, at the brainstem nuclei of the dorsal vagal complex — the nucleus tractus solitarius and area postrema.

4. Nabilone works well for chemotherapy-induced nausea and vomiting. Does that mean it is a good choice for PONV?

   Answer

   No — cannabinoids are effective for CINV but are not effective for managing PONV. The two indications should not be assumed to transfer.

Every viva on this topic, with answers→