Show the model answerAttempt it first — that is what makes it stick
6 marks
Classification of antiemetics, with one example and a mechanism for each class
What earns the marks6 marks
| Classify by receptor | Not by chemical group, and not by indication — the receptor is what makes the mechanism follow |
|---|---|
| One example per class | The question says one. Give one, and give the one in common use |
| A mechanism for each | Receptor, direction of the action, and the site it acts at |
| Name the site | Central at the trigger zone or the vomiting centre, peripheral, or vestibular |
| Enough classes to earn six | Six receptor classes, plus the ones credited beyond them |
Read the question: The stem asks for one example per class and a brief mechanism. Six well-made lines earn more than three classes described at length, and a list of drug names with no receptor attached answers only half of what was asked.
| Class | Example | Mechanism | Site |
|---|---|---|---|
| 5-HT3 antagonists | Ondansetron | Antagonism at the 5-HT3 receptor, an excitatory ligand-gated cation channel | Peripheral at the vagal afferents in the gut, and central at the area postrema — one drug blocks both ends of the reflex |
| Dopamine (D2) antagonists | Metoclopramide | Antagonism at the D2 receptor | Chemoreceptor trigger zone |
| Antihistamines | Cyclizine | Antagonism at the histamine H1 receptor, with significant muscarinic antagonism contributing | Area postrema, vomiting centre, vestibular nucleus and nucleus tractus solitarius |
| Anticholinergics (antimuscarinics) | Hyoscine | Antagonism at muscarinic acetylcholine receptors, blocking transmission from the vestibular apparatus | Vestibular system, near the trigger zone |
| Corticosteroids | Dexamethasone | Not established — proposed central inhibition of prostaglandin synthesis, control of endorphin release, and an anti-inflammatory effect reducing serotonin release in the gut | Central |
| NK1 antagonists | Aprepitant | Antagonism of substance P at the neurokinin-1 receptor, a G-protein-coupled receptor | Dorsal vagal complex — nucleus tractus solitarius and area postrema |
4 marks
Comparing the side effects of metoclopramide and ondansetron
What earns the marks4 marks
| The central difference | Metoclopramide crosses the blood-brain barrier and is a D2 antagonist; ondansetron is 5-HT3 specific |
|---|---|
| Extrapyramidal effects | Metoclopramide yes, named individually; ondansetron none — say so explicitly |
| What they share | QTc prolongation, headache, and cardiovascular effects after rapid intravenous administration |
| Opposite gut effects | Prokinetic against constipation |
| Compare and contrast | Both halves — a list of one drug's effects then the other's is not a comparison |
Read the question: “Compare and contrast” is not two lists side by side. Structure the answer by effect, not by drug, so that each line does the comparing. And state the absence of extrapyramidal effects with ondansetron as a positive point — it is the single most important contrast between these two drugs and it disappears if the answer only lists what each one does.
| Effect | Metoclopramide | Ondansetron |
|---|---|---|
| Where they differ | ||
| Extrapyramidal effects | Yes, and the defining problem: acute dystonia (oculogyric crisis, opisthotonus, trismus, torticollis), akathisia and parkinsonism. May appear up to 72 hours after a dose, and are more common in young females, at about 1 in 5000 | None. It is specific for the 5-HT3 subtype with no action at dopamine, histamine, adrenergic or cholinergic receptors, so it is free of the neurological effects seen with dopamine antagonists |
| Neuroleptic malignant syndrome | Rarely precipitated | Not a feature |
| Sedation and agitation | Sedation, more common with long-term administration; agitation occasionally after intramuscular premedication | Not a feature |
| Prolactin | Raised — dopamine is the prolactin release-inhibiting factor | Unaffected |
| Gastrointestinal effect | Prokinetic: contraction of the lower oesophageal sphincter and gastric fundus, increased gastric and small-intestinal motility. Abdominal cramps | The opposite direction — constipation is a recognised effect, and diarrhoea is also commonly reported |
| Contraindications | Caution, if at all, in Parkinson's disease, restless legs syndrome and other dopamine-related movement disorders | Reduce the dose in hepatic impairment |
| Where they are alike | ||
| QTc prolongation | Recognised | Slight prolongation, and an association shared across the whole 5-HT3 class |
| After rapid intravenous administration | Hypotension, tachycardia and bradycardia have been reported | Bradycardia and flushing |
| Headache | Recognised | The commonest effect: about 3 patients per 100 treated develop a headache they would not otherwise have had |
| Given together | Cardiac arrhythmias and atrioventricular conduction disturbance have been reported after the two are coadministered intravenously | The same report — this is an interaction between them, not an effect of either alone |
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.
Metoclopramide and domperidone are both D2 antagonists. Why does only one of them cause extrapyramidal effects?
Answer
Metoclopramide crosses the blood–brain barrier and acts directly on central D2 receptors — the same property that produces its extrapyramidal and sedative effects. Domperidone shares the same D2-antagonist mechanism but does not cross the blood–brain barrier, so it is far less likely to cause them.
Metoclopramide is widely available, but it isn’t a first-line antiemetic. Why?
Answer
Its antiemetic efficacy is modest — a trial of 30 studies found systemic metoclopramide 10 mg reduced 24-hour PONV against placebo with a number needed to treat of 7.8, and roughly half of clinical studies found it no better than placebo. Set against that modest benefit are its extrapyramidal risk, sedation, and the other problems that follow from crossing the blood–brain barrier.
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.