Show the model answerAttempt it first — that is what makes it stick
5 marks
Central nervous system effects of antiemetics
What earns the marks5 marks
| Organise by effect | By TYPE of CNS effect, not drug by drug |
|---|---|
| Breadth, not depth | “Briefly discuss” rewards a structured sweep, not depth on one drug |
| Name the receptor | So each effect follows from what is blocked |
| Effect | Mechanism | Drugs |
|---|---|---|
| Sedation | Central H1 antagonism, central muscarinic antagonism, or central D2 antagonism, depending on class | Hyoscine (most sedating anticholinergic), the antihistamines (cyclizine, dimenhydrinate, diphenhydramine, promethazine), chlorpromazine (most sedating phenothiazine), droperidol |
| Extrapyramidal effects | Central dopamine (D2) antagonism in the nigrostriatal pathway — oculogyric crisis, akathisia, dystonia | Phenothiazines (prochlorperazine most, chlorpromazine less), droperidol, metoclopramide. Domperidone and amisulpride are far less likely — see the trap below |
| Central anticholinergic syndrome | Central muscarinic antagonism — restlessness and hallucinations through to somnolence and unconsciousness | Hyoscine, atropine — not glycopyrrolate, a quaternary amine that cannot cross the blood–brain barrier |
| Neuroleptic malignant syndrome | Severe central D2 antagonism — rare but serious | Phenothiazines, droperidol, metoclopramide |
| Amnesia | Central muscarinic antagonism (hyoscine) or GABA-A agonism (midazolam, used as an antiemetic adjunct) | Hyoscine, midazolam |
| Altered mood, agitation and thought | Central D2 antagonism (isolation of the reticular activating system from its afferent connections) or hyperprolactinaemia from the same mechanism | Chlorpromazine (neurolepsy at treatment dose); droperidol (post-treatment anxiety reported in up to 25% of patients for up to 48 hours); metoclopramide (agitation after IM premedication) |
Read the question: “Briefly discuss” at 5 marks each rewards a structured sweep across the relevant drugs, not deep detail on one. Organise part (a) by type of CNS effect, not drug by drug.
The organising idea worth stating explicitly is that these effects are not properties of the drug classes in the abstract — they are properties of drugs that reach the CNS. Metoclopramide and domperidone share an identical D2-antagonist mechanism, but only metoclopramide crosses the blood–brain barrier, so only metoclopramide produces extrapyramidal effects, sedation and the (rare) neuroleptic malignant syndrome. The same logic separates hyoscine and atropine (uncharged tertiary amines, both cross) from glycopyrrolate (a permanently charged quaternary amine, does not cross and has no central effects at all).
5 marks
Drugs that cause tocolysis
What earns the marks5 marks
| Organise by class | By class of tocolytic, not by naming drugs alone |
|---|---|
| Mechanism per class | And the caution that goes with it |
| Class | Example | Mechanism | Caution |
|---|---|---|---|
| β2-adrenoceptor agonist | Ritodrine, terbutaline | β2-agonism relaxes uterine smooth muscle — the same receptor and mechanism used for bronchodilation in asthma | Tachycardia (β1 effect); ritodrine is used specifically to treat premature labour |
| Magnesium sulfate | Magnesium sulfate | Ca²⁺-antagonism-mediated smooth muscle relaxation, alongside its other actions (anticonvulsant, vasodilator) | Pulmonary oedema has been associated with its use as a tocolytic; may prolong neuromuscular blockade |
| Calcium channel blocker | Nifedipine | Reduces Ca²⁺ influx into vascular and uterine smooth muscle, reducing tone | Used as an additional tocolytic agent alongside the classes above |
| NSAID | Indomethacin | Prostaglandin-synthesis inhibition — prostaglandins promote uterine contraction | Requires periodic fetal echocardiography, since premature closure of the ductus arteriosus is a recognised complication |
| Oxytocin receptor antagonist | Atosiban | Competitive antagonism at the oxytocin receptor | Not available for use in the United States; used in Europe, including for tocolysis following open fetal surgery |
Volatile anaesthetic agents also relax uterine smooth muscle in a dose-dependent way and are used deliberately for this effect during procedures such as external cephalic version or open fetal surgery — worth naming if the question is read as “drugs that produce tocolysis” in the broadest sense, rather than only the drugs given specifically to prevent preterm labour.
If this came up in the viva
Viva points
Hyoscine and atropine can both cause the central anticholinergic syndrome. Why can’t glycopyrrolate?
Answer
Glycopyrrolate is a synthetic quaternary amine — permanently charged — so unlike the naturally occurring tertiary amines hyoscine and atropine, it cannot cross the blood–brain barrier and has no central effects 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.