Show the model answerAttempt it first — that is what makes it stick
Before either note
How a two-drug short note is marked
What earns the marks
| A structure for each | Class, receptor and mechanism, kinetics, dose, adverse effects, clinical use |
|---|---|
| Equal weight | Two drugs, one allocation — split it evenly rather than by how much you know |
| Receptor first | Everything else in a short note follows from the receptor and where it sits |
| Numbers where they exist | A dose or a selectivity ratio distinguishes a good note from a general one |
| No overlap hunting | These two drugs have nothing to do with each other; do not manufacture a link |
Read the question: “Write short notes” asks for notes, not two essays. Headed lines under a consistent set of subheadings score better than continuous prose, and they make an uneven split obvious to you while you can still fix it.
Short note 1
Dexmedetomidine
| Heading | Content |
|---|---|
| Class and structure | Imidazole on a dimethylphenyl scaffold. It is the single S-enantiomer of medetomidine, which is what the prefix means. |
| Mechanism | Agonist at the α2 adrenoceptor, selective for α2 over α1 by about 1600:1 — against clonidine's 220:1. Sedation arises from action at α2A receptors in the locus coeruleus, which is a different route from the GABA-A drugs and is why it spares respiratory drive. |
| Effects | Sedation from which the patient is rousable, anxiolysis, analgesia and an opioid-sparing effect of about 50%. Respiratory drive is largely preserved, which is the property that usually decides between it and a GABA-A drug. |
| Dose | Loading 0.5 to 1 µg/kg over 10 minutes, then an infusion of 0.1 to 1 µg/kg/hour. The loading dose is given slowly, or omitted, for the reason in the next row. |
| Cardiovascular | Biphasic. An initial fall in mean arterial pressure of about 13% from central sympatholysis, then a rise of about 12% as higher concentrations reach peripheral post-synaptic α2 receptors on vascular smooth muscle and cause vasoconstriction. Heart rate falls by up to 29% and cardiac output by up to 35%. |
| Adverse effects | In a phase III trial of 401 patients: hypotension 30%, hypertension 12%, bradycardia 9%. Dry mouth. Bradycardia and hypotension are the ones that stop an infusion. |
| Uses | Sedation in intensive care and for procedures, including awake fibreoptic intubation where a co-operative, breathing patient is the point; as an anaesthetic adjunct for its opioid-sparing effect. |
The drug is taught in full, with its structure and the locus coeruleus mechanism, in the intravenous induction agents lesson.
Short note 2
Metoclopramide
| Heading | Content |
|---|---|
| Class and structure | Substituted benzamide. Small and lipophilic, molecular weight about 300, and it crosses the blood-brain barrier freely — which is the single fact the rest of this note follows from. |
| Mechanism | Three actions, and all three should be named with their direction: dopamine D2 antagonism, which is the antiemetic action; 5-HT3 antagonism, which may contribute to it; and 5-HT4 agonism peripherally at higher doses, which belongs with the prokinetic action. The prokinetic effect on the stomach is a separate cholinergic mechanism. |
| Site | Central at the chemoreceptor trigger zone for the antiemetic effect; peripheral in the gut for the prokinetic one. |
| Prokinetic effect | Contraction of the lower oesophageal sphincter and gastric fundus, increased gastric and small-intestinal motility, and decreased pyloric and duodenal muscle activity as the stomach contracts. This is why it appears in aspiration prophylaxis. |
| Dose | 10 mg is the standard clinical dose. As an antiemetic it appears most effective at 20 mg given at the end of anaesthesia rather than at induction; 20 to 25 mg is more effective still but produces more akathisia. |
| Kinetics | Well absorbed from the gut, but first-pass metabolism varies widely, giving an oral bioavailability range of 30 to 90%. May be given intravenously. Conjugated in the liver and excreted, with some unchanged drug, in the urine. |
| Adverse effects | Extrapyramidal effects up to 72 hours after a dose, more common in young females at about 1 in 5000; akathisia after intravenous administration; sedation with long-term use; rarely neuroleptic malignant syndrome; hypotension, tachycardia and bradycardia after rapid intravenous administration. |
| Cautions | Use with caution, if at all, in Parkinson's disease, restless legs syndrome and other dopamine-related movement disorders. |
The adverse-effect list is not a list to memorise. It is one action — D2 antagonism — read off the different places the receptor occurs, and the reason metoclopramide has all of them while domperidone has almost none is that metoclopramide enters the brain and domperidone does not:
Metoclopramide is taught in full in the antiemetics lesson.
If this came up in the viva
Viva points
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.