Show the model answerAttempt it first — that is what makes it stick
5 marks
Metoclopramide
What earns the marks5 marks
| Both actions | Antiemetic AND prokinetic — the second is often forgotten |
|---|---|
| Name the receptors | D2, 5-HT3 and 5-HT4 |
| Agonist or antagonist | At each one |
| LOS tone | Its effect on the lower oesophageal sphincter |
| Side effects | With who is at risk, not just a list |
| Property | Detail |
|---|---|
| Antiemetic dose | 10–20 mg IV, most effective given at the end of anaesthesia rather than at induction |
| Prokinetic / aspiration prophylaxis dose | 10 mg IV |
| Central nervous system | Crosses the blood–brain barrier; extrapyramidal effects up to 72 hours after administration — more common in the young, the elderly, at high doses or with renal impairment (roughly 1 in 5000 overall, more in young females); sedation with long-term use; rare neuroleptic malignant syndrome; agitation after IM premedication |
| Cardiovascular | Hypotension, tachycardia and bradycardia after rapid IV administration; acute conduction abnormalities |
| Gastrointestinal | Abdominal cramps; delayed healing of intestinal anastomosis |
| Endocrine / metabolic | Raised plasma prolactin; hypokalaemia and sodium retention; may precipitate intermittent porphyria |
| Other | Inhibits plasma cholinesterase; urticaria and angioedema; interacts with antidepressants, antipsychotics and CYP450 inhibitors |
| Kinetics | Well absorbed from the gut; variable first-pass metabolism gives a wide oral bioavailability range (30–90%); conjugated in the liver and excreted, with some unchanged drug, in the urine |
Commonly lost: Most recalled metoclopramide only as an antiemetic, forgetting the prokinetic action behind its use in aspiration prophylaxis.
Commonly lost: Some stated it reduces gastric acid secretion or decreases gastric motility — the opposite of what it does.
Commonly lost: Side effects were recalled without noting that extrapyramidal symptoms are commoner in the young, the elderly, at high dose and in renal impairment; few mentioned porphyria or plasma cholinesterase inhibition.
5 marks
Dantrolene
| Property | Detail |
|---|---|
| Presentation | Capsules, and vials of orange powder containing dantrolene 20 mg, mannitol 3 g and sodium hydroxide; each vial reconstituted with 60 mL water to a solution of pH 9.5 |
| Treatment dose (MH) | Initial 2.5 mg/kg IV, then 1 mg/kg every 5 minutes until metabolic signs resolve; no fixed upper limit, though little added benefit above 10 mg/kg |
| Other uses | Neuroleptic malignant syndrome, chronic spasticity of voluntary muscle, ecstasy (MDMA) intoxication |
| Administration caution | Highly irritant if extravasated; a diuresis follows IV administration, reflecting its mannitol content |
| Chronic use | Associated with hepatitis and pleural effusion |
| Kinetics | Variable oral bioavailability; ≈ 85% plasma protein-bound (albumin); hepatically metabolised and renally excreted |
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 used for both aspiration prophylaxis and PONV. Is that the same pharmacological action twice, or two different ones?
Answer
Two different mechanisms in the same molecule. The prokinetic effect that makes it useful for aspiration prophylaxis — increased gastric emptying and increased lower oesophageal sphincter tone — comes from a separate cholinergic action on the gut. The antiemetic effect is dopamine (D2) receptor antagonism at the CTZ, a distinct receptor and a distinct site. Attributing both actions to the same receptor is a common examiner-flagged error.
How does dantrolene work in malignant hyperthermia?
Answer
It binds the ryanodine receptor (RYR1) on the sarcoplasmic reticulum of striated muscle, uncoupling the excitation–contraction process and preventing the excessive release of Ca2+ that drives MH’s generalised muscle rigidity. Vascular smooth muscle and cardiac muscle are not primarily dependent on sarcoplasmic-reticulum Ca2+ release for contraction, so they are relatively spared — dantrolene has little effect on the muscle action potential or on non-depolarising block duration.
What dose of dantrolene would you give to treat suspected malignant hyperthermia?
Answer
An initial 2.5 mg/kg IV, followed by 1 mg/kg every 5 minutes until the metabolic signs begin to resolve. There is no fixed upper limit, but little additional benefit is seen above a total of 10 mg/kg. Treatment continues on intensive care and should not stop until symptoms have fully resolved, since MH may recur.