Show the model answerAttempt it first — that is what makes it stick
4 marks
Drugs used for aspiration prophylaxis
What earns the markspart (a)
| Read the question | Aspiration prophylaxis — NOT antiemetics |
|---|---|
| The classes | Antacid, H2 antagonist, prokinetic |
| For each | Example, mechanism, and what it does not do |
| Class | Example | Dose | Mechanism |
|---|---|---|---|
| Non-particulate antacid | Sodium citrate | 0.3 M, 30 mL orally | Neutralises existing gastric acid without leaving particulate matter that itself worsens aspiration pneumonitis |
| H2 receptor antagonist | Ranitidine | 50 mg IV | Specific, competitive antagonism at gastric parietal cell H2 receptors — reduces acid volume and acidity, with no effect on gastric emptying or lower oesophageal sphincter tone |
| Prokinetic | Metoclopramide | 10 mg IV | D2 antagonism increases gastric emptying and lower oesophageal sphincter tone, coordinating gastric–pyloric–small intestinal motility |
Commonly lost: Part (a) asks about acid aspiration prophylaxis, not antiemetics. Many answered it as an antiemetics question and lost the marks.
6 marks — only 13% scored 6.0 or more
Disadvantages of metoclopramide as a sole antiemetic
What earns the markspart (b)
| Disadvantages = side effects | Plus why it is not first-line |
|---|---|
| By system | Extrapyramidal, cardiovascular, endocrine, haematological |
| Not the pathophysiology | Of nausea and vomiting — no marks |
Every disadvantage below traces back to two facts about metoclopramide’s pharmacology. First, its antiemetic action works through dopamine (D2) receptor antagonism at the CTZ — a single mechanism against a reflex with several converging inputs (dopamine, serotonin, histamine, acetylcholine, substance P), so it does nothing against the stimuli that arrive through the other pathways, which is the pharmacological reason roughly half of clinical trials find it no better than placebo. Second, unlike domperidone — which shares the same D2-antagonist mechanism but does not cross the blood–brain barrier — metoclopramide readily crosses the blood–brain barrier, which is what lets it act directly on the CTZ but is also the direct cause of essentially every central disadvantage below.
| Category | Disadvantage |
|---|---|
| Efficacy | Does not antagonise the multiple stimuli that drive nausea and vomiting — roughly half of clinical studies found it no better than placebo |
| Central nervous system | Crosses the blood–brain barrier: sedation, agitation, dry mouth, extrapyramidal side effects, neuroleptic malignant syndrome |
| Cardiovascular | Hypotension, tachy- or bradyarrhythmias after rapid IV bolus administration |
| 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 |
Commonly lost: More than 60% described the pathophysiology of nausea and vomiting instead of answering the question. No marks were given for it.
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.