Show the model answerAttempt it first — that is what makes it stick
5 marks
Ephedrine
What earns the marks5 marks
| Treat as a short note | Two unrelated drugs, five marks each — not one essay |
|---|---|
| Presentation and dose | With the dosing interval |
| Mechanism | Direct and indirect sympathomimetic action |
| Effects by system | And the reason for tachyphylaxis |
| Property | Detail |
|---|---|
| Class | Mixed (α and β) sympathomimetic amine — found naturally in certain plants, synthesised for medical use |
| Presentation | Tablets, elixir, nasal drops, and a solution for injection containing 30 mg/mL. Exists as four isomers; only the L-isomer is active |
| Uses | IV to treat hypotension associated with regional anaesthesia (including obstetric spinal/epidural, though see the trap below); also used for bronchospasm, nocturnal enuresis and narcolepsy |
| Mechanism | Both direct and indirect sympathomimetic actions; also inhibits the action of MAO on noradrenaline. The indirect action makes it prone to tachyphylaxis as noradrenaline stores in sympathetic nerve terminals become depleted with repeated dosing |
| System | Effect |
|---|---|
| Cardiovascular | Increases cardiac output, heart rate, blood pressure, coronary blood flow and myocardial oxygen consumption; may precipitate arrhythmias |
| Respiratory | Respiratory stimulant; causes bronchodilation |
| Renal | Decreases renal blood flow; glomerular filtration rate falls |
| Interactions | Extreme caution in patients taking MAO inhibitors |
Kinetics. Well absorbed orally, intramuscularly and subcutaneously. Unlike adrenaline, ephedrine is not metabolised by MAO or COMT, giving it a longer duration of action and an elimination half-life of 4 hours. Some is metabolised in the liver, but 65% is excreted unchanged in the urine.
5 marks
Ondansetron
What earns the marks5 marks
| Receptor and site | 5-HT3, central and peripheral |
|---|---|
| Dose and interval | Well answered in this session |
| Side effects | Also well answered |
| The two negatives | No extrapyramidal effects; not effective in motion sickness |
| Property | Detail |
|---|---|
| Presentation | Tablets (4–8 mg); orodispersible lyophilisate (4–8 mg); suppository (16 mg); solution for slow IV injection (2 mg/mL) |
| Uses | CINV, radiotherapy-induced nausea and vomiting, PONV. Licensed above 2 years of age |
| Oral bioavailability | ≈ 60%, therapeutic blood concentration by 30–60 minutes |
| Protein binding | ≈ 75% |
| Metabolism | Hepatic — hydroxylation then glucuronide conjugation to inactive metabolites; reduce the dose in hepatic impairment |
| Half-life | 3–4 hours |
Commonly lost: Most did not mention that ondansetron does not cause extrapyramidal effects — a genuine advantage over droperidol and metoclopramide — and a few wrongly stated that it causes involuntary movements.
Commonly lost: Most also missed that ondansetron is not effective in motion sickness, despite being useful for PONV and chemotherapy- or radiotherapy-induced emesis.
Side effects: headache, flushing, constipation and bradycardia following rapid intravenous administration; diarrhoea and transient rises in liver transaminases have also been reported (in chemotherapy patients, where the chemotherapy itself may be responsible), and slight QTc prolongation. For every 100 patients given ondansetron for PONV prophylaxis, about 20 will not vomit who would otherwise have done so (number needed to treat), and about 3 will develop a headache who would not otherwise have had one (number needed to harm).
If this came up in the viva
Viva points
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.
Ondansetron and droperidol are both used for PONV prophylaxis at similar efficacy. Why is ondansetron free of the extrapyramidal effects droperidol can cause?
Answer
Ondansetron is specific for the 5-HT3 receptor, with no meaningful activity at dopamine, histamine, adrenergic or cholinergic receptors. Droperidol acts as a dopamine (D2) antagonist, and it is D2 blockade that produces extrapyramidal effects — a receptor ondansetron does not touch.
Why does ephedrine show tachyphylaxis with repeated dosing?
Answer
Ephedrine has both direct and indirect sympathomimetic actions, and the indirect component depends on releasing noradrenaline from sympathetic nerve terminals. Repeated doses progressively deplete those noradrenaline stores, so the indirect contribution — and therefore the overall pressor effect — wanes with successive doses.