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PH6.2 | PH6.2 | Prokinetics and Antiemetics — SDL Guide — SDL Guide (Part 3)

Clinical Decision-Making — Choosing the Right Antiemetic

Rational antiemetic selection requires matching the drug to the dominant receptor pathway driving the nausea in each clinical context. This is the single most important integrating principle of this module: the same symptom of nausea and vomiting has completely different neurochemical substrates depending on its cause, and a drug that works for one cause will fail for another not because of dose or formulation issues, but because it blocks the wrong receptor at the wrong node in the reflex arc. This principle applies directly and immediately in every clinical environment you will work in: the emergency department (opioid nausea vs vertigo), the oncology ward (acute CINV vs delayed CINV vs anticipatory phase), the surgical recovery room (PONV), and antenatal care (pregnancy nausea). Recognising that identical symptoms have different solutions depending on mechanism is the mark of a prescribing physician rather than a prescription-follower.

Rational antiemetic selection requires matching the drug to the dominant receptor pathway driving the nausea in each clinical context. This is the single most important integrating concept of this module: the same symptom (nausea) has different neurochemical substrates depending on the cause, and a drug that works for one cause will fail for another. The principle applies directly in every clinical setting you will encounter as a house officer or resident.

Clinical decision map by aetiology:

Context	Dominant pathway	First-line agent(s)	Avoid
CINV — acute phase (0–24 h)	5-HT₃ (vagal + CTZ)	Ondansetron + dexamethasone	—
CINV — delayed phase (24–120 h)	NK₁ (substance P)	Aprepitant + dexamethasone (add to 5-HT₃ for HEC)	Ondansetron alone
CINV — anticipatory phase	Conditioned reflex ± anxiety	Lorazepam (benzodiazepine) ± behavioural therapy	—
PONV	5-HT₃ + D₂ (multiple)	Ondansetron + dexamethasone ± droperidol	—
Motion sickness	Vestibular H₁/M₁	Scopolamine (transdermal) or promethazine/cyclizine	Ondansetron (ineffective)
Pregnancy nausea (mild)	Mixed	Ginger first; doxylamine + B₆ (pyridoxine); promethazine	Metoclopramide only short-course if others fail
Opioid-induced nausea	CTZ D₂/NK₁	Metoclopramide, haloperidol, ondansetron	—
Gastroparesis (nausea)	D₂ excess in myenteric plexus	Metoclopramide (max 5 days) or domperidone	Long courses (EPS/cardiac risk)
Parkinson's disease nausea	CTZ D₂ (iatrogenic on levodopa)	Domperidone or ondansetron	All central D₂ blockers
Vertigo/vestibular nausea	H₁/M₁ vestibular	Promethazine, cyclizine, prochlorperazine	5-HT₃ antagonists

Dexamethasone as an adjunct: Corticosteroids (dexamethasone 4–8 mg IV) enhance the antiemetic effect of both 5-HT₃ antagonists and NK₁ antagonists for CINV and PONV by an incompletely understood mechanism. Dose reduction is required when combined with aprepitant (CYP3A4 inhibition by aprepitant doubles dexamethasone exposure — use 50% of the usual dose).

Self-Assessment — Prokinetics and Antiemetics

Self-assessment is the mechanism through which declarative pharmacological knowledge converts into procedural clinical skill — the ability to act correctly under pressure without hesitation. The vignettes in the quiz below are constructed around the highest-yield distinctions in this module: the BBB penetration difference between metoclopramide and domperidone, the CINV phase-specific drug selection (acute vs delayed), the mechanism-based failure of ondansetron in motion sickness, and the identification of a safe antiemetic in Parkinson's disease. For each question, apply the receptor pathway map you have studied — if you find yourself guessing from drug name familiarity, the answer may accidentally be right but the reasoning will fail you in a novel clinical scenario where the same names appear in a different context.

The clinical vignettes in this self-assessment are designed to test your ability to apply receptor pharmacology to patient management — not just recognise drug names. For each scenario, identify the dominant nausea pathway involved, match it to the correct drug class, and consider which drugs would be contraindicated and why. Pay particular attention to the Parkinson's disease scenario (which drug is safe) and the CINV scenario (which phase requires which drug class) — these are the highest-yield clinical distinctions from this module.

Work through the micro-quiz questions below before reviewing the explanations. If you find yourself selecting an answer based on drug name familiarity rather than mechanism, revisit the pathway diagram and the clinical decision table above.