PH6.2 | PH6.2 | Prokinetics and Antiemetics — SDL Guide — Summary & Reflection

KEY TAKEAWAYS

Prokinetics and Antiemetics — Key Points:

Vomiting reflex arc: CTZ (D₂/5-HT₃/NK₁, outside BBB) + gut vagal afferents (5-HT₃) + vestibular (H₁/M₁) + cortex → NTS → vomiting motor output. Matching drug to pathway is the central skill.

Prokinetics:
- Metoclopramide (D₂ + 5-HT₄): crosses BBB → EPS risk; max 5 days; antiemetic + prokinetic.
- Domperidone (peripheral D₂): no BBB penetration → safe in Parkinson's; QT risk; max 30 mg/day.
- Cisapride: WITHDRAWN (fatal torsades) — do not prescribe.
- Prucalopride: 5-HT₄ agonist, colon-selective, chronic constipation only.

Antiemetics by aetiology:
- CINV acute: 5-HT₃ antagonist (ondansetron) + dexamethasone.
- CINV delayed: add NK₁ antagonist (aprepitant) — aprepitant inhibits CYP3A4 → halve dexamethasone dose.
- Motion sickness: H₁ antihistamine (promethazine/cyclizine) or scopolamine (transdermal M₁) — ondansetron does NOT work.
- Parkinson's nausea: domperidone or ondansetron ONLY — all central D₂ blockers worsen parkinsonism.
- Pregnancy nausea: ginger first; doxylamine + B₆; promethazine; metoclopramide short-course.

ADR headline: Metoclopramide → EPS (nigrostriatal D₂ block); domperidone → QT (hERG block); ondansetron → constipation + mild QT; promethazine → sedation + anticholinergic.

REFLECT

You are prescribing for a 34-year-old woman in her first trimester who is experiencing debilitating nausea and vomiting. She asks whether she can take ondansetron, which a friend recommended. Think through: (a) what is the dominant pathway for pregnancy nausea — does ondansetron address it? (b) What does the safety evidence say about ondansetron in the first trimester (there are conflicting signals about cardiac septal defects in some studies — how certain are you that it is safe)? (c) What would you prescribe first, and what would you try second if that fails? This scenario illustrates that pharmacological knowledge must be integrated with drug safety data — and that 'popular' does not mean 'evidence-based' or 'safe in all contexts.'