A 58-year-old man with advanced gastric cancer is admitted for palliative care. He is on morphine 20 mg 6-hourly for pain and complains of persistent nausea and vomiting. His renal function is normal (eGFR 78 mL/min/1.73 m²), and he is not on any other medications. The palliative care team wants to add an antiemetic that is particularly effective for opioid-induced nausea and vomiting (OINV). Which agent is most appropriate?

## Opioid-Induced Nausea and Vomiting (OINV) Management **Key Point:** OINV is mediated primarily by **dopamine (D~2~) and histamine (H~1~) pathways** in the chemoreceptor trigger zone, NOT by 5-HT~3~ or NK~1~ receptors. This is mechanistically distinct from chemotherapy-induced CINV. ### Pathophysiology of OINV 1. **Dopamine release** in chemoreceptor trigger zone (area postrema) → D~2~ receptor activation 2. **Vestibular sensitivity** → H~1~ receptor involvement 3. **Gastric dysmotility** → delayed gastric emptying ### Antiemetic Efficacy in OINV | Agent | Mechanism | Efficacy in OINV | Notes | |-------|-----------|---|---| | **Haloperidol** | D~2~ antagonist (central) | **Excellent** | Gold standard for OINV; low cost; crosses BBB | | Aprepitant | NK~1~ antagonist | Poor | Designed for CINV; minimal role in OINV | | Ranitidine | H~2~ antagonist | Minimal | Blocks gastric acid, not nausea pathways | | Domperidone | D~2~ antagonist (peripheral) | Weak | Does not cross BBB; peripheral action only | **High-Yield:** **Haloperidol 1.5–3 mg daily** (PO or IM) is the first-line antiemetic for OINV in palliative care. It is: - Inexpensive - Effective at low doses (minimal extrapyramidal side effects at antiemetic doses) - Available in multiple formulations (tablet, liquid, IM) - Well-tolerated in elderly patients **Clinical Pearl:** In palliative care, haloperidol is preferred over metoclopramide because: 1. Metoclopramide requires normal renal function for efficacy (this patient has eGFR 78, so it would work, but haloperidol is still preferred) 2. Haloperidol has a longer duration of action (12–24 hrs vs. 4–6 hrs for metoclopramide) 3. Lower risk of tardive dyskinesia at antiemetic doses ### Dosing in Palliative Care - **Haloperidol 1.5 mg PO/IM once or twice daily** - Titrate up to 3–5 mg daily if needed - Can be combined with a laxative (opioids cause constipation, which worsens nausea) **Mnemonic:** **OPIOID NAUSEA = DOPAMINE PROBLEM** → Use dopamine antagonist (haloperidol, metoclopramide). NOT 5-HT~3~ antagonists (those are for CINV and post-operative nausea). [cite:KD Tripathi 8e Ch 16; Palliative Care Guidelines 2023]