A 45-year-old woman with chronic back pain has been on morphine 30 mg twice daily for 8 months. She now reports constipation for the past 3 weeks (bowel movements only once every 4–5 days, hard stools, abdominal bloating) unresponsive to increased dietary fibre and water intake. She is unwilling to reduce opioid dose due to inadequate pain control. What is the most appropriate next step in management?

Explanation

## Opioid-Induced Constipation (OIC): Pharmacological Management ### Pathophysiology of OIC Opioids bind μ-receptors throughout the GI tract: - **Stomach & small bowel:** ↓ propulsive contractions, ↑ segmental contractions → delayed transit - **Colon:** ↑ water reabsorption, ↓ defecation reflex - **Result:** Hard, infrequent stools despite adequate fibre and hydration **Key Point:** Tolerance develops to analgesia and euphoria, but NOT to constipation. Opioid-induced constipation is a dose-dependent, persistent side effect that requires proactive management. ### Management Hierarchy | Step | Intervention | Efficacy | Limitations | |------|--------------|----------|-------------| | 1 | Fibre + fluids + exercise | Mild benefit | Often insufficient for opioid-induced OIC | | 2 | Stool softeners (docusate) | Minimal | Does not address reduced motility | | 3 | Osmotic laxatives (PEG, lactulose) | Moderate | May cause bloating, cramping | | 4 | **Peripherally acting μ-antagonists** | **Excellent** | **Specific for OIC; no CNS effects** | | 5 | Stimulant laxatives (senna, bisacodyl) | Moderate | Risk of dependence, electrolyte loss | ### Peripherally Acting Opioid Antagonists (PAORA) **High-Yield:** These agents block μ-receptors in the GI tract WITHOUT crossing the blood–brain barrier, so they reverse OIC without precipitating withdrawal or reducing analgesia. #### Naloxegol - **Dose:** 12.5 mg daily (or 25 mg if inadequate response) - **Mechanism:** PEGylated naloxone; poor oral bioavailability; acts locally in GI tract - **Onset:** 4–12 hours - **Efficacy:** 40–50% of patients achieve ≥3 spontaneous bowel movements/week - **Advantages:** Once-daily dosing, minimal systemic absorption #### Methylnaltrexone (Relistor) - **Dose:** 8–12 mg SC once or twice daily (or 450 mg PO daily) - **Mechanism:** Quaternary ammonium compound; does not cross BBB - **Onset:** 30–60 minutes (SC), 1–2 hours (PO) - **Efficacy:** ~50% achieve laxation within 4 hours of SC dose - **Advantages:** Rapid onset; useful for acute OIC in palliative care #### Alvimopan - **Use:** Restricted to hospitalized patients post-abdominal surgery (not chronic OIC) **Clinical Pearl:** Peripherally acting antagonists are superior to traditional laxatives because they specifically address the μ-receptor-mediated mechanism of OIC without systemic opioid reversal. ### Why NOT Switch to Fentanyl? Although transdermal fentanyl may have a slightly lower OIC incidence in some patients, constipation is NOT opioid-specific — it occurs with all μ-agonists. Switching opioids is not evidence-based for OIC management and risks inadequate pain control during transition. **Mnemonic:** **PAORA** = Peripherally Acting Opioid Receptor Antagonists (naloxegol, methylnaltrexone, alvimopan) [cite:KD Tripathi 8e Ch 33; Harrison 21e Ch 474]