A 52-year-old woman with chronic back pain has been on sustained-release morphine 60 mg twice daily for 18 months. She now reports severe constipation (bowel movement once every 4–5 days, hard stools) despite dietary fiber and increased water intake. She denies nausea, sedation, or respiratory depression. Her pain is well-controlled. What is the most appropriate pharmacological intervention?

Explanation

## Opioid-Induced Constipation (OIC) Management **Key Point:** Opioid-induced constipation is a predictable, dose-dependent adverse effect mediated by mu-opioid receptors in the GI tract. It does NOT develop tolerance and requires proactive management. **High-Yield:** Peripherally acting mu-opioid receptor antagonists (PAMORAs) — **naloxegol**, methylnaltrexone, alvimopan — selectively block opioid receptors in the GI tract WITHOUT crossing the blood–brain barrier, thus preserving analgesia while reversing constipation. **Mnemonic: PAMORA** — **P**eripherally **A**cting **M**u-**O**pioid **R**eceptor **A**ntagonist. ### Why Naloxegol Is Correct 1. **Mechanism:** Quaternary ammonium derivative of naloxone; does not cross BBB 2. **Effect:** Blocks mu receptors in enteric nervous system, restores GI motility 3. **Preserves analgesia:** Central opioid effects (pain relief) remain intact 4. **Guideline-recommended:** First-line pharmacological agent for OIC in patients with good pain control 5. **Dosing:** 12.5–25 mg once daily (naloxegol); 8–12 mg SC every other day (methylnaltrexone) ### Management Algorithm for OIC ```mermaid flowchart TD A[Opioid-induced constipation]:::outcome --> B{Pain control adequate?}:::decision B -->|Yes| C[Maintain opioid dose]:::action B -->|No| D[Increase opioid dose]:::action C --> E{Constipation severity?}:::decision E -->|Mild-moderate| F[Laxatives + stool softeners]:::action E -->|Severe/refractory| G[Add PAMORA<br/>naloxegol/methylnaltrexone]:::action D --> H[Reassess GI tolerance]:::action G --> I[Bowel function restored]:::outcome F --> J{Improved?}:::decision J -->|No| G J -->|Yes| K[Continue regimen]:::action ``` ### Why Other Options Are Wrong | Option | Problem | |--------|----------| | **Reduce morphine** | Pain is well-controlled; dose reduction risks inadequate analgesia and is not indicated for OIC management | | **Switch to gabapentin** | Patient has chronic back pain (likely somatic/neuropathic mixed); morphine is more effective. Switching abandons proven analgesia | | **IV naloxone** | Naloxone is a non-selective antagonist; IV administration crosses BBB and reverses ALL opioid effects, including analgesia. Causes acute withdrawal, severe pain, and is contraindicated | **Clinical Pearl:** OIC is the most common opioid adverse effect (60–80% of patients) and the leading cause of opioid discontinuation. Unlike tolerance to respiratory depression or euphoria, tolerance to constipation does NOT develop. Proactive prevention (laxatives, high fiber) and pharmacological reversal (PAMORAs) are essential. [cite:KD Tripathi 8e Ch 31; Harrison 21e Ch 476]