## First-Line Opioid in Opioid-Naive Patients **Key Point:** Morphine is the WHO-recommended and gold-standard first-line strong opioid for opioid-naive patients with moderate-to-severe cancer pain. ### Why Morphine? 1. **Oral bioavailability**: Available in multiple formulations (immediate-release, sustained-release tablets, liquid) allowing flexible titration 2. **Predictable pharmacokinetics**: Well-understood dose-response relationship; easier to titrate in opioid-naive patients 3. **Active metabolites**: Morphine-6-glucuronide and morphine-3-glucuronide contribute to analgesia and side effects, allowing assessment of tolerance 4. **Cost-effectiveness**: Significantly cheaper than alternatives; critical in resource-limited settings 5. **Reversibility**: Naloxone antagonism is reliable and well-established ### Dosing Strategy in Opioid-Naive Patients - Start with **immediate-release oral morphine**: 5–10 mg every 4 hours - Titrate by 25–50% every 24–48 hours based on pain control - Once stable, convert to **sustained-release** formulation for convenience - Maintain breakthrough doses of immediate-release morphine (10–20% of total daily dose) **Clinical Pearl:** The "analgesic ladder" (WHO) mandates weak opioids (codeine, tramadol) before strong opioids in opioid-naive patients with moderate pain; morphine is reserved for severe pain or failure of weak opioids. **High-Yield:** Morphine is preferred over fentanyl patches in opioid-naive patients because patches deliver a fixed dose and cannot be rapidly titrated — they are reserved for opioid-tolerant patients with stable pain. [cite:KD Tripathi 8e Ch 31]
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