Morphine

• Moderate to severe pain management
• Cancer pain
• Postoperative pain
• Chronic pain in opioid-tolerant patients (extended-release)
• End-of-life care and palliative medicine
• Dyspnea in terminal illness

Morphine is the prototypical opioid analgesic and remains the standard against which all other opioids are compared. As a naturally occurring alkaloid derived from the opium poppy, it has been used for pain relief for centuries. Today, morphine is essential for treating moderate to severe pain, particularly in cancer, postoperative settings, and end-of-life care, though its use requires careful consideration of risks including addiction, abuse, and overdose.

Mechanism of Action

Morphine is a full agonist at mu-opioid receptors, with additional activity at kappa and delta receptors. Binding to mu receptors in the central nervous system produces analgesia, euphoria, respiratory depression, and physical dependence. Morphine also activates the descending inhibitory pain pathway and alters the perception of and emotional response to pain in higher brain centers.

Peripheral effects include decreased gastrointestinal motility (causing constipation), histamine release (causing itching and hypotension), and suppression of the cough reflex. The combination of central and peripheral effects accounts for both the therapeutic benefits and side effect profile of morphine.

Available Formulations

Morphine is available in numerous formulations to address different clinical needs. Immediate-release formulations include oral tablets and solution, suppositories, and injectable solutions for IV, IM, subcutaneous, epidural, and intrathecal administration. Extended-release formulations (MS Contin, Kadian, MorphaBond) are available for chronic pain requiring around-the-clock therapy. Concentrated oral solutions are available for patients with difficulty swallowing.

FDA-Approved Indications

Morphine is FDA-approved for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Extended-release formulations are indicated only for patients who are opioid-tolerant and require around-the-clock pain control for an extended period. Morphine is also used for dyspnea management in end-of-life care and has been used historically as a treatment for pulmonary edema.

Dosing Guidelines

Morphine dosing must be individualized based on pain severity, prior opioid exposure, patient-specific factors, and response. For opioid-naive patients with severe acute pain, initial IV doses of 2-4 mg every 3-4 hours or oral doses of 10-15 mg every 4 hours may be appropriate. Doses should be titrated to effect. For extended-release formulations, patients must be opioid-tolerant (typically defined as receiving at least 60 mg oral morphine equivalents daily for at least one week).

Opioid Conversion Considerations

When converting between opioids or formulations, use established equianalgesic tables but apply conservative dose reductions (25-50%) due to incomplete cross-tolerance. Morphine oral bioavailability is approximately 30%, so parenteral doses are significantly lower than equivalent oral doses. Always monitor closely after any conversion.

Important Safety Considerations

Morphine carries boxed warnings for addiction, abuse, and misuse; life-threatening respiratory depression; neonatal opioid withdrawal syndrome; and interaction with benzodiazepines or other CNS depressants causing profound sedation, respiratory depression, coma, and death. Extended-release formulations carry additional warnings about risks from crushing or chewing tablets. Naloxone should be available when using morphine, and patients/caregivers should be educated about overdose recognition and response.

Drug Interactions

Concurrent use with benzodiazepines, other CNS depressants, or alcohol significantly increases the risk of respiratory depression and death; reserve concomitant use for patients without alternatives. CYP3A4 inhibitors may increase morphine effects; CYP3A4 inducers may decrease effects. MAO inhibitors can cause serotonin syndrome or opioid toxicity. Anticholinergic drugs may increase constipation and urinary retention risk.

Special Populations

Dose reduction is required in hepatic impairment (active metabolites may accumulate) and renal impairment (accumulation of morphine-6-glucuronide can cause toxicity). Elderly patients require lower initial doses and careful titration due to altered pharmacokinetics and increased sensitivity. Use during pregnancy, particularly near delivery, can cause neonatal opioid withdrawal syndrome. Morphine passes into breast milk; benefits and risks should be considered.

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