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Drug Reference

morphine

opioid analgesic· Brands: MSIR, MST Continus, Oramorph, Sevredol, ZomorphIMIVPOPRSC

Mechanism of action
Morphine is a full agonist at the mu opioid receptor, which mediates its analgesic, euphoric, and sedative effects. Activation of these receptors in the spinal cord and brain modulates the perception of pain and the emotional response to it. It also inhibits the release of neurotransmitters such as substance P. Additionally, morphine suppresses the cough reflex and respiratory drive, and it increases smooth muscle tone in the gastrointestinal tract, leading to constipation.
Pharmacokinetics
Oral morphine has low bioavailability (25-50%) due to extensive first-pass metabolism. It is metabolised in the liver to morphine-6-glucuronide, which is a more potent analgesic, and morphine-3-glucuronide, which has no analgesic activity. The active metabolite may accumulate in renal impairment. Peak plasma concentration occurs 1-2 hours after oral administration. Morphine is distributed widely and crosses the blood-brain barrier. Elimination is primarily renal as glucuronides, with a half-life of 2-3 hours, which is prolonged in renal impairment.
Indications & dosing

Acute severe pain (e.g., postoperative, trauma)

Titrate to effect; monitor respiratory rate and sedation.

  • adult · IV: 2–10 mg every 4 hours PRN · Titrate to effect; monitor respiratory rate and sedation.

Chronic pain

Immediate release for breakthrough pain or in opioid-naive patients.

  • adult · PO: 10–20 mg every 4 hours PRN · Immediate release for breakthrough pain or in opioid-naive patients.

Chronic pain (modified release)

For regular analgesia; convert from immediate release requirements.

  • adult · PO: 10–30 mg twice daily · For regular analgesia; convert from immediate release requirements.

Cancer pain

Titrate to effect; use modified release for continuous control.

  • adult · PO: 10–20 mg every 4 hours PRN · Titrate to effect; use modified release for continuous control.

Dyspnea in palliative careoff-label

May be off-label; monitor respiratory depression.

  • adult · SC: 2–5 mg every 4 hours PRN · May be off-label; monitor respiratory depression.

Pain in children

Based on body weight; avoid in infants < 1 month except under specialist care.

  • pediatric · IV: 0.1–0.2 mg/kg every 4 hours PRN · Based on body weight; avoid in infants < 1 month except under specialist care.
Contraindications & precautions
  • Severe respiratory depression · Avoid morphine in patients with significant respiratory compromise, as it worsens respiratory function.
  • Acute severe asthma · Without access to resuscitation facilities, do not use morphine in acute severe asthma.
  • Paralytic ileus · Morphine reduces gastrointestinal motility and may exacerbate ileus.
  • Known hypersensitivity to morphine or other opioids · Cross-sensitivity can occur.
  • Severe hepatic impairment · Reduced metabolism increases risk of accumulation; use with extreme caution and dose reduction.
  • Reduce dose in renal impairment to avoid accumulation of active metabolites.
  • Reduce dose in hepatic impairment as metabolism is impaired.
  • Use with caution in patients with raised intracranial pressure; respiratory depression can worsen cerebral haemodynamics.
  • Use with caution in patients with hypotension or hypovolaemia, as morphine can cause vasodilation and additive effects.
  • Use with caution in patients at risk of urinary retention, such as those with prostatic hypertrophy.
  • Monitor for respiratory depression and sedation, especially in opioid-naive patients or when doses are increased.
Adverse effects
  • Constipation
  • Nausea and vomiting
  • Drowsiness
  • Respiratory depressionserious
  • Hypotension
  • Pruritus
  • Urinary retention
  • Confusion
Interactions
  • diazepammajorAvoid concomitant use unless absolutely necessary. If co-prescribed, prescribe the lowest effective doses for the shortest duration, monitor vital signs and level of consciousness frequently, and ensure that naloxone and resuscitative equipment are immediately available. Dose reduction of one or both agents may be required. Warn patients and caregivers about the signs of respiratory depression and excessive sedation.
Renal & hepatic adjustment
  • eGFR 30–60: Consider reducing the dose by 25% to 50% and extending the dosing interval. Monitor closely for adverse effects.
  • eGFR 10–29: Use with caution; consider alternative opioid. Reduce dose by 50% and extend interval, or avoid use.
  • eGFR 0–9: Avoid use in severe renal impairment (eGFR under 10 mL/min) due to accumulation of active metabolites. (avoid)
  • Hepatic impairment (mild): Use with caution; no dose adjustment usually required. Monitor for increased opioid effects.
  • Hepatic impairment (moderate): Reduce initial dose by 25% to 50% and titrate slowly. Consider alternative opioid.
  • Hepatic impairment (severe): Avoid use in severe hepatic impairment; consider alternative analgesic. (avoid)
Monitoring, pregnancy & toxicity
  • Pain score · Assess regularly, especially after dose changes.
  • Respiratory rate · Monitor for respiratory depression; check hourly after initial dose and with dose increases.
  • Sedation level · Monitor for excessive sedation; use a sedation scale.
  • Blood pressure · Monitor for hypotension, especially with IV administration.
  • Bowel function · Monitor for constipation; implement bowel regimen.
  • Renal function · Monitor creatinine/eGFR to guide dosing and detect accumulation.
  • Pregnancy: Morphine is not recommended during pregnancy, especially in the first and last trimesters, unless clearly necessary and maternal benefit outweighs fetal risk. Prolonged use can cause neonatal opioid withdrawal syndrome and respiratory depression. If used, closely monitor the neonate.
  • Toxicity: Respiratory depression (rate below 12 breaths per minute) and miosis · Administer naloxone (opioid antagonist); repeat doses as needed. Support ventilation and oxygenation.
  • Toxicity: CNS depression progressing to coma · Supportive care: airway maintenance, IV access, close monitoring. May require repeated naloxone due to short half-life.
  • Toxicity: Bradycardia and hypotension · Administer IV fluids and atropine for bradycardia if symptomatic. Monitor continuously.
  • Toxicity: Nausea and vomiting · Antiemetic therapy; consider opioid rotation or dose reduction.
Antidotes & reversal
  • Naloxone · Titrate to adequate ventilation; shorter half-life than the opioid - observe for re-sedation.
Clinical notes
Morphine is indicated for the relief of moderate to severe pain, including pain associated with cancer and myocardial infarction. It is also used in palliative care for dyspnoea. It should be prescribed with caution in opioid-naive patients, those with respiratory disease, or renal impairment. Common adverse effects include constipation, nausea, vomiting, and drowsiness. Respiratory depression is the most serious risk; naloxone is the antidote. Tolerance and dependence can occur with prolonged use. In the UK, morphine is a controlled drug and prescribing must comply with the Misuse of Drugs Act.

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BNF; local formulary