MORPHINE

1. Drug Name

• Generic Name: Morphine

• Brand Names: MS Contin, Avinza, Kadian, Morphabond, Duramorph, various generics.

2. Drug Classification

• Class: Opioid analgesic

• Subclass: Naturally occurring opioid alkaloid (derived from opium poppy)

3. Mechanism of Action

• Primary Action: Morphine is a potent agonist at μ-opioid receptors in the central nervous system (CNS), producing analgesia by inhibiting pain signal transmission in the spinal cord and brain.

• Analgesic Effects: Morphine blocks pain transmission by binding to presynaptic μ-receptors in the dorsal horn of the spinal cord, reducing neurotransmitter release (e.g., substance P, GABA, dopamine) and decreasing perception of pain.

• Additional Effects: Morphine also produces sedation, respiratory depression, and euphoria through its CNS effects. It influences the brain’s reward and addiction pathways, which can contribute to its abuse potential.

4. Pharmacokinetics

• Absorption: Well absorbed from the gastrointestinal tract with bioavailability of approximately 20-40% due to first-pass metabolism.

• Distribution: Large volume of distribution (Vd) at 2-4 L/kg; 30-40% protein-bound in plasma. Crosses the blood-brain barrier and placenta.

• Metabolism: Primarily metabolized in the liver to morphine-3-glucuronide and morphine-6-glucuronide, which have analgesic activity.

• Excretion: Half-life (t½) is around 2-4 hours. Excreted mainly via the kidneys, with some active metabolites (morphine-6-glucuronide) contributing to prolonged effects.

• Special Considerations: In renal impairment, active metabolites may accumulate, increasing risk of toxicity; dosing adjustments are required.

5. Indications

• Primary Indications:

  • Management of moderate to severe pain, particularly in cancer and palliative care.

  • Acute pain management (e.g., post-surgical pain).

• Off-label Uses:

  • Sometimes used for refractory dyspnea (shortness of breath) in palliative care.

• Beneficial Populations: Patients with chronic pain unresponsive to non-opioid analgesics and those in palliative or end-of-life care.

6. Dosage and Administration

• Adult Dosing:

  • Acute Pain: 10-30 mg orally every 4 hours as needed.

  • Chronic Pain: Individualized dosing, often starting at 15-30 mg extended-release tablets every 8-12 hours.

• Pediatric Dosing: Dosage based on weight and age; not recommended for children under 2 years.

• Routes: Oral, intravenous (IV), intramuscular (IM), subcutaneous, epidural, and intrathecal.

• Renal/Hepatic Adjustments: Adjust doses or increase dosing intervals for patients with renal or hepatic impairment.

7. Contraindications

• Hypersensitivity to morphine or any opioids.

• Severe respiratory depression in unmonitored settings.

• Acute or severe bronchial asthma.

• Use with MAO inhibitors or within 14 days of such therapy due to the risk of serotonin syndrome.

8. Warnings and Precautions

• Black Box Warnings: Risks of addiction, abuse, and misuse; life-threatening respiratory depression; neonatal opioid withdrawal syndrome with prolonged use during pregnancy; risks associated with accidental exposure.

• Pregnancy and Lactation: Prolonged use in pregnancy can cause neonatal withdrawal syndrome; morphine is excreted in breast milk and should be used with caution.

• Monitoring Parameters: Respiratory rate, signs of sedation, blood pressure, and signs of opioid misuse or dependence.

• Special Considerations: Caution in elderly patients and those with respiratory or CNS depression; use lower doses in patients with renal impairment due to accumulation of active metabolites.

9. Adverse Effects

• Common Adverse Effects (>10%): Constipation, nausea, vomiting, drowsiness, dizziness, sedation, headache, and pruritus.

• Less Common but Clinically Significant: Dry mouth, urinary retention, euphoria, sweating.

• Serious Adverse Reactions: Respiratory depression, severe hypotension, bradycardia, anaphylactic reactions, tolerance, dependence, and withdrawal symptoms upon abrupt discontinuation.

10. Drug Interactions

• Major Drug Interactions:

  • CNS Depressants (e.g., benzodiazepines, alcohol): Increased risk of sedation, respiratory depression, and death.

  • MAO Inhibitors (e.g., phenelzine, tranylcypromine): Risk of severe reactions including serotonin syndrome.

  • Anticholinergic Drugs: May increase risk of urinary retention and severe constipation.

• Food-Drug Interactions: Food may delay absorption without affecting overall bioavailability.

• Lab Test Interference: Potential false positives in certain opioid drug screens.

11. Clinical Pharmacology

• Pharmacodynamic Profile: Morphine’s pharmacologic effects are mainly through μ-opioid receptor activation. It decreases neurotransmitter release and hyperpolarizes neurons, reducing the perception of pain and producing sedation and euphoria.

• Additional Effects: Morphine has cough suppressant properties and can reduce gastrointestinal motility, which leads to constipation.

12. Special Populations

• Pregnancy: Category C; risks of fetal harm, especially in prolonged use.

• Lactation: Use with caution as morphine is excreted in breast milk, and the risk of neonatal opioid effects exists.

• Geriatric Use: Elderly patients are more sensitive to adverse effects, especially respiratory depression; start with lower doses.

• Renal/Hepatic Impairment: Increased risk of toxicity due to accumulation of active metabolites in renal dysfunction; dosage adjustment is recommended.

13. Therapeutic Uses

• First-Line Use: Indicated as a potent analgesic for severe pain when alternative therapies are inadequate.

• Combinational Therapy: Often combined with non-opioid analgesics for synergistic effects in pain management.

• Clinical Trials and Efficacy: Morphine remains the gold standard for managing severe pain, especially in cancer and end-of-life care, with substantial evidence supporting its efficacy.

14. Monitoring and Follow-Up

• Recommended Lab Tests: Renal and liver function tests in long-term use, serum electrolytes.

• Patient Symptom Checklists: Regular monitoring for respiratory issues, constipation, and signs of misuse.

• Therapeutic and Toxic Levels: Monitor for efficacy and signs of overdose, especially in renal impairment or altered mental states.

15. Overdose Management

• Symptoms of Overdose: Respiratory depression, stupor, coma, miosis, hypotension, bradycardia.

• Treatment Protocols:

  • Naloxone is the primary antidote for opioid overdose, administered IV with repeated dosing as necessary.

  • Supportive Measures: Airway support, oxygenation, and ventilation; IV fluids for hypotension.

• Monitoring in Overdose: Continuous monitoring of respiratory and cardiovascular function.

16. Patient Counseling Information

• Key Counseling Points:

  • Take morphine only as directed to avoid risk of dependence and overdose.

  • Avoid using other CNS depressants, including alcohol, while on morphine.

  • Be cautious about potential constipation; maintain hydration and dietary fiber.

  • Report any signs of difficulty breathing, confusion, or severe drowsiness immediately.

• Signs Requiring Immediate Attention: Respiratory difficulties, confusion, extreme drowsiness, or symptoms of an allergic reaction.