Morphine

Usage

• Morphine is primarily prescribed for the management of moderate to severe acute and chronic pain, including post-surgical pain, pain associated with myocardial infarction, and pain due to cancer. It’s also used in palliative care to alleviate suffering.
• Pharmacological classification: Opioid analgesic, narcotic.
• Mechanism of Action: Morphine exerts its analgesic effects primarily by binding to mu-opioid receptors in the central nervous system, inhibiting pain signal transmission and altering pain perception. It also has effects on delta and kappa-opioid receptors.

Alternate Names

• Morphine sulfate, morphine hydrochloride, MS Contin, Infumorph, Mitigo, Roxanol, Kadian, Avinza.
• Brand names vary considerably depending on the country and specific formulation.

How It Works

• Pharmacodynamics: Morphine binds to mu-opioid receptors, predominantly in the brain, spinal cord, and gastrointestinal tract. This binding inhibits the release of neurotransmitters involved in pain transmission (e.g., substance P, glutamate), activates descending inhibitory pain pathways, and modulates pain perception in the brain. This leads to analgesia, sedation, euphoria, and respiratory depression.
• Pharmacokinetics:
  • Absorption: Morphine can be administered orally, intravenously, intramuscularly, subcutaneously, epidurally, intrathecally, and rectally. Bioavailability varies depending on the route of administration, with oral bioavailability being relatively low due to first-pass metabolism.
  • Metabolism: Primarily metabolized in the liver by glucuronidation to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). M6G is an active metabolite with analgesic properties, while M3G lacks analgesic activity but may contribute to neurotoxicity.
  • Elimination: Morphine and its metabolites are primarily excreted by the kidneys. Accumulation can occur in patients with renal impairment.
• Mode of Action: Morphine’s primary mode of action involves binding to mu-opioid receptors, which are G protein-coupled receptors. This binding leads to a cascade of intracellular events including inhibition of adenylate cyclase, decreased cAMP production, opening of potassium channels, closing of calcium channels, and hyperpolarization of neurons, reducing neuronal excitability.
• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Morphine primarily acts as an agonist at mu-opioid receptors. There is some interaction with other opioid receptors, such as delta and kappa.

Dosage

Standard Dosage

Adults:

• Intravenous: 2.5-15 mg every 4-5 minutes, or 0.5-2.0 mg/hour by continuous infusion.
• Oral: 10-30 mg every 4 hours (immediate-release) or 15-30 mg every 8-12 hours (extended-release). The dosage should be adjusted to individual needs.
• Subcutaneous: 5-10 mg every 4 hours.

Children:

• Intravenous: 0.05-0.1 mg/kg every 5-15 minutes, or 0.01-0.05 mg/kg/hour by continuous infusion (maximum 4 mg/hour).
• Oral: 0.1 - 0.2 mg/kg/dose every four hours if necessary.
• Pediatric dosing must be carefully calculated based on weight and age. Extreme caution is advised in neonates and premature infants should not receive morphine.

Special Cases:

• Elderly Patients: Start with lower doses and titrate cautiously due to age-related changes in pharmacokinetics.
• Patients with Renal Impairment: Reduce dose and/or increase dosing interval due to reduced clearance. Avoid morphine in severe renal impairment where possible.
• Patients with Hepatic Dysfunction: Reduce dose and titrate cautiously due to impaired metabolism.
• Patients with Comorbid Conditions: Dosage adjustments may be necessary based on coexisting conditions.

Clinical Use Cases

• Intubation: 100-200 mcg/kg IV as premedication.
• Surgical Procedures: Varies based on procedure and patient condition; may be administered IV, epidurally, or intrathecally.
• Mechanical Ventilation: 0.8–35 mg/hr or Continuous IV infusion: 2-5 mg bolus followed by 1 mg/hr.
• Intensive Care Unit (ICU) Use: Titrated to effect for analgesia and sedation; usually administered by continuous IV infusion.
• Emergency Situations: IV boluses titrated to effect.

Dosage Adjustments

• Dosage adjustments are based on pain response, side effects, renal/hepatic function, and concurrent medications.

Side Effects

Common Side Effects:

• Constipation, nausea, vomiting, drowsiness, dizziness, lightheadedness, sweating.

Rare but Serious Side Effects:

• Respiratory depression, hypotension, bradycardia, seizures, allergic reactions.

Long-Term Effects:

• Tolerance, dependence, opioid-induced hyperalgesia, adrenal insufficiency.

Adverse Drug Reactions (ADR):

• Respiratory depression, anaphylaxis, severe hypotension.

Contraindications

• Hypersensitivity to morphine, respiratory depression, acute or severe asthma, hypercarbia, paralytic ileus, increased intracranial pressure.

Drug Interactions

• CNS depressants (e.g., alcohol, benzodiazepines), anticholinergics, MAO inhibitors, CYP3A4 inhibitors/inducers, other opioids.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (FDA).
• Morphine crosses the placenta and can cause neonatal respiratory depression. Use during pregnancy only if the benefits clearly outweigh the risks.
• Morphine is excreted in breast milk and can affect nursing infants.

Drug Profile Summary

• Mechanism of Action: Mu-opioid receptor agonist.
• Side Effects: Constipation, nausea, vomiting, drowsiness, respiratory depression.
• Contraindications: Respiratory depression, hypersensitivity.
• Drug Interactions: CNS depressants, CYP3A4 inhibitors/inducers.
• Pregnancy & Breastfeeding: Use with caution; potential for neonatal respiratory depression.
• Dosage: Varies widely depending on indication, route, and patient condition.
• Monitoring Parameters: Respiratory rate, oxygen saturation, blood pressure, pain level, sedation level.

Popular Combinations

• Morphine is often combined with non-opioid analgesics (e.g., acetaminophen, NSAIDs) for synergistic pain relief.

Precautions

• Monitor for respiratory depression, particularly in elderly patients and those with respiratory disease.
• Avoid rapid IV administration.
• Address constipation prophylactically.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for morphine?

A: Morphine dosage is highly individualized and depends on the route of administration, patient’s age, weight, condition, and the severity of pain. See detailed dosing guidelines above.

Q2: How should morphine be administered?

A: Morphine can be administered intravenously, intramuscularly, subcutaneously, orally, rectally, epidurally, and intrathecally.

Q3: What are the most serious side effects of morphine?

A: Respiratory depression, hypotension, bradycardia, and allergic reactions.

Q4: What are the signs of morphine overdose?

A: Pinpoint pupils, respiratory depression, loss of consciousness, and unresponsiveness.

Q5: How is morphine overdose treated?

A: Administer naloxone, an opioid antagonist, to reverse the effects of morphine.

Q6: Can patients develop tolerance to morphine?

A: Yes, tolerance to the analgesic and other effects of morphine can develop with prolonged use, requiring dose increases.

Q7: Is morphine addictive?

A: Yes, morphine is a controlled substance with a high potential for physical and psychological dependence.

Q8: What precautions are necessary when prescribing morphine to elderly patients?

A: Start with lower doses and titrate slowly due to age-related decline in renal and hepatic function.

Q9: What is the difference between morphine sulfate and morphine hydrochloride?

A: These are different salt forms of morphine, but they are considered clinically equivalent in terms of dosing.

Q10: Can morphine be used during pregnancy?

A: Morphine can be used during pregnancy if clinically necessary, but it carries risks of fetal harm, particularly neonatal respiratory depression. It should be used with caution and under close monitoring.