Morphine (MS Contin®)
| Morphine |  |
|---|---|
| Brand Names | MS Contin®, Kadian®, Roxanol® |
| Drug Class | Opioid (Full μ-agonist) |
| Primary Indication | Moderate–Severe Pain |
| Relative Potency | 1× (Reference Standard) |
| Histamine Release | Yes |
| Respiratory Depression | Yes (dose-dependent) |
| Weight Effect | Neutral |
| Elimination | Renal (active metabolites) |
| Controlled Substance | Schedule II |
| FDA Approval | 1941 |
Overview
Morphine is a full μ-opioid receptor agonist and serves as the reference standard for opioid potency comparisons.
It is used for moderate to severe acute and chronic pain and remains the prototypical opioid against which other agents are measured.
Morphine produces dose-dependent analgesia with no ceiling effect, but also carries dose-dependent risk of respiratory depression.
Mechanism of Action
Receptor Activity
- Full μ-opioid receptor agonist
- Gi-protein coupled receptor activation
Cellular Effects
- ↓ cAMP production
- ↑ Potassium efflux → neuronal hyperpolarization
- ↓ Calcium influx → ↓ substance P & glutamate release
Net Effect
- Reduced spinal and supraspinal pain transmission
- Altered emotional response to pain
Indications
- Acute moderate to severe pain
- Chronic severe pain
- Cancer-related pain
- Palliative care
IV morphine:
- Acute coronary syndromes (historical use; now more cautious)
Contraindications
Absolute:
- Significant respiratory depression
- Acute severe bronchial asthma
- Paralytic ileus
Relative / Caution:
- Renal impairment
- Hepatic impairment
- Hypotension
- Traumatic brain injury
- Obstructive sleep apnea
Dosing
Immediate-Release (oral):
- 10–30 mg every 4 hours
Extended-Release:
- Every 8–12 hours depending on formulation
IV dosing:
- Titrated carefully based on pain and respiratory status
Dose adjustments required in renal impairment.
Pharmacokinetics
Absorption:
- Oral and IV
Bioavailability:
- ~20–40% (significant first-pass metabolism)
Metabolism:
- Hepatic glucuronidation
- Morphine-3-glucuronide (inactive)
- Morphine-6-glucuronide (active, potent)
Half-life:
- ~2–4 hours
Elimination:
- Renal excretion of active metabolites
Renal failure increases risk of accumulation and toxicity.
Adverse Effects
Common:
- Sedation
- Constipation
- Nausea / vomiting
- Pruritus (histamine-mediated)
- Hypotension
Serious:
- Respiratory depression
- Physical dependence
- Opioid use disorder
Histamine release is more pronounced than with synthetic opioids.
Constipation persists despite tolerance.
Drug Interactions
CNS depressants:
- Benzodiazepines
- Alcohol
- Other opioids
Additive respiratory depression risk.
Monitoring
Clinical:
- Pain control
- Sedation level
- Respiratory rate
High-risk patients:
- Renal function monitoring
- Blood pressure monitoring
Clinical Pearls
- Gold standard for opioid potency comparison.
- Causes more histamine release than fentanyl or hydromorphone.
- Avoid or reduce dose in renal failure due to active metabolite accumulation.
- No ceiling effect (full μ agonist).
- Significant first-pass metabolism → lower oral bioavailability than oxycodone.
Toxicity
Classic opioid toxidrome:
- CNS depression
- Respiratory depression
- Miosis
- Decreased bowel sounds
Treatment:
Comparison Within Class
Compared to Oxycodone:
- Lower oral bioavailability
- More histamine release
Compared to Hydromorphone:
- Less potent
- More histamine release
Compared to Fentanyl:
- Much less potent
- Less lipophilic
- More hypotension