====== Morphine (MS Contin®) ======

<WRAP right 340px>
<WRAP infobox>
^ Morphine | {{ :neuro:opioids:morphine2dcsds.svg?200 |}} |
| Brand Names | MS Contin®, Kadian®, Roxanol® |
| Drug Class | [[neuro:opioids:start|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 |
</WRAP>
</WRAP>

===== 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.

<WRAP clear></WRAP>

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===== 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  

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===== Indications =====

  * Acute moderate to severe pain  
  * Chronic severe pain  
  * Cancer-related pain  
  * Palliative care  

IV morphine:
  * Acute coronary syndromes (historical use; now more cautious)  

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<WRAP contra>
===== Contraindications =====

Absolute:
  * Significant respiratory depression  
  * Acute severe bronchial asthma  
  * Paralytic ileus  

Relative / Caution:
  * Renal impairment  
  * Hepatic impairment  
  * Hypotension  
  * Traumatic brain injury  
  * Obstructive sleep apnea  
</WRAP>

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<WRAP details>
===== 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.
</WRAP>

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<WRAP details>
===== 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.
</WRAP>

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<WRAP details>
===== 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.

</WRAP>

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<WRAP details>
===== Drug Interactions =====

CNS depressants:
  * Benzodiazepines  
  * Alcohol  
  * Other opioids  

Additive respiratory depression risk.

</WRAP>

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<WRAP monitoring>
===== Monitoring =====

Clinical:
  * Pain control  
  * Sedation level  
  * Respiratory rate  

High-risk patients:
  * Renal function monitoring  
  * Blood pressure monitoring  

</WRAP>

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<WRAP pearls>
===== 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.  
</WRAP>

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===== Toxicity =====

Classic opioid toxidrome:
  * CNS depression  
  * Respiratory depression  
  * Miosis  
  * Decreased bowel sounds  

Treatment:
  * [[neuro:opioids:naloxone|Naloxone]]

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===== Comparison Within Class =====

Compared to [[neuro:opioids:oxycodone|Oxycodone]]:
  * Lower oral bioavailability  
  * More histamine release  

Compared to [[neuro:opioids:hydromorphone|Hydromorphone]]:
  * Less potent  
  * More histamine release  

Compared to [[neuro:opioids:fentanyl|Fentanyl]]:
  * Much less potent  
  * Less lipophilic  
  * More hypotension  

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===== Related =====

  * [[neuro:opioids:start|Opioids]]
  * [[neuro:opioids:oxycodone|Oxycodone]]
  * [[neuro:opioids:hydromorphone|Hydromorphone]]
  * [[neuro:opioids:fentanyl|Fentanyl]]
  * [[neuro:opioids:naloxone|Naloxone]]