Morphine Sulfate | Medication Reference

Bedside Snapshot

Drug Class: Opioid analgesic; prototypical μ-opioid receptor agonist
Core Uses: Classic μ-opioid agonist for moderate-to-severe pain; compared with fentanyl it is less lipophilic, slower onset, longer duration, more histamine release, and has renally cleared active metabolites
IV Adult Bolus for Acute Pain: 2–4 mg IV (≈0.03–0.1 mg/kg) every 5–10 minutes, titrated to effect, with careful monitoring of respiratory status and blood pressure
IV PCA Settings (Example): Demand dose 1 mg, lockout 6–10 minutes, with or without background infusion; total hourly limit often 6–10 mg (institution-specific protocols vary widely)
Oral Immediate-Release (Opioid-Naïve): 5–15 mg PO every 4 hours as needed for moderate-to-severe pain; start low in high-risk patients
Oral Extended-Release (Opioid-Tolerant): 15–30 mg PO every 8–12 hours in opioid-tolerant patients, titrated cautiously based on total daily opioid requirements
Onset: IV onset ~5 minutes with peak analgesia at 15–30 minutes; duration of effect usually 3–4 hours. Oral onset ~30 minutes (IR) with peak at 60–90 minutes, duration 4–6 hours (longer for ER formulations)
Major Acute Risks: Respiratory depression, sedation, hypotension (especially in hypovolemia/vasodilation), nausea, vomiting, pruritus, urinary retention, and ileus; histamine release can cause flushing, bronchospasm, and venodilation/hypotension
Major Chronic Risks: Tolerance, physical dependence, opioid use disorder, hypogonadism/endocrinopathy, constipation, hyperalgesia, and overdose risk especially with other sedatives or in comorbid respiratory disease

Brand & Generic Names

Generic Name: Morphine sulfate (most parenteral and oral formulations)
Brand Names: MS Contin, Kadian, Roxanol, Duramorph, Infumorph, others; multiple generics—availability is region- and institution-specific

Medication Class

Opioid analgesic; prototypical μ-opioid receptor agonist

Pharmacology

Mechanism of Action:

Morphine is a prototypical μ-opioid receptor agonist; it also has weaker κ- and δ-receptor activity
μ-receptor activation inhibits adenylate cyclase, decreases cAMP, and modulates ion channels (enhanced K⁺ efflux, reduced Ca²⁺ influx)
This leads to neuronal hyperpolarization and reduced neurotransmitter release (e.g., substance P, glutamate) in ascending pain pathways (spinal cord dorsal horn, brainstem, thalamus, cortex) and enhances descending inhibitory pathways, producing analgesia and blunting the emotional response to pain
At the medullary respiratory centers, morphine reduces responsiveness to CO₂ and hypoxia, causing dose-dependent respiratory depression, decreased respiratory rate, and potential apnea
Morphine also acts on μ receptors in the GI tract, reducing peristalsis and increasing sphincter tone, contributing to constipation and risk of ileus
Peripheral and central μ-receptor activation can cause histamine release from mast cells, leading to vasodilation, pruritus, and hypotension; this is more prominent with morphine than with synthetic opioids like fentanyl or hydromorphone

Pharmacokinetics (IV and Oral):

Formulations: Parenteral (IV/IM/SC) morphine sulfate usually 1–10 mg/mL; oral immediate-release tablets/solutions and extended-release tablets/capsules in a wide range of strengths; epidural/intrathecal preservative-free formulations for neuraxial use
Onset (IV): Analgesia usually begins within 5 minutes; peak effect around 15–30 minutes; duration about 3–4 hours after a single bolus
Onset (PO IR): Analgesic effect typically begins within 30 minutes, peaks at 60–90 minutes, and lasts 4–6 hours. Extended-release formulations have delayed peak and 8–24 hour duration depending on product
Distribution: Morphine is less lipophilic than fentanyl, leading to slower CNS penetration and onset but a more prolonged effect. Volume of distribution is ~3–5 L/kg
Protein Binding: Approximately 30–35% bound to plasma proteins
Metabolism: Primarily hepatic glucuronidation via UGT2B7 to morphine-3-glucuronide (M3G, inactive for analgesia but potentially neuroexcitatory) and morphine-6-glucuronide (M6G, active and more potent than morphine at μ receptors)
Elimination: M3G and M6G are renally excreted; elimination half-life of morphine is typically 2–4 hours in adults with normal renal function, but M6G has a longer half-life and can accumulate in renal impairment, leading to prolonged sedation and respiratory depression
Renal Impairment: Both M3G and M6G accumulate; dose reductions, extended dosing intervals, or preference for alternative opioids (e.g., fentanyl) are recommended in moderate-to-severe CKD
Hepatic Impairment: Decreased first-pass metabolism may increase oral bioavailability and reduce clearance; initial doses should be conservative with careful titration

Indications

Management of moderate-to-severe acute pain (trauma, post-operative, myocardial infarction, renal colic, severe abdominal pain) where opioid therapy is appropriate
Chronic cancer and palliative pain management (oral, subcutaneous, IV, and sometimes neuraxial routes)
Adjunct to anesthesia and procedural sedation as an analgesic component
Epidural and intrathecal morphine for postoperative and chronic pain (specialist-directed)
Severe traumatic injuries requiring parenteral opioid analgesia
Acute coronary syndromes with severe chest pain (use is increasingly selective due to possible interactions with antiplatelet absorption and masking of ischemia)
Postoperative pain following major surgery (e.g., abdominal, thoracic, orthopedic)
Pain crises in conditions such as sickle cell disease or pancreatitis

Dosing & Administration

Available Forms:

IV/IM/SC Solution: Common concentrations include 1 mg/mL, 2 mg/mL, 4 mg/mL, 5 mg/mL, and 10 mg/mL vials or prefilled syringes; verify specific stock at your institution
Oral Immediate-Release Tablets: 5 mg, 10 mg, 15 mg, 30 mg; oral solution often 10 mg/5 mL or 20 mg/mL (concentrated)
Extended-Release Tablets/Capsules: 15 mg, 30 mg, 60 mg, 100 mg, 200 mg (strengths vary by product)
Neuraxial (Epidural/Intrathecal): Preservative-free formulations (e.g., 0.5–1 mg/mL) for use by anesthesia/pain specialists

Critical Safety Warning: Always double-check concentration and route—parenteral vs oral solutions can be confused, and neuraxial preparations must be preservative-free. Never confuse immediate-release with extended-release formulations.

Standard Dosing – Morphine (IV and Oral – Always Follow Local Protocols and Opioid Guidelines):

Indication / Population	Dose & Route	Frequency / Titration	Notes
Adult acute moderate-to-severe pain – IV bolus (opioid-naïve)	2–4 mg IV (≈0.03–0.1 mg/kg)	Every 5–10 min as needed, titrated to pain, sedation, and respiratory status	Use lower end in elderly, frail, or hemodynamically unstable patients
Adult IV PCA (example – institution-specific)	Demand dose 1 mg IV; lockout 6–10 min	Optional basal 0–1 mg/hour; hourly limit often 6–10 mg	Follow local PCA protocols; adjust for age, comorbidities, and opioid tolerance
Adult oral immediate-release (opioid-naïve moderate-to-severe pain)	5–15 mg PO IR	Every 4 hours as needed	Start low (e.g., 5 mg) in high-risk patients; reassess frequently
Adult extended-release (opioid-tolerant)	15–30 mg PO ER	Every 8–12 hours, titrated based on total daily opioid needs	Convert from total 24-hour opioid dose; use equianalgesic tables and reduce for incomplete cross-tolerance
Pediatric acute pain – IV (specialist)	0.05–0.1 mg/kg IV (max per dose per protocol)	Every 2–4 hours or smaller doses q5–10 min titrated	Neonates/infants require smaller doses and close monitoring
Renal impairment (adult)	Use reduced doses (e.g., 1–2 mg IV) with prolonged intervals	Titrate cautiously; consider avoiding morphine in advanced CKD	Prefer fentanyl or hydromorphone for severe CKD/ESRD when possible

Equianalgesic Considerations:

A common reference point: 10 mg IV morphine ≈ 25–30 mg PO morphine in terms of analgesic effect (approximately 1:2.5–3 IV:PO ratio). Actual conversions vary based on patient factors and duration of therapy
When converting between opioids or routes, total 24-hour dose is calculated and then reduced by 25–50% for incomplete cross-tolerance, especially when switching to a new opioid or to a long-acting formulation
Equianalgesic charts differ slightly by source; always use your institution's reference and clinical judgment when making conversions

Contraindications

Contraindications (Relative/Absolute Depending on Context):

Significant respiratory depression in unmonitored settings without airway support
Acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment
Known hypersensitivity to morphine or other opioid components
Paralytic ileus (for oral formulations)

Major Precautions:

Elderly, frail, and opioid-naïve patients: Increased sensitivity to sedation and respiratory depression; start at the lowest effective dose with slow up-titration
Chronic lung disease (COPD, OSA, neuromuscular weakness): High risk of CO₂ retention and hypoventilation; consider lower doses, non-opioid adjuncts, and continuous monitoring
Intracranial pathology or elevated ICP: CO₂ retention from hypoventilation can worsen ICP; careful titration and monitoring are essential
Hemodynamic instability: Histamine-mediated vasodilation can exacerbate hypotension; consider fentanyl or hydromorphone as alternatives in unstable patients
Renal impairment: Accumulation of M3G/M6G increases risk of prolonged sedation, respiratory depression, and neurotoxicity; avoid or dose-reduce and monitor closely
Concomitant CNS depressants (benzodiazepines, gabapentinoids, alcohol, sedative-hypnotics): Additive respiratory and CNS depression; adjust dosing and monitoring accordingly
History of substance use disorder: Higher risk of misuse and diversion; use structured pain agreements, PDMP checks, and multidisciplinary management

Adverse Effects

Common:

Sedation and drowsiness
Respiratory depression and hypoventilation (dose-dependent)
Nausea, vomiting, and dyspepsia
Constipation and decreased GI motility
Pruritus and flushing (often histamine-mediated)
Urinary retention

Serious:

Severe respiratory depression and apnea: Particularly in high doses or with co-administered sedatives
Profound hypotension: Especially in hypovolemic or hemodynamically unstable patients
Opioid use disorder, tolerance, and withdrawal: With chronic use
Seizures or neuroexcitation: With high levels of M3G metabolites in renal failure
Anaphylaxis or severe hypersensitivity: Rare

Special Populations

Pediatrics: Use weight-based dosing (0.05–0.1 mg/kg IV for acute pain); neonates/infants require smaller doses and close monitoring with specialist guidance
Pregnancy: Opioids cross the placenta; chronic use during pregnancy can lead to neonatal abstinence syndrome; use lowest effective dose for shortest duration when necessary
Older Adults: Increased sensitivity to respiratory depression and sedation; start with lower doses (e.g., 1–2 mg IV or 2.5–5 mg PO) and titrate slowly
Renal Impairment: Active metabolites (M3G, M6G) accumulate; reduce doses by 50–75% and extend intervals, or consider alternative opioids like fentanyl
Hepatic Impairment: Decreased metabolism; start with lower doses and titrate cautiously with close monitoring

Monitoring

Pain scores and functional improvement: Vs. baseline
Respiratory rate, depth, and pattern: Continuous pulse oximetry when appropriate, and capnography for high-risk or sedated patients
Level of consciousness/sedation: (e.g., RASS, Pasero Opioid-induced Sedation Scale) and frequent reassessment after dose changes
Blood pressure and heart rate: In patients at risk of hypotension or bradycardia
Bowel function: Need for prophylactic bowel regimen in patients on repeated or chronic dosing
Signs of opioid toxicity: Pinpoint pupils, somnolence, hypoventilation; readiness to administer naloxone in case of overdose

Clinical Pearls

Morphine vs. fentanyl comparison: Compared with fentanyl, morphine is slower-onset, longer-acting, and more histaminergic; this can be beneficial for sustained analgesia but problematic in hypotension or bronchospasm.

Renal impairment caution: In significant renal impairment, avoid or minimize morphine in favor of opioids without active renally cleared metabolites (e.g., fentanyl); if morphine must be used, extend dosing intervals and monitor very closely.

Bowel regimen necessity: Always pair morphine with an aggressive bowel regimen when used beyond brief ED dosing to prevent opioid-induced constipation and ileus.

Multimodal analgesia strategy: Use multimodal analgesia (acetaminophen, NSAIDs where appropriate, regional blocks, ketamine, etc.) to reduce total opioid requirement and adverse effects.

Opioid conversion guidance: When converting between IV and PO or between different opioids, use updated equianalgesic tables and reduce calculated doses for incomplete cross-tolerance, particularly in medically complex patients.

Naloxone reversal strategy: Naloxone reversals should be titrated in small aliquots to restore adequate respirations rather than fully abolish analgesia, minimizing catecholamine surge and severe pain.

References

1. Chou, R., et al. (2016). CDC guideline for prescribing opioids for chronic pain—United States, 2016. JAMA, 315(15), 1624–1645. https://doi.org/10.1001/jama.2016.1464
2. DrugBank Online. (2024). Morphine (DB00295). DrugBank. https://go.drugbank.com/drugs/DB00295
3. Kalso, E., Edwards, J. E., Moore, R. A., & McQuay, H. J. (2004). Opioids in chronic non-cancer pain: Systematic review of efficacy and safety. Pain, 112(3), 372–380. https://doi.org/10.1016/j.pain.2004.09.019
4. StatPearls. (2024). Morphine. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK526115/
5. Pasero, C., & McCaffery, M. (2011). Pain assessment and pharmacologic management. Mosby/Elsevier.