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morphine sulfate

Brand: MS Contin, Morphabond, Kadian, MSIR

⚠ BBW ISMP High Alert Prototype Drug
Drug Class: opioid analgesic
Drug Family: opioid
Subclass: full mu-opioid agonist / phenanthrene
Organ Systems: cns

Mechanism of Action

Full agonist at mu-opioid receptors in the CNS (periaqueductal gray, dorsal horn) and peripheral nervous system, inhibiting adenylyl cyclase, hyperpolarizing neurons, and reducing release of nociceptive neurotransmitters (substance P, glutamate).

mu-opioid receptors (MOR)kappa-opioid receptorsdelta-opioid receptors

Indications

  • moderate-to-severe acute pain
  • chronic cancer pain
  • acute pulmonary edema (IV)
  • dyspnea in palliative care

Contraindications

  • paralytic ileus
  • acute respiratory depression
  • concurrent MAOIs
  • acute asthma (without resuscitation)

Adverse Effects

Common

  • constipation (universal, does not develop tolerance)
  • nausea/vomiting
  • sedation
  • pruritus (histamine release)
  • urinary retention
  • miosis

Serious

  • respiratory depression
  • apnea
  • coma
  • physical dependence
  • hyperalgesia (chronic high-dose)

Pharmacokinetics (ADME)

Absorption Variable oral bioavailability 15–65% due to extensive first-pass metabolism
Distribution Protein binding ~35%; Vd ~3–4 L/kg; crosses BBB (less readily than lipophilic opioids)
Metabolism Hepatic glucuronidation (UGT2B7) to morphine-6-glucuronide (M6G — active, potent) and morphine-3-glucuronide (M3G — inactive, neuroexcitatory)
Excretion Renal; M6G accumulates in renal failure — increase dosing interval in CKD
Half-life 2–4 hours
Onset IV: 5 min; IM: 10–30 min; oral: 30–60 min
Peak IV: 20 min; oral IR: 60 min
Duration 3–5 hours (IR); 8–12 hours (ER)
Protein Binding 35%
Vd 3–4 L/kg

Drug Interactions

Drug / Agent Mechanism Severity
benzodiazepines/CNS depressants additive respiratory depression — leading cause of opioid overdose death major
MAOIs serotonin syndrome and/or hypotension/hypertension major
naloxone competitive antagonist — reverses analgesia and precipitates withdrawal moderate

Nursing Considerations

  1. Assess respiratory rate before each dose; hold and notify provider if RR <10/min or SpO2 <92%; have naloxone immediately available
  2. Bowel regimen (stimulant laxative such as senna) must be initiated simultaneously with morphine — constipation does not self-resolve and causes significant morbidity
  3. Use WHO pain ladder: reassess pain 30 minutes after IV and 1 hour after oral administration; titrate to effect
  4. In opioid-naive patients, start low (2–4 mg IV q4h); use appropriate equianalgesic conversion tables when rotating opioids to avoid under- or over-dosing

Clinical Pearls

  • Morphine-6-glucuronide (M6G) is 3–6 times more potent than morphine and accumulates in renal failure — morphine should be used cautiously or avoided in CKD; hydromorphone or fentanyl are preferred
  • Morphine releases histamine from mast cells (not an IgE-mediated allergy), causing pruritus and flushing — true morphine allergy is rare; codeine and meperidine also release histamine; fentanyl does not

Safety Profile

Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

Acute Pulmonary Edema (IV) Chronic Cancer Pain Dyspnea In Palliative Care Moderate-to-severe Acute Pain Opioid Analgesic
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