Morphine
Duramorph · MS Contin · Roxanol
Phenanthrene μ-opioid agonist (prototype opioid, potency reference = 1)
μ-opioid receptor agonist. Active metabolite morphine-6-glucuronide (M6G) is analgesic and renally cleared — accumulates in renal failure → prolonged sedation/respiratory depression. Causes histamine release.
Indications
- •Intraop/postop analgesia
- •PCA
- •Preservative-free neuraxial analgesia
- •Acute cardiogenic pulmonary edema
Dosing
| Context | Adult | Pediatric |
|---|---|---|
| IV bolus | 2–10 mg (0.05–0.1 mg/kg), titrate | 0.05–0.1 mg/kg IV |
| PCA | 1 mg q6–10 min, ± basal | 0.01–0.02 mg/kg q8–15 min |
| Intrathecal (preservative-free) | 0.1–0.3 mg | — |
| Epidural (preservative-free) | 2–5 mg | — |
Pharmacokinetics
Onset 5–10 min IV (slow — low lipid solubility), peak ~20 min, duration 3–4 h. Hepatic glucuronidation; renal excretion of M6G.
Hemodynamic effects
Histamine release → venodilation, ↓preload, hypotension (esp. large/rapid doses).
Respiratory effects
Dose-dependent depression. Neuraxial morphine → DELAYED respiratory depression (rostral CSF spread) up to 12–24 h.
Side effects
- !Histamine release (pruritus, hypotension, bronchospasm)
- !Respiratory depression
- !N/V, constipation, urinary retention
- !M6G accumulation in renal failure → prolonged effect
Contraindications
- ×Severe renal impairment (relative — M6G)
- ×MAOI within 14 days (relative)
- ×Hemodynamic instability (relative — histamine)
Reversal / antidote
Naloxone
Clinical pearls
- ★Neuraxial morphine gives long analgesia but needs 12–24 h respiratory monitoring (delayed depression).
- ★Avoid in renal failure — use hydromorphone or fentanyl instead (no active renally-cleared metabolite).
- ★Histamine release (pruritus/hypotension) distinguishes it from fentanyl/hydromorphone.
Other drugs in Narcotics & Analgesics
- Fentanyl
μ-opioid receptor agonist. ~100× potency of morphine.
- Remifentanil
μ-opioid agonist. Ester linkage hydrolyzed by nonspecific tissue + plasma esterases — no organ-dependent clearance.
- Hydromorphone
μ-opioid agonist ~5–7× more potent than morphine. No clinically significant active metabolites → safer than morphine in renal failure. Less histamine release.
- Sufentanil
Most potent opioid in common clinical use — ~1000× morphine, ~10× fentanyl. High lipid solubility.
- Alfentanil
μ-opioid agonist ~1/5–1/10 the potency of fentanyl but FASTEST onset of the family — low pKa means a high non-ionized fraction at physiologic pH.
- Meperidine
μ-opioid agonist ~1/10 morphine, plus κ-agonism (anti-shivering). Active metabolite normeperidine is renally cleared, proconvulsant, and neurotoxic.
- Methadone
μ-opioid agonist with NMDA-receptor antagonism (blunts tolerance + opioid-induced hyperalgesia) and monoamine reuptake inhibition. Very long, variable half-life.
Suggested reading
- •Stoelting & Hines, Pharmacology & Physiology in Anesthetic Practice, 6e
- •Miller's Anesthesia, 9e
- •FDA package insert
