Morphine

Quick Answer

Morphine is the prototypical phenanthrene μ-opioid receptor (MOR) agonist, the gold standard against which other opioids are compared. Structure: Phenanthrene backbone (5-ring structure), tertiary amine, two hydroxyl groups at positions 3 and 6. Mechanism: Selective μ-opioid receptor agonist (supraspinal, spinal, peripheral); MOR coupled to Gi/o proteins reducing cAMP, opening K+ channels (hyperpolarization), closing Ca2+ channels (reduced neurotransmitter release); produces analgesia, euphoria, respiratory depression, miosis, reduced GI motility. Receptor subtypes: μ1 (supraspinal analgesia), μ2 (respiratory depression, euphoria, dependence), μ3 (peripheral effects). Pharmacokinetics: Variable oral bioavailability (20-30% first-pass metabolism), IM/SC bioavailability 100%, protein binding 30%, volume of distribution 1-6 L/kg, pKa 7.9 (mostly ionized at pH 7.4). Metabolism: Hepatic glucuronidation (UGT2B7) to morphine-3-glucuronide (M3G—neuroexcitatory, no analgesia, may cause myoclonus, seizures) and morphine-6-glucuronide (M6G—active metabolite, more potent than morphine, longer half-life, accumulates in renal failure causing delayed respiratory depression). Elimination: Renal (90% as metabolites), half-life 2-4 hours (morphine), 6-8 hours (M6G—accumulates with renal impairment). Dosing: IV bolus 0.05-0.1 mg/kg, infusion 0.01-0.03 mg/kg/hour, oral 0.3 mg/kg (immediate release), epidural 2-5 mg, intrathecal 0.1-0.5 mg. Side effects: Respiratory depression (dose-dependent, reduced CO2 response, reduced hypoxic drive), nausea/vomiting (CTZ activation, vestibular sensitivity), constipation (μ-receptors in GI tract, reduced peristalsis, increased sphincter tone), pruritus (histamine release, central mechanisms), urinary retention (detrusor relaxation, sphincter contraction), miosis (Edinger-Westphal nucleus), histamine release (vasodilation, hypotension, bronchospasm—not immune-mediated). Contraindications: Severe respiratory depression, acute asthma (relative), raised intracranial pressure (relative), paralytic ileus. Drug interactions: CNS depressants (additive respiratory depression), MAOIs (serotonin syndrome, excitatory effects), anticholinergics (severe constipation, ileus). Clinical pearls: Not suitable for infusions in renal failure (M6G accumulation—use fentanyl or hydromorphone instead); histamine release can be minimized by slow IV injection; equipotent dose conversion: morphine 10 mg IV = morphine 30 mg PO = oxycodone 15-20 mg PO = fentanyl 100 μg IV. [1-10]