Fentanyl

Quick Answer

Fentanyl is a synthetic phenylpiperidine opioid agonist with 100× potency of morphine and rapid onset (1-2 minutes IV), making it ideal for intraoperative analgesia and balanced anaesthesia. Mechanism: Selective μ-opioid receptor (MOR) agonist, supraspinal and spinal analgesia, modulates pain transmission in dorsal horn. Pharmacokinetics: High lipid solubility (logP 4.0), rapid blood-brain barrier penetration (onset 1-2 min), large volume of distribution (Vdss 4 L/kg), redistribution t½α 1-2 minutes, elimination t½β 2-4 hours. Metabolism: Hepatic CYP3A4 N-dealkylation to norfentanyl (inactive), 75% clearance hepatic, 25% renal. Dosing: IV bolus 1-2 μg/kg, infusion 1-5 μg/kg/hour, neuraxial (epidural) 50-100 μg, intrathecal 10-25 μg. Context-sensitive half-time: 20-30 minutes after 1-hour infusion, 60-90 minutes after 4-hour infusion (redistribution limited, metabolism dominates). Side effects: Dose-dependent respiratory depression (reduced responsiveness to CO₂ and hypoxia), bradycardia (vagal stimulation), chest wall rigidity ("wooden chest" with rapid high-dose IV, treat with naloxone or muscle relaxant), nausea/vomiting (chemoreceptor trigger zone), pruritus (especially neuraxial, histamine-independent). Contraindications: Known hypersensitivity, severe respiratory depression, acute asthma (relative). Drug interactions: CYP3A4 inhibitors (erythromycin, ketoconazole, grapefruit) prolong effect; MAOIs risk serotonin syndrome; benzodiazepines synergistic respiratory depression. Indigenous considerations: Higher rates of chronic pain and opioid use may alter tolerance; careful titration required. [1-10]