naloxone

Naloxone is a synthetic opioid antagonist that competitively binds mu (μ), kappa (κ), and delta (δ) opioid receptors with highest affinity for the mu receptor, displacing opioid agonists and reversing their effects. It has no significant agonist activity, making it useful purely for reversal rather than analgesia.

Mechanism: By blocking mu receptors, naloxone reverses opioid-induced respiratory depression, sedation, and miosis. Onset of action is rapid (2-3 min IV, slightly slower IM/intranasal), but its duration (30-90 minutes) is often shorter than that of the opioid being reversed (e.g., methadone, fentanyl patches, extended-release oxycodone), necessitating repeat dosing or a naloxone infusion to prevent recurrence of toxicity as naloxone wears off before the opioid is cleared.

Clinical use: First-line treatment for suspected opioid overdose presenting with the triad of CNS depression, pinpoint pupils, and respiratory depression. Increasingly distributed to laypersons and first responders in intranasal or auto-injector form given the opioid epidemic. Also used diagnostically to distinguish opioid-induced coma from other causes.

Adverse effects: Precipitates acute opioid withdrawal in opioid-dependent patients (agitation, tachycardia, hypertension, piloerection, vomiting, diarrhea, yawning). Can also unmask pain that was being masked by opioids, sometimes precipitating pulmonary edema or arrhythmias in rare cases. Titrate carefully in dependent patients to avoid severe withdrawal.

Contrast with naltrexone: Naltrexone is a longer-acting oral opioid antagonist used for maintenance therapy in opioid use disorder and alcohol use disorder, not for acute reversal.

Boards relevance: High-yield for pharmacology (opioid receptor pharmacology, agonist vs antagonist), toxicology (overdose management), and emergency medicine (ABCs, reversal agents). Key point: naloxone does not reverse effects of non-opioid CNS depressants (e.g., benzodiazepines - flumazenil is used for that).