Opioid Overdose and Antidote
A 26-year-old man is found unresponsive; his friend reports heroin use. He responds only to painful stimulus with a Glasgow Coma Scale score of 7. Respiratory rate is 6 breaths/min and oxygen saturation is 84% on room air. Pupils are constricted to 1 mm, there are needle marks in the left antecubital fossa, and capillary blood glucose is 6.1 mmol/L. Which of the following is the most appropriate antidote?
- A.Flumazenil
- B.NaloxoneCorrect
- C.Atropine
- D.Physostigmine
Explanation
The triad of depressed consciousness, respiratory depression and pinpoint pupils is the classic opioid toxidrome, and naloxone is the specific antidote. Naloxone is a competitive antagonist at the mu opioid receptor that displaces the agonist within 1 to 2 minutes when given intravenously, restoring respiratory drive. It should be titrated in small increments, typically 0.04 to 0.4 mg intravenously repeated as needed, with the aim of restoring adequate ventilation rather than full consciousness, because abrupt complete reversal in a dependent user precipitates agitation, vomiting with aspiration risk, and occasionally acute pulmonary oedema. Its half-life of 30 to 90 minutes is shorter than that of most opioids, particularly long-acting preparations such as methadone or modified-release oxycodone, so patients require prolonged observation and sometimes a continuous infusion to avoid recurrence of respiratory depression. Naloxone can be given intramuscularly or intranasally when intravenous access is unavailable. Flumazenil reverses benzodiazepines, which cause sedation with relatively preserved respiration and normal pupils, and it can precipitate seizures in mixed overdose or chronic benzodiazepine use, so it is rarely used. Atropine is the antidote for cholinergic poisoning such as organophosphate exposure, where pupils are also small but there is salivation, lacrimation, bronchorrhoea, bradycardia and fasciculation. Physostigmine reverses central anticholinergic toxicity, which presents with dilated pupils, dry flushed skin, hyperthermia and delirium. Airway support and oxygenation always take priority over the antidote itself.
Why each option
- A.
- Flumazenil reverses benzodiazepines, which cause sedation with normal pupils, and risks precipitating seizures.
- B.
- Correct. Naloxone competitively antagonises mu opioid receptors and rapidly reverses opioid-induced respiratory depression.
- C.
- Atropine treats cholinergic excess, which also causes miosis but with salivation, bronchorrhoea and fasciculation.
- D.
- Physostigmine is used for anticholinergic delirium with dilated pupils, dry skin and hyperthermia.
Reference: Goldfrank's Toxicologic Emergencies, 11th ed., 2019; UpToDate 2025, Acute opioid intoxication in adults
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