Pharmacology & TherapeuticsPending review

Opioid Overdose

Mu-opioid receptor agonism blunts the brainstem's response to rising carbon dioxide, causing the respiratory depression that actually kills, and naloxone reverses this by displacing the opioid, but often for less time than the opioid itself remains active.

First principles

One receptor effect explains the whole toxic triad

Opioids act on mu-opioid receptors throughout the central nervous system. In the brainstem respiratory centres, this blunts the normal ventilatory drive response to rising carbon dioxide, producing respiratory depression. In the pathway controlling pupillary tone, mu-receptor activation produces miosis (pinpoint pupils). Diffuse central mu-receptor activation also causes sedation and reduced consciousness. The classic triad is not three independent findings but one receptor mechanism expressed in three anatomical locations.

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Educational content pending clinical review. Not medical advice.