What specific physiological effect of opioids leads to pinpoint pupils observed in overdose cases?

The specific physiological effect of opioids that leads to pinpoint pupils (miosis) observed in overdose cases is the activation of mu (μ) opioid receptors in the Edinger-Westphal nucleus of the brainstem. The Edinger-Westphal nucleus is a cranial nerve nucleus that controls the parasympathetic outflow to the eye. Opioids, particularly those with high affinity for mu receptors, stimulate these receptors in the Edinger-Westphal nucleus. This stimulation increases parasympathetic activity, which in turn causes the pupillary sphincter muscle to contract. The pupillary sphincter muscle is responsible for constricting the pupil. When this muscle contracts excessively due to opioid-induced parasympathetic activation, the pupils become very small, appearing as 'pinpoints.' This pupillary constriction is a classic sign of opioid toxicity and overdose because it is a direct result of the drug's action on this specific brainstem nucleus. While other factors may influence pupil size, the direct activation of mu opioid receptors in the Edinger-Westphal nucleus is the primary driver of pinpoint pupils in opioid overdose.