Antagonists & Reversal

Compounds that occupy the opioid receptors without activating them, displacing agonists already bound. The family holds three distinct jobs and they are not interchangeable. Naloxone is for acute reversal: poorly absorbed by mouth, given by injection or nasal spray, and shorter-acting than many of the agonists it displaces, so re-sedation after someone wakes is an expected event and not a sign the reversal failed. Naltrexone and nalmefene are for blockade and maintenance — long-acting, and started in someone not fully withdrawn they precipitate withdrawal.

Methylnaltrexone, naloxegol and naldemedine are peripherally restricted: they barely enter the brain, they treat opioid constipation, and they will not reverse an overdose. Nothing in this family acts outside the opioid receptors, so where benzodiazepines, alcohol or an α₂ agonist such as xylazine are also involved, reversing the opioid part leaves the rest exactly as it was.