naltrexone

Naltrexone is a synthetic opioid antagonist structurally related to naloxone but with better oral bioavailability and a longer half-life, allowing once-daily oral dosing or monthly IM depot injection (Vivitrol). Mechanism: competitively binds mu-opioid receptors, blocking the effects of exogenous opioids and reducing dopamine release in the mesolimbic reward pathway, which decreases alcohol cravings and reward from alcohol consumption. Clinical uses: (1) Alcohol use disorder - reduces heavy drinking days and cravings, considered first-line pharmacotherapy along with acamprosate; (2) Opioid use disorder - used for relapse prevention after detoxification to maintain abstinence, patient must be opioid-free for 7-10 days before starting to avoid precipitated withdrawal. Contraindications/cautions: must not be given to patients currently using opioids or in acute opioid withdrawal (will precipitate severe withdrawal symptoms); patients on naltrexone who then relapse and use opioids are at risk of respiratory depression/overdose due to loss of tolerance combined with high doses attempted to overcome blockade. Hepatotoxicity is a boxed warning - monitor LFTs, avoid in acute hepatitis or liver failure. Naltrexone does not have abuse potential or physical dependence liability (unlike methadone/buprenorphine). Difference from naloxone: naloxone is used for acute opioid overdose reversal (short-acting, IV/IM/intranasal), naltrexone is used for long-term relapse prevention (longer-acting, oral/IM depot). Compare with disulfiram (aversive therapy via aldehyde dehydrogenase inhibition) and acamprosate (NMDA modulator) as other alcohol use disorder treatments - naltrexone does not cause the disulfiram-like reaction with alcohol.