Which analgesic's respiratory depression is not readily reversed by naloxone?

Which analgesic's respiratory depression is not readily reversed by naloxone?

• A. Propoxyphene
• B. Methadone
• C. Hydromorphone
• D. Buprenorphine

Answer: (D)

Respiratory depression from opioids is reversed by naloxone by displacing the drug from mu receptors, but how effectively this works depends on the drug’s receptor properties. Buprenorphine is a partial mu-opioid receptor agonist with very high affinity and a slow dissociation from the receptor. Because it binds tightly and occupies mu receptors for a long time, standard doses of naloxone struggle to displace it, and the reversal of respiratory depression can be incomplete or unreliable. In practice, reversal may require large or repeated doses of naloxone, and there’s also a risk of precipitating withdrawal in dependent individuals. In contrast, propoxyphene, methadone, and hydromorphone act as full mu agonists with lower receptor affinity than buprenorphine, so naloxone can more readily outcompete them and reverse the respiratory depression at typical dosing. Therefore, the analgesic whose respiratory depression is not readily reversed by naloxone is buprenorphine.

Respiratory depression from opioids is reversed by naloxone by displacing the drug from mu receptors, but how effectively this works depends on the drug’s receptor properties. Buprenorphine is a partial mu-opioid receptor agonist with very high affinity and a slow dissociation from the receptor. Because it binds tightly and occupies mu receptors for a long time, standard doses of naloxone struggle to displace it, and the reversal of respiratory depression can be incomplete or unreliable. In practice, reversal may require large or repeated doses of naloxone, and there’s also a risk of precipitating withdrawal in dependent individuals.

In contrast, propoxyphene, methadone, and hydromorphone act as full mu agonists with lower receptor affinity than buprenorphine, so naloxone can more readily outcompete them and reverse the respiratory depression at typical dosing.

Therefore, the analgesic whose respiratory depression is not readily reversed by naloxone is buprenorphine.