Clinical Pearls

Considering Nalbuphine for Opioid-Naïve Patients

Mellar P. Davis, MD FCCP FAAHPM, and Zankhana Mehta, MD

As we face a shortage of common parenteral opioids, we should get reacquainted with an old friend for some and a new friend for others. When faced with acute pain in the opioid naïve, consider nalbuphine. Nalbuphine was removed from the schedule II drug list in 1976 and determined a safe opioid by the Drug Enforcement Administration. It initially was manufactured by DuPont Pharmaceuticals, based in Wilmington, DE, and is presently being manufactured by LGM Pharma, based in Nashville, TN.

Nalbuphine is a kappa-1 and kappa-3 receptor partial agonist for both G-proteins and beta arrestin-2. Because it is a partial agonist for beta arrestin-2, it has reduced side effects relative to pentazocine, a full agonist for beta arrestin-2. As a result, side effects such as dysphoria and hallucinations are much less severe with nalbuphine than with pentazocine.^1,2 Unlike pentazocine, nalbuphine does not activate sigma-1 receptors, which causes analgesic tolerance.³