Does nalbuphine have a niche in managing pain?

Abstract

Nalbuphine has been commercially available for 40 years for the treatment of acute pain; few studies have centered on management of chronic pain. Nalbuphine unique pharmacology is an advantage in pain management. It is µ antagonist, partial κ agonist for G-proteins and beta-arrestin-2. Benefits are related to G-protein interactions resulting in less nausea, pruritus, and respiratory depression than morphine. At low doses, nalbuphine reduces side effects particularly respiratory depression without loss of analgesia when combined with potent opioids. Nalbuphine pharmacokinetics are moderately altered in renal failure. Several studies have found that nalbuphine reduces uremic pruritus. Nalbuphine has drawbacks: it is not an oral formulation, it causes withdrawal in patients on sustained released opioids, and it cannot be used to treat an opioid withdrawal syndrome. Nalbuphine, despite being a µ receptor antagonist produces a drug-liking effect and can be abused. There are very few deaths associated with nalbuphine alone in part due to the fact it is rarely used but also related to a ceiling on respiratory depression.

Preemptive Intravenous Nalbuphine for the Treatment of Post-Operative Visceral Pain: A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial

“…Parenteral nalbuphine readily crosses the blood–brain barrier, takes effect about 2 min after administration, and reaches peak serum level after 5 min, and the action ranges from 2 to 6 h [ 21 ]. Systemic κ-agonists act as particularly effective analgesics in a wide variety of preclinical visceral pain models [ 22 , 23 ].…”

Effectiveness of nalbuphine, a κ‐opioid receptor agonist and μ‐opioid receptor antagonist, in the inhibition of INa, IK(M), and IK(erg) unlinked to interaction with opioid receptors

“…Such an inhibition occurring within a clinically therapeutic range is not linked to agonistic or antagonistic effects on opioid receptors. Inasmuch as Na V channels play a role in neuropathic pain syndromes (Akbarali & Dewey, 2017;Catterall et al, 2003;Theile & Cummins, 2011), NALmediated inhibition of I Na could be of clinical relevance (e.g., antinociceptive effect) (Barry & Zuo, 2005;Bindra et al, 2018;Chen et al, 2014;Davis et al, 2018;Withey et al, 2018). The modifications by NAL are thus important and lend credence to the notion that such actions are linked to their neurological or adverse actions (Bodnar, 2017;Candy, Jones, Vickerstaff, Larkin, & Stone, 2018;Dinges et al, 2018;Raghav et al, 2018).…”

“…. It can relieve moderate to severe pain and itching, the mechanisms are thought to be its binding to opioid receptors (Bodnar, 2017;Chen et al, 2014;Davis, Fernandez, Regel, & McPherson, 2018;Mathur et al, 2017;Pereira & Stander, 2018;Reszke & Szepietowski, 2018;Tubog, Harenberg, Buszta, & Hestand, 2018;Withey, Paronis, & Bergman, 2018). Alternatively, it can be used to balance anesthesia, for preoperative and postoperative analgesia, and for obstetrical analgesia (Bindra, Kumar, & Jindal, 2018;Kim, Kim, Lee, Chung, & Hong, 2011).…”

Comparison of Postoperative Analgesic Effects Between Nalbuphine and Fentanyl in Children Undergoing Adenotonsillectomy: A Prospective, Randomized, Double-Blind, Multicenter Study

“…Fentanyl, another potent, short-acting opioid agonist, is also a widely used painkiller during short surgical procedures and however, the major worry to clinicians is that the utility of fentanyl has been noted to be quite narrow in comparison of its plasma levels between effective analgesia and significant respiratory depression (Yassen et al, 2006;Yassen et al, 2007;Yassen et al, 2008;Boom et al, 2013), By contrast, NSAIDS would be an ideal option of treatment for tonsillectomy pain with a lower incidence of PONV and non-detrimental impact on respiration, but the concern over the potential postoperative hemorrhage caused by NSAIDS has limited its clinical application (Marret et al, 2003;Møiniche et al, 2003;Lake and Khater, 2004). Nalbuphine is a 6-transmembrane MOR agonist as is buprenorphine and butorphanol all of which have a ceiling on respiratory depression (Davis et al, 2018). In addition, Nalbuphine is an opioid agonist-antagonist, active on mu and kappa receptors (Martinelli et al, 2014) to provide analgesia and certain antipruritic effects (Romagnoli and Keats, 1980) and have less undesirable outcomes.…”