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Oliceridine, a biased, selective opioid agonist, has shown a 3-fold preferential activation of the G-protein (i.e., analgesia) over β-arrestin pathway. β-arrestin activation is believed to be associated with higher adverse events, such as constipation, respiratory depression, and desensitization. There is no literature of use in patients with burn injuries. We hypothesized the use of oliceridine would provide adequate and safe analgesia after acute burn injury. Ten patients received oliceridine as their sole opioid for up to 7 days, which was compared to a random, historical cohort receiving standard of care (i.e, fentanyl, oxycodone, hydromorphone, and morphine). The historical control group was initially matched 2:1 (though 2 patients were ultimately excluded) with the oliceridine group according to age, percent total body surface area burned (TBSA), and number of operations. No patient had a history of known opioid, cocaine, or methamphetamine use, as this was an exclusion criterion for the prospectively enrolled group. Baseline numerical rating scale (NRS) was similar for both groups [9 (7.8, 10) vs 9.5 (8.8, 10); p = 0.360). Over the 7-day period, mean daily pain scores significantly decreased in both groups. However, use of oliceridine was associated with a significantly larger decrease in mean pain score [-0.74 (-1.36, -0.12), p = 0.0215]. There was no difference in average daily morphine milligram equivalents (MME) [-14.02 (-67.22, 39.19), p = 0.5939]. There were no unexpected adverse events related to oliceridine. Oliceridine demonstrated significant pain relief, which was maintained over the 7-day study period. The control group demonstrated initial relief, which was not maintained despite similar MME.
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http://dx.doi.org/10.1016/j.burns.2024.107343 | DOI Listing |
Burns
November 2024
Department of Pharmacy, Regional One Health, Firefighter's Burn Center, Regional One Health, 877 Jefferson Avenue, Memphis, TN 38103, USA.
Oliceridine, a biased, selective opioid agonist, has shown a 3-fold preferential activation of the G-protein (i.e., analgesia) over β-arrestin pathway.
View Article and Find Full Text PDFEur J Pharmacol
November 2024
Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, 980-8578, Japan; Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan. Electronic address:
The μ-opioid receptor (MOR) is a G-protein-coupled receptor (GPCR) that mediates both analgesic effects and adverse effects of opioid drugs. Despite extensive efforts to develop a signal-biased drug, drugs with sufficiently reduced side effects have not been established, in part owing to lack of comprehensive signal transducer profiles of MOR. In this study, by profiling the activity of signal transducers including G proteins and GPCR kinases (GRKs), we revealed an unprecedented mechanism of selective GRK3 activation by Gβ, leading to β-arrestin recruitment.
View Article and Find Full Text PDFPain Manag
September 2024
Department of Anesthesiology, Division of Women's Anesthesia, Duke University Medical Center Box 3094, Durham, NC 27710, USA.
Acute pain management requires balancing analgesia with adverse effects risk. The voltage-gated sodium channel NaV1.8 plays an important role in pain physiology, and its inhibition was shown to have analgesic effects.
View Article and Find Full Text PDFDrug Des Devel Ther
October 2024
Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People's Republic of China.
Pain Ther
December 2024
Department of Critical Care Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
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