Benefit and risk evaluation of biased mu-receptor agonist oliceridine versus morphine

Background: To improve understanding of the respiratory behavior of oliceridine, a mu-opioid receptor agonist that selectively engages the G-protein-coupled signaling pathway with reduced activation of the beta-arrestin pathway, the authors compared its utility function with that of morphine. It was hypothesized that at equianalgesia, oliceridine will produce less respiratory depression than morphine and that this is reflected in a superior utility.Methods: Data from a previous trial that compared the respiratory and analgesic effects of oliceridine and morphine in healthy male volunteers ( n = 30) were reanalyzed. A population pharmacokinetic-pharmacodynamic analysis was performed and served as basis for construction of utility functions, which are objective functions of probability of analgesia, P(analgesia), and probability of respiratory depression, P(respiratory depression). The utility function = P(analgesia >= 0.5) - P(respiratory depression >= 0.25), where analgesia >= 0.5 is the increase in hand withdrawal latency in the cold pressor test by at least 50%, and respiratory depression >= 0.25 is the decrease of the hypercapnic ventilatory response by at least 25%. Values are median +/- standard error of the estimate.Results: The two drugs were equianalgesic with similar potency values (oliceridine: 27.9 +/- 4.9 ng/ml; morphine 34.3 +/- 9.7 ng/ml; potency ratio, 0.81; 95% CI, 0.39 to 1.56). A 50% reduction of the hypercapnic ventilatory response by morphine occurred at an effect-site concentration of 33.7 +/- 4.8 ng/ml, while a 25% reduction by oliceridine occurred at 27.4 +/- 3.5 ng/ml (potency ratio, 2.48; 95% CI, 1.65 to 3.72; P < 0.01). Over the clinically relevant concentration range of 0 to 35 ng/ml, the oliceridine utility function was positive, indicating that the probability of analgesia exceeds the probability of respiratory depression. In contrast, the morphine function was negative, indicative of a greater probability of respiratory depression than analgesia.Conclusions: These data indicate a favorable oliceridine safety profile over morphine when considering analgesia and respiratory depression over the clinical concentration range

Effects of a respiratory functional training program on pain and sleep quality in patients with fibromyalgia: A pilot study

Objective: To evaluate the effect of 8-week respiratory functional training program on pain tolerance, sleep, and urinary antioxidant and cortisol levels in 18 patients with fibromyalgia. Methods: Participants underwent a 12-week intervention: 4 weeks as control and 8 weeks of breathing exercises. Pain tolerance assay was done by using an algometer, whereas sleep quality was evaluated by actigraphy and by the Pittsburgh Sleep Quality Index. Cortisol and antioxidant levels were determined using commercial assay kits. Results: Increases in the pain tolerance threshold were detected in the occiput point after one month of intervention as well as in the low cervical and second rib points after one and two months. Actigraphy revealed a decrease in sleep latency, whereas sleep questionnaire showed improvements in sleep quality, sleep duration and sleep efficiency. No changes in cortisol and antioxidant levels were detected. Conclusion: The 8-week breathing exercise intervention reduced pain and improved sleep quality