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• W2169794329 abstract "Background To study the influence of morphine on chemical control of breathing relative to the analgesic properties of morphine, the authors quantified morphine-induced analgesia and respiratory depression in a single group of healthy volunteers. Both respiratory and pain measurements were performed over single 24-h time spans. Methods Eight subjects (four men, four women) received a 90-s intravenous morphine infusion; eight others (four men, four women) received a 90-s placebo infusion. At regular time intervals, respiratory variables (breathing at a fixed end-tidal partial pressure of carbon dioxide of 50 mmHg and the isocapnic acute hypoxic response), pain tolerance (derived from a transcutaneous electrical acute pain model), and arterial blood samples were obtained. Data acquisition continued for 24 h. Population pharmacokinetic (sigmoid Emax)-pharmacodynamic models were applied to the respiratory and pain data. The models are characterized by potency parameters, shape parameters (gamma), and blood-effect site equilibration half-lives. All collected data were analyzed simultaneously using the statistical program NONMEM. Results Placebo had no systematic effect on analgesic or respiratory variables. Morphine potency parameter and blood-effect site equilibration half-life did not differ significantly among the three measured effect parameters (P &gt; 0.01). The integrated NONMEM analysis yielded a potency parameter of 32 +/- 1.4 nm (typical value +/- SE) and a blood-effect site equilibration half-life of 4.4 +/- 0.3 h. Parameter gamma was 1 for hypercapnic and hypoxic breathing but 2.4 +/- 0.7 for analgesia (P &lt; 0.01). Conclusions Our data indicate that systems involved in morphine-induced analgesia and respiratory depression share important pharmacodynamic characteristics. This suggests similarities in central mu-opioid analgesic and respiratory pathways (e.g., similarities in mu-opioid receptors and G proteins). The clinical implication of this study is that after morphine administration, despite lack of good pain relief, moderate to severe respiratory depression remains possible." @default.
• W2169794329 created "2016-06-24" @default.
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• W2169794329 date "2004-11-01" @default.
• W2169794329 modified "2023-10-08" @default.
• W2169794329 title "Simultaneous Measurement and Integrated Analysis of Analgesia and Respiration after an Intravenous Morphine Infusion" @default.
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• W2169794329 doi "https://doi.org/10.1097/00000542-200411000-00021" @default.
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