Significance of multiple neurochemicals that regulate respiration

Current efforts to characterize the neuronal mechanisms that underlie automatic breathing generally adopt a ‘minimalist’ approach. In this review, we survey three of the many neurochemicals that are known to be present in rapheneurons and may be involved in respiration. Specifically, we ask the question, ‘Is the minimalist approach consistent with the large number of neuronal types and neurochemicals found in respiratory centres?’6 page(s

A pharmacokinetic and pharmacodynamic study of oral oxycodone in a human experimental pain model of hyperalgesia

Background and Objective: Oxycodone is not as well characterized, with respect to its pharmacokinetic/pharmacodynamic properties, as other opioids. Moreover, the pharmacodynamic profile of oxycodone can be affected by changes in the pain system, e.g. hyperalgesia. Therefore, the aim of this study was to investigate the pharmacokinetic/pharmacodynamic profiles of oxycodone in a human experimental pain model of hyperalgesia. Methods: Twenty-four healthy subjects received oral oxycodone (15 mg) or placebo. Pharmacodynamics were assessed utilizing a multimodal, multi-tissue paradigm where pain was assessed from skin (heat), muscle (pressure) and viscera (heat and electricity) before and 30, 60 and 90 minutes after induction of generalized hyperalgesia evoked by perfusion of acid and capsaicin in the oesophagus. Venous blood samples were obtained for quantification of oxycodone plasma concentrations before and 5, 10, 15, 30, 45, 60, 90 and 120 minutes after drug administration. Results: Oxycodone blood concentrations could be described by a one-compartment model but, given the necessarily short timescale of the study, the concentrations were represented by linear interpolation for subsequent pharmacodynamic models. Time-dependent changes in the pain measures in the placebo arm of the study were represented by linear or quadratic functions. The time course of the pain measures in the oxycodone arm was taken to be the time course for the placebo arm plus a concentration-effect relationship that was either zero (no drug effect), linear or a maximum effect (Emax) model. For three of the four pain measures, there was a time-dependent change after administration of placebo (e.g. due to the development of generalized hyperalgesia). Conclusion: There was a measurable effect of oxycodone, compared with placebo, on all pain measures, and a linear concentration-effect relationship without an effect delay was demonstrated. This could indicate an initial peripheral analgesic effect of oxycodone.Anne E. Olesen, Richard Upton, David J.R. Foster, Camilla Staahl, Lona L. Christrup, Lars Arendt-Nielsen and Asbjørn M. Drewe