Opioid therapy : a trade-off between opioid-analgesia and opioid-induced respiratory depression

Abstract

Conclusions that may be drawn from the data in this thesis: 1. The ideal drug for antagonism of respiratory depression has not yet been found. At present naloxone seems the most appropriate drug although reversal of respiratory depression coincides with loss of analgesia. New reversal agents acting via non-opioidergic pathways are under investigation and are aimed at reversal of opioid-induced respiratory depression without compromising analgesia. 2. Mathematical modelling of the non-steady state effects of respiratory depression by opioids yields comprehensible results. Still, despite adequate prediction of a drug's respiratory behaviour on a population level, the model does not allow individual prediction. 3. Utility functions may serve as a composite function to describe the effect-side effect profile of a drug. The utility function of fentanyl is predominantly negative except at low dose, indicating that for the dose tested the probability of respiratory depressions exceeds the probability for analgesia. 4. MR30365/07, an opioid acting at all three classical opioid receptors, produces in contrast to fentanyl ceiling in respiratory depression but not analgesia over the dose range tested. This effect remains to be validated in further studies.