Pharmacodynamics in the elderly

An overview is given of the influence of age on the pharmacodynamics of drugs used during general and locoregional anaesthesia. For some groups of agents a distinct separation into age-related changes in the pharmacokinetics and pharmacodynamics is possible, whereas for others the literature indicates only that responses in the elderly are enhanced. I start with an overview of the influence of age on cardiovascular and neuroendocrine function and include a short account of the state-of-the-art in pharmacodynamic modelling. The physiological changes that occur with age are associated with an increased sensitivity to the effects of anaesthetic agents. For most intravenous hypnotic agents, and inhalational anaesthetic agents, the increased sensitivity with age is, at least in part, explained by altered pharmacodynamics. For opioids and local anaesthetics applied for blockade of the central nervous system, the pharmacodynamic involvement is not always clear. For neuromuscular blocking agents, pharmacodynamic involvement appears to be nearly absent in the reduced dose requirements seen with age--so that the latter appear to be caused by altered pharmacokinetics. Future studies, using pharmacokinetic-pharmacodynamic (PK-PD) mixed-effects modelling, should further explore this area to obtain clinically applicable data for improving our insight into the delivery of anaesthetics to the elderly and improving the quality of anaesthesia in this fast-growing population.