Best practice & research. Clinical anaesthesiology
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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. ⋯ 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.
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Nitrous oxide interacts with vitamin B12 resulting in selective inhibition of methionine synthase, a key enzyme in methionine and folate metabolism. Thus, nitrous oxide may alter one-carbon and methyl-group transfer most important for DNA, purine and thymidylate synthesis. Long-term exposure to high concentrations of nitrous oxide may cause megaloblastic bone-marrow depression and neurological symptoms. ⋯ Recent studies seem to suggest a correlation between nitrous oxide anaesthesia and hyperhomocysteinaemia which is accepted to be an independent risk factor for coronary artery disease. As for today, available data do not support the notion that exposure to trace amounts of nitrous oxide is associated with impaired fertility or an increased risk of developing cancer. Emission of nitrous oxide from medical use is estimated to contribute less than 0.05% to total annual greenhouse gas emission.
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Best Pract Res Clin Anaesthesiol · Mar 2003
Interaction of inhalational anaesthetics with CO2 absorbents.
We review the currently available carbon dioxide absorbents: sodium hydroxide lime (=soda lime), barium hydroxide lime, potassium-hydroxide-free soda lime, calcium hydroxide lime and non-caustic lime. In general, all of these carbon dioxide absorbents are liable to react with inhalational anaesthetics. However, there is a decreasing reactivity of the different absorbents with inhalational anaesthetics: barium hydroxide lime > soda lime > potassium-hydroxide-free soda lime > calcium hydroxide lime and non-caustic lime. ⋯ Whether or not compound A, a gaseous compound formed by the reaction of sevoflurane with normally hydrated absorbents, is still a matter of concern is discussed. Even after very high loading with this compound, during long-lasting low-flow sevoflurane anaesthesias, no clinical or laboratory signs of renal impairment were observed in any of the surgical patients. Finally, guidelines for the judicious use of different absorbents are given.
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Toxicology has matured since it was defined as the 'science of poisons'. Modern toxicology is no longer anthropocentric but takes on different views at various biological systems, including ecosystems. Each will interact specifically when exposed to defined chemical agents, including drugs. ⋯ The key to understanding is in the host proteins that interact with the drug and mediate the cellular response. Hence, the proteom, i.e. the complete set of proteins of a cell, an individual or a species, determines how an exposed biological system may interact with the manifold of different xenobiotics. Structure-activity studies try to find out useful predictive parameters for risk and toxicity assessment.
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The halogenated inhalational anaesthetics halothane, enflurane, isoflurane and desflurane can produce metabolic hepatocellular injury in humans to a variable extent. During metabolism of these anaesthetics, tissue acetylation occurs due to the formation of reactive intermediates. Proteins modified by acetylation may constitute neo-antigens with a potential for triggering an antibody-mediated immune response. ⋯ Another source of concern is the products of degradation from reactions with carbon dioxide absorbents. Most important is compound A, which has been shown to exhibit nephrotoxicity in rodents. However, no significant changes in renal function parameters have been reported in surgical patients.