Best practice & research. Clinical anaesthesiology
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Opioids are the most potent analgesics. Toxicity results either from effects mediated by variation in affinity and intrinsic efficacy at specific opioid receptors or, rarely, from a direct toxic effect of the drugs. For some adverse effects, opioids exhibit a 'dual pharmacology' whereby these effects are usually observed only in pain-free individuals, and are not seen in patients in pain. ⋯ Non-steroidal anti-inflammatory drugs (NSAIDs) are known to act by inhibiting COX-1 and COX-2 isoenzymes to various degrees. Toxicity arises primarily from undesired inhibition at these enzyme sites. Knowledge of the mechanism of action of these drugs is fundamental to the understanding of their potential for toxicity, the details of which are still emerging.
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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.
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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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Studies on the toxic effects of muscle relaxants are difficult to design because of the need for mechanical ventilation and, consequently, concomitant administration of anaesthetic drugs which may influence the results. The following overview shows that muscle relaxants are weak toxic agents with regard to their teratogenicity, carcinogenicity and cytotoxic effects (including tissue- and organ-damaging effects). ⋯ Muscle relaxants and their metabolites may interact with muscarinic and nicotinic receptors in other organs and the ganglionic system, for example in the cardiovascular system. Direct stimulation of mast cells, with consequent release of histamine, after administration of muscle relaxants may clinically impose as toxic reactions.
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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.