Best practice & research. Clinical anaesthesiology
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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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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 complications of failure, neural injury and local anaesthetic toxicity are common to all regional anaesthetic techniques, and individual techniques are associated with specific complications. All potential candidates for regional anaesthesia should be thoroughly evaluated and informed of potential complications. Central neural blockades still account for more than 70% of regional anaesthesia procedures. ⋯ Pain on injection and paraesthesias while performing regional anaesthesia are danger signals of potential injury and must not be ignored. The incidence of systemic toxicity to local anaesthetics has significantly decreased in the past 30 years, from 0.2 to 0.01%. Peripheral nerve blocks are associated with the highest incidence of systemic toxicity (7.5 per 10,000) and the lowest incidence of serious neural injury (1.9 per 10,000).
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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.