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Pharmacogenetics and Anaesthesiology

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Pharmacogenetics was initiated in the 1950s by the observation of prolonged postoperative apnoea due to an inherited reduction in metabolism of the neuromuscular blocking agent succinylcholine. The enzyme butyrylcholinesterase is responsible for the hydrolysis of succinylcholine. Besides the normal (usual, U) variant, there are atypical (A), silent (S), fluoride-resistant (F), and J, K, and H variants of butyrylcholinesterase with decreased hydrolytic activity or reduced plasma concentration. Malignant hyperthermia is a potentially fatal anaesthetic disorder whose inherited nature was recognised in 1960. Linkage analyses have located the primary genetic site of malignant hyperthermia in the gene encoding for the skeletal muscle type ryanodine receptor and today over 30 mutations have been identified in this gene. The standard diagnostic procedure to test for malignant hyperthermia susceptibility is the invasive in vitro muscle contracture test. However, present and future research focuses on molecular genetic investigations for selected individuals. Of additional importance to the anaesthesiologist are the genetic influences on the pharmacology of opioids, benzodiazepines, adrenergic drugs, volatile anaesthetics, and responses to pain. Recent data also suggest an association between specific genotypes and the risk of adverse peri-operative clinical outcomes. Identification of such genotypes may not only provide insight into the variable responses of patients to anaesthetic drugs, but it also might potentially decrease anaesthetic morbidity and mortality through pre-operative risk assessment and administration of prophylactic therapy.
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Keywords: anaesthesia; betaadrenergic receptor; butyrylcholinesterase; cytochrome p450; opioids; pharmacogenetics; pharmacogenomics; ryanodine receptor; succinylcholine; volatile anaesthetics

Document Type: Review Article

Affiliations: Department of Anaesthesia, University Clinics, Kantonsspital, CH-4031 Basel, Switzerland.

Publication date: June 1, 2004

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  • Current Pharmacogenomics provides comprehensive overviews of all current research on pharmacogenomics and pharmacogenetics. All areas of the field from pre-clinical to clinical research are covered, including related areas such as genomics, proteomics, target discovery, bioinformatics and novel diagnostics. This international journal is peer-reviewed and publishes both mini- and full review articles.

    The journal has become essential reading for all researchers and clinicians with interests in pharmacogenomics and pharmacogenetics.
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