E M Zeidler1, A E Goetz, C Zöllner. 1. Klinik und Poliklinik für Anästhesiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Deutschland, e.pech@uke.de.
Abstract
BACKGROUND: Pharmacogenetics deals with hereditary factors which influence the pharmacodynamics and pharmacokinetics of drugs leading to individual diverse reactions. Also in anesthesiology differences in the pharmacogenetics of patients can lead to relevant alterations in the pharmacodynamics of drugs. AIM: This article provides a summary of polymorphisms relevant to commonly used anesthetic agents and the clinical relevance in patients treated with these compounds. It describes the possibilities, the problems and limits of pharmacogenetic diagnostics and therapy and explains how this follows the target of individualized medicine. MATERIAL AND METHODS: This article describes in detail the alterations in pharmacodynamics and pharmakokinetics relevant for anesthesia and their clinical significance. Based on the results of current studies, an overview of the most important drugs in anesthesiology with significant polymorphisms is given. These include opioids, muscle relaxants, volatile anesthetic agents, non-steroidal anti-inflammatory drugs (NSAIDs), benzodiazepines, antiemetics and cardiovascular drugs as well as platelet aggregation inhibitors, anticoagulants and the so-called new oral anticoagulants. RESULTS: Genetic alterations can lead to substantial modifications in the effectiveness of drugs. Genetic alterations of opioid receptors and the enzyme cytochrome P450 (CYP) 2D6 can result in a failure of analgesia after administration of opioids. Alterations in plasma cholinesterase activity are associated with a prolonged effectiveness of muscle relaxants. Polymorphisms in ryanodine receptors can contribute to the development of the feared MH in patients after administration of volatile anesthetics or succinylcholine. CONCLUSION: The study results presented here emphasize that these days knowledge on pharmacogenetics should not be missing in modern induction of anesthesia. In the future a blood sample could enable physicians to identify pharmacologically relevant markers. And these could guide the decision on the prescription of drugs and their appropriate dose, in order to achieve the lowest risk of side effects and the highest effectiveness of the active substance.
BACKGROUND: Pharmacogenetics deals with hereditary factors which influence the pharmacodynamics and pharmacokinetics of drugs leading to individual diverse reactions. Also in anesthesiology differences in the pharmacogenetics of patients can lead to relevant alterations in the pharmacodynamics of drugs. AIM: This article provides a summary of polymorphisms relevant to commonly used anesthetic agents and the clinical relevance in patients treated with these compounds. It describes the possibilities, the problems and limits of pharmacogenetic diagnostics and therapy and explains how this follows the target of individualized medicine. MATERIAL AND METHODS: This article describes in detail the alterations in pharmacodynamics and pharmakokinetics relevant for anesthesia and their clinical significance. Based on the results of current studies, an overview of the most important drugs in anesthesiology with significant polymorphisms is given. These include opioids, muscle relaxants, volatile anesthetic agents, non-steroidal anti-inflammatory drugs (NSAIDs), benzodiazepines, antiemetics and cardiovascular drugs as well as platelet aggregation inhibitors, anticoagulants and the so-called new oral anticoagulants. RESULTS: Genetic alterations can lead to substantial modifications in the effectiveness of drugs. Genetic alterations of opioid receptors and the enzyme cytochrome P450 (CYP) 2D6 can result in a failure of analgesia after administration of opioids. Alterations in plasma cholinesterase activity are associated with a prolonged effectiveness of muscle relaxants. Polymorphisms in ryanodine receptors can contribute to the development of the feared MH in patients after administration of volatile anesthetics or succinylcholine. CONCLUSION: The study results presented here emphasize that these days knowledge on pharmacogenetics should not be missing in modern induction of anesthesia. In the future a blood sample could enable physicians to identify pharmacologically relevant markers. And these could guide the decision on the prescription of drugs and their appropriate dose, in order to achieve the lowest risk of side effects and the highest effectiveness of the active substance.
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