PHARMACOGENETICS OF ANESTHESIOLOGICAL SUPPORT

O. Skavinska, L. Fishchuk, Y. Cherniavska, V. Pokhylko, O. Yevseienkova, Z. Rossokha
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引用次数: 0

Abstract

Pharmacogenetics studies the relationship between a person’s individual genetic characteristics and the human body’sresponse to the action of various drugs, particularly the occurrence of undesirable side eff ects. Thanks to the development of the latest technologies and methods, this branch of medical genetics and clinical pharmacology is developing very actively. Data are being accumulated, special databases are being created with the aim of creating individual genetic passports in the future, which will allow the selection of personalized treatment schemes.Anesthesiology is a special area of pharmacogenetic research because, more than any other medical specialty, it ischaracterized by polypharmacy-the simultaneous or sequential administration of many drugs. The same dose of a drug may be inadequate for some patients and may be life-threatening or cause unwanted side eff ects for others. Today, information about genetic factors is being used by clinicians to prescribe drugs to tailor drug therapy to a patient’s genome. In anesthesiology, the principles of pharmacogenetics have been explained for neuromuscular blocking agents, opioid metabolism, different types of anesthetics, and postoperative nausea and vomiting. On the other hand, a large number of anesthetics have a narrow therapeutic index.This review summarizes the most recent data from the scientifi c literature on the pharmacogenetics of diff erent types ofanesthetics. Inhalational anesthetics are halogenated derivatives of methyl ethyl ether, the exact mechanism of action of which is not yet fully understood. One of the rare but very serious side eff ects of all halogenated anesthetics is malignant hyperthermia, a genetically determined autosomal dominant disorder that manifests as a hypermetabolic response to drug administration. The dosage of intravenous anesthetics should also be carefully determined, taking into account the patient’s age, cardiovascular, hepatic, and renal status, concomitant drug therapy, and genetic factors. Ontogeny and genetic variability of drug-metabolizing enzymes are interrelated because genetic variability in drug-metabolizing enzyme expression cannot be assessed until the required protein is suffi ciently expressed. Pharmacogenetic variants may contribute to unpredictable drug exposure at the same weight- based drug dose.There are a number of potentially clinically applicable pharmacogenetic data in newborns, but more research is needed toconfi rm these fi ndings and understand how to incorporate them into clinical care.The selection of drugs and dosing regimens based on a patient’s pharmacogenomic profi le may be an important part of thefuture of medicine. Personalized treatment based on the specifi c variants in the genome will ultimately reduce the incidence of side eff ects and length of hospital stay for patients and save healthcare costs. Although pharmacogenomics and its application in clinical practice are still in their infancy, different variants and their implications for many clinical areas, including anesthesiology, are emerging every day.
麻醉支持的药物遗传学
药物遗传学研究个人遗传特征与人体对各种药物作用的反应之间的关系,特别是不良副作用的发生。由于最新技术和方法的发展,医学遗传学和临床药理学的这一分支正在积极发展。麻醉学是药物遗传学研究的一个特殊领域,因为麻醉学比其他任何医学专科都更具有多药治疗的特点--同时或连续使用多种药物。相同剂量的药物对某些病人来说可能不够,而对另一些病人来说则可能危及生命或引起不必要的副作用。如今,临床医生正在利用遗传因素的信息来开药,以便根据病人的基因组来调整药物治疗。在麻醉学领域,药物遗传学的原理已被应用于神经肌肉阻断剂、阿片类药物代谢、不同类型的麻醉剂以及术后恶心和呕吐等方面。本综述总结了科学文献中关于不同类型麻醉药药物遗传学的最新数据。吸入麻醉剂是甲乙醚的卤代衍生物,其确切的作用机制尚未完全清楚。恶性高热是所有卤代麻醉剂中罕见但非常严重的副作用之一,这是一种由基因决定的常染色体显性遗传疾病,表现为用药后的高代谢反应。静脉注射麻醉剂的剂量也应谨慎确定,同时考虑到患者的年龄、心血管、肝脏和肾脏状况、伴随药物治疗以及遗传因素。药物代谢酶的本体和遗传变异是相互关联的,因为在所需蛋白质充分表达之前,无法评估药物代谢酶表达的遗传变异。药物基因变异可能会导致在相同体重的药物剂量下出现不可预测的药物暴露。在新生儿中存在许多可能适用于临床的药物基因数据,但还需要更多的研究来确认这些发现,并了解如何将其纳入临床护理。根据基因组中的特定变异进行个性化治疗,最终将降低副作用的发生率,缩短患者的住院时间,节省医疗费用。尽管药物基因组学及其在临床实践中的应用仍处于起步阶段,但不同的变异及其对包括麻醉学在内的许多临床领域的影响每天都在出现。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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