MacKenzie Meghan, Hall Richard
Pharmacy Department, Nova Scotia Health Authority, Halifax, NS, Canada.
College of Pharmacy, Dalhousie University, Halifax, NS, Canada.
Can J Anaesth. 2017 Jan;64(1):45-64. doi: 10.1007/s12630-016-0748-1. Epub 2016 Oct 17.
Knowledge of how alterations in pharmacogenomics and pharmacogenetics may affect drug therapy in the intensive care unit (ICU) has received little study. We review the clinically relevant application of pharmacogenetics and pharmacogenomics to drugs and conditions encountered in the ICU.
We selected relevant literature to illustrate the important concepts contained within.
Two main approaches have been used to identify genetic abnormalities - the candidate gene approach and the genome-wide approach. Genetic variability in response to drugs may occur as a result of alterations of drug-metabolizing (cytochrome P [CYP]) enzymes, receptors, and transport proteins leading to enhancement or delay in the therapeutic response. Of relevance to the ICU, genetic variation in CYP-450 isoenzymes results in altered effects of midazolam, fentanyl, morphine, codeine, phenytoin, clopidogrel, warfarin, carvedilol, metoprolol, HMG-CoA reductase inhibitors, calcineurin inhibitors, non-steroidal anti-inflammatory agents, proton pump inhibitors, and ondansetron. Changes in cholinesterase enzyme function may affect the disposition of succinylcholine, benzylisoquinoline muscle relaxants, remifentanil, and hydralazine. Genetic variation in transport proteins leads to differences in the response to opioids and clopidogrel. Polymorphisms in drug receptors result in altered effects of β-blockers, catecholamines, antipsychotic agents, and opioids. Genetic variation also contributes to the diversity and incidence of diseases and conditions such as sepsis, malignant hyperthermia, drug-induced hypersensitivity reactions, cardiac channelopathies, thromboembolic disease, and congestive heart failure.
Application of pharmacogenetics and pharmacogenomics has seen improvements in drug therapy. Ongoing study and incorporation of these concepts into clinical decision making in the ICU has the potential to affect patient outcomes.
关于药物基因组学和药物遗传学的改变如何影响重症监护病房（ICU）的药物治疗，相关研究较少。我们综述了药物遗传学和药物基因组学在ICU中遇到的药物及病症方面的临床相关应用。
我们选择了相关文献来说明其中包含的重要概念。
已采用两种主要方法来识别基因异常——候选基因法和全基因组法。药物代谢（细胞色素P[CYP]）酶、受体和转运蛋白的改变可能导致药物反应的基因变异性，从而导致治疗反应增强或延迟。与ICU相关的是，CYP - 450同工酶的基因变异会导致咪达唑仑、芬太尼、吗啡、可待因、苯妥英、氯吡格雷、华法林、卡维地洛、美托洛尔、HMG - CoA还原酶抑制剂、钙调神经磷酸酶抑制剂、非甾体抗炎药、质子泵抑制剂和昂丹司琼的效果改变。胆碱酯酶功能的变化可能影响琥珀酰胆碱、苄基异喹啉类肌肉松弛剂、瑞芬太尼和肼屈嗪的处置。转运蛋白的基因变异导致对阿片类药物和氯吡格雷的反应存在差异。药物受体的多态性导致β受体阻滞剂、儿茶酚胺、抗精神病药物和阿片类药物的效果改变。基因变异也导致了诸如脓毒症、恶性高热、药物性过敏反应、心脏离子通道病、血栓栓塞性疾病和充血性心力衰竭等疾病和病症的多样性及发病率。
药物遗传学和药物基因组学的应用已使药物治疗得到改善。持续的研究并将这些概念纳入ICU的临床决策中有可能影响患者的治疗结果。
