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      Pharmacogenomics of Medications Commonly Used in the Intensive Care Unit

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          Abstract

          In the intensive care unit (ICU) setting, where highly variable and insufficient drug efficacies, as well as frequent and unpredictable adverse drug reactions (ADRs) occur, pharmacogenomics (PGx) offers an opportunity to improve health outcomes. However, PGx has not been fully evaluated in the ICU, partly due to lack of knowledge of how genetic markers may affect drug therapy. To fill in this gap, we conducted a review to summarize the PGx information for the medications commonly encountered in the ICU.

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          Most cited references 123

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          Pharmacogenetics: from bench to byte--an update of guidelines.

          Currently, there are very few guidelines linking the results of pharmacogenetic tests to specific therapeutic recommendations. Therefore, the Royal Dutch Association for the Advancement of Pharmacy established the Pharmacogenetics Working Group with the objective of developing pharmacogenetics-based therapeutic (dose) recommendations. After systematic review of the literature, recommendations were developed for 53 drugs associated with genes coding for CYP2D6, CYP2C19, CYP2C9, thiopurine-S-methyltransferase (TPMT), dihydropyrimidine dehydrogenase (DPD), vitamin K epoxide reductase (VKORC1), uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), HLA-B44, HLA-B*5701, CYP3A5, and factor V Leiden (FVL).
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            Severe adverse cutaneous reactions to drugs.

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              Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update.

              Cytochrome P450 (CYP)2C19 catalyzes the bioactivation of the antiplatelet prodrug clopidogrel, and CYP2C19 loss-of-function alleles impair formation of active metabolites, resulting in reduced platelet inhibition. In addition, CYP2C19 loss-of-function alleles confer increased risks for serious adverse cardiovascular (CV) events among clopidogrel-treated patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention (PCI). Guideline updates include emphasis on appropriate indication for CYP2C19 genotype-directed antiplatelet therapy, refined recommendations for specific CYP2C19 alleles, and additional evidence from an expanded literature review (updates at http://www.pharmgkb.org).
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                04 December 2018
                2018
                : 9
                Affiliations
                1Department of Emergency and Critical Care Medicine, Shanghai Tenth People's Hospital, Tongji University , Shanghai, China
                2Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota , Minneapolis, MN, United States
                Author notes

                Edited by: Ulrich M. Zanger, Dr. Margarete Fischer-Bosch Institut für Klinische Pharmakologie (IKP), Germany

                Reviewed by: Andrew A. Somogyi, University of Adelaide, Australia; Miia Turpeinen, University of Oulu, Finland

                *Correspondence: R. Stephanie Huang rshuang@ 123456umn.edu

                This article was submitted to Pharmacogenetics and Pharmacogenomics, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2018.01436
                6289166
                f0c4c94e-63a8-42c8-a1e1-721e374de460
                Copyright © 2018 Zhou, Skaar, Jacobson and Huang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 143, Pages: 15, Words: 13595
                Funding
                Funded by: Foundation for the National Institutes of Health 10.13039/100000009
                Funded by: Avon Foundation for Women 10.13039/100000142
                Categories
                Pharmacology
                Review

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