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Genetic predisposition to adverse drug reactions in the intensive care unit.
Crit Care Med. 2010 Jun; 38(6 Suppl):S106-16.CC

Abstract

Adverse drug reactions are a significant public health problem that leads to mortality, hospital admissions, an increased length of stay, increasing healthcare costs, and withdrawal of drugs from market. Intensive care unit patients are particularly vulnerable and are at an elevated risk. Critical care practitioners, regulatory agencies, and the pharmaceutical industry aggressively seek biomarkers to mitigate patient risk. The rapidly expanding field of pharmacogenomics focuses on the genetic contributions to the variability in drug response. Polymorphisms may explain why some groups of patients have the expected response to pharmacotherapy whereas others experience adverse drug reactions. Historically, genetic association studies have focused on characterizing the effects of variation in drug metabolizing enzymes on pharmacokinetics. Recent work has investigated drug transporters and the variants of genes encoding drug targets, both intended and unintended, that comprise pharmacodynamics. This has led to an appreciation of the role that genetics plays in adverse drug reactions that are either predictable extensions of a drug's known therapeutic effect or idiosyncratic.This review presents the evidence for a genetic predisposition to adverse drug reactions, focusing on gene variants producing alterations in drug pharmacokinetics and pharmacodynamics in intensive care unit patients. Genetic biomarkers with the strongest associations to adverse drug reaction risk in the intensive care unit are presented along with the medications involved. Variant genotypes and phenotypes, allelic frequencies in different populations, and clinical studies are discussed. The article also presents the current recommendations for pharmacogenetic testing in clinical practice and explores the drug, patient, research study design, regulatory, and practical issues that presently limit more widespread implementation.

Authors+Show Affiliations

Department of Pharmacy and Therapeutics and Center for Clinical Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. pempey@pitt.edu

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

20502164

Citation

Empey, Philip E.. "Genetic Predisposition to Adverse Drug Reactions in the Intensive Care Unit." Critical Care Medicine, vol. 38, no. 6 Suppl, 2010, pp. S106-16.
Empey PE. Genetic predisposition to adverse drug reactions in the intensive care unit. Crit Care Med. 2010;38(6 Suppl):S106-16.
Empey, P. E. (2010). Genetic predisposition to adverse drug reactions in the intensive care unit. Critical Care Medicine, 38(6 Suppl), S106-16. https://doi.org/10.1097/CCM.0b013e3181de09f8
Empey PE. Genetic Predisposition to Adverse Drug Reactions in the Intensive Care Unit. Crit Care Med. 2010;38(6 Suppl):S106-16. PubMed PMID: 20502164.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic predisposition to adverse drug reactions in the intensive care unit. A1 - Empey,Philip E, PY - 2010/5/27/entrez PY - 2010/6/4/pubmed PY - 2010/7/24/medline SP - S106 EP - 16 JF - Critical care medicine JO - Crit. Care Med. VL - 38 IS - 6 Suppl N2 - Adverse drug reactions are a significant public health problem that leads to mortality, hospital admissions, an increased length of stay, increasing healthcare costs, and withdrawal of drugs from market. Intensive care unit patients are particularly vulnerable and are at an elevated risk. Critical care practitioners, regulatory agencies, and the pharmaceutical industry aggressively seek biomarkers to mitigate patient risk. The rapidly expanding field of pharmacogenomics focuses on the genetic contributions to the variability in drug response. Polymorphisms may explain why some groups of patients have the expected response to pharmacotherapy whereas others experience adverse drug reactions. Historically, genetic association studies have focused on characterizing the effects of variation in drug metabolizing enzymes on pharmacokinetics. Recent work has investigated drug transporters and the variants of genes encoding drug targets, both intended and unintended, that comprise pharmacodynamics. This has led to an appreciation of the role that genetics plays in adverse drug reactions that are either predictable extensions of a drug's known therapeutic effect or idiosyncratic.This review presents the evidence for a genetic predisposition to adverse drug reactions, focusing on gene variants producing alterations in drug pharmacokinetics and pharmacodynamics in intensive care unit patients. Genetic biomarkers with the strongest associations to adverse drug reaction risk in the intensive care unit are presented along with the medications involved. Variant genotypes and phenotypes, allelic frequencies in different populations, and clinical studies are discussed. The article also presents the current recommendations for pharmacogenetic testing in clinical practice and explores the drug, patient, research study design, regulatory, and practical issues that presently limit more widespread implementation. SN - 1530-0293 UR - https://www.unboundmedicine.com/medline/citation/20502164/Genetic_predisposition_to_adverse_drug_reactions_in_the_intensive_care_unit L2 - https://dx.doi.org/10.1097/CCM.0b013e3181de09f8 DB - PRIME DP - Unbound Medicine ER -