title: Pharmacogenomics and pharmacogenetics for the intensive care unit: a narrative review.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  We selected relevant literature to illustrate the important concepts contained within.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pharmacy Department, Nova Scotia Health Authority, Halifax, NS, Canada.|College of Pharmacy, Dalhousie University, Halifax, NS, Canada.
authors.forename: Meghan
authors.initials: M
authors.lastname: MacKenzie
authors.affiliation: Departments of Anesthesia, Pain Management and Perioperative Medicine and Critical Care Medicine and Pharmacology, Dalhousie University and the Nova Scotia Health Authority, Halifax, NS, B3H 3A7, Canada. rihall@dal.ca.
authors.forename: Richard
authors.identifier: http://orcid.org/0000-0001-7666-889X
authors.initials: R
authors.lastname: Hall
mesh_terms: D000066491:Clinical Decision-Making; D003422:Critical Care / Q000379:methods*; D004358:Drug Therapy / Q000379:methods*; D006801:Humans; D010597:Pharmacogenetics