title: Pharmacogenomics in the intensive care unit: focus on potential implications for clinical practice.
abstract: Critically ill patients often are at high-risk for adverse drug reactions (ADRs), mainly due to alterations in pharmacokinetic and pharmacodynamic (PK/PD) parameters. These PK/PD differences in can also lead to inadequate therapeutic response to many commonly used drugs in this patient population. Frequently in the critically ill patient, medications are utilized based on a "trial-and-error" approach. Furthermore, drug dosing in the critically ill largely remains a "one-size-fits-all" phenomenon, utilizing dosing based on PK studies in healthy volunteers. Known differences in gene variation among the general population can greatly alter response to drug therapy. The use of pharmacogenomics (PGX) to aid in the development of individualized pharmacotherapeutic regimens, potentially may reduce ADRs and increase therapeutic efficacy. Potential uses of PGX include: identification of patients who are particularly susceptible to ADRs; and patients whom are more likely to benefit from a particular drug therapy, based on the patient's own genetic profile. This review will focus on potential applications of PGX in the critically ill, including management of acute coronary syndromes (ACS), invasive fungal infections, and pain management. Current barriers to PGX-guided therapy in the critically ill and recent patent developments in the clinical application of PGX will also be discussed.
authors.forename: John M
authors.initials: JM
authors.lastname: Allen
authors.affiliation: Department of Pharmacotherapeutics and Clinical Research; University of South Florida College of Pharmacy; Tampa, FL 33612, USA. john_allen262@yahoo.com.
authors.forename: Shyam
authors.initials: S
authors.lastname: Gelot
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000701:Analgesics, Opioid / Q000378:metabolism / Q000627:therapeutic use; D000935:Antifungal Agents / Q000378:metabolism / Q000627:therapeutic use; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007362:Intensive Care Units; D009181:Mycoses / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010146:Pain / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010330:Patents as Topic; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D012709:Serum Albumin / Q000235:genetics / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D000935:Antifungal Agents; D010975:Platelet Aggregation Inhibitors; D012709:Serum Albumin; D065731:Cytochrome P-450 CYP2C19; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase