Pharmacogenomics and Implications for Nursing Practice.

Pharmacogenomics is one of the many "omics" fields of study (transcriptomics, lipidomics, metabolomics, and phenomics) that have risen as the result of the human genome project and the growing understanding of the science of genomics. Genomics, the study of the structure, content, function, and evolution of genomes, has become relevant to healthcare professionals largely due to the advances in molecular technologies, particularly DNA sequencing (Table 1). Genomics is changing the nature of medicine and delivery of health care and the ability to examine and ultimately comprehend the nature of disease and drug action at the molecular level. Obtaining this goal is the ultimate basis of "precision medicine": to characterize or individualize care for human disease (National Institutes of Health, 2015). Precision medicine, a recent term, includes not just the right drug for the right individual (formerly called personalized medicine), but also the right drug for the specific disease type afflicting the specific individual. Precision medicine will allow for much more specific and successful therapeutic interventions than are now possible (Collins & Varmus, 2015).Many of the differences observed in how individuals respond to drugs are inherited and, therefore, are at least in part due to the genetic makeup of the patient (Kalow, 2004). Pharmacogenetics was coined in 1959 by a German geneticist (Vogel, 1959) and has been an active area of research even before the genomic revolution. While the terms pharmacogenetics and pharmacogenomics are often used interchangeably, pharmacogenetics is generally used to refer to the role of single genes in drug response while pharmacogenomics is the broader term that encompasses the role of the entire genome, including gene-gene interactions in drug response. The selection of studies and web resources for this review was done using the authors' expertise in the study and practice in pharmacogenomics and pharmacogenetics. The resources and references have been selected based on their clear representation of the foci of this article.Pharmacogenomics has the ultimate aim of identifying the many underlying genetic factors that play a role in the efficacy or toxicity of all drugs. Pharmacogenomics is one of the most rapidly growing fields of biomedical science and is becoming integral to all aspects of drug discovery, design, and development. The basic proposition of pharmacogenomics is the knowledge of the specific genetic factors that affect drug response. As a result, it will be possible to adjust dosages or suggest alternative therapies to avoid toxicities in patients and yield optimal patient outcomes. The definitions of these terms can be found in Table 1.Pharmacogenetics is the study of genetic factors that explain the response of patients to correctly dosed drugs. However, it is crucial to recognize that many environmental factors, including age, lifestyle, diet, and concurrent drug therapies, will also determine how a patient will respond to a drug. These nongenetic factors often play a larger role in a patient's response to a given drug (Nebert, Zhang, & Vesell, 2008).One classic example of the role of environmental factors in shaping drug response is drug inducers and inhibitors of the cytochrome P450 (CYP 450) enzyme system. Many drugs may induce or inhibit the activity of the P450 (CYP 450) metabolizing enzyme system, resulting in drug-drug interactions with possible adverse reactions or therapeutic failures. For example, many statins (3-hydroxy-3-methyl-glutaryl-coenzyme A [HMG-CoA] reductase inhibitors) taken to lower plasma cholesterol levels are known inhibitors of specific cytochrome P450 enzymes (Transon, Leeman, & Dayer, 1996; Zhou, 2009). The cytochrome P450 gene, CYP2D6, is one member of this family of enzymes responsible for the metabolism of thousands of exogenous and endogenous compounds. CYP2D6 codes for an enzyme largely responsible for the conversion of codeine to morphine in the liver. …