Pharmacogenomics: the path to individualised patient care
Preventing adverse drug events In the UK, a study of almost 19 000 admissions showed that 6.5% of patient admissions to two
738
NHS hospitals were related to adverse drug reactions (Davies et al, 2009). Adverse drug reactions are also one of the leading causes of hospitalisations and deaths in the USA, accounting for more than 100 000 deaths and over 2 million serious cases each year (Duke Center for Personalized and Precision Medicine, 2013). Being aware of our clients’ genetic susceptibility to adverse drug reactions can help prevent serious, but avoidable reactions.Warfarin (Coumadin) is a prime example, as it is one of the most challenging drugs to manage. It is one of the leading causes of adverse drug reactions leading to hospitalisations worldwide (Jonas and Wines, 2013). The predominant enzyme that metabolises warfarin is cytochrome P450 2C9 (CYP2C9). The human gene that codes for CYP2C9 has a number of variant alleles. Clients who have the mutant alleles have a reduced ability to metabolise warfarin. For those clients, a standard dose of warfarin reaches a higher level in the bloodstream and has a longer-than-normal half life. Variant alleles are found in approximately 30% of the USA population, resulting in varying degrees of difficulty in metabolising warfarin (Vail, 2007). This example shows how pharmacogenomics is individualising care by analysing genotypes to predict a safe and effective dose of warfarin.The Food and Drug Administration (FDA) in the USA recommends a pharmacogenomics test for CYP2C9 variants for every patient about to begin anticoagulation therapy (Scibona et al, 2014). So far, no recommendations have been noted from the UK Medicines and Healthcare products Regulatory Agency (MHRA) or the European Medicines Agency (EMA) regarding pharmacogenomic testing for warfarin. Clopidogrel (Plavix) is another example of a drug where pharmacogenomics is important. It is a prodrug that is transformed into its active form by numerous cytochrome P450 (CYP450) enzymes in the liver, one being CYP2C19. Variants of this gene have been associated with differences in the bioavailabilty of clopidogrel (Plavix). Clients with one or two copies of these variant alleles may be intermediate or poor metabolisers of clopidogrel (Plavix) and may produce a lesser amount of the active form of the drug. One study conducted in 2008 and 2009 shows those clients who have the variant allele CYP219*2 may have an increased risk of cardiovascular events owing to
their unresponsiveness to clopidogrel (Plavix), leading to the possibility of adverse outcomes. These patients may require a dose adjustment or a selection of an alternative medication such as ticagrelor (Brilinta/Brilique) (Jonas and Wines, 2013). As a result of this finding, the product label of clopidogrel (Plavix) includes a boxed warning describing the increased risk of cardiovascular events among poor metabolisers and that a genetic test is available to identify CYP2C19 polymorphisms (Jonas and Wines, 2013). However, prescribers are not required to pursue genetic testing of their clients. Prescribing information for clopidogrel in the European Union includes similar elements as in the USA, cautioning that CYP2C19 poor metabolisers may form less of the active metabolite and, therefore, experience reduced antiplatelet activity and generally exhibit a higher cardiovascular event rate following a myocardial infarction than do patients with normal CYP2C19 functions. It also advises that tests are available to identify a patient’s CYP2C19 genotype (Shah and Shah, 2012).
Targeting individual alleles Do we give a medication or not? How do we know? For certain conditions, medications are prescribed to target a patient’s alleles. For example, breast cancer patients should receive trastuzumab (Herceptin) in addition to their traditional breast cancer medication regime if they test positive for the human epidermal growth factor receptor 2 (HER2) (Howington et al, 2011). Women with metastatic breast cancer who over-express the protein product of HER2 have aggressive disease and poor prognosis. Trastuzumab (Herceptin) is an antibody against the HER2 gene and works by binding to the receptor sites on the cell surface, limiting the amount of cell division that occurs and prevents the growth of cancer (Centre for Genetics Education, 2013). Tumour markers have emerged over the past decades as targets and/or markers of treatment efficacy. Improved treatment efficacy is a result of tailoring treatment to the individual’s tumour mutations (Duke Center for Personalized and Precision Medicine, 2013). The pharmacogenomics for treating the human immunodeficiency virus (HIV) are important. For example, the common medication for treatment of HIV, abacavir
British Journal of Nursing, 2014, Vol 23, No 13
British Journal of Nursing.Downloaded from magonlinelibrary.com by 193.061.135.034 on July 17, 2015. For personal use only. No other uses without permission. . All rights reserved.
© 2014 MA Healthcare Ltd
D
o you know what pharmacogenomics is? I posed this question to many of my colleagues, and the majority were not familiar with it. With nurses being the largest group of staff in the NHS, a knowledge base of pharmacogenomics is important in order for us to provide our patients with the best, most up-to-date care. Nurses are working in all types of healthcare settings and have the opportunity to educate and treat many individuals. Pharmacogenomics is an emerging topic in the field and nurses need to be prepared to make use of it when caring for their patients. First, it is imperative we understand what genomics is. Genomics is the study of human genes and their function, including the interactions with other genes and the environment. It is the interaction between a person’s genetic makeup and other factors such as food and environmental toxins, lifestyle, and stress (Wilkinson and Treas, 2011; National Human Genome Research Institute; 2014). Pharmacogenomics, which combines pharmacology and genomics, is the study of how genes affect a person’s response to medications. Currently, most drugs are available as a ‘one-size-fits-all’ approach. However, not everyone responds the same way (Genetics Home Reference, 2014).An individual’s genetic makeup accounts for approximately 20–95% of variability in drug disposition and effects (Crews et al, 2012). Understanding a person’s genetic makeup is important to developing individualised drugs that our patients will respond to better and to which they will have less chance of developing an adverse drug reaction. Genes that contribute to patients’ drug sensitivity, resistance and toxicity have been identified through pharmacogenomics. Improved drug dosing, prevention of adverse drug reactions, better drug efficacy, and progress in cancer care are being made as a result of pharmacogenomics (Duke Center for Personalized and Precision Medicine, 2013). Clients will be prescribed the most effective medications with the fewest side effects, based on their genome-driven response to those medications (The Jackson Laboratory for Genomic Medicine, 2014).
Comment (Ziagen), should only be given to HIV-positive patients who do not have the HLA-B*5701 allele. Patients with this allele are more likely to incur hypersensitivity reactions to abacavir than patients without the allele. In addition, medications such as carbamazepine (Tegretol) and allopurinol (Zyloprim) should be avoided to decrease the chance of sensitivity reactions for clients with this allele. The FDA has approved genetic testing before patients receive abacavir (Howington et al, 2011). The EMA (2012) European Public Assessment Report (EPAR) states that screening for the HLAB*5701 allele should be carried out before initiating abacavir treatment and recommends screening in patients of unknown HLAB*5701 allele status who are reinitiating treatment with abacavir. Owing to a high risk of hypersensitivity reaction, abacavir is not recommended in individuals carrying this allele (PharmGKB, 2014a).
Pharmacogenomics and cancer Cancer is a leading cause of morbidity and mortality, and failed treatments can be lifethreatening. Being able to predict the response of a patient who has cancer to a particular treatment will have a significant impact.Tumours may have specific disease-defining mutations, but a patient’s germline genetic variation will also affect drug response. Currently, most cancer treatment includes using cytotoxic chemotherapy. Studies of cell-line pedigrees treated with different chemotherapeutic agents have shown that some cytotoxic effects are probably inherited. For example, the standard dose of mercaptopurine (Purinethol) for treatment of acute lymphoblastic leukaemia (ALL) results in life-threatening toxicity for individuals with certain variant alleles of thiopurine S-methyltransferase (TPMT). The FDA recommends genotyping for TPMT, and individuals with inactive alleles are often treated more successfully with reduced doses of mecaptopurine (Purinethol) (Wheeler et al, 2013). The EMA EPAR for mercaptopurine contains information regarding its metabolism by TPMT, and that patients with reduced activity are at increased risk of severe toxicity and likely require a reduced dose. TPMT genotyping or phenotyping can be used to identify these patients, although this should not replace close monitoring of blood counts (PharmGKB, 2014b).
© 2014 MA Healthcare Ltd
The future of pharmacogenomics The use of pharmacogenomics in current practice is limited, but studies in clinical trials are in progress. Pharmacogenomics will allow for the further development of or expansion upon drugs tailored to individuals for treating numerous
British Journal of Nursing, 2014, Vol 23, No 13
health problems, including cancer, HIV (and autoimmune deficiency syndrome (AIDS)), cardiovascular disease, Alzheimer’s disease, and asthma (Genetics Home Reference, 2014). It is the responsibility of nurses to stay proactive in identifying the changes needed to ensure that they are competent in genetics and genomics.
Recommendations Going back to the question ‘Do you know what pharmacogenomics is?’ brings us to the recommendation that genomics needs to be implemented into or further expanded on in nursing education. Nurses account for the largest segment of the healthcare provider community in the UK and the USA, placing them in the position to translate genomics into health care. However, the insufficient competency in this subject matter puts them at a decreased capacity to provide education, perform assessments that identify patients at risk for diseases, facilitate referrals to genetic specialists, interpret genetic test results, understand the adverse events of targeted therapies, and recognise inhibitors or inducers of medications based on genetic drug metabolism (Calzone and Jenkins, 2012). In the past, the call to integrate genomics education into nursing curricula has been made (Badzek et al, 2008). The UK nursing programme in the NHS National Genetics Education and Development Centre based in Birmingham uses the UK nursing genetics competencies to raise awareness of the relevance of genetics, work collaboratively with policy stakeholders, and provide practical help to integrate genetics and genomics into curricula and courses (Calzone et al, 2010). Genetic/genomic nurse leaders from the USA, UK, Brazil, Japan, Taiwan, Ireland, and Australia identified lack of effective presentation of genetics/genomics in nursing curricula and obstacles within healthcare settings as major barriers to integration of genetics and genomics into all aspects of nursing practice (Calzone et al, 2010). With all of the current advances in genomics and pharmacogenomics, nursing needs to raise standards of care by implementing genomics into the nursing curriculum, which will provide nurses with the necessary additional tools to care for their patients even more effectively.
Summary Pharmacogenomics is leading the path to individualised patient care. This will provide for more effective medications with fewer adverse events and lead to better, healthier lives for our patients. Future discoveries in pharmacogenomics knowledge will ultimately benefit our patients, their families, and the
community.As nurses, we must be committed to being lifelong learners of genomic information BJN for our patients now and in the future. Badzek L, Turner M, Jenkins JF (2008) Genomics and nursing practice: Advancing the nursing profession. The Online Journal of Issues in Nursing 13(1): doi:10.3912/ OJIN.Vol13No01Man01 Calzone KA, Jenkins J (2012) Genomics education in nursing in the United States. In: Pepper GA, Wysocki KJ, Kasper, CE, eds, Annual Review of Nursing Research Volume 29: Genetics. Springer Publishing Co, New York: 151-72 Calzone KA, Cashion A, Feetham S et al (2010). Nurses transfroming health care using genetics and genomics. Nursing Outlook 58: 26-35 Centre for Genetics Education (2013) Fact sheet 25: Pharmacogenetics/pharmacogenomics. http://tinyurl.com/ ljaae26 (accessed 1 July 2014) Crews K, Hicks JK, Pui C, Relling MV, Evans WE (2012). Pharmacogenomics and individualized medicine: Translating science into practice. Clin Pharmacol Ther 92(4): 467-75. doi: 10.1038/clpt.2012.120. Davies EC, Green CF, Taylor S, Williamson PR, Mottram DR, Pirmohamed M (2009). Adverse drug reactions in hospital in-patients: A prospective analysis of 3695 patient-episodes. PLOS ONE. doi:10.1371/journal. pone.0004439 Duke Center for Personalized and Precision Medicine (2013) Pharmacogenomics http://tinyurl.com/qgarc3k (accessed 1 July 2014) European Medicines Agency (2012) European Public Assessment Report: Ziagen. http://tinyurl.com/ q3q5qza (accessed 3 July 2014) Genetics Home Reference (2014) What is pharmacogenomics? http://tinyurl.com/p3xsonb (accessed 1 July 2014) Howington L, Riddlesperger K, Cheek D (2011) Essential nursing competencies for genetics and genomics: implications for critical care. Crit Care Nurse 31(5): e1-7. doi: 10.4037/ccn2011867. The Jackson Laboratory for Genomic Medicine (2014) Personalized medicine and genomics. http://tinyurl. com/l8e5kc2 (accessed 1 July 2014) Jonas DE, Wines R (2013) Pharmacogenomic testing and the prospect of individualized treatment. N C Med J 74: 485-93 National Human Genome Research Institute (2014) Frequently Asked Questions About Genetic and Genomic Science http://www.genome.gov/19016904 PharmGKB (2014a) European Medicines Agency (EMA) Label for abacavir and HLA-B. http://tinyurl.com/ o9rj2an (accessed 2 July 2014) PharmGKB (2014b) European Medicines Agency (EMA) Label for mercaptopurine and TPMT. http://tinyurl. com/mdwr9vc (accessed 3 July 2014) Scibona P, Angiman F, Vazquez C et al (2014) Individualization of drug therapy in older people. Reviews in Clinical Gerontology 24(2): 145-57. doi:10.1017/ s0959259814000033 Shah R, Shah D (2012) Personalized medicine: is it a pharmacogenetic mirage? Br J Clin Pharmacol 74(4): 698-721. doi: 10.1111/j.1365-2125.2012.04328.x. Vail J (2007) Pharmacogenomics: The end of trial-anderror medicine? Int J Pharm Compd 11(1): 59-65 Wheeler HE, Maitland ML, Dolan ME, Cox NJ, Ratain MJ (2013) Cancer pharmacogenomics: strategies and challenges. Nat Rev Genet 14(1):23-34. doi: 10.1038/ nrg3352. Epub 2012 Wilkinson JM,Treas LS (2011) Fundamentals of Nursing. 2nd edn. FA Davis Company, Philadelphia
Mark R Adelung
Nursing Clinical Instructor School of Nursing, Ocean County College PhD Candidate, Kean University Union, New Jersey, USA
Virginia M Fitzsimons
Professor and Executive Director School of Nursing, Kean University Union, New Jersey, USA
739
British Journal of Nursing.Downloaded from magonlinelibrary.com by 193.061.135.034 on July 17, 2015. For personal use only. No other uses without permission. . All rights reserved.
Preventing adverse drug events In the UK, a study of almost 19 000 admissions showed that 6.5% of patient admissions to two
738
NHS hospitals were related to adverse drug reactions (Davies et al, 2009). Adverse drug reactions are also one of the leading causes of hospitalisations and deaths in the USA, accounting for more than 100 000 deaths and over 2 million serious cases each year (Duke Center for Personalized and Precision Medicine, 2013). Being aware of our clients’ genetic susceptibility to adverse drug reactions can help prevent serious, but avoidable reactions.Warfarin (Coumadin) is a prime example, as it is one of the most challenging drugs to manage. It is one of the leading causes of adverse drug reactions leading to hospitalisations worldwide (Jonas and Wines, 2013). The predominant enzyme that metabolises warfarin is cytochrome P450 2C9 (CYP2C9). The human gene that codes for CYP2C9 has a number of variant alleles. Clients who have the mutant alleles have a reduced ability to metabolise warfarin. For those clients, a standard dose of warfarin reaches a higher level in the bloodstream and has a longer-than-normal half life. Variant alleles are found in approximately 30% of the USA population, resulting in varying degrees of difficulty in metabolising warfarin (Vail, 2007). This example shows how pharmacogenomics is individualising care by analysing genotypes to predict a safe and effective dose of warfarin.The Food and Drug Administration (FDA) in the USA recommends a pharmacogenomics test for CYP2C9 variants for every patient about to begin anticoagulation therapy (Scibona et al, 2014). So far, no recommendations have been noted from the UK Medicines and Healthcare products Regulatory Agency (MHRA) or the European Medicines Agency (EMA) regarding pharmacogenomic testing for warfarin. Clopidogrel (Plavix) is another example of a drug where pharmacogenomics is important. It is a prodrug that is transformed into its active form by numerous cytochrome P450 (CYP450) enzymes in the liver, one being CYP2C19. Variants of this gene have been associated with differences in the bioavailabilty of clopidogrel (Plavix). Clients with one or two copies of these variant alleles may be intermediate or poor metabolisers of clopidogrel (Plavix) and may produce a lesser amount of the active form of the drug. One study conducted in 2008 and 2009 shows those clients who have the variant allele CYP219*2 may have an increased risk of cardiovascular events owing to
their unresponsiveness to clopidogrel (Plavix), leading to the possibility of adverse outcomes. These patients may require a dose adjustment or a selection of an alternative medication such as ticagrelor (Brilinta/Brilique) (Jonas and Wines, 2013). As a result of this finding, the product label of clopidogrel (Plavix) includes a boxed warning describing the increased risk of cardiovascular events among poor metabolisers and that a genetic test is available to identify CYP2C19 polymorphisms (Jonas and Wines, 2013). However, prescribers are not required to pursue genetic testing of their clients. Prescribing information for clopidogrel in the European Union includes similar elements as in the USA, cautioning that CYP2C19 poor metabolisers may form less of the active metabolite and, therefore, experience reduced antiplatelet activity and generally exhibit a higher cardiovascular event rate following a myocardial infarction than do patients with normal CYP2C19 functions. It also advises that tests are available to identify a patient’s CYP2C19 genotype (Shah and Shah, 2012).
Targeting individual alleles Do we give a medication or not? How do we know? For certain conditions, medications are prescribed to target a patient’s alleles. For example, breast cancer patients should receive trastuzumab (Herceptin) in addition to their traditional breast cancer medication regime if they test positive for the human epidermal growth factor receptor 2 (HER2) (Howington et al, 2011). Women with metastatic breast cancer who over-express the protein product of HER2 have aggressive disease and poor prognosis. Trastuzumab (Herceptin) is an antibody against the HER2 gene and works by binding to the receptor sites on the cell surface, limiting the amount of cell division that occurs and prevents the growth of cancer (Centre for Genetics Education, 2013). Tumour markers have emerged over the past decades as targets and/or markers of treatment efficacy. Improved treatment efficacy is a result of tailoring treatment to the individual’s tumour mutations (Duke Center for Personalized and Precision Medicine, 2013). The pharmacogenomics for treating the human immunodeficiency virus (HIV) are important. For example, the common medication for treatment of HIV, abacavir
British Journal of Nursing, 2014, Vol 23, No 13
British Journal of Nursing.Downloaded from magonlinelibrary.com by 193.061.135.034 on July 17, 2015. For personal use only. No other uses without permission. . All rights reserved.
© 2014 MA Healthcare Ltd
D
o you know what pharmacogenomics is? I posed this question to many of my colleagues, and the majority were not familiar with it. With nurses being the largest group of staff in the NHS, a knowledge base of pharmacogenomics is important in order for us to provide our patients with the best, most up-to-date care. Nurses are working in all types of healthcare settings and have the opportunity to educate and treat many individuals. Pharmacogenomics is an emerging topic in the field and nurses need to be prepared to make use of it when caring for their patients. First, it is imperative we understand what genomics is. Genomics is the study of human genes and their function, including the interactions with other genes and the environment. It is the interaction between a person’s genetic makeup and other factors such as food and environmental toxins, lifestyle, and stress (Wilkinson and Treas, 2011; National Human Genome Research Institute; 2014). Pharmacogenomics, which combines pharmacology and genomics, is the study of how genes affect a person’s response to medications. Currently, most drugs are available as a ‘one-size-fits-all’ approach. However, not everyone responds the same way (Genetics Home Reference, 2014).An individual’s genetic makeup accounts for approximately 20–95% of variability in drug disposition and effects (Crews et al, 2012). Understanding a person’s genetic makeup is important to developing individualised drugs that our patients will respond to better and to which they will have less chance of developing an adverse drug reaction. Genes that contribute to patients’ drug sensitivity, resistance and toxicity have been identified through pharmacogenomics. Improved drug dosing, prevention of adverse drug reactions, better drug efficacy, and progress in cancer care are being made as a result of pharmacogenomics (Duke Center for Personalized and Precision Medicine, 2013). Clients will be prescribed the most effective medications with the fewest side effects, based on their genome-driven response to those medications (The Jackson Laboratory for Genomic Medicine, 2014).
Comment (Ziagen), should only be given to HIV-positive patients who do not have the HLA-B*5701 allele. Patients with this allele are more likely to incur hypersensitivity reactions to abacavir than patients without the allele. In addition, medications such as carbamazepine (Tegretol) and allopurinol (Zyloprim) should be avoided to decrease the chance of sensitivity reactions for clients with this allele. The FDA has approved genetic testing before patients receive abacavir (Howington et al, 2011). The EMA (2012) European Public Assessment Report (EPAR) states that screening for the HLAB*5701 allele should be carried out before initiating abacavir treatment and recommends screening in patients of unknown HLAB*5701 allele status who are reinitiating treatment with abacavir. Owing to a high risk of hypersensitivity reaction, abacavir is not recommended in individuals carrying this allele (PharmGKB, 2014a).
Pharmacogenomics and cancer Cancer is a leading cause of morbidity and mortality, and failed treatments can be lifethreatening. Being able to predict the response of a patient who has cancer to a particular treatment will have a significant impact.Tumours may have specific disease-defining mutations, but a patient’s germline genetic variation will also affect drug response. Currently, most cancer treatment includes using cytotoxic chemotherapy. Studies of cell-line pedigrees treated with different chemotherapeutic agents have shown that some cytotoxic effects are probably inherited. For example, the standard dose of mercaptopurine (Purinethol) for treatment of acute lymphoblastic leukaemia (ALL) results in life-threatening toxicity for individuals with certain variant alleles of thiopurine S-methyltransferase (TPMT). The FDA recommends genotyping for TPMT, and individuals with inactive alleles are often treated more successfully with reduced doses of mecaptopurine (Purinethol) (Wheeler et al, 2013). The EMA EPAR for mercaptopurine contains information regarding its metabolism by TPMT, and that patients with reduced activity are at increased risk of severe toxicity and likely require a reduced dose. TPMT genotyping or phenotyping can be used to identify these patients, although this should not replace close monitoring of blood counts (PharmGKB, 2014b).
© 2014 MA Healthcare Ltd
The future of pharmacogenomics The use of pharmacogenomics in current practice is limited, but studies in clinical trials are in progress. Pharmacogenomics will allow for the further development of or expansion upon drugs tailored to individuals for treating numerous
British Journal of Nursing, 2014, Vol 23, No 13
health problems, including cancer, HIV (and autoimmune deficiency syndrome (AIDS)), cardiovascular disease, Alzheimer’s disease, and asthma (Genetics Home Reference, 2014). It is the responsibility of nurses to stay proactive in identifying the changes needed to ensure that they are competent in genetics and genomics.
Recommendations Going back to the question ‘Do you know what pharmacogenomics is?’ brings us to the recommendation that genomics needs to be implemented into or further expanded on in nursing education. Nurses account for the largest segment of the healthcare provider community in the UK and the USA, placing them in the position to translate genomics into health care. However, the insufficient competency in this subject matter puts them at a decreased capacity to provide education, perform assessments that identify patients at risk for diseases, facilitate referrals to genetic specialists, interpret genetic test results, understand the adverse events of targeted therapies, and recognise inhibitors or inducers of medications based on genetic drug metabolism (Calzone and Jenkins, 2012). In the past, the call to integrate genomics education into nursing curricula has been made (Badzek et al, 2008). The UK nursing programme in the NHS National Genetics Education and Development Centre based in Birmingham uses the UK nursing genetics competencies to raise awareness of the relevance of genetics, work collaboratively with policy stakeholders, and provide practical help to integrate genetics and genomics into curricula and courses (Calzone et al, 2010). Genetic/genomic nurse leaders from the USA, UK, Brazil, Japan, Taiwan, Ireland, and Australia identified lack of effective presentation of genetics/genomics in nursing curricula and obstacles within healthcare settings as major barriers to integration of genetics and genomics into all aspects of nursing practice (Calzone et al, 2010). With all of the current advances in genomics and pharmacogenomics, nursing needs to raise standards of care by implementing genomics into the nursing curriculum, which will provide nurses with the necessary additional tools to care for their patients even more effectively.
Summary Pharmacogenomics is leading the path to individualised patient care. This will provide for more effective medications with fewer adverse events and lead to better, healthier lives for our patients. Future discoveries in pharmacogenomics knowledge will ultimately benefit our patients, their families, and the
community.As nurses, we must be committed to being lifelong learners of genomic information BJN for our patients now and in the future. Badzek L, Turner M, Jenkins JF (2008) Genomics and nursing practice: Advancing the nursing profession. The Online Journal of Issues in Nursing 13(1): doi:10.3912/ OJIN.Vol13No01Man01 Calzone KA, Jenkins J (2012) Genomics education in nursing in the United States. In: Pepper GA, Wysocki KJ, Kasper, CE, eds, Annual Review of Nursing Research Volume 29: Genetics. Springer Publishing Co, New York: 151-72 Calzone KA, Cashion A, Feetham S et al (2010). Nurses transfroming health care using genetics and genomics. Nursing Outlook 58: 26-35 Centre for Genetics Education (2013) Fact sheet 25: Pharmacogenetics/pharmacogenomics. http://tinyurl.com/ ljaae26 (accessed 1 July 2014) Crews K, Hicks JK, Pui C, Relling MV, Evans WE (2012). Pharmacogenomics and individualized medicine: Translating science into practice. Clin Pharmacol Ther 92(4): 467-75. doi: 10.1038/clpt.2012.120. Davies EC, Green CF, Taylor S, Williamson PR, Mottram DR, Pirmohamed M (2009). Adverse drug reactions in hospital in-patients: A prospective analysis of 3695 patient-episodes. PLOS ONE. doi:10.1371/journal. pone.0004439 Duke Center for Personalized and Precision Medicine (2013) Pharmacogenomics http://tinyurl.com/qgarc3k (accessed 1 July 2014) European Medicines Agency (2012) European Public Assessment Report: Ziagen. http://tinyurl.com/ q3q5qza (accessed 3 July 2014) Genetics Home Reference (2014) What is pharmacogenomics? http://tinyurl.com/p3xsonb (accessed 1 July 2014) Howington L, Riddlesperger K, Cheek D (2011) Essential nursing competencies for genetics and genomics: implications for critical care. Crit Care Nurse 31(5): e1-7. doi: 10.4037/ccn2011867. The Jackson Laboratory for Genomic Medicine (2014) Personalized medicine and genomics. http://tinyurl. com/l8e5kc2 (accessed 1 July 2014) Jonas DE, Wines R (2013) Pharmacogenomic testing and the prospect of individualized treatment. N C Med J 74: 485-93 National Human Genome Research Institute (2014) Frequently Asked Questions About Genetic and Genomic Science http://www.genome.gov/19016904 PharmGKB (2014a) European Medicines Agency (EMA) Label for abacavir and HLA-B. http://tinyurl.com/ o9rj2an (accessed 2 July 2014) PharmGKB (2014b) European Medicines Agency (EMA) Label for mercaptopurine and TPMT. http://tinyurl. com/mdwr9vc (accessed 3 July 2014) Scibona P, Angiman F, Vazquez C et al (2014) Individualization of drug therapy in older people. Reviews in Clinical Gerontology 24(2): 145-57. doi:10.1017/ s0959259814000033 Shah R, Shah D (2012) Personalized medicine: is it a pharmacogenetic mirage? Br J Clin Pharmacol 74(4): 698-721. doi: 10.1111/j.1365-2125.2012.04328.x. Vail J (2007) Pharmacogenomics: The end of trial-anderror medicine? Int J Pharm Compd 11(1): 59-65 Wheeler HE, Maitland ML, Dolan ME, Cox NJ, Ratain MJ (2013) Cancer pharmacogenomics: strategies and challenges. Nat Rev Genet 14(1):23-34. doi: 10.1038/ nrg3352. Epub 2012 Wilkinson JM,Treas LS (2011) Fundamentals of Nursing. 2nd edn. FA Davis Company, Philadelphia
Mark R Adelung
Nursing Clinical Instructor School of Nursing, Ocean County College PhD Candidate, Kean University Union, New Jersey, USA
Virginia M Fitzsimons
Professor and Executive Director School of Nursing, Kean University Union, New Jersey, USA
739
British Journal of Nursing.Downloaded from magonlinelibrary.com by 193.061.135.034 on July 17, 2015. For personal use only. No other uses without permission. . All rights reserved.
