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Modern Uses of Pharmacogenetics

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In 2004, the National Surgical Adjuvant Breast and Bowel Project (NSABP) published a study which indicated that chemotherapy only had a positive outcome for specific cancer-treatment subjects (Paik, et al., 2004). Medical research shows that heritability can influence how certain pharmaceutical drugs elicit reactions when treated on humans (Haga & Burke, 2004). This has recently led to the idea that individualized treatment based on sequencing in the human genome is the most efficient way to cure patients suffering from variable conditions (Adams, 2008). Pharmacogenetics is the study of how different individuals respond to drugs based on gene variations to both predict the efficacy of certain medication and understand adverse drug reactions (Falrex, 2018). The most crippling setbacks to progress in pharmacogenetic research are the potentials for bias and conflicting findings among studies.

Since the time of Pythagoras, it was discovered that ingestion of fava beans resulted in different reactions when eaten by different individuals; for some, there was no reaction, and for others ingestion was fatal (Pirmohamed, 2001). This drew the important conclusion that two people sometimes elicit different physiological reactions from ingesting the same thing. As more clinical research had been conducted into this phenomenon, it was discovered that differing reactions are directly related to genetics. An early discovery which validated the existence of pharmacogenetic phenomena was that the efficacy of the anti-tuberculosis drug isoniazid is nullified by a genetic deficiency in the enzyme N-acetyltransferase (Bönicke & Lisboa, 1957). Later studies continue to corroborate the claim that genetics influence the production of certain enzymes involved in drug metabolism (Pinto & Dolan, 2012). The way that these enzymes determine the human body’s ability to metabolize drugs is the foundation of pharmacogenetic research.

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Because genetic factors contribute to the human body’s metabolism, sometimes positively intended effects of certain drugs are not just nullified, but they are worsened. An adverse reaction (ADR) is defined as a “noxious or unintended reaction to a drug that is administered in standard doses” (Vervloet & Durham, 1998). The occurrence of ADRs is a pressing concern because they are unintended reactions to drugs intended for healing purposes; many cases of ADRs can be severe and occasionally life-threatening (Pirmohamed & Park, 2003). Since evidence shows that the occurrence of ADRs is related to genetics in the same way that drug efficacy is, pharmacogenetic research is being widely conducted in efforts to improve the quality of medicine and individualized treatment (Wilke, et al., 2007). Studies related to pharmacogenetic analysis have driven a lot of progress in improving the efficiency of clinical practice, but have also been met with several challenges.

Pharmacogenetic studies operate through genome-wide association. Genome-wide association works by sequencing the genome in clinical patients and finding common variants that lead to certain diseases (European Bioinformatics, 2018). In the case of pharmacogenetic analysis, genome-wide association studies find common loci in individuals who display similar reactions when faced with drugs (Daly, 2010). One example of this is in the field of pediatric oncology, a medical practice related to hematology; in the case of pharmacogenetics, studies are focused on blood diseases and cancers in patients. In 2016, a study was published that used genome-wide association to correlate genetic factors to ADRs when patients with metastatic colorectal cancer were being treated with the pediatric medicine irinotecan (Mlakar, et al., 2016). The problem with researching the pharmacogenetic effects of irinotecan in that study was that no replication studies existed to corroborate the results, and so further validation was needed (Mlakar, et al., 2016). Despite so much research currently being done in pharmacogenetics, only the largest effects of genetics on drug usage have been detected (Daly, 2010). “This failure to replicate findings may result from a lack of high-quality pharmacogenetic studies, as well as unresolved methodological and statistical issues” (Ross, et al., 2012). Even if there are challenges in making novel discoveries in the field of pharmacogenetics, medical research is being widely conducted into the subject.

Current research in the field of pharmacogenetics means that individualized treatment and effective use of medicine will continue to increase in clinical practice. The way genetics influences how bodies metabolize drugs has been proven to vary between positive, negative, and neutral outcomes (Adams, 2008). Genome-wide association studies that relate common loci between many humans who show similar effects are the main source that drives pharmacogenetic research (Daly, 2010). There have been many successes of recent research in the field, yet there have also been many challenges that are slowing down the progress made in pharmacogenetic research, such as the lack of quality pharmacogenetic studies being produced. In retrospect, the acquisition of empirical data in the field of pharmacogenetics using genome-wide association studies is revolutionizing the way doctors treat patients in the modern health care industry, and continued research could improve treatment methods of life-threatening issues like cancer.

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