pharmacogenetic variation in drug action slideshare
Pharmacogenetics encompasses variation in genes that encode drug-metabolizing enzymes, drug transporters, and drug targets, as well as other specific genes related to the action of drugs. Genomic medicine, which uses DNA variation to individualise and improve human health, is the subject of this Series of papers. Variations in the CYP2D6 gene determine whether an individual is a fast or slow metaboliser of certain medications. Genomic factors may play a role in the pathogenesis of both predictable and idiosyncratic adverse drug reactions (ADRs). Effective use of pharmacogenomic data can affect choice and dosage of medication to maximize therapeutic efficacy and reduce adverse drug reactions. Some are quite simple and accurate, e.g. Bahar M, Setiawan D, Hak E, Wilffert B. Pharmacogenetics of drugâdrug interaction and drugâdrugâgene interaction: a systematic review on CYP2C9, CYP2C19 and CYP2D6. The targets of drug action may be quite diverse, including for example, membrane-bound receptors, ion channels, enzymes and DNA. Earlier, the study of pharmacogenetics was only of academic interest, but now it helps the pharmaceutical industry in the documentation of metabolism of a new drug development before registration. 49.2.5 Pharmacogenetics. Pharmacogenetic variation (eg, in acetylation, hydrolysis, oxidation, or drug-metabolizing enzymes) can have clinical consequences (see table Examples of Pharmacogenetic Variations). Allopurinol (Zyloprim®) for gout. A slight variation in deoxyribonucleic acid (DNA) can result in a subtle change in a protein which translates into major differences in how the protein functions. A particular protein may have an important role in drug treatment for one of several reasons, including the following: The protein plays a role in breaking down the drug. The information of drug metabolism and enzymes involved for the process will help to ⦠Pharmacogenetic research aims to study how genetic variation may influence drug efficacy and/or toxicity; pharmacogenomics expands this quest to the entire genome. Pharmacogenetic findings may help to uncover new drug targets, illuminate pathophysiology, clarify disease heterogeneity, aid in the fine-mapping of genetic associations, and contribute to personalized treatment. This involves all the pharmacologically active genes, how they manifest their variations, how they interact to produce PHENOTYPES, and how these phenotypes affect drug responses.DNA MICROARRAYS/CHIPS should be useful in determining how genetic variation influences individual responses to a given drug or class of drugs. Changes in the CYP3A5 enzyme could affect how the drug is broken down. pharmacogenomics analysis of the effects of GENOMICS on drug responses. IC 50 values as a measure of ligand affinity, while others are more complex with large errors e.g. Most of the early and best-known examples of pharmacogenetics involved the way genetic variation altered a drug⦠Some patient-related factors (eg, renal function, genetic makeup, sex, age) can be used to predict the pharmacokinetic parameters in populations. Drug efficacy and safety are determined by the interplay of multiple processes that regulate pharmacokinetics (PK) (absorption, distribution, metabolism, and excretion) and pharmacodynamics (PD) (drug action). February 25, 2020 1. 1 Over 100 medications approved by the Food and Drug Administration contain PG information in their product labels. Paving the way to better drug labeling. A good example is the cytokine CYP2D6, a protein which plays a role in the bodyâs metabolism of many drugs. A slight variation in the deoxyribonucleic acid (DNA) sequence can result in a subtle change in a protein which translates into major differences in how the protein functions. As a fundamental element in precision medicine, pharmacogenomics, the study of responses of individuals to medication based on their genomic information, enables the evaluation of some specific genetic variants responsible for an individualâs ⦠There is great variation in drug-response phenotypes, and a âone size fits allâ paradigm for drug delivery is flawed. Furthermore, drug resources and drug labeling often provide recommendations for dose adjustments based on renal function assessment; however, there is typically very little evidence from controlled studies to validate those recommendations. Drug response can be impacted by several factors including diet, comorbidities, age, weight, drugâdrug interactions, and genetics. If the drug is broken down too quickly, it can increase the risk of rejecting the transplant organ. The idea that genetic variation can be used to individualise drug therapyâthe topic addressed hereâis often viewed as within reach for genomic medicine. Pharmacogenomics is the study of the role of inherited and acquired genetic variation in drug response. In these studies, multiple anti-TB drugs were utilized in some research, while some other adopts the single-drug therapy. Individual genetic variation in key genes involved in the metabolism, transport, or drug target can contribute to risk of adverse events 108 or treatment failure. Such variation ranges from failure to respond to a drug to adverse drug reactions and drug-drug interactions when several drugs are taken concomitantly. The role of cytochrome P450 (CYP)2C9 and CYP2C19 genetic variation in risk for phenytoin-induced cutaneous adverse drug events is not well understood independently of the human leukocyte antigen B (HLA-B)*15:02 risk allele. Pharmacogenetics (PG) examines inherited or acquired variations in genes that dictate drug response, disposition, or toxicity and explores how these variations can be used to optimize medication therapy. Pharmacogenetic tests, along with other information about patients and their disease or condition, can play an important role in drug therapy. Individual variation in response to drugs is a substantial clinical problem. Secondly, variation in the anti-TB drugs administered in the studies we analyzed limited the possibility of examining the association of DME with any specific drug. The clinical consequences range from patient discomfort through serious clinical illness to the occasional fatality. Pharmacogenetic research attempts to identify the genetic variants associated with antidepressant response to both understand the mechanism of action of pharmacotherapies and to predict outcome. Pharmacogenomics is the study of how human genetic information impacts drug response, and it aims to improve efficacy and reduced side effects. The individual variation in drug metabolism rate has been known for several years (William et al., 2001). Pharmacogenetics - Pharmacogenetics is a branch of pharmacology that studies interindividual variations in the DNA sequence in relation to the response to drugs, both in terms of efficacy and toxicity. Pharmacogenomics is the study of genomic variation underlying responses to drugs, which includes pharmacogenetics as referring to variations in DNA (see Chapter 31). It helps with the absorption or transport of the drug. The interindividual genetic variations in drug metabolizing enzymes and transporters influence the efficacy and toxicity of numerous drugs. Pharmacokinetics of a drug depends on patient-related factors as well as on the drugâs chemical properties. A single genetic variation in the HLA-B gene can lead to a painful skin reaction in ⦠We hypothesized that 1) genetic variation associated with drug transporters, metabolizers, targets, and mechanisms of action would modify the effect of specific drugs and 2) the existing evidence would be insufficient to recommend clinical use of pharmacogenetic interactions because of a lack of well-conducted studies across diverse populations. Biologists developed a broad variety of biological and pharmacological test systems producing different kinds of data. The protein is the target of the drug. Genotype-to-phenotype associations lie at the heart of pharmacogenomics, wherein all phenotypes of interest relate to drug effects (toxicities, response, drug levels in the blood, or drug effects on other biomarkers of drug action in the body). Nicotine-dependence pharmacogenetics research is an emerging field, and a number of studies have begun to characterize the clinical relevance and predictive power of genetic variation in drug-metabolizing enzymes and drug target genes for response to medication. These genomic variations may relate to drug disposition (pharmacokinetics, PK) or drug action (ph armacodynamics, PD) or to individualâs susceptibility. It has some role in a series of molecular events triggered by the drug. Consequently, there may be subsets of patients with a different benefit -risk profile. Genes implicated in the pharmacokinetics or pharmacodyamics of antidepressants have been shown to predict response; however, the failure of some findings to replicate has been disappointing. In diabetes, ⦠Adverse drug reaction in patients causes more than 2 million hospitalizations including 100,000 deaths per year in the United States. This adverse drug reaction could be due to multiple factors such as disease determinants, environmental and genetic factors. Currently, variations in around 20 genes provide useful predictions of reactions to 80â100 drugs â about 7% of drugs approved by the US Food and Drug Administration. Pharmacogenetics encompasses variation in genes that encode drug transporters, drug-metabolizing enzymes and drug targets, as well as specific genes related to the action of drugs. In the US, the Food and Drug Administration (FDA) now requires a â¦