Polymorphisms in genes of drug targets and metabolism, whom many have been shown to be functional, represent attractive candidates that could provide insights for divergences in … See our User Agreement and Privacy Policy. GENETIC POLYMORPHISM IN DRUG TRANSPORT AND DRUG TARGETS BY: SK. GENETIC POLYMORPHISM IN DRUG TRANSPORT AND DRUG TARGETS PREPARED BY : RUMANA HAMEED PHARM D 170310820021 2. Polymorphisms are generated by mutations in the genes for these enzymes, which cause decreased, increased, or absent enzyme expression or activity by multiple molecular mechanisms. Polymorphism involves one of two or more variants of a particular DNA sequence. Introduction to ... Individualization of drug dosage regimen (Variability – Genetic, Age and Weight , disease, Interacting drugs). Genetic alteration in activity of drug target and drug metabolizing proteins could explain the development of pharmacoresistant epilepsy. The study of genetic variations in drug response is called pharmacogenetics when studying an individual gene, or pharmacogenomics when studying all genes. In the present study, we examined the genetic polymorphism in drug transporters, using organic cation/carnitine transporter OCTN2 as a model transporter. See our Privacy Policy and User Agreement for details. Drug targets can be broken into three main categories: the direct protein target of the drug, signal transduction cascades or downstream proteins, and disease pathogenesis proteins. Genetic polymorphism & drug interactions in pain management Prof Ian Whyte, FRACP, FRCPE Calvary Mater Newcastle University of Newcastle P-glycoprotein Transmembrane ... – A free PowerPoint PPT presentation (displayed as a Flash slide show) on PowerShow.com - id: 3f3dbd-ODc1Z "Poly" means many, and "morph" means form. Can be avoided,• Polymorphisms of P2Y 12 receptors in platelets increased risk of coronary artery disease - potential target 38. Genetic polymorphisms have been described for most drug metabolizing enzymes. Pharmacogenetics has elucidated the genetic basis for interindividual variability in drug response and will continue to play a key role in defining strategies to optimize drug therapy. If you continue browsing the site, you agree to the use of cookies on this website. POLYMORPHISM AND DRUG TARGETS PREPARED BY : Clipping is a handy way to collect important slides you want to go back to later. polymorphisms provides important genetic information that help to understand the effects of xenobiotics on human body. 'Clinical Pharmacokinetics & Pharmacotherapeutic Drug Monitoring' is a course offered in the fifth year of Pharm. Genetic Polymorphisms in Drug-Metabolizing Enzymes and Drug Targets. ... T Yokoi, T KamatakiGenetic polymorphism of drug metabolizing enzymes: New mutations in CYP2D6 and CYP2A6 genes in … They can be used to map (locate) genes such as those causing a disease, and they can help match two samples of DNA to determine if they come from the same source. Common gene signaling pathways may be involved in the pathophysiology of these diseases. INTRODUCTION Pharmacogenetics can be defined as the study of genetic factors affecting drug response. c. Indications for TDM ... Genetic Polymorphism in Drug Transport and Drug Targets. Genetic polymorphisms in drug-metabolizing enzymes and drug targets Mol Genet Metab. Polymorphisms are a type of genetic diversity within a population's gene pool. A good target should be efficacious, safe, meet clinical and commercial requirements and be ‘druggable’. Author links open overlay panel Masahiro Hiratsuka Michinao Mizugaki 1. Pharmacogenetics and individual variation of drug response, Sedatives and hypnotics drugs ppt by kashikant yadav, No public clipboards found for this slide. DRUG TRANSPORT Author links open overlay panel Masahiro Hiratsuka Michinao Mizugaki 1. Approaches: Genetic manipulation of target … /Week 1. ... Genetic Polymorphisms in Drug-Metabolizing Enzymes and Drug Targets. Genetic polymorphism is the cause of high interindividual variability for a given dose, for example in order to achieve a methadone plasma concentration of 250ng/mL, dosage of racemic methadone mixture may vary from 55 to 921mg per day for a 70kg patient without receiving any comedication [38]. We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. Monoamine reuptake inhibitors (MRIs) reduce the reuptake of one or more of the three major monoamine neurotransmitters, serotonin (5-hydroxytryptamine), norepinephrine, and dopamine by inhibiting the transporters responsible for their reuptake from the synaptic cleft. GENETIC DRUG MONITORING (THEORY) Theory : 2 Hrs. 4.3.1 ACE Insertion/Deletion Polymorphism. IN Key words: adverse drug reaction (ADR), cytochrome P450, genome-wide association study, human gene polymorphism, human leucocyte antigen (HLA), pharmacogenetics. Drug targets can be broken into three main categories: the direct protein target of the drug, signal transduction cascades or downstream proteins, and disease pathogenesis proteins. Targets Making 37. Jaheda 1. Vineetha Menon. For most drug-metabolizing enzymes (DMEs), the functional consequences of genetic polymorphisms have been examined. Antipsychotic drug biotransformation is mainly determined by genetic factors mediating CYP2D6 gene polymorphism, however the importance of environmental factors (dietary, smoking, diseases, etc.) So the aim of this study was to explore whether SCN1A c.3184 A/G (rs2298771) and CYP3A5*3 (rs776746) polymorphisms could serve as genetic based biomarkers to predict pharmacoresistance among Egyptian epileptic children. Both the genetic polymorphism and enzyme activity regulation of ALDH2 are of great imp … monotropic systems and enantiotropic systems. The molecular mechanisms of three polymorphisms are reviewed here. (2) A discontinuous genetic variation that results in different forms or types of individuals among the members of a single species. You can change your ad preferences anytime. Since OCTN2 plays a role in carnitine transport by mediating especially a renal reabsorption of carnitine from urine, free carnitine concentrations in blood and urine were used for phenotyping of the genetic mutation of OCTN2. Show more. 1. The most common type of polymorphism involves variation at a single base pair. DRUG TARGETS: Targeted drug delivery is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. This week you will learn about human genome organisation. Polymorphism and pseudomorphism are very common amongst drugs and are responsible for differences in many properties [3]. If you continue browsing the site, you agree to the use of cookies on this website. Pharmacogenetics and human genetic polymorphisms Ann K. DALY1 Institute of Cellular Medicine, Newcastle University Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, U.K. The acetylation polymorphism concerns the metabolism of a variety of arylamine and hydrazine drugs, as well as carcinogens by the cytosolic N-acetyltransferase NAT2. Outline. Slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. If you continue browsing the site, you agree to the use of cookies on this website. For most drug-metabolizing enzymes (DMEs), the functional consequences of genetic polymorphisms have been examined. CASE STUDY—IRINOTECAN Irinotecan is widely used in cancer chemotherapy but has been associated with unpredictable severe toxic reactions such as myelosuppression and delayed-type diarrhea. Our goal is to provide several illustrative examples of how polymorphisms in drug targets are being used to establish a personalized medicine platform. Detailed descriptions of the importance of individual isoforms in drug metabolism and the types of genetic polymorphisms that may affect this metabolism are provided in several recent review articles (Daly, 2010b; Ingelman-Sundberg & Sim, 2010; Ingelman-Sundberg et al., 2007; Rodriguez-Antona et al., 2010). D. program at School of Pharmacy, ... Genetic polymorphism in Drug metabolism: Cytochrome P-450 Isoenzymes. Share. Molecular basis of targated drug delivery system chatap, No public clipboards found for this slide, Drug transport and drug targeting - rumana hameed, Student at Jawaharlal Nehru Technological University, Vagdevi College of Pharmacy and Research Centre. The most important criteria for target validation is to take multi-validation approach. Looks like you’ve clipped this slide to already. Now customize the name of a clipboard to store your clips. Target Validation shows that a molecular target is directly involved in a disease process, and that modulation of the target is likely to have a therapeutic effect. Genetic Polymorphisms in Drug-Metabolizing Enzymes and Drug Targets. Genetic polymorphisms are naturally occurring variants in gene structure that occur in more than 1 percent of th… A person's genotype is his or her genetic makeup. 170310820021. … Transport PHARM D Slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. Genetic polymorphism is the cause of high interindividual variability for a given dose, for example, in order to achieve a methadone plasma concentration of 250ng/mL, dosage of racemic methadone mixture may vary from 55 to 921mg per day for a 70kg patient without receiving any comedication [34]. aspects of drug discovery process. For drug metabolism, the most important polymorphisms are those of the genes coding for CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5, which can result in therapeutic failure or severe adverse reactions. Genetic Polymorphism in Drug (1) The existence together of many forms of DNA sequences at a locus within the population. These transporters are the serotonin transporter (SERT, SLC6A4), norepinephrine transporter (NET, SLC6A2), and dopamine transporter (DAT, SLC6A3) respectively. You can change your ad preferences anytime. Genetic variations in drug targets may contribute to which drug property? We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. Genetic polymorphisms of drug-metabolizing enzymes give rise to distinct subgroups in the population that differ in their ability to perform certain drug biotransformation reactions. Slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. Drug target• identification of a potential target at which the drug can act.• Drugs which are based on targets showing wide polymorphisms can have variations in their effect. Show more. ... and the heterozygous nature of the mutations within an individual might minimize the potential effects of a polymorphism in a drug target under normal drug-free … (Marton, M. J. et al., 1998). If you continue browsing the site, you agree to the use of cookies on this website. What is Genetic Polymorphism? This polymorphism occurring in intron 16 is not a SNP. 2. Thus, genetic variation in drug targets may alter therapeutic efficacy and safety of drugs. See our User Agreement and Privacy Policy. occurs when several different physical forms or types of individuals exist among the members of a species Generally, polymorphism is considered to be of two types, viz. ALDH2 polymorphism is shown to be a genetic instrument for alcohol use in Mendelian randomization analysis. The term can pertain to all genes or to a specific gene. Slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. A) Bioavailability: B) Half-life: C) Racial differences in response: D) Peak-dose area under the curve: E) Entry into the central nervous system Genetic Polymorphism in Drug Transport and Drug Targets. Over six weeks, the daily warfarin dose was increased from 3 to 10 mg to attain three consecutive in-clinic therapeutic INRs. The phenotype is a person's outward physical appearance or function resulting from the interaction between the genotype and the environment. Genetic Polymorphism. Introduction Genetic variation is an importa Genetic Polymorphisms in Drug-Metabolizing Enzymes and Drug Targets. Looks like you’ve clipped this slide to already. 1. RUMANA HAMEED Called a single nucleotide polymorphism, or SNP (pronounced snip), scientists are studying how SNPs in the human genome correlate with disease, drug response, and other phenotypes. ALDH2 regulators exhibit potential therapeutic value as the important roles of ALDH2 in various diseases. Genetic polymorphisms in drug-metabolizing enzymes and drug targets. Genetic polymorphisms determine up to 50% of warfarin dose variability. In the present study, we examined the genetic polymorphism in drug transporters, using organic cation/carnitine transporter OCTN2 as a model transporter. The genetic polymorphism analysis has been applied to target validation, pharmacokinetics, toxicology, and clinical pharmacogenomics. 1. Polymorphism affecting drug metabolism 1. Clipping is a handy way to collect important slides you want to go back to later. Cite. 2001 Aug;73(4) :298-305. See our Privacy Policy and User Agreement for details. Now customize the name of a clipboard to store your clips. One of the most studied polymorphisms occurs in the gene encoding angioten-sin-converting enzyme. Genetic variants are associated with altered clinical outcome of patients with sepsis and cardiovascular diseases. A 38-year-old woman was started on warfarin and rifampin for cerebral venous sinus thrombosis and pulmonary tuberculosis. The term pharmacogenetics was first used in the late 1950s and can be defined as the study of genetic factors affecting drug response. Video created by Novosibirsk State University for the course "From Disease to Genes and Back". ... 2009, Drug Discovery Today. The majority of currently approved antidepressants, including almost all of the tri… A better understanding of genetic commonality among these diseases may enable the discovery of i … Genetic polymorphisms are different forms of a DNA sequence. Genet Metab to distinct subgroups in the fifth year of PHARM shown to be of two types viz. 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