This document provides an introduction to the key concepts of pharmacogenomics. It defines pharmacogenetics and pharmacogenomics, exploring the historical perspectives of the field including important early milestones. The document outlines the scope and applications of pharmacogenomics, including more accurate drug dosing and development based on a patient's genetic profile. It also introduces some of the basic concepts regarding the human genome, gene expression and control, and genetic variation, which are important to pharmacogenomics.
Pharmacogenomics is the study of how genes affect individual responses to drugs. It combines pharmacology and genomics to develop safe and effective personalized medications and dosages based on a person's genetic makeup. The goal is to improve treatment outcomes by predicting drug effectiveness and reducing adverse reactions. Challenges include implementing genetic tests in clinical practice and addressing cost, ethical and legal issues. Future applications include developing tailored drugs for many diseases and faster, more targeted clinical trials through biomarkers.
INTRODUCTION
What is pharmacogenomics
History
Principle
So what’s new about pharmacogenomics?
single nucleotide polymorphism (SNP)?
Genes commonly involved in pharmacogenomic drug metabolism and response
The anticipated benefits of pharmacogenomics
Pharmacogenetics Research/Database Program
Some of the barriers to using pharmacogenomics
Conclusion
References
Pharmacogenetics and pharmacogenomics is an upcoming branch in therapeutics. Various pharmacogenomic tests are currently available to aid in actual clinical practice. It has shown to have promising results in personalized medicine It is my attempt to compile the basic concepts from various books, articles, and online journals. Please feel free to comment.
Pharmacogenomics leads to more personalized drug therapy by understanding how an individual's genetics affects their response to medications. Variations in genes can impact drug receptors, metabolism, and other factors. Understanding these genetic differences could allow doctors to prescribe safer and more effective medications at the right dose for each patient.
DDS personalised medicines M.Pharma 1st Sem Pharmaceutics.pptxkushaltegginamani18
The document discusses personalized medicines and customized drug delivery systems. It defines personalized medicine as using genetic profiling and other individual patient characteristics to guide medical treatment. Customized drug delivery systems aim to optimize drug therapy for each patient by controlling dosage and delivery through technologies like bioelectronic medicines, 3D printing of pharmaceuticals, and telepharmacy.
This document provides an introduction to pharmacogenomics. It defines pharmacogenomics as the study of how genetic variations affect drug response and metabolism. It discusses key concepts like interracial and individual variability in drug metabolism due to single nucleotide polymorphisms and variable number tandem repeats. Case studies on tamoxifen metabolism and alcohol metabolism are presented. Challenges to implementing pharmacogenomics in clinical practice are noted. Applications to drug development and personalized medicine are mentioned.
The document discusses the role of genomics in pharmacogenomics and drug development. It defines key terms like pharmacogenomics and pharmacogenetics. It explains how genomics technologies can help optimize drug efficacy and minimize toxicity by identifying genetic variations that influence individual drug responses. Genomic information from the human genome project can aid drug target identification and reduce bottlenecks in development. Single nucleotide polymorphisms are discussed as the most common genetic variations affecting drug metabolism. The applications of pharmacogenomics in precision medicine to improve drug safety and efficacy are summarized.
Technologies like cheap genomic sequencing are enabling patients to receive entirely customized therapy based on their genetic, molecular, and metabolic makeup. Personalized medicine will both increase patient outcomes and decrease side effects and unwanted complications. Prominent considerations of the role of pharmacists in health care management include the distribution of drugs and supplies, delivering drug-related information, and consultation to meet the needs of patients and health team members so their role is also very prominent in personalized medicine in the future.
Pharmacogenomics is the study of how genes affect individual responses to drugs. It combines pharmacology and genomics to develop safe and effective personalized medications and dosages based on a person's genetic makeup. The goal is to improve treatment outcomes by predicting drug effectiveness and reducing adverse reactions. Challenges include implementing genetic tests in clinical practice and addressing cost, ethical and legal issues. Future applications include developing tailored drugs for many diseases and faster, more targeted clinical trials through biomarkers.
INTRODUCTION
What is pharmacogenomics
History
Principle
So what’s new about pharmacogenomics?
single nucleotide polymorphism (SNP)?
Genes commonly involved in pharmacogenomic drug metabolism and response
The anticipated benefits of pharmacogenomics
Pharmacogenetics Research/Database Program
Some of the barriers to using pharmacogenomics
Conclusion
References
Pharmacogenetics and pharmacogenomics is an upcoming branch in therapeutics. Various pharmacogenomic tests are currently available to aid in actual clinical practice. It has shown to have promising results in personalized medicine It is my attempt to compile the basic concepts from various books, articles, and online journals. Please feel free to comment.
Pharmacogenomics leads to more personalized drug therapy by understanding how an individual's genetics affects their response to medications. Variations in genes can impact drug receptors, metabolism, and other factors. Understanding these genetic differences could allow doctors to prescribe safer and more effective medications at the right dose for each patient.
DDS personalised medicines M.Pharma 1st Sem Pharmaceutics.pptxkushaltegginamani18
The document discusses personalized medicines and customized drug delivery systems. It defines personalized medicine as using genetic profiling and other individual patient characteristics to guide medical treatment. Customized drug delivery systems aim to optimize drug therapy for each patient by controlling dosage and delivery through technologies like bioelectronic medicines, 3D printing of pharmaceuticals, and telepharmacy.
This document provides an introduction to pharmacogenomics. It defines pharmacogenomics as the study of how genetic variations affect drug response and metabolism. It discusses key concepts like interracial and individual variability in drug metabolism due to single nucleotide polymorphisms and variable number tandem repeats. Case studies on tamoxifen metabolism and alcohol metabolism are presented. Challenges to implementing pharmacogenomics in clinical practice are noted. Applications to drug development and personalized medicine are mentioned.
The document discusses the role of genomics in pharmacogenomics and drug development. It defines key terms like pharmacogenomics and pharmacogenetics. It explains how genomics technologies can help optimize drug efficacy and minimize toxicity by identifying genetic variations that influence individual drug responses. Genomic information from the human genome project can aid drug target identification and reduce bottlenecks in development. Single nucleotide polymorphisms are discussed as the most common genetic variations affecting drug metabolism. The applications of pharmacogenomics in precision medicine to improve drug safety and efficacy are summarized.
Technologies like cheap genomic sequencing are enabling patients to receive entirely customized therapy based on their genetic, molecular, and metabolic makeup. Personalized medicine will both increase patient outcomes and decrease side effects and unwanted complications. Prominent considerations of the role of pharmacists in health care management include the distribution of drugs and supplies, delivering drug-related information, and consultation to meet the needs of patients and health team members so their role is also very prominent in personalized medicine in the future.
Pharmacogenomics is the study of how genetic factors affect individual responses to drugs. It aims to develop effective and safe medications tailored to a person's genetic profile. Variations in genes involved in drug metabolism and transport can impact drug efficacy and toxicity between individuals. Understanding these genetic differences may help optimize drug selection and dosing on a personalized level. While pharmacogenomics offers advantages like improved drug response and safety, challenges remain in fully validating results and identifying all relevant genetic variations due to drug pathways' complexity.
pharmacogenomics helps to improve healthcare sector by providing information about variability among genes for a particular class of drug hence reduces adverse drug reactions.
Pharmacogenomics aims to optimize drug therapy based on a patient's genotype. Genetic factors can account for 20-95% of variability in drug response. Polymorphisms like SNPs that occur in over 1% of a population can impact drug metabolism and effects. Pharmacogenomic testing targets biomarkers for specific drug classes to determine efficacy and avoid toxicity. While it has potential to improve prescribing, limitations include many genes influencing drugs and ethical issues. Personalized medicine based on pharmacogenomics is still developing.
Pharmacogenomics examines genetic variations that influence individual drug responses. Single nucleotide polymorphisms (SNPs) can predict good, bad, or no response to a drug. DNA microarrays efficiently identify SNPs to personalize treatment. This allows excluding non-responsive patients from trials, improving drug safety and efficacy. Currently, pharmacogenomics guides cancer treatment and medications metabolized by cytochrome P450 enzymes to prevent overdosing. Benefits include tailored therapy and safer drugs, though complexity challenges wide implementation.
1) Personalized medicine aims to provide customized medical care tailored to individual patients based on their genes, proteins, and environment. This involves optimizing drug therapy based on a patient's predicted response and risk factors.
2) Customized drug delivery systems and 3D printing allow for personalized dosages forms and treatments. Telepharmacy uses technology to provide pharmacy services to remote areas.
3) Pharmacogenomics studies how a patient's genes affect their response to drugs to optimize treatment. It can help identify non-responders, avoid adverse events, and determine the proper drug dosage. Pharmacogenetic testing provides this genetic information.
Genomics is the study of genomes through recombinant DNA, sequencing, and bioinformatics. It focuses on analyzing genome structure and function at a large scale. Genomics studies entire genomes rather than individual genes. This involves sequencing DNA and RNA and using computational methods to analyze large amounts of genomic data beyond what the human mind can comprehend alone. Genomics aims to help understand human health and disease at a personal level to optimize healthcare.
PERSONALIZED MEDICINE and customised drug delivery L-1.pptxSumant Saini
1. Personalized medicine aims to provide tailored treatment based on an individual's unique attributes by using diagnostic tools to identify biological markers, often genetic, to help assess which medical treatments will be most effective.
2. Pharmacogenomics plays a key role by studying how genetic variations affect individual responses to drugs to optimize efficacy and minimize adverse reactions. This allows for more targeted therapies and precise dosing.
3. The Human Genome Project mapped the entire human genetic code, opening up possibilities for diagnosing and treating diseases based on a person's genetic profile. Now, molecular testing guides treatment decisions and replaces some invasive procedures.
Pharmacogenetics- Introduction, History with case StudyPushpak Bhati
Pharmacogenetics is the study of how an individual's genetic makeup influences their response to drugs. It allows for a personalized medication approach to optimize drug selection and dosing based on genetic factors. Integrating pharmacogenomics into clinical decision making can streamline treatment by minimizing adverse events and improving outcomes through more effective strategies. Proactive pharmacogenetic testing holds promise in preventing medication issues by offering a personalized, preventative approach to care. While challenges remain, advancements in technology and research are advancing pharmacogenetics' role in precision medicine.
Pharmacogenomics is the study of how a person's genetics affect their response to drugs. It combines pharmacology and genomics to develop personalized medications. Genetic polymorphisms, or variations, in genes that code for drug-metabolizing enzymes and drug targets can impact drug efficacy and safety between individuals. Understanding a patient's genetic profile through pharmacogenomic testing allows doctors to predict treatment outcomes and tailor drug regimens to optimize therapy and reduce adverse reactions. While this promises more precise medication selection and dosing, challenges remain in clinician knowledge, availability of testing, complexity of multiple gene involvement, and cost of pharmacogenomic implementation in clinical practice.
Soal dan Pembahasan Farmakogenomik dan Personalized MedicineNesha Mutiara
Materi farmakologi molekular farmakogenomik dan personalized medicine :
- penjelasan farmakogenomik, farmakogenetik, dan personalized medicine
- mekanisme kerja molekular warfarin dan clopidogrel terkait farmakogenomik
This Presentation is about Pharmacogenomics and Pharmacogenetics , its Working , application, History.
It also contain a little bit info related to polypharmacy and its effects.
You can also see information regarding Drug Metabolism Phase, and drug Metabolizing Enzymes like CYPs, VKORC1, TPMT
Pharmacogenomics- a step to personalized medicinesApusi Chowdhury
Pharmacogenomics aims to optimize drug therapy based on a patient's genotype to maximize efficacy and minimize adverse effects. It involves studying how genetic factors influence individual responses to drugs in terms of absorption, distribution, metabolism, and excretion. Genetic polymorphisms like SNPs that occur in over 1% of the population can impact a drug's effects. Pharmacogenomic testing identifies biomarkers related to drug metabolism and targets to determine effective treatments and dosages for patients. While it holds promise for improving drug development and personalized medicine, limitations include insufficient validation and high costs.
Pharmacogenomics refers to the study of the relationship between specific DNA-sequence variation and drug effect, for example, variation in haplotype versus variation in therapeutic outcome
Genomics, proteomics, and bioinformatics are important fields that help advance drug development. Genomics studies entire genomes and can identify disease-associated genes. Proteomics identifies the proteins expressed in a sample and how they differ between healthy and diseased tissues. Bioinformatics uses computers to store and analyze biochemical and biological data, especially related to genomics. These fields help discover new drug targets, validate existing targets, select drug candidates, study mechanisms of action and toxicity. Integrating omics data from genomics to proteomics provides a more comprehensive understanding of biological systems compared to individual fields alone.
This document discusses genomics, proteomics, bioinformatics, pharmacogenomics, and the human genome project. It provides information on how genetic polymorphisms can influence drug disposition by affecting metabolizing enzymes and transporters. The human genome project mapped the entire human genome sequence to further the goals of personalized medicine based on an individual's genetic profile. Single nucleotide polymorphisms are particularly important for understanding how individuals respond differently to drugs.
The document discusses pharmacogenomics, which examines how an individual's genetic inheritance affects their response to medications. It provides examples of genetic factors that influence drug metabolism and response, such as variants affecting warfarin effectiveness and isoniazid metabolism. While pharmacogenomic testing could optimize drug therapy, barriers include cost and ethical concerns regarding discrimination and access to care.
Biotechnology is the use of living organisms to develop products and technologies. Pharmaceutical biotechnology applies biotechnology principles to develop drugs. The majority of current drugs are biologics such as antibodies, nucleic acids, and vaccines. Biotechnology methods are important in drug research and development, with key applications in oncology, metabolic disorders, and musculoskeletal disorders. Examples of biotech drugs include insulin for diabetes, gene therapy to replace mutated genes, clotting factors for hemophilia, human serum albumin for burns treatment, and engineered enzymes for enzyme deficiencies.
Personalized Medicine Pharmacogenomics-.pptAiswaryaA41
The document discusses personalized medicine and pharmacogenomics. It defines key terms like personalized medicine, pharmacogenomics, and pharmacogenetics. Personalized medicine aims to tailor treatment to an individual's unique genetic characteristics and biomarkers to improve health outcomes. The Precision Medicine Initiative launched by President Obama aims to advance this approach. Examples are provided of drugs like warfarin and abacavir where genetic testing can optimize dosing and reduce adverse reactions. Challenges include integrating pharmacogenomics into clinical practice and addressing ethical issues, but personalized medicine may improve drug development and patient care.
This document discusses precision psychiatry and the use of various "omics" technologies to advance precision medicine approaches in psychiatry. It outlines how genomics, pharmacogenomics, transcriptomics, and metabolomics can provide insights into the pathophysiology of mental illnesses and help determine individualized treatment approaches. Challenges include the complexity of gene-environment interactions, barriers to implementing pharmacogenomic testing in clinical practice, and the need for more work to develop multi-omics biomarkers that can predict disease risk and treatment response at the individual level.
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Pharmacogenomics is the study of how genetic factors affect individual responses to drugs. It aims to develop effective and safe medications tailored to a person's genetic profile. Variations in genes involved in drug metabolism and transport can impact drug efficacy and toxicity between individuals. Understanding these genetic differences may help optimize drug selection and dosing on a personalized level. While pharmacogenomics offers advantages like improved drug response and safety, challenges remain in fully validating results and identifying all relevant genetic variations due to drug pathways' complexity.
pharmacogenomics helps to improve healthcare sector by providing information about variability among genes for a particular class of drug hence reduces adverse drug reactions.
Pharmacogenomics aims to optimize drug therapy based on a patient's genotype. Genetic factors can account for 20-95% of variability in drug response. Polymorphisms like SNPs that occur in over 1% of a population can impact drug metabolism and effects. Pharmacogenomic testing targets biomarkers for specific drug classes to determine efficacy and avoid toxicity. While it has potential to improve prescribing, limitations include many genes influencing drugs and ethical issues. Personalized medicine based on pharmacogenomics is still developing.
Pharmacogenomics examines genetic variations that influence individual drug responses. Single nucleotide polymorphisms (SNPs) can predict good, bad, or no response to a drug. DNA microarrays efficiently identify SNPs to personalize treatment. This allows excluding non-responsive patients from trials, improving drug safety and efficacy. Currently, pharmacogenomics guides cancer treatment and medications metabolized by cytochrome P450 enzymes to prevent overdosing. Benefits include tailored therapy and safer drugs, though complexity challenges wide implementation.
1) Personalized medicine aims to provide customized medical care tailored to individual patients based on their genes, proteins, and environment. This involves optimizing drug therapy based on a patient's predicted response and risk factors.
2) Customized drug delivery systems and 3D printing allow for personalized dosages forms and treatments. Telepharmacy uses technology to provide pharmacy services to remote areas.
3) Pharmacogenomics studies how a patient's genes affect their response to drugs to optimize treatment. It can help identify non-responders, avoid adverse events, and determine the proper drug dosage. Pharmacogenetic testing provides this genetic information.
Genomics is the study of genomes through recombinant DNA, sequencing, and bioinformatics. It focuses on analyzing genome structure and function at a large scale. Genomics studies entire genomes rather than individual genes. This involves sequencing DNA and RNA and using computational methods to analyze large amounts of genomic data beyond what the human mind can comprehend alone. Genomics aims to help understand human health and disease at a personal level to optimize healthcare.
PERSONALIZED MEDICINE and customised drug delivery L-1.pptxSumant Saini
1. Personalized medicine aims to provide tailored treatment based on an individual's unique attributes by using diagnostic tools to identify biological markers, often genetic, to help assess which medical treatments will be most effective.
2. Pharmacogenomics plays a key role by studying how genetic variations affect individual responses to drugs to optimize efficacy and minimize adverse reactions. This allows for more targeted therapies and precise dosing.
3. The Human Genome Project mapped the entire human genetic code, opening up possibilities for diagnosing and treating diseases based on a person's genetic profile. Now, molecular testing guides treatment decisions and replaces some invasive procedures.
Pharmacogenetics- Introduction, History with case StudyPushpak Bhati
Pharmacogenetics is the study of how an individual's genetic makeup influences their response to drugs. It allows for a personalized medication approach to optimize drug selection and dosing based on genetic factors. Integrating pharmacogenomics into clinical decision making can streamline treatment by minimizing adverse events and improving outcomes through more effective strategies. Proactive pharmacogenetic testing holds promise in preventing medication issues by offering a personalized, preventative approach to care. While challenges remain, advancements in technology and research are advancing pharmacogenetics' role in precision medicine.
Pharmacogenomics is the study of how a person's genetics affect their response to drugs. It combines pharmacology and genomics to develop personalized medications. Genetic polymorphisms, or variations, in genes that code for drug-metabolizing enzymes and drug targets can impact drug efficacy and safety between individuals. Understanding a patient's genetic profile through pharmacogenomic testing allows doctors to predict treatment outcomes and tailor drug regimens to optimize therapy and reduce adverse reactions. While this promises more precise medication selection and dosing, challenges remain in clinician knowledge, availability of testing, complexity of multiple gene involvement, and cost of pharmacogenomic implementation in clinical practice.
Soal dan Pembahasan Farmakogenomik dan Personalized MedicineNesha Mutiara
Materi farmakologi molekular farmakogenomik dan personalized medicine :
- penjelasan farmakogenomik, farmakogenetik, dan personalized medicine
- mekanisme kerja molekular warfarin dan clopidogrel terkait farmakogenomik
This Presentation is about Pharmacogenomics and Pharmacogenetics , its Working , application, History.
It also contain a little bit info related to polypharmacy and its effects.
You can also see information regarding Drug Metabolism Phase, and drug Metabolizing Enzymes like CYPs, VKORC1, TPMT
Pharmacogenomics- a step to personalized medicinesApusi Chowdhury
Pharmacogenomics aims to optimize drug therapy based on a patient's genotype to maximize efficacy and minimize adverse effects. It involves studying how genetic factors influence individual responses to drugs in terms of absorption, distribution, metabolism, and excretion. Genetic polymorphisms like SNPs that occur in over 1% of the population can impact a drug's effects. Pharmacogenomic testing identifies biomarkers related to drug metabolism and targets to determine effective treatments and dosages for patients. While it holds promise for improving drug development and personalized medicine, limitations include insufficient validation and high costs.
Pharmacogenomics refers to the study of the relationship between specific DNA-sequence variation and drug effect, for example, variation in haplotype versus variation in therapeutic outcome
Genomics, proteomics, and bioinformatics are important fields that help advance drug development. Genomics studies entire genomes and can identify disease-associated genes. Proteomics identifies the proteins expressed in a sample and how they differ between healthy and diseased tissues. Bioinformatics uses computers to store and analyze biochemical and biological data, especially related to genomics. These fields help discover new drug targets, validate existing targets, select drug candidates, study mechanisms of action and toxicity. Integrating omics data from genomics to proteomics provides a more comprehensive understanding of biological systems compared to individual fields alone.
This document discusses genomics, proteomics, bioinformatics, pharmacogenomics, and the human genome project. It provides information on how genetic polymorphisms can influence drug disposition by affecting metabolizing enzymes and transporters. The human genome project mapped the entire human genome sequence to further the goals of personalized medicine based on an individual's genetic profile. Single nucleotide polymorphisms are particularly important for understanding how individuals respond differently to drugs.
The document discusses pharmacogenomics, which examines how an individual's genetic inheritance affects their response to medications. It provides examples of genetic factors that influence drug metabolism and response, such as variants affecting warfarin effectiveness and isoniazid metabolism. While pharmacogenomic testing could optimize drug therapy, barriers include cost and ethical concerns regarding discrimination and access to care.
Biotechnology is the use of living organisms to develop products and technologies. Pharmaceutical biotechnology applies biotechnology principles to develop drugs. The majority of current drugs are biologics such as antibodies, nucleic acids, and vaccines. Biotechnology methods are important in drug research and development, with key applications in oncology, metabolic disorders, and musculoskeletal disorders. Examples of biotech drugs include insulin for diabetes, gene therapy to replace mutated genes, clotting factors for hemophilia, human serum albumin for burns treatment, and engineered enzymes for enzyme deficiencies.
Personalized Medicine Pharmacogenomics-.pptAiswaryaA41
The document discusses personalized medicine and pharmacogenomics. It defines key terms like personalized medicine, pharmacogenomics, and pharmacogenetics. Personalized medicine aims to tailor treatment to an individual's unique genetic characteristics and biomarkers to improve health outcomes. The Precision Medicine Initiative launched by President Obama aims to advance this approach. Examples are provided of drugs like warfarin and abacavir where genetic testing can optimize dosing and reduce adverse reactions. Challenges include integrating pharmacogenomics into clinical practice and addressing ethical issues, but personalized medicine may improve drug development and patient care.
This document discusses precision psychiatry and the use of various "omics" technologies to advance precision medicine approaches in psychiatry. It outlines how genomics, pharmacogenomics, transcriptomics, and metabolomics can provide insights into the pathophysiology of mental illnesses and help determine individualized treatment approaches. Challenges include the complexity of gene-environment interactions, barriers to implementing pharmacogenomic testing in clinical practice, and the need for more work to develop multi-omics biomarkers that can predict disease risk and treatment response at the individual level.
Applications of genomics and proteomics pptIbad khan
Applications of genomics and proteomics ppt
genomics and proteomics ppt
in the field of health genomics and proteomics ppt
oncology ppt
biomedical application of genomics and proteomics ppt
agriculture application of genomics and proteomics ppt
proteomics in agriculture ppt
diagnosis of infectious disease ppt
personalized medicine ppt
Similar to Chapter 1 Introduction to Pharmacogenomics.pptx (20)
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Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
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5-hydroxytryptamine or 5-HT or Serotonin is a neurotransmitter that serves a range of roles in the human body. It is sometimes referred to as the happy chemical since it promotes overall well-being and happiness.
It is mostly found in the brain, intestines, and blood platelets.
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2. Learning contents
• Basic concepts of pharmacogenetics vs Pharmacogenomics
• Historical Perspectives of pharmacogenomics
• Scope and application of pharmacogenomics
• Introduction to human genome
• Gene expression and control of gene expression
• Genetic variation
6/21/2023 Pharmacogenomics 2
3. Introduction
All patients with same diagnosis
1
2
Responders and patients
not predisposed to toxicity
Non-responders and
Toxic responders
Treat with alternative drug or dose
Treat with conventional drug
or dose
6/21/2023 Pharmacogenomics
3
5. Intro…..…
• Pharmacogenetics
– Study of how genetic differences in a SINGLE gene
influence variability in drug response (i.e., efficacy and
toxicity)
• Pharmacogenomics
– Study of how genetic (genome) differences in
MULTIPLE genes influence variability in drug response
(i.e., efficacy and toxicity)
6/21/2023 Pharmacogenomics 5
6. Intro…
• The term pharmacogenetics often is used interchangeably with
the term pharmacogenomics
• However, pharmacogenetics generally refers to monogenetic
variants that affect drug response, whereas pharmacogenomics
refers to the entire spectrum of genes that interact to determine
drug efficacy and safety
In conclusion both have been defined as the study of variability
in drug response due to heredity.
Genetic polymorphism
6/21/2023 Pharmacogenomics 6
7. Intro…
Generally pharmacogenomics deals on:
• DNA sequence variation Vs Pharmacokinetic/dynamic inter individual
variation on drug
metabolizing enzyme
transporter
receptor and related pathway proteins
• “Correlating heritable genetic variation to drug response”
Ultimate goal
• understand how someone's genetic make-up determines, how well a medicine
works in his or her body, as well as what side effects are likely to occur.
• “Right medicine for the right patient”
6/21/2023 Pharmacogenomics
7
8. Historical Perspectives
• Friedrich Vogel coined the term “pharmacogenetics” (1959)
define a new science aimed to study the influence of
inherited factors on drug response variability through
genetic and pharmacological knowledge and methods
• Evidence for a genetic basis of clinical syndromes associated
with
when antimalarial drugs (e.g. primaquine): haemolytic
anemia in patients with G6PD deficiency ‘1950s)
6/21/2023 Pharmacogenomics 8
9. Historical …
• The discovery of the first pharmacogenetic deficiency at the
molecular level occurred in the 1980s when
Gonzales and his colleagues cloned the CYP2D6 gene and
characterized the genetic polymorphism responsible for
the decreased expression of the CYP2D6 enzyme
Decreased expression levels of CYP2D6:
↓mRNA were previously identified as responsible
for reduced metabolism and adverse response to
debrisoquine
6/21/2023 Pharmacogenomics
9
10. Historical …
• This research gave rise to several studies based on the use of
efficient molecular technologies linked
to classical pharmacological phenotypization
genetic population studies
– Resulted in: the identification of several polymorphisms in
genes involved in drug metabolism and mechanism of action
6/21/2023 Pharmacogenomics 10
11. Table: Some important milestones in the history of pharmacogenomics
6/21/2023
Pharmacogenomics 11
12. Historical …
Nowadays it has already been possible
• to identify several variations in the structure of genes codifying
enzymes of drug metabolism
transporter proteins or
target proteins (receptors, ion channels, enzymes) of drugs
• And to correlate these gene variations to inter-individual
variations in the response to xenobiotics.
6/21/2023 Pharmacogenomics 12
13. Historical …
• Many genetic factors, predictive of toxicity and response to
pharmacological treatments, have thus been identified
• Nowadays, pharmacogenetic and pharmacogenomic tests may
help clinicians to choose the best treatment and safest dose
for each patient.
6/21/2023 Pharmacogenomics 13
14. Scope and application of pharmacogenomics
pharmacogenomics have the following applications:
– Development of drugs that maximise therapeutic effects
but decrease damage to nearby healthy cells
– Prescription of drugs based on a patient’s genetic profile
– More accurate methods of determining dosages
– Development of vaccines made of genetic material
6/21/2023 Pharmacogenomics 14
15. Scope and application ……
– Detect diseases at an earlier stage, when it is easier to
treat effectively
– Increase patient compliance with therapy
– Improve the selection of targets for drug discovery and
reduce the time, cost, and failure rate of clinical trials
– Reduce the overall cost of healthcare
Treatment individualization
6/21/2023 Pharmacogenomics 15
16. Economic aspects of Pharmacogenetics
• Pharmacoeconomically, pharmacogenomics is highly important to
reduce health care cost via
decreasing the number of unnecessary screening and diagnostic
tests ordered
identifying individuals genetically at high risk for the common
diseases of adulthood (hypertension, heart disease, cancer and
diabetes), allowing for extensive environmental intervention
leading to more rapid recovery since the correct medication and
dosing for the individual patient will lead to the end of “trial and
error” prescribing
6/21/2023 Pharmacogenomics 16
17. Introduction to human genome
• Genes are segments of deoxyribonucleic acid (DNA) that
contain the code for a specific protein that functions in one or
more types of cells in the body
• Genes are contained in chromosomes, which are mainly in
the cell nucleus
• A chromosome contains hundreds to thousands of genes
• Every human cell contains 23 pairs of chromosomes, for a
total of 46 chromosomes.
6/21/2023 Pharmacogenomics 17
18. Human genome…..
• Genotype is a complete set of instructions on how that person’s
body synthesizes proteins and thus how that body is supposed to
be built and function
• The phenotype is the actual structure and function of a person’s
body
For example, hair color, weight, or the presence or absence of
a disease
• During DNA replication, and subsequent inheritance, it is often
said that what is passed from one generation to the next is the
“information” in the genes
6/21/2023
Pharmacogenomics
18
20. Gene expression
• Gene expression is the process by which the genetic code
(nucleotide sequence) of a gene is used to direct protein synthesis
The process involves two main stages:
• Transcription: the production of mRNA by the enzyme RNA
polymerase, and the processing of the resulting mRNA molecule
• Translation: the use of mRNA to direct protein synthesis
Some genes are responsible for the production of other forms of RNA that
play a role in translation, including tRNA and rRNA
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22. Control of gene expression
• Controlling gene expression is often accomplished by
controlling transcription initiation
• Regulatory proteins bind to DNA to either block or stimulate
transcription, depending on how they interact with RNA
polymerase
Control of transcription initiation can be:
• Positive control – increases transcription when activators bind
DNA
• Negative control – reduces transcription when repressors bind
to DNA regulatory regions called operators
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23. Genetic variation
• Genetic variation is the d/ce in the nucleotide sequence of DNA
b/n individuals of a species
• Mutation is the main source of genetic variation
• This variation, which is called a polymorphism, is largely
responsible for differences between how humans respond to
drugs
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24. Genetic variation ……
Molecular mechanisms of Mutation
• The most common genetic variants(90%) are single nucleotide
polymorphism substitutions (SNPs; pronounced “snips”).
Where one nucleotide replaced by an other
occur approximately once in every 100 to 300 base pairs
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25. Genetic variation ……
Examples of genetic variants include the following:
• Insertion–deletion (indel)polymorphisms
nucleotide or nucleotide sequence is either added to or deleted
from a DNA sequence
• Tandem repeats
a nucleotide sequence repeats in tandem (e.g., if “AG” is the
nucleotide repeat unit, “AGAGAGAGAG” is a five-tandem
repeat)
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26. Genetic variation ……
• Frameshift mutation
there is an insertion/deletion polymorphism
the number of nucleotides added or lost is not a multiple of
three
resulting in disruption of the gene’s reading frame
• Premature stop codon polymorphisms
there is premature termination of the polypeptide chain by a
stop codon
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27. Genetic variation ……
• Causes of mutation
- Errors in replication and recombination
- Chemical mutagenes: dyes, benzene, pesticides
- Irradiation: UV light, X-rays
- Spontaneous changes: deamination or depurination
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