Pharmacogenomics.pptx

Study of how an individual’s genetic inheritance affects the body’s response to drugs

1. Pharmacogenomics Submitted to : Dr Gurpreet Kaur Department of Plant Breeding and Genetics Submitted by : Anusha K.R L-2021-H-88-D PhD 1 st year Department of Vegetable Science

2. Pharma, the Greek word i.e. Pharmacon , related to drugs. Genomics, related to the genome. Pharmacogenetics is the study of the genetic basis for variation in drug response.

3. Dose and medicine selection based on the genomic profile Refers to how variation in one single gene influences the response to a single drug Study of how an individual’s genetic inheritance affects the body’s response to drugs. What is Pharmacogenomics?

4. D eals with the influence of genetic variation on drug response by co-relating gene expression or polymorphism with a drug's efficacy or toxicity. It intends to identify individuals who are either more likely or less likely to respond to a drug and those who require altered doses of certain drugs. Study of the variations in a targeted gene, or group of functionally related genes for variability in drug response U se of genetic information to guide the choice of drug and dose on an individual basis.

5. What is the need of Pharmacogenomics? To develop effective, safe medications and doses that will be tailored to a person’s genetic makeup. "One size fit all" is applicable to most drugs but doesn’t work the same way for everyone. Difficult to predict who gets the benefit and who will experience negative side effects.

6. Why do drugs work differently in different people? Occupational exposures Diet Diseases Age Drug activation Drug deactivation Gender Alcohol intake/ Smoking

7. Foundation of Pharmacogenomics Mutation The difference in the DNA code that occurs in less than 1% of the population. Often associated with rare diseases like Cystic fibrosis, sickle cell anemia, Huntington's disease Polymorphism Difference in the DNA code that occurs in more than 1% of the population A single polymorphism is less likely to be the main cause of a disease Polymorphisms often have no visible clinical impact

8. May result in a different amino acid or stop codon May result in a change in protein function No effect A Single Nucleotide Polymorphism (SNP) are DNA sequence variation that occurs when a single nucleotide in the genome sequence is altered. Occur in at least 1% of the population and makeup about 90% of all human genetic variation

9. Genetic polymorphisms in drug-metabolizing enzymes, transporters, receptors, and other drug targets causes inter-individual differences in the efficacy and toxicity of many medications

10. Goals of Pharmacogenomics Maximize drug efficacy Minimize drug toxicity Predict patients who will respond to intervention Aid in new drug development

11. The value of pharmacogenomics to the pharmaceutical industry The scope of clinical pharmacogenomics includes: the identification and characterization of candidate genes and polymorphisms the correlation of polymorphisms with therapy,clinical outcomes and drug effects the development of molecular genetic tests for prediction of drug response, or drug selection and dosing based on genotype or gene expression.

12. Adequate therapeutic response

13. Genetic polymorphism in drug transport P-Glycoprotein multidrug transporter (MDR1) Vincristine, vinblastine, doxorubicin, daunorubicin MDR1 - major cause for Low drug level in cells

14. Genetic polymorphisms in drug metabolism CYP2D6 - Tricyclic antidepressants Poor metabolizers - high plasma concentration-toxic effects. Rapid metabolizers - low plasma concentrations - therapeutic failure Codeine (as analgesic) Poor metabolizers - therapeutic failure CYP2C9 -Warfarin-slow metabolism-high risk of bleeding CYP2C19 Clopidogrel- Loss of function alleles - decreased activation of clopidogrel

15. Barriers to pharmacogenomics progress Complexity of finding gene variations that affect drug response Limited drug alternatives No incentives for drug companies to make multiple Pharmacogenomics products

16. Advantages of Pharmacogenomics To predict a patient's response to drugs To develop 'customized' prescriptions To minimize or eliminate adverse events To improve efficacy and patient compliance To improve rational drug development To improve the accuracy of determining appropriate dosages of drugs To screen and monitor certain diseases To develop more powerful, safer vaccines To allow improvements in drug research and development (R&D) and the approval of new drugs

17. Disadvantages Many genes are involved in drug action, making the drug target very difficult Insufficient validation of study results Identification of small inter-individual variations in everyone’s gene is very difficult Expensive Ethical issues

18. Conclusion There is general acceptance that the field of pharmacogenomics is going to be one of the first areas to impact clinical care following the completion of the human genome. However, although there are many opportunities, there are also significant challenges, challenges, which will require a multidisciplinary effort, not only within healthcare but also within the commercial sector. There is a need to build upon recent successes; however, this is going to require funding, and indeed of all the 'economics' will be the ultimate driver.

19. Thank you