pharmacogenomics and pharmacoeconomics.pptx

pharmacogenomics and pharmacoeconomics.pptx

1. Pharmacogenomics And Pharmacogenetics Presented by – Dr Shivansh Verma PG JR1 MD Pharmacology SRMS IMS BLY

2. Learning Objectives History Definition Genetic Polymorphism Examples of pharmacogenomics

3. History Heredity influences drug response, and this was first described in 1956 with the identification of glucose-6-phosphate dehydrogenase (G6PD) deficiency, leading to hemolytic reactions after ingestion of fava beans, later on to certain therapeutic drugs like the antimalarial drug primaquine, sulfonamides, nitrofurantoin, and high-dose ascorbic acid. Friedrich Vogel first coined the term "pharmacogenetics" in 1959, when he defined it as the "study of the role of genetics in drug response.

4. Pharmacogenomics Pharmacogenomics is the branch of pharmacology that deals with the effect of a persons genetic makeup on the response to drug. Factors include age Body Weight Comparatively it’s a new field which combines pharmacology and genomics to develop effective, safe medications that will be personalized to a person’s genetic makeup.

5. We will come across two terms here Pharmacogenetics Pharmacogenomics It includes study of a single gene influencing a single drug response. E.g Influence of one gene coding for CYP2C9 on warfarin dose. It includes study of entire spectrum of gene influencing drug response. E.g Influence of multiple gene coding for CYP2C9,VKORC1 &CYP4F2 on warfarin dose.

6. The goals of pharmacogenomics are as follows: 1. To optimize drug therapy-choose the right drug at the right dose for the right duration. 2. Reduce the risk of serious adverse responses or loss of response. 3. Reduce health care costs associated with hospitalizations and outpatient visits due to adverse drug responses and multiple drug prescriptions.

7. Types of Genetic Polymorphism Genetic variation may affect either the drug pharmacokinetics or drug pharmacodynamics or both by affecting gene coding for the following: a. Drug-metabolizing enzymes. b. Drug transporters. C Drug targets. d. Disease-associated genes

8. Polymorphism in drug metabolizing enzymes Polymorphism in drug-metabolizing enzymes refers to genetic variations that influence an individual's ability to metabolize drugs. . These genetic differences can impact enzyme activity, leading to variations in drug response and potential side effects. Key drug-metabolizing enzymes include cytochrome P450 enzymes. Genetic polymorphisms in these enzymes can affect drug metabolism rates, leading to variations in drug efficacy and safety among individuals.

9. Some Examples Of Pharmacogenetic Polymorphism In Drug Metabolizing Enzymes CYP2D6 - TCA S SSRI ,Beta Blockers, Opioid Analgesics CYP2C9 – Warfarin is a narrow therapeutic index drug and routine monitoring of the INR . Individuals carrying any of the variant CYP2C9 *2 or *3 allels exhibit reduced enzyme activity ,leading to reduced elimination of Warfarin causing Inc. plasma conc Higher incidence of Bleeding Phase II Enzymes N-acetyl transferase: This acetylates INH and exist in two forms NAT1 & NAT2. Polymorphism in NAT2 results in rapid and slow acetylator phenotypes and modulates INH toxicity Fast acetylators will rapidly acetylate acetyl hydrazine to nontoxic metabolite, while in slow acetylator acetyl hydrazine will not be acetylated but will be oxidized to a hepatotoxic metabolite. CYP2C19 – Drugs including PPI and Antiplatelet drugs are metabolized by CYP2C19 OMEPRAZOLE is inactivated by CYP2C19 individuals with these variants have decreased clearance Phase I Enzymes

10. Polymorphism In Drug Target Genes Polymorphism in drug target genes refers to variations in the DNA sequence of genes that encode proteins targeted by drugs. These variations can impact the function or expression of the protein, influencing individual responses to medications. Understanding such polymorphisms is crucial for personalized medicine, as they can affect drug efficacy, toxicity, and overall treatment outcomes. Researchers often study genetic diversity to tailor drug regimens based on an individual's unique genetic profile.

11. Challenges In Pharmacogenomic Implementation The increasing understanding of pharmacogenomics will help clinicians to predict the drug therapy outcomes ,based on patients genotype Challenges In Pharmacogenomic Implementation in clinical practice are as follows: Clinician's knowledge about genetic determinants of drug response. Availability of biomarker testing. Multiple genes are likely to be involved in certain drug behaviors, making it very complex to identify the biomarkers. Pharmacoeconomics of biomarkers testing.

12. Application of Pharmacogenomics to Disease Management and Drug Development Advantages include :- It eliminates the trial and error approach to drug prescription and consequent adverse drug reactions, for example, use of abacavir in HIV infection. It allows a clinician to avoid certain medications or modulate the dose if pharmacogenetic variability predisposes to adverse effects, for example, warfarin and clopidogrel dose modification for desired effect . It decreases the overall cost of health care by reducing the cost of managing the adverse reaction associated with polymorphism. It helps in development of new drugs, for example, imatinib ,a selective tyrosine kinase inhibitor, was created for treatment of chronic myeloid leukemia that are Philadelphia chromosome positive. • It promotes development of new drugs, focusing on treating genetically determined rare disease.

13. Ethical Issues The "genetic information nondiscrimination law" prohibits health insurance companies and employers from dis-criminating against individuals based on genetic information . Although pharmacogenomics is in its infancy with multiple challenges, understanding the genetic basis of variability in drug response to medication and accordingly modification of the prescription will become a necessary trend in drug and dose selection in the coming future.

14. Thank you