PERSONALIZED MEDICINE AND PHARMACOGENETICS

CATEGORIES OF PATIENT FOR PERSONALIZED MEDICINE

1. SUSTAINED RELEASE/CONTROL RELEASE FORMULATION TOPIC :- Personalized medicine & Pharmacogenetics Submitted by:- ARAVINDA D 1 st sem M pharma Dept of pharmaceutics V.V. Puram college of pharmacy Bangalore-70 Submitted to:- Dr. KALAVATHY D J Professor dept of pharmaceutics V.V. Puram college of pharmacy Bangalore-70 1

2. CONTENTS INTRODUCTION DEFINITION PHARMACOGENETICS CATEGORIES OF PATIENTS FOR PERSONALIZED MEDICINES 2

3. INTRODUCTION Personalized medicine (PM) has the potential to tailor therapy with the best response and highest safety margin to ensure better patient care. By enabling each patient to receive earlier diagnoses, risk assessments, and optimal treatments, PM holds promise for improving health care while also lowering costs. 3

4. PM offers a structural model for efficient health care; it is preventive, coordinated, and proven. PM works best with a network of electronic health records that link clinical and molecular information to make it easier to help patients and their physicians make appropriate treatment decisions. The goals of PM :- The Right Drug The Right Patient The Right Disease The Right Time The Right Dosage Genetic and metabolic data will allow drugs to be tailored to patient subgroups PM may be considered an extension of traditional approaches to understanding and treating disease but with greater precision. 4

5. Modern advances in personalized medicine rely on technology that confirms a patients fundamental biology, DNA, RNA, or protein ,which ultimately leads to confirming disease. The concept of personalized medicine can be applied to new and transformative approaches to health care. Personalized medicine is the study of patients' unique environmental influences as well as the totality of their genetic code-their genome-to tailor personalized risk assessments, diagnoses, prognoses, and treatments. 5

6. It can indicate susceptibility to certain diseases before they become manifest, allowing the physician and patient to set out a plan for monitoring and prevention. PM approaches are becoming “best practice” in hospitals in order to ensure that patients with serious conditions such as “cancer” are given the optimum therapy from the start. 6

7. DEFINITION Personalized medicine is the tailoring of medical treatment to the individual characteristics of each patient. 7

8. ADVANTAGES Directing targeted therapy and reducing trial-and-error prescribing. It increases the opportunity to prevent disease. It helps to avoid adverse drug reactions. Increases the treatment options. Improves the quality of life. Reveal additional or alternative uses for medicines and drug candidates. 8

9. DISADVANTAGES The response to a medication may be a result of the interactions of multiple gene. Greater cost of diagnostic/biomarkers. It is more time consuming. Re education of health care professionals. Need to track individual health information . 9

10. APPLICATIONS OF PERSONALIZED MEDICINE Shift Emphasis in Medicine from Reaction to Prevention. Select Optimal Therapy. Make Drugs Safer. Increase Patient Compliance to Treatment. Rescue Drugs Failing Clinical Trials. Decreases the drug side effects. 10

11. PHARMACOGENETICS Pharmacogenetics is the study of the genetic difference in a single gene influences variability in drug responses. The goal of pharmacogenetics is to individualize the drug therapy to a person’s unique genetic makeup . 11

12. PHARMACOKINETICS:- What the body does to the drug dose, dosage regimen, delivery form Drug fate: Absorption, distribution, metabolism, and elimination of drugs (ADME) Pharmacodynamics:- What the drug does to the body Biochemical and physiological effects of drugs mechanism of drug action relationship between drug concentration and effect Pharmacokinetics and pharmacodynamics are essential to assess the drug efficacy. 12

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14. PHARMACOGENOMICS:- Pharmacogenomics involves study of the role of genes and their genetic variation (DNA,RNA level) in the molecular basis of disease and therefore the resulting pharmacologic impact of drugs on that disease. To determine whether a patient is a rapid or slow metabolizer,the patient is given a known substrate for that enzyme and the patient’s intrinsic clearance is measured. 14

15. Pharmacogenetics and Pharmacogenomics PHARMACOGENETIC :- It is the study of how genetic difference in a single gene influences variability in drug response ( efficacy and toxicity). PHARMACOGENOMICS:- It is the study of how genetic (genome) difference in a multiple gene influences variability in drug response (efficacy and toxicity). Pharmacogenetics and pharmacogenomics are expected to play an important role in the development of better medicines for populations and targeted therapies with improved benefit/risk ratios for individuals 15

16. GOALS OF PHARMACOGENOMIC AND PHARMACOGENETICS :- PK differences in different phenotypes and genotypes.  Use genotypes as a covariant for PK/PD in clinical trial analysis Explain outliers in PK/PD in clinical trials Sort subjects into genotypic categories by clinical effectiveness Determine if ADR is relative to certain genotypes 16

17. GENETIC POLYMORPHISM :- It is the natural variations in our genes that play a role in our risk of getting or not getting certain disease . Genetic polymorphisms  are  defined  as the occurrence of multiple alleles at a locus, where at least two alleles occur with a frequency greater than 1%. Polymorphism or genetic variation with a frequency greater than 1% of the population , in genetic sequences can affect patient therapeutic response or metabolism of given drug. 17

18. A MAJOR SOURCES FOR POLYMORPHISM:- Single Nucleotide Polymorphisms (SNPs) Single base change in DNA A A GC C TA AAGC T TA SNPs arise as a consequence of mistakes during normal DNA replication. NORMAL Other sources of variation Insertions SNPs Deletions Translocation DELETION duplications INSERTION TRANSLOCATION 18

19. GENETIC POLYMORPHISM IN DRUG METABOLISM DRUG METABOLISM:- The metabolism of drugs and other xenobiotics into more hydrophilic metabolites is essential for their elimination from the body, as well as for termination of their biological and pharmacological activity. Drug metabolism or biotransformation reactions are classified as either phase I functionalization reactions or phase II biosynthetic (conjugation reactions). Genetic Polymorphisms in Genes that Can Influence Drug Metabolism by phase 1& 2 enzymes 19

20. PHASE 1 ENZYMES ENZYMES SUBSTRATES CLINICAL COSEQUENCES CYP1A2 Acetaminophen , caffeine , Paraxanthine , propranolol Decreases theophylline metabolism CYP1B1 Estrogen metabolites Possible increase in cancer risk. CYP2A6 Coumarin , Nicotine , Halothane Decreases the nicotine metabolism and cigarette addiction CYP2C9 Tolbutamide , warfarin , phenytoin , NSAIDS Anticoagulant effect on warfarin CYP2C19 Omeprazole , hexobarbital metharbital , propranolol , phenytoin Peptic ulcer responds to ulcer 20

21. P450 Enzymes in Drug Metabolism The polymorphic P450 (CYP) enzyme superfamily is the most important system involved in the biotransformation of many endogenous and exogenous substances including drugs, toxins, and carcinogens. Genotyping for CYP polymorphisms provides important genetic information that help to understand the effects of xenobiotics on human body. 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. 21

22. PHASE 2 ENZYMES:- ENZYME Substrate Clinical Consequence Glutathione transferase (GSTM1, M3, T1) Busulfan, aminochrome , dopachrome, adrenochrome, nor adrenochrome Possible increases cancer risk; cisplatin induced ototoxicity Sulfotransferases Steroids, acetaminophen, tamoxifen, estrogens , dopamine Possible inc or dec cancer risk; clinical outcomes in women receiving tamoxifen for breast cancer Thiopurine methyltransferase Mercatopurine , thioguanine, azathioprine Thiopurine toxicity and efficacy, risk of second cancer 22

23. CATEGORIES OF PATIENTS FOR PERSONALISED MEDICINE Based on age group: Pediatrics Adults Geriatrics Based on gender: Male Female Based on body mass Based on physiological & pathological conditions Based on environmental conditions Based on genetic history 23

24. REFERANCE :- polymorphismaffectingdrugmetabolism-180430092727.pdf The Case for Personalized Medicine.pdf ptj35_10p560.pdf A text book for DDS by Prafull P.Patil ,BHUSHAN P Gayakwad , Dr Surajj Sarode Internet source 24

25. THANK YOU 25