Personalized medicine and customized drug delivery system

It includes personalized medicine, pharmacogenetics and customized drug delivery system as per M Pharm syllabus

1. DOSAGE FORMS FOR PERSONALIZED MEDICINES PRESENTED BY: LANIYA NASRIN K 1 ST SEMESTER M.PHARM DEPT.OF PHARMACEUTICS FACULTY IN-CHARGE: Smt.JISHA MOHANAN DEPT.OF PHARMACEUTICS SUBJECT: DRUG DELIVERY SYSTEM GOVERNMENT MEDICAL COLLEGE ,THIRUVANANTHAPURAM

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3. PERSONALIZED MEDICINES 01 3

4. PERSONALIZED MEDICINES 4 It is also referred as individualized medicine or precision medicine . The medical treatment based on the individual characteristic of each patients that not only Improves ability to diagnose and treat disease, but offers the potential to detect disease at an earlier stage. It is a form of medicine that uses information from patient’s genotype to initiate a preventive measure against the development of disease or condition .

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6. 6 NEED OF PERSONALIZED MEDICINE

7. Less trial & error No toxicity 7 SELECTION OF PERSONALIZED MEDICINE

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9. 9 THERAPY TEST CLINICAL GUIDANCE BREAST CANCER HER2: TUMORS WITH HER2 OVER EXPRESSION TRANSTUZUMAB RECOMMENDED EPILEPSY HLA-B*1502 :HLA-B*1502 POSITIVE PATIENTS SHOW SKIN REACTION ON TREATMENT WITH CARBAMAZEPINE CHOOSE ALTERNATIVE DRUG ATRIAL FIBRILLATION CYP2C9: DOSE OF WARFARIN THERAPY PARTLY DEPEND ON THIS GENOTYPES DOSE OF WARFARIN APPLICATION OF PERSONALIZED MEDICINES

10. 10 THERAPY TEST CLINICAL GUIDANCE IMMUNOSUPRESIVE THERAPY THIOPURINE METHYLTRANSFERASE :AZATHIOPRINE IS A PRODRUG CONVERTED TO MERCAPTOPURINE THAT UNDERGOES METHYLATION TO INACTIVE METABOLITE BY TPMT PATIENTS WITH DECREASED TMPT FUCTION HAVE HIGHER RISK FOR TOXICITY WITH AZATHIOPRINE ANTI-PLATELET MEDICATION CYP2C19 : CLOPIDOGREL IS A PRODRUG THAT REQUIRES METABOLIC ACTIVATION BY CYP2C19 USE ALTERNATIVE ANTI-PLATELET AGENT FOR PATIENTS WITH DECREASED CYP2C19

11. ADVANTAGES DISADVANTAGES Directing targeted therapy. Increase opportunity to prevent disease. It helps to avoid ADR. Increased treatment options Improve Quality of life. Greater cost of diagnostic/ biomarkers It is more time consuming Re-education of health care professionals Need to track individual health information 11

12. PERSONALIZED MEDICINES Disease prevention and management guidelines Application of genotype information Evidence based recommendation Tools and guidelines for improved risk communication Genetic testing, pharmacogenetics and phenotype assessment pharmacogenetics PRECISION MEDICINES EVIDENCE BASED MEDICINE PATIENT CENTRED CARE 12

13. PHARMACOGENETICS 02 13

14. PHARMACOGENETICS PHARMAKON + GENETIKOS Drugs Genes/genomes The study or clinical testing of genetic variation that assists in individual patient’s response to drugs OR Effect of genetic variation on drug response OR It is the study of how genetic difference in a single gene influences variability in drug response PHARMACOGENOMICS It is the study of how genetic (genome) difference In a multiple gene influences variability in drug response OR It is a branch of pharmacology concerned with using DNA and amino acid and Sequence data to inform drug development and testing 14

15. pharmacogenetics and pharmacogenomics are expected to play important role in development of better medicines with Improved benefits for individuals. pharmacogenomics pharmacogenetics Single gene Whole genome Smaller effect: multiple variant Large effect: variant effect 15

16. 16 GOALS OF PHARMACO-GENETICS

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18. PHARMACOGENETIC VARIATIONS 1.GENETIC POLYMORPHISM When a specific allele occur in at least 1% of the Population, it is said to be genetic polymorphism Allele-Any one of two/more alternative form of a gene that arise by mutation and are found at the same place on chromosome. 18

19. 19 Understanding of patients genetic determinants of drug metabolism and the consequences of the polymorphism used to Design personalized dosing regimen INFLUENCE OF GENETIC POLYMORPHISM

20. 20 ENZYME / RECEPTOR FREQUENCY OF POLYMORPHISM DRUG DRUG EFFECT / ADR CYP2C9 14-28% HETEROZYGOTES WARFARIN HEMMORHAGE CYP2D6 5-10% POOR MATABOLIZER ANTI-ARRHYTHMIC PRO-ARRHYTHMIC CYP2C19 3-6% WHITES OMEPRAZOLE HIGH RATE WITH CLARITHROMYCIN N-ACETYL TRANSFERASE 40-70% WHITES SULPHONAMIDE HYPERSENSITIVITY 2.POLYGENIC INFLUENCES Individual’s response to a drug or normal biological variation depends on: ENVIRONMENTAL FACTORS : Diet, Age, Infection, Other Drugs, Exercise Level, Occupational Exposure, Tobacco, Alcohol, sex… GENETIC FACTORS: Genetic variation may result in altered protein sequences and function EXAMPLES OF GENETIC POLYMORPHISM AFFECTING ENZYMES AND DRUG RECEPTORS

21. The pharmacokinetics of a drug can be altered by sequence variation in drug disposition gene. It include ADME The plasma concentration of the parent drug/its active metabolite may be affected by a genetic polymorphism---- Altering the function of a protein that involved in the disposition of the drug The pharmacodynamic of a drug can be altered by sequence variation drug target gene. pharmacological effects of a drug are exerted by modulating activities of enzymes / receptors. 21

22. 22 1.CANDIDIATE GENE STUDIES In patients who have better drug response, the candidate gene approach tests how frequent an allele. Genes are selected based on their known physiological/pharmacological response or drug response. It is a useful tool of study a genetic association with drug response if there is plausible link b/w gene and the drug response. 2. Genome wide association Study (GWAS) The role of common genetic variation in disease/drug response surveyed by GWAS GWAS was done by genotyping In large sets of SNPs across the genome It a great tool to discover new function of a gene, to identify a new genetic biomarker used to evaluate drug response. It help to understand complete disease

23. BENEFITS OF PHARMACOGENETICS LIMITATION OF PHARMACOGENETICS Better , safer drugs More accurate methods of determining appropriate drug dosages. Advanced screening for diseases Better vaccines Improvement in drug discovery and approval process Decrease overall cost of healthcare Improve choice of drug To predict patients response to drug The drug response is probably affected by multiple gene. The drug response might be from certain pattern of polymorphism rather than only a single polymorphism. Holding sensitive information on someone's genetic raise questions of privacy and security Ethical dilemma in disease prognosis and treatment choices. 23

24. CATEGORIES OF PATIENTS FOR PERSONALIZED MEDICINES 03 24

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26. 1. DISEASE RELATED CATEGORIES OF PATIENTS FOR PERSONALIZED MEDICINE PERCENTAGE OF PATIENTS WHERE HAVE ITS IMPACT, THE REMAINING PATIENT NOT HAVE ANY RESPONSE TO DRUG 26

27. 1.A-PATIENT WITH DEPRESSION Anti-depressant medication and specific psychotherapies have similar success in the 1st line treatment of moderate depression. In fact, individuals vary widely in response to specific treatment personalized medicine promises best treatment for any individuals. In order to provide Personalized medicine for depression, we must identify characteristics of individuals PRESCRIPTION FOR FLUOXETINE,PAROXETINE,CITALOPRAM OR VENLATAXINE GENETIC TESTING COMPLETED RECEIVED ALERT PHENOTYPE WITHOUT ALERT: Ultra-rapid Intermediate Extensive Intermediate to extensive PHENOTYPE WITH ALERT: Poor Poor to intermediate Consider alternative medication 27

28. 1.B-PATIENT WITH ASTHMA It is a common lung disease In this the inhalation of the -adrenergic and Corticosteroids is used. One of the characteristic of asthma is resistance or reduce responsiveness to treatment. Now, pharmacogenetics studies have mainly concerned adrenergic receptor gene Additional research is needed in order to evaluate the clinical utility of genomic testing.   1.C-PATIENT WITH CARDIAC ARRYTHMIA CVS disease heritable traits and family history information is useful for risk prediction Determining genetic Information may also be applied for risk prediction. More evidence regarding genetic background can provide guidance for selective effective treatment and preventive strategies in individuals with particular genotype. 28

29. 1.D-PATIENT WITH MIGRAINE The etiology is still not fully known The neuronal system ( glutaminergic, Dopaminergic, serotoninergic and GABA) whose functionality is Partly attributable, to genetically determined factors. Genetic factors have been implicated to migraine its etiology, tendency to become chronic, the sensitivity to pharmacological treatment. personalized medicine is designed, to achieve therapeutic success. 1.E-PATIENT WITH CANCER precision medicine is an approach to patient care that allows doctors to select treatments that are most likely to help patients based on genetics understanding of disease. TARGETED THERAPY BIOMARKERS HER2-Targeted in breast cancer HER2,PR,ER,BRCA1 EGFR-targeted in non-small cell lung cancer P53,KRAS ALK-targeted lung cancer CEA,EGFRI,KRAS EGFR-targeted in colorectal cancer EBCA2,CTC,PSCA 29

30. 30 2.BASED ON GENETIC POLYMORPHISM Genetic polymorphism is a difference in DNA sequence among individuals, groups or population. Variation in gene associated with pharmacokinetic and pharmacodynamic of drug may result in toxic, altered or no response. These variants can be used for developing biomarkers for diagnosis and therapeutics categorization of a particular disease. GWAS- -Genome wide association studies have discovered many genetic variants related to different lethal diseases.

31. 2.A-CYTOCHROME P450 GENETIC POLYMORPHISM Responsible for metabolizing more than 30 types of enzyme . It can be determine how quickly and effectively these agents eliminated from body. The CYP450 test can be used to determine dosing and effects of specific antidepressant medications, anti-coagulants such as warfarin and PPIs 2.B-DIFFERENT FAMILIES OF ENZYME POLYMORPHISM 1. Thiopurine Methyltransferase Thiopurine methyl transferase breakdowns a chemotherapy drug called Azathioprine To treat leukaemia's disorders and autoimmune disorders. Therefore blood test done before treatment begins 31

32. 32 2. UGT1A1 ENZYME This enzyme determine how the body breakdown Irinotecan , a chemotherapy drug for treating colorectal cancer. In patient with deficiency of this enzyme the medication can build up to toxic levels lead to suppression of bone marrow infection. Test genetic variation before treatment.

33. 3.BASED ON GENOMICS 3.A-OPTIMISING DRUG-RESPONSE: GENE-DRUG INTERACTIONS A person’s genetic constitution can be determined in order to address gene-drug interactions. The aim is to optimize drug efficacy and to minimize adverse event from drug treatment. Applications include genetic-based and genomics tests that commonly target medicines that are administered to populations with specific gene variant. In gene-drug interaction, the focus is directed to metabolism genes/genes related to the Immune system. 33

34. 3.B-GENE BASED DRUG TARGETING Another area of individualization is the development of molecular mechanism specific treatment also called gene-based drug targeting. Different research efforts are undertaken in disease areas in associated with disease. Mainly in cystic fibrosis and thrombosis patients. 3.C-PREDICTION AND DIAGNOSIS Individualization efforts are undertaken to: Diagnose more accurately Predicts risk of disease These efforts provide greater insight into patient’s constitution, contributing to a better diagnosis 34

35. 35 4.BASED ON EPIGENETIC AND OTHER FACTORS Epigenetic factors: such as age, sex, liver and kidney function, lifestyle , previous disease and ADR decides therapeutic response of drug Age: old age patient have high risk of ADR due to the poor rates of physiology and metabolism Gender: a level of different hormones between a male and female has been observed, which may cause different response to a drug in male and female And pregnancy and lactation affect outcome of treatment Others: environmental chemicals, drugs and natural compounds can alter the efficacy of drug by drug-drug interaction, drug-herb interaction.

36. CUSTOMISED DRUG DELIVERY SYSTEM 04 36

37. 37 CUSTOMISED drug delivery System It is a medical procedure that separates patients into different groups with medical decisions, practices, Interventions and products to the Individual patient based on their predicted response or risk of disease It is based on persons: DNA exposure to environmental factors types and amount of stress they experience what they eat

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39. 39 BIOELECTRONIC MEDICINES It is a tiny implanted device treating by changing the electronic impulse in nerves to and from specific organs. Examples: Heart pacemaker, Hepaliver, Bionic eye, cochlear limbs, Biosensor 3D PRINTING The process of making three dimensional Solid objects from a Digital file by layer to layer fabrication. Types: Inkjet printing, Direct write, Fused deposition modelling, Thermal ink and jet printing TELEPHARMACY Deliver pharmaceuticals via telecommunication. Types : Inpatient, Remote dispensing, Remote counselling

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41. BIOELECTRONIC MEDICINES Bioelectronic medicines are a tiny implanted device treating disease by changing the electronic impulses in nerves to and from specific organs Bioelectronic medicines is a new approach to treat and diagnose disease and injury. Bioelectronic medicines uses device technology to read and modulate the electrical activity with the body's nervous system, opening to real time diagnostics and treatment options for patients 41

42. HOW IT WORKS? MECHANISM 42

43. VARIOUS BIOELECTRONIC DEVICES BIOELECTRONIC DEVICES INSERTED LOCATION USES PACEMAKER HEART PACEMAKER HEART REGULATE HEART BEAT,TREAT ARRYTHMIA BRAIN PACEMAKER BRAIN TREAT PARKINSON’S AND EPILEPTIC TREMOR’S BIONIC EYE EYE RESTORE VISION DURING RETINAL BLINDNESS,ZOOMING IN AN DISTINCT OBJECT BIOSENSORS BODY TO MONITOR THE BODY TEMPERATURE COCHLEAR IMPLANTS ATTACHED TO BACKSIDE OF EAR TO HELP PROFOUNDLY DEAF WHO GET NO BENEFIT FROM HEARING AIDS 43

44. BIOELECTRONIC DEVICES INSERTED LOCATION USES BIOLUNG LUNGS EXCHANGE OF GASES HEPALIVER(HEPALIFE’S BIOREACTORS) LIVER PROVIDE CLEANSING AND FLUID BALANCE ON CONTINOUS BASIS ARTIFICIAL LIMBS LIMBS HOLDING,CONTROL, MODIFY AND MANIPULATE AS PER NEEDS 44

45. COCHLEAR IMPLANT BIONIC EYE BIOLUNG 45

46. 46 PACEMAKERS

47. ADVANTAGES DISADVANTAGES The introduction of various revolutionary technique in medicine field These Implants provides targeted treatment by controlling the neural signals going to specific organs. device would minimal/even zero side effects It will avoid or overcome the Problems faced by conventional dosage forms With merging with nanotechnology, aimed at increasing selectivity and Specificity of cellular control Customisable for each patient Better results lead people more faith in modern medical sciences costly process single part of chip damaged the total technique will be meaningless-bionic eye chances to get electrical Shock Installation of an implant may cause harm to our body 47

48. PREVIOUS YEAR QUESTIONS 06 10 MARKS Describe the concept of personalized medicine 5 MARKS Explain about pharmacogenetics Explain in brief about bioelectronic medicine 123 Definition and approaches for personalized medicines Personalized medicine The importance and applications of pharmacogenetics 48

49. 07 49 Textbook of drug delivery system by Praful P Patil, Bhushan P Gayakwad, page no:56-66 Application of personalised medicine; National institute for public heath and the environment; RIVM report 2015-0177. www.personalizedMedicineCoalition.org Textbook of personal medicine, 2 nd edition- Kewal K Jain MD Personalised Medicine unveiled – pharmacogenetic testing-www.thermofisher.com. Personalized medicine -NCBP, NIH REFERENCES

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