Drug Invention and the Pharmaceutical Industry, Intro to Pharmacogenetics PDF

Welcome to Pharmacology! One of the major subjects in second year This is a one year subject Textbook: Goodman and Gilman’s Pharmacological Basis of Therapeutics, 13th edition (2018) Chairman: Dr. Genevieve Dable-Tupas, RN, MD, MMCE, FPPS, FPSECP  Welcome...

Welcome to Pharmacology! One of the major subjects in second year This is a one year subject Textbook: Goodman and Gilman’s Pharmacological Basis of Therapeutics, 13th edition (2018) Chairman: Dr. Genevieve Dable-Tupas, RN, MD, MMCE, FPPS, FPSECP  Welcome to Pharmacology! IMD 23A Lecture Schedule: Mondays: 1 to 2:30PM; 3 to 4:30PM Laboratory: Mondays: 5:00 to 7:00 PM Format: Case Studies (M-TBL alternate with SGD) Grading: Lecture 65%; Laboratory 35% – Lecture: 40% Quizzes; 60% Term exam  Welcome to Pharmacology! IMD 23B Lecture Schedule: Thursdays: 1 to 2:30PM; 3 to 4:30PM Laboratory: Thursdays: 5:00 to 7:00 PM Format: Case Studies (M-TBL alternate with SGD) Grading: Lecture 65%; Laboratory 35% – Lecture: 40% Quizzes; 60% Term exam Learning Outcomes for the Course Review of Physiology, Biochemistry and Pathology Understanding of Basic Principles in Pharmacology in relation to physiology, biochemistry and pathology Application of basic principles in case studies and in future real case scenarios  Pharmacology Pharmacology – from Greek φάρμακον (pharmakon) "poison" in classic Greek; "drug" in modern Greek; – and -λογία, (logia) which means "study of” or "knowledge of”; – is the branch of medicine and biology concerned with the study of drugs.  Genevieve Dable-Tupas, RN, MD, MMCE, FPPS, FPSECP Associate Professor 2 Chairman, Dept. of Pharmacology College of Medicine, Davao Medical School Foundation, Inc Director, Research and Publication, DMSFI. Introduction In the past most drugs have been discovered either by identifying the active ingredient from traditional remedies or by serendipitous discovery. But now we know diseases are controlled at molecular and physiological level. Shape of a molecule at atomic level is well understood. Information of Human Genome Drug Discovery Early Experiences with Plants to Modern Chemistry History of Drug Discovery : Pre 1919 1970s 1980s Herbal Drugs Rise of Biotechnology Commercialization of Serendiptious discoveries Use of IT Drug Discovery Combinatorial Chemistry 1920s, 30s 1960s 1990s Vitamins Breakthrough in Etiology Robotics Vaccines Automation 1940s 1950s Antibiotic Era New technology, R&D Boost due to WW2 Discovery of DNA  Target Lead Medicinal In Vitro In Vivo Clinical Selection Discovery Chemistry Studies Studies Trials and Therapeutics Cellular and Synthesis and Library Drug Affinity Animal Genetic Isolation Development and models of Targets Selectivity Disease States Genomics Combinatorial SAR Studies Cell Disease Behavioural Chemistry Models Studies Proteomics Assay In Silico MOA Functional development Screening Imaging Bioinformatics High- Chemical Lead Ex-Vivo Throughput Synthesis Candidate Studies Screening Refinement  Drug Discovery & BASIC RESEARCH Development-Timeline PRECLINICAL CLINICAL TRIALS FDA 10,000-25,000 10-20 REVIEW 1 FDA COMPOUNDS COMPOUNDS 5-10 COMPOUNDS APPROVED DRUG ~6.5 YEARS ~7 YEARS ~1.5 YEARS  Clinical trials: Set of procedures in medical research and Phase-I drug development to study the safety and efficacy of new drug. Phase-II Essential to get marketing approval from Phase-III regulatory authorities. May require up to 7 years. Phase-IV Target Selection Lead Medicinal In Vitro In Vivo Clinical Discovery Chemistry Studies Studies Trials  Phase I: First stage of testing in human subjects. Phase-I 10-100 Healthy Volunteers Open label (months to 1 yr) Phase-II Concerned With: Phase-III – Human Toxicity (Safety) – Tolerability Phase-IV Target Selection Lead Medicinal In Vitro In Vivo Clinical Discovery Chemistry Studies Studies Trials  Phase II: Controlled Clinical Evaluation. Phase-I 50-500 Participants (1-2yrs) Randomized and Controlled (can be Placebo- Phase-II controlled); maybe blinded Concerned With: Phase-III – Efficacy – Dose range Phase-IV – Drug Interaction Target Selection Lead Medicinal In Vitro In Vivo Clinical Discovery Chemistry Studies Studies Trials  Phase III: Extended Clinical Trials Phase-I Most expensive & time consuming 250-1000 Patients (3-5 yrs) Phase-II Usually:Controlled Double Blind Technique Phase-III Concerned With: – Safety, Efficacy in larger pop’n Phase-IV – Comparison with other Drugs or placebo Target Selection Lead Medicinal In Vitro In Vivo Clinical Discovery Chemistry Studies Studies Trials  Phase IV: Post Marketing Surveillance Phase-I Thousands of participants; open label Designed to detect any rare or long-term Phase-II adverse effects, compliance, drug-drug interaction Phase-III Adverse Drug Reaction Monitoring Phase-IV Pharmacovigilance Target Selection Lead Medicinal In Vitro In Vivo Clinical Discovery Chemistry Studies Studies Trials  DRUG Drug Discovery & DISCOVERY Development-Timeline PRECLINICAL CLINICAL TRIALS FDA 10,000 250 REVIEW 1 FDA COMPOUNDS COMPOUNDS 5 COMPOUNDS APPROVED DRUG ~6.5 YEARS ~7 YEARS ~1.5 YEARS Drug Development Cost Break-up R&D Function % Discovery/Basic Research Synthesis & Extraction 10.0 Biological Screening & testing 14.2 Preclinical Testing Toxicology & Safety testing 4.5 Pharmaceutical Dosage Formulation 7.3 Clinical Trials Phase I, II, III 29.1 Phase IV 11.7 Manufacturing & QC 8.3 IND & NDA 4.1 Bioavailability 1.8 Others 9.0 Total 100.0  Intellectual Property and Patents Monopoly of selling the product they have developed for a number of years 20 yrs from patent filing However drug dev’t takes 10 to 15 yrs Extension is allowed à allows drug companies 10-12yrs patent protection Implications  “Me Too vs. True Innovation” Structurally similar drug with molecular modification Eg. Ofloxacin to Levofloxacin Cetirizine to Levocetirizine Simvastatin to Atorvastatin Omeprazole to Esomeprazole Pharmacogenetics Thank You!