Scope of pharmacology

SCOPE

1. Scope Of Pharmacology Dr.Ankita Jire Jr 1 Dept of Pharmacology GMC Nagpur GUIDED BY DR. V. M. Motghare Professor & Head Dept Of Pharmacology DR. Chaitali Bajait Assistant Professor Dept Of Pharmacology

2. Overview Introduction Past- History Materia medica Pharmacy Present- Academics Research Industries Special Domains Future- Proteomics Pharmacogenomics & pharmacogenetics Bioinformatics Nanomedicine Summary

3. Introduction Definition : “Pharmacology- study of substances that interact with living systems through chemical processes, by binding to regulatory molecules and activating or inhibiting normal body processes.” SCOPE : An area in which something Acts OR Operates OR Has power OR Control

4. Past..... History Rudolph Bucheim 1 st laboratory for drug research Investigation of drug is a task of pharmacologist Oswald Schmiedeberg - Father of Modern Pharmacology 1 st journal in Pharmacology

5. Materia medica Book contaning names of herbs and medicine prepared fom it Dioscorides –Father of materia medica Methods for purifying active agents from crude materials were absent hence real understanding of mechanism of action was absent

6. Pharmacy Science and technique of preparing and dispencing drugs Includes collection,identification,purification , isolation, synthesis, standerdization and quality control of medicinal substances Pharmacology is an essential component in the study of pharmacy

7. Present Universe of Pharmacology

8. Stages of drug development Research

9. Drug discovery phase 1.Random screening 2.Serendipity (Happy observation ,by chance) 3.Rational drug designing 4.Designing of a prodrug or active metabolite as a drug

10. Preclinical/Experimental phase AIM- To satisfy all requirements that are needed before a compound is considered fit to be tested in human Require 1.5-2 yrs Out of 10,000 compounds screened only 10 qualify for preclinical evaluation

11. Deals with effect of various pharmacological agents on different animal species Aims: Find out the therapeutic agent suitable for human use Study of toxicity of the drugs Study the mechanism and site of action of drugs

12. Done by – 1)In Vitro Study-Receptor characterization Enzyme inhibition Cytokine activity 2)In Vivo Study-Animal experiments

13. Clinical trial phase Systematic study of new drug in human subjects Phase 1 -Healthy volunteers (25-100) , Open label Determines- safe dose - pharmacokinetics - any predictable toxicity Phase 2 -patient with target disease Determine -efficacy -definitive end point A)Early phase 2- (200 patients) Single blind

14. B)Late phase 2- (200-400 patients) Double blind Phase 3- (1000-5000+) Large scale multicentre double blind To further establish safty and efficacy These 3 phses take 5-6 yrs -New drug application for licensing Phase 4- post licensing phase No fixed duration Periodic safety update report(PSUR) is to be submitted

15. REVERSE PHARMACOLOGY “ Reverse pharmacology is the science of integrating documented clinical/experimental hits, into leads by transdisciplinary exploratory studies and further developing these into drug candidates by experimental and clinical research.” EXAMPLES OF REVERSE PHARMACOLOGY Rauwolfia alkaloids in hypertension Psoralens in vitiligo

16. Concept of reverse pharmacology It relates routine ‘Lab to clinic’ progress of discovery to ‘Clinic to lab’. Conventional molecule mice man Reverse pharmacology man mice molecule In the process, safty remains most important starting point and efficacy becomes matter of validation

17. Academics Undergraduate education -Introduction to drugs -Mechanisms of actions -Prescription writing - Pharmaceutical preparations -Identification of Adverse drug reactions

18. Postgraduate education Basic research Experimental pharmacology pharmacokinetics - dynamics Pharmacovigilance Clinical pharmacology Therapeutic drug monitoring

19. Term coined by Harry Gold in 1950s Basic science of pharmacology: application of pharmacological principles and methods in the real world Makes pharmacology more attractive by bridging basic science and clinical science Platform for collaborative efforts between academia and pharmaceutical industry. Clinical Pharmacology

20. Frontiers of clinical pharmacology Clinical trials BA/BE studies Prescription audit Antibiotic stewardship Drug use survey Rational use of medicines TDM service

21. BA/BE studies- Bioavailability- Helps us deciding dose Bioequivalent: Two drugs expected to be same for all intents & purposes Prescription audit: T o develop a list of essential drugs Rational use of drugs Antibiotic stewardship A set of coordinated strategies to improve the use of antimicrobial medications enhancing patient health outcomes, reducing resistance to antibiotics, decreasing unnecessary costs .

22. Drug use survey Study of the marketing, distribution, prescription and use of drugs in a society with special emphasis on the resulting medical, social and economic consequences.“ Rational Use Of Medicines -Appropriate indication -STEP Criteria i.e. Safety,Tolerability,Efficacy,Price -Correct dispensing and appropriate instructions to patient -Adequate monitoring of patients adherence to the treatment -Watch for adverse effects of drugs

23. Therapeutic drug monitoring Concept of TDM is to individualise drug dosage to attain certain target plasma concentration Uses: 1)Drugs with low margin of safty EX.Digoxin,Theophylline , Antidepressants, Lithium 2)If individual variations are large EX.Antidepressants , Lithium 3)In case of Poisoning 4)To check patient compliance EX.Psychopharmacological agents

24. Clinical Pharmacology: Making Its Heartbeats Felt By this time the busy clinicians have started understanding the different approach of a clinical pharmacologist in answering several drug and therapeutics related questions. The need for generating local treatment guidelines had long been realized by our fellow clinicians. The first such guideline, which was generated in the institute by WHO ;For the management of community-acquired pneumonia, clinical pharmacologists were invited as a part of the team of experts

25. Industries Research: New Drug Development Medical advisor Medical transcription Medico marketing Product management Contract research organization Training

26. Medical Advisor 1.The analysis of the health of populations. 2. The evaluation of primary care services. 3. Planning of services. 4. Advice on effective prescribing 5.Education for general practitioners . Medical transcription The process of transcription or converting voice-recorded reports as dictated by physicians and/or other healthcare professionals, into text format .

27. Medico-marketing   Business of advertising or otherwise promoting the sale of pharmaceuticals or drugs Contract research organization(CRO) A service organization that provides support to the pharmaceutical and biotechnology industries in the form of outsourced pharmaceutical research services (for both drugs and medical devices). CROs specifically provide clinical-study and clinical-trial support for drugs and/or medical devices.

28. Training To medical representatives To physicians Academy for Clinical Excellence (ACE) Indian Society for Clinical Research (ICSR)

29. Special Domains Pharmacovigilance Pharmacoeconomics Pharmacoepidemiology Chronopharmacology

30. Pharmacovigilance Pharmacovigilance ( Pharmakon -Drug; Vigilare -To keep watch) Definition (WHO) - ‘the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other possible drug related problems’. Adverse drug reactions (ADRs) were 4th most common cause of death in US in 1997

31. The role of pharmacovigilance can be divided into three main areas: .

32. Pharmacovigilance Programme of India ( PvPI )  WHO established its Programme for International Drug Monitoring in response to the thalidomide disaster detected in 1961. Uppsala andWHO together promotes Pharmacovigilance at the country level. At the end of 2010, 134 countries were part of the WHO Pharmacovigilance Programme. The programme is coordinated by The Indian Pharmacopoeia Commission (IPC) located at Ghaziabad.

33. ADR reporting through Vigiflow Vigiflow is web based Individual Case Safty Report(ICSR) management system that is specially designed for use by national centres in the WHO programme for International drug monitoring Vigiflow 5.1(Released on 14 june 2013) Subscription for vigiflow is free in India

34. Pharmacoeconomics Pharmacoeconomics is a branch of health economics which particularly focuses upon the costs and benefits of drug therapy It is an innovative method that aims to decrease health expenditures, while optimising healthcare results. Involves two major methodologies Cost Analys i s Cost Outcome

35. Cost Analysis- Considers costs of providing healthcare products or services Cost Outcome-

36. Pharmacoeconomic methods are used to assist physicians, hospitals, insurers, patients and healthcare professionals in making important decisions as to what drug therapies should be chosen

37. Pharmacoeconomics is used to determine which drug should be included in the formulary by choosing the most effective treatment at the lowest price. It has been found that 86% of hospital pharmacists indicate that pharmacoeconomic data is used in formulary decision-making Pharmacoeconomic studies consider the total costs incurred from the disease – both direct and indirect costs

38. Pharmacoepidemiology Study of drugs among people Pharmacon = Drugs Epi = amongs Demos = people Logous = study Pharmacoepidemiology is study of use and effects of drugs in large no. of persons

39. Pharmacoepidemiology is the application of epidemiologic reasoning ,methods , and Knowledge to the study of uses and effects of drugs in human population

40. Pharmacoepidemiology Involves: Causality and incidence of ADRs Effectiveness of new drugs in defined population Pattern of prescribing in a particular health care facility area Strategies to improve prescribing Economic impact of drug use

41. Chronopharmacology The study of how the effects of drugs vary with biological timing and endogenous periodicities A method used in pharmacokinetics to describe the  diurnal changes in plasma drug concentrations. Ex. H2 blockers should taken in evening or early night when acid secretion is increasing

42. Glucocorticoids Major adverse effect — adrenocortical supression Significantly attenuated if correctly timed to circadian rhythms. Best tolerated when ingested as a single daily dose in the morning at start of the daily activity span Moderate dose in evening between dinner and bedtime , risk of adrenocortical suppression is heightened, even after a few days of treatment

43. Future…. Proteomics Pharmacogenomics and pharmacogenetics Bioinformatics Nanomedicine

44. Proteomics Proteomics is the large-scale study of proteins, particularly their structures and functions Proteomics is the study of the proteome—the “ PROTEin complement of the genOME Disease mechanism or drug effects both affect a protein profile and, vice versa , characterising protein profiles reveals information for the understanding of disease and therapy.

45. Proteomics In Disease Treatment Many human diseases are caused by a normal protein being modified improperly. This also can only be detected in the proteome, not the genome. The targets of almost all medical drugs are proteins. By identifying these proteins, proteomics aids the progress in disease treatment.

46. Pharmacogenomics and pharmacogenetics Pharmacogenomics is use of genetic information to guide the choice of drug and dose ;on an individual basis Analysis and comparison of the entire genome of a single species or of multiple species A genome is the set of all genes possessed by an organism Pharmacogenetics is study of genetic basis for variability in drug response

47. Role of pharmacogenomics In new drug discovery In clincal trial Reintroduction of withdrawn or failure compound Identification of responder and nonresponder In maximizing efficacy In minimizing adverse drug reactions

48. Future of pharmacogenetics Genetic/genomic interindividual variability may lead to genotype-specific development of new drugs Once adequate genotype/phenotype studies have been conducted, molecular diagnostic tests will be developed that detect >95% of the important genetic variants for the majority of polymorphisms Genetic tests have the advantage that they need only be conducted once during an individual’s lifetime.

49. Bioinformatics Bioinformatics is the unified discipline formed from the combination of biology, computer science, and information technology The mathematical, statistical and computing methods that aim to solve biological problems using DNA and amino acid sequences and related information The primary goal of bioinformatics is to increase the understanding of biological processes

50. Nanomedicine Nanomedicine is defined as the monitoring,repair , construction and control human biological systems at the molecular level using engineered nanodevices and nanostructures Nanomedicine offers delivery of potential drugs which were previously beyond reach of microscale drugs due to specific biological barriers.

51. Current applications of nanotechnology in medicine range from research involving diagnostic devices and drug delivery vehicles to robots that can enter the body and perform specific tasks. Nanopharmacology - Drug design and drug delivery to selected targets to improve pharmacodynamics and kinetic profiles toward safer and effective treatment Nanomedicine offers delivery of potential drugs which were previously beyond reach of microscale drugs due to specific biological barriers.

52. Summary Pharmacology is backbone of medicine For rational use of drugs in day to day clinical practice knowledge of pharmacology becomes essential It has wide scope in Research,Academics,Industries which opens us doors for opportunities in career development With technology development,it is going to be more advanced in future for tretment of patients

53. References Kshirsagar N, Kumar V. Clinical pharmacology: Prospects and development in India. Indian J Pharmacol 2011;43:489-91 . Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998;279: 1200-5. The importance of pharmacovigilance . Geneva: World Health Organization; 2002. General pharmacology-Basic concepts(HL Sharma & KK Sharma)2 nd edition Basic And Clinical Pharmacology( Katzung )12 th edition A report by, Dr Albert I Wertheimer and Nicole Chaney Founding Director and Director of Research, Center for Pharmaceutical Health Services Research, Temple University

54. Reverse Pharmacology And Registratiion Of Ayurvedic Drugs – by Ashok D.B. Vaidya , Research Director, Kasturba Health Society, ICMR Advanced Centre of Reverse Pharmacology. Robert Freitas , Nanomedicine 2, 1999, available at http://www.foresight.org / Nanomedicine