Scope Of Pharmacology

Dr.Ankita JireJr 1

Dept of PharmacologyGMC Nagpur

GUIDED BY DR. V. M. Motghare Professor & HeadDept Of Pharmacology

DR. Chaitali BajaitAssistant ProfessorDept Of Pharmacology

OverviewIntroductionPast-History Materia medica Pharmacy

Present-Academics Research Industries Special Domains

Future- Proteomics Pharmacogenomics & pharmacogenetics Bioinformatics NanomedicineSummary

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

Past.....History

• Rudolph Bucheim• 1st laboratory for drug research

• Investigation of drug is a task of pharmacologist

• Oswald Schmiedeberg- • Father of Modern Pharmacology

• 1st journal in Pharmacology

Materia medica• Book contaning names of herbs and medicine prepared fom it

• Dioscorides –Father of materia medica

• Methods for purifying activeagents from crude materials were absent hence real understanding of mechanism of action was absent

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

PresentUniverse of Pharmacology

Special Domai

ns

• Stages of drug development

Drug discovery phase

Preclinical phase

Clinical trial phase

Research

Drug discovery phase1.Random screening

2.Serendipity (Happy observation ,by chance)

3.Rational drug designing

4.Designing of a prodrug or active metabolite as a drug

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

• 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

Done by –1)In Vitro Study-Receptor characterization Enzyme inhibition Cytokine activity

2)In Vivo Study-Animal experiments

Clinical trial phaseSystematic study of new drug in human subjectsPhase 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

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

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 hypertensionPsoralens in vitiligo

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

Academics• Undergraduate education -Introduction to drugs

-Mechanisms of actions -Prescription writing - Pharmaceutical preparations -Identification of Adverse drug reactions

• Postgraduate education

• Basic research

• Experimental pharmacology

• pharmacokinetics - dynamics

• Pharmacovigilance

• Clinical pharmacology

• Therapeutic drug monitoring

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

Frontiers of clinical pharmacology

Clinical trialsBA/BE studies Prescription auditAntibiotic stewardshipDrug use survey

Rational use of medicinesTDM service

•BA/BE studies-Bioavailability-Helps us deciding dose

Bioequivalent: Two drugs expected to be same for all intents & purposes

•Prescription audit: To develop a list of essential drugs Rational use of drugs

•Antibiotic stewardshipA set of coordinated strategies to improve the use of antimicrobial medicationso enhancing patient health outcomes,oreducing resistance to antibiotics, o decreasing unnecessary costs.

•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

Therapeutic drug monitoring• Concept of TDM is to individualise drug dosage to

attain certain target plasma concentration• Uses:1)Drugs with low margin of saftyEX.Digoxin,Theophylline, Antidepressants, Lithium

2)If individual variations are largeEX.Antidepressants, Lithium

3)In case of Poisoning

4)To check patient complianceEX.Psychopharmacological agents

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

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

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 prescribing5.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.

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.

TrainingTo medical representatives

To physicians

Academy for Clinical Excellence (ACE)

Indian Society for Clinical Research (ICSR)

Special Domains• Pharmacovigilance

• Pharmacoeconomics

• Pharmacoepidemiology

• Chronopharmacology

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

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

.To identify, quantify and document drug-related problems

To contribute to reduce the risk of drug-related problems in healthcare systems.

To increase knowledge and understanding of factors and mechanisms which are responsible for drug-related injuries

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.

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

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 Analysis Cost Outcome

Cost Analysis- Considers costs of providing healthcare products or services

Cost Outcome-

Cost Minimization Analysis

Cost Effectiveness Analysis

Cost Benefit Analysis

Cost Utility Analysis

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

•Pharmacoeconomics is used to determine whichdrug should be included in the formulary bychoosing the most effective treatment at the lowestprice.

•It has been found that 86% of hospitalpharmacists indicate that pharmacoeconomic data isused in formulary decision-making

•Pharmacoeconomic studies consider the total costsincurred from the disease – both direct and indirectcosts

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

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

Pharmacoepidemiolo

gy

Epidemiology

ClinicalPharmac

ology

•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

Chronopharmacology• The study of how the effects of drugs vary with

biological timing and endogenous periodicities• A method used in pharmacokinetics to describe th

e diurnal changes in plasma drug concentrations.

Ex.• H2 blockers should taken in evening or early night

when acid secretion is increasing

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

Future….• Proteomics

• Pharmacogenomics and pharmacogenetics

• Bioinformatics

• Nanomedicine

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.

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.

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

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

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.

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

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.

•Current applications of nanotechnology in medicine rangefrom 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.

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

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 HealthOrganization; 2002.

• General pharmacology-Basic concepts(HL Sharma & KK Sharma)2nd edition

• Basic And Clinical Pharmacology(Katzung)12th 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

•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 athttp://www.foresight.org / Nanomedicine