introduction to practical pharmacology, various experimental animal uses, CPCSEA guidelines, different phases of clinical trial, pre-clinical trial, important pharmacological definition

1. Introduction to Practical
Pharmacology
Dr. Likith HV (JR – I; Presenter)
Dr. Abhijeet Joshi (Presentation supervisor)

2. Table of Contents
 Definitions
 Metrology
 New drug Discovery
 Animals used in experimental pharmacology
 Different phases of Clinical trial

3. Pharmacology
o Derived from pharmacon (an active principle) and logos (a
discourse)
o It is the science that deals with drugs
o Objective : To provide a scientific data to choose a drug treatment of
proven efficacy and safety .

4. Some important definitions
 Pharmacokinetics: Study of absorption,distribution,metabolism and
excretion of drugs and their relationship to pharmacological response.
(What does the body do to the drugs?)
 Pharmacodynamics: Quantitative study of effects of the drugs. (What
does the drug do to the body? )
 Efficacy: The maximum response that can be elicited by the drug
 Therapeutic dose : The amount of the drug required to effect the cure
of a disease or to correct the manifestations of a deficiency of a
particular factor in the diet

5. The practical aspects of pharmacology can be considered
under
 Pharmacy
 Experimental Pharmacology
 Clinical Pharmacology

6. Pharmacy
 The science of Identification
 selection
 preservation
 standardisation
 compounding and dispensing of medicine for easy, effective and palatable
administration.

7. Clinical Pharmacy
 The science of drug formulations
 their stability
 shelf life
 handling and also education of the patient about the compliance

8. 1 Teaspoon ?????

9. Metrology
 The scientific study of measurements
 Prescription orders should always be written in the metric system (In mg
or ml)
 For convenience domestic measures like teaspoon, table spoon is used –
Domestic System
 Weight – kilogram
Capacity- litres

10. 1 Kilogram 1000 g
1 gram 1000 mg
1 milligram 1000 µg
1 microgram 1000 ng
1 litre 1000 ml
1 cup 5-6 ounces
1 glass 8 ounces
1 wine glass 2 ounces
65 ml 4 dessert spoon
30 ml 2 table spoons
0.05 ml 1 drop
4 ml 1 teaspoon
1 Ounce = 29.57 ml

11. Weight/Weight
Weight/Volume
Volume/Volume
?
1% w/w – 1 gram of solute in 100gm of solution
1% w/v – 1 gram of solute in 100 ml of solution
1% v/v – 1 ml of solute in 100 ml of solution

12. Experimental Pharmacology
 Science that deals with the study of drugs in experimental animals
or on cell cultures .
 Objective : To study the pharmacological profile of a drug including
its kinetics, dynamics and mechanism of actions .
 The animals used are Rat, Mouse, Rabbits and Guinea pigs .

13. New Drug Development
NEW DRUG : A new substance of chemical ,biological or
biotechnological origin for which adequate data need to be
generated and submitted to the regulatory authority in
order to judge the efficacy and safety for the proposed
claim.

14. Drug Discovery
 Insilco Trail
 Pre Clinical Trail
 Clinical Trail

15. Insilco Trial
 AIM : To discover a lead compound
 Approach : Target approach (i.e. finding a suitable compound to the target )
 Here it involves computer based molecular modelling of compounds and can
produce a compound that best fit the receptor.
Structure of the target Drug library structure of many compounds
Screening of compounds
(Throughput Screening)
Hit compound Lead Compound

16.  Hit Compound : A molecule with confirmed structure, confirmed activity in
primary throughput screening
 Lead : A hit series with proven structure activity relationship.
Lead compound
Approval from Ethics Committee
Pre clinical trial /Animal trial

17. Pre clinical trial
 Done on Animals
 Guidelines : Animal ethical guidelines
 The trial should be done in 2 species of animals
 Objectives : Pharmacokinetics
Pharmacodynamics
Toxicity – Side effects, Carcinogenic potential (2Years)
teratogenicity (acc to gestational period)
Efficacy
Mutagenicity – Can’t be obtained from animal study.
Obtained from micro-organism, AMES Test

18. Animals used in experimental pharmacology
RAT
o Weight : 200 gms
o Used to develop various models simulating human
diseases(Liver diseases, diabetes and gastric ulcer
o To test various psychopharmacological agents
o Study of analgesics and anti-convulsants
o Used for toxicity studies

19. Mice
o Weight : 25gms
o USED:
Toxicological studies
Teratogenicity studies
Drugs acting on CNS
Studies related to genetics and cancer research

20. Rabbits
o Weight : 1.5 – 2.5 kg
o USED :
Pyrogen testing
Drugs used in glaucoma
Study on miotic and mydriatic
Studies related to anti-fertility agents

21. Guinea Pig
o Weight : 350 - 400 gms
o Its physiology is most close to human physiology
o Highly susceptible to TB and anaphylaxis
o USED : Test the drugs of asthma
Anaphylactic and immunological studies
Study of histamine and anti-histamines
Evaluation of local anaesthetic

22. CPCSEA
 Committee for the Purpose of Control and Supervision on
Experiments on Animals
 Goal : To promote the humane care of animals used in biomedical
and behavioural research and testing with the basic objective of
providing specifications that will enhance animal wellbeing, quality
in the pursuit of advancement of biological knowledge that is
relevant to humans and animals.

23. Handling and care of animals
 Handled in such a way that it should not be subjected to pain
 While lifting , it should be held firmly from the base of the tail and
not the tip
 While feeding the neck should be held firmly
 The animal racks should be cleaned on regular basis
 Rats should not be kept more than 5 per cage
 Experimental animals should be taken care like humans and not like
animals

25. Prior to any clinical evaluation should obtain clear answers
to the important questions
 Is there any need for a new drug under consideration ?
 What is the probable risk involved in giving the drug to humans?
Is it worth the risk ?
 Are the data from animal studies adequate ?
 Does the new drug seem promising ?

26. Clinical trials
 Done on humans after a successful pre clinical trial
 Conducted by clinical pharmacologists
 After pre clinical trial success IND application to DCGI (Drug Controller
General of India), New Delhi
 Needs to be approved by the regulatory authority (DCGI) and Institutional
Clinical Ethics Committee (IEC)
 Guidelines : GCP guidelines (Good clinical practices)
 Prior Informed Consent of both, volunteers and patients is mandatory
 Phases : Phase 1
Phase 2
Phase 3
Phase 4

27. Phase 0 studies
 Sample size : very small , 10 – 15
 Sub therapeutic micro doses of the drug are administered for approximately
a week and pharmacokinetic properties are assessed
 Advantages : Cost saving
increases the efficiency of the drug development
programme

28. Phase 1 clinical trial
 Done on normal healthy volunteers
 Sample size : It is kept low ,10 – 100
 Objectives : Determine the safety and tolerability
Pharmacodynamics and pharmacokinetics
 Its an open label study
 Exceptions : For toxic drugs like anticancer/ immunosuppressant drugs

29. Phase 2 clinical trial
 Done on Patients
 Sample size : 50 – 500
 1 st time the lead compound is given to the patient
 It is a single blinded study i.e. only patient is blind
 Objectives : To determine the dose regimen & dose – response relationship
To explore the efficacy
 Maximum drug failure occurs in this phase .

30. Phase 3 Trial
 Multicentric trial
 Sample size : >1000
 Objective: To cross check the value of Phase2 trial àka cross checking trial
 It’s a double blinded study
After Phase 3 Trial
New Drug Application (NDA)
(Permission to launch the drug in the market)

31. Phase 4 Clinical trials
(Post marketing surveillance)
 Done to assure the efficacy and the safety of the drugs
 Reporting can be done by any person
 Helps in early detection of ADR’s and also in recognition of
unanticipated additional benefits which result in additional,
secondary uses for drugs

35. Examination point of view(Spotters/Viva)
 What is Pharmacy?
 Which are the various experimental animals used for experimental
pharmacology ?
 Write 2 uses of rat/rabbits/mouse/guinea pig ?
 What is metrology ?
 What are the different phases of clinical trial ?

36. Thank you