1. THE LINK BETWEEN ORTHODOX AND TRADITIONAL MEDICINE Obafemi .O. Johnson
ETHNOPHARMACOLOGY
THE LINK BETWEEN ORTHODOX AND TRADITIONAL MEDICINE
Obafemi .O. Johnson

2. Outline Introduction to ethnopharmacology
Objectives of ethnopharmacology
General strategies/procedures for screening and evaluation of traditional medicines
Drug screening procedures
Pharmacological screening
Toxicity studies
Clinical trials
Conclusion

3. Introduction
Ethnopharmacology constitutes the study of plant, mineral and animal substances used to affect health other than orthodox medicine.
The prefix ‘ethno’ means preventive and therapeutic modalities other than western medicine
It is concerned with seeking rationale for use of traditional medicine handed down from generation to generation.

4. The subject is mainly concerned with the observation, description and experimental investigation of biological activity and the active substance of plants and animals used in traditional medicine of past and present cultures

5. Artemisinin, an antimalarial was obtained from Quinghaoso, (Artemisia annua) a plant used for treatment of malaria in china
NIPRISAN, a drug developed by NIPRID for the management of sickle cell anaemia, was discovered from a herbal preparation in Nigeria.

6. TRADITIONAL MEDICINE
Tangible components Non tangible components

7. Tangible components
- plants, minerals and animal materials for the prevention and treatment of disease
- the practice of some surgical procedures such as circumcision, bone setting, TBA’s e.t.c.

8. non tangible components
Spiritism, incantations and rituals

9. Ethnopharmacology does not evaluate the non- tangible components of traditional medical practice

10. Western/botanical and ethnotaxonomic classifications
Ethnopharmacology is a multidisciplinary study that encompasses:
Western/botanical and ethnotaxonomic classifications
Assessments of how plants are perceived and used in varied sociocultural contexts
Constituent analyses and investigations of pharmacological activities
Examinations of the physiological or clinical impact of plant use on human health

11. Ethnopharmacology is a multidisciplinary field involving various professionals such as botanists, pharmacologists, pharmacognosists, chemists, physiologists, pathologists, toxicologists, pharmacists, medical doctors.

12. Objectives of Ethnopharmacology
To establish a realistic approach to traditional medicine so as to promote and further contribute to modern medical practice
To explore the resources of traditional medicine in the light of modern science with a view to rationalise the most effective and useful tehniques while discouraging dangerous practices

13. Objectives of Ethnopharmacology cont’d
To promote the integration of sound knowledge and experimentation techniques both in traditional and modern medicine
To encourage collaboration amongst researchers world wide in the determination of the effectiveness of plants and their medical utilization.

14. General strategies for screening and evaluation of traditional medicines
Literature Survey
Plant Selection
Plant collection and processing
Drug screening procedures

15. Literature Survey
A comprehensive literature survey must be carried out prior to any biological testing in screening of traditional medicines
Literature survey is essential to obtaining information on previous works on plants, various uses for the plants in different parts of the world, whether the plants are widespread or found in few areas, whether they are known to be toxic or not

16. Literature survey involves the browsing of scientific journals
Computerised data bases completely or partially devoted to traditional medicine are available and make literature search more effective. e.g. NAPRALERT, AFLORA, PHARMEL
AFLORA (African ethnobotany), PHARMEL (African traditional medicine)

17. Plant Selection
After thorough literature survey, the plant to investigate must be selected
Involves the decision on which material to collect and on what basis

18. Priority should be given to plants that already have evidence of safety and efficacy based on local use or published data

19. Plant selection can be based on the following: Folkloric Information
Presence of phytochemical Constituents
Combination of folkloric information and presence of phytochemical constituents
Blind random selection
Blind random selection: most likely to be followed by broad screening procedure

20. Plant collection and processing
After plant selection, botanical identity must be established and site for their procurement located. Voucher specimen must be preserved and the number given
Plant must be collected at the appropriate time and season as chemical constituents of plants vary from season to season or at different times of the day. (must be stated)
Plant collection must be done carefully to minimise adulteration

21. In Processing, drying should not be done under direct sunlight and to avoid photolysis leading degradation of active principles. Shade drying is more effective.
Crude extraction involving the use of solvents is carried out to extract the active principle. Solvents used can be polar e.g. ethanol, water or non-polar e.g. pet. ether
Extract can then be freeze dried or evaporated to dryness, wrapped in aluminium foil and properly stored

22. Drug screening procedures
The stages involved in the development of medicinal substances include:
Evaluation of literature data (screening and evaluation procedure)
Animal experiments (preclinical screening)
-pharmacological screening
-toxicological screening
Formulation studies
Clinical trials (Clinical screening)

23. Evaluation of literature data (screening and evaluation procedure)
To obtain up-to-date information on screening and evaluation methods/procedures
Gives valuable information on possible pharmacological properties (previous synthesis, SARs, previous isolation e.t.c.)
Helps to prevent duplication of previous studies on same materials

24. Pharmacological screening and evaluation procedures
Involves designing animal experiments in a manner that will yield maximum information relevant to human physiology and disease.
Proper experimental model for pharmacological screening should be based on simplicity, rapidity, reproducibility and cheapness

25. Certain factors can modify pharmacological effects in experimental animals viz:
Dose of the agent
Route of administration
Season, environmental temperature and humidity
Day and night cycle
Psychological stress influencing the animals
Health condition of laboratory animals
Age and body weight of lab. Animals
Species differences
Genetic factors
Sex differences

26. Variation from sample to sample Unexpected dose-response relationships
Some problems of pharmacological screening include:
Variation from sample to sample
Unexpected dose-response relationships
Variation within samples from the same batch of plant material
Failure to obtain positive results with an extract containing known active principles

27. Pharmacological screening and evaluation procedures
Based on physiological responses /techniques, pharmacological screening is generally classified into two viz:
-Quantitative techniques
-Qualitative techniques

28. Quantitative techniques
Mainly dose-response relationships
Mostly determined by using the increasing physiological response of an organism induced by increasing doses of a test substance
Sometimes however, it is impossible to obtain a dose-dependent response
Dose response curves give valuable information about the specificity of an effect, mechanism of action, efficacy determination
Also useful for ED50 determination

29. Qualitative techniques
Generally used for preliminary pharmacological screening
The aim is generally limited to understanding whether the agent under investigation has effect on a certain physiological system or not
Easier and less expensive than quantitative techniques

30. Phases of pharmacological screening
Primary screening
Secondary screening
Tertiary screening

31. Primary pharmacological screening
Pharmacological screening procedures are categorised into 4 depending on the objectives of the project:
Simple screen/single goal screen
Blind screen/broad based
Programmed screening
Mechanism based screens

32. Simple screen/single goal screen
Here, a pharmacological model or test are used to screen plants for a particular pharmacological activity. E.g. tests for analgesia, hypoglycemic activity
The objective here is to use suitable sufficently accurate methods rather than a battery of tests
Sometimes involves running multiple plants through the same pharmacological model
It is a useful way to screen natural products with long traditional use in a particular disease

33. Blind screen/broad based
Employs a battery of tests to cover a broad area of biological activity i.e. the extract/natural product is being investigated for various pharmacological activities
Is a technique that can be used for detecting pharmacological activity in a group of substances with no history of use
Feng & associates in 1962 utilized 7 different isolated organ preparations to screen aqeous extracts of about 55 west indian plants
Obsolete
E.g. Feng & associates in 1962 utilised different isolated organ preparations (guinea pig ileum, rat uterus, rat hindlimb, rat phrenic diaphragm, rat stomach fundus, rabbit duodenum and rabbit heart) to screen aqeous extracts of about 55 west indian plants

34. Programmed screening
Programmed screen is midway between the simple screen and blind screen
Here, a programme of testing using a battery of tests is employed but with the aim of screening is more limited than for blind screening
Greater precision in the results is expected

35. Mechanism based screens
Utilises the knowledge of molecular and biochemical basis for pathogenesis of disease
Involves choosing molecular targets for the inhibition of disease progression and natural products are screened based on these
They are becoming important bioassays for natural products due to their specificity, ability to handle very large number of samples, use of in-vitro systems

36. Secondary pharmacological screening
If promising activity has been found in primary screening, then a sizeable quantity of authenticated material is acquired and secondary screening conducted
Seeks to confirm in another specie of laboratory animals the activity noted in the primary screen
Should be standardised so as to allow comparisons with clinically useful library drugs

37. Should be conducted using either solvent free extractives or semi pure/pure chemical
This screening is carried out to support a major decision which must be given at the end of this phase {whether the plant is worth more investigating & development}

38. Tertiary pharmacological screening
Consists of :
Chemical structure determination
Classical pharmacological research
Toxicological research

39. Involves many expert (and expensive) scientists who will have to work together in a team effort
Therefoer must be carried out using only chemically pure material hence larger ammounts of authenticated crude material will be required on a regular basis until a synthetic or semi synthetic procedure can be developed
Never really ceases even after the drug is released for sale because there always remains some facet left unexplained and open for f
Expensive and time consuming

40. Follow up studies
Usually undertaken once a standardised extract or pure compound shows promising activity (i.e. after pri, sec & tert screen).
They include studies on:
-Specific pharmacological action
-General pharmacology
-pharmacokinetics

41. Toxicity Studies
Tests for the possible harmful effects of the compound.
Acute toxicity (LD50)
Sub acute toxicity {behavioural, biochemical and histological studies}
Chronic toxicity {same as above}
Teratogenicity
Mutagenicity
Carcinogenicity
Reproductive studies
Acute= usually 24 hrs if no signs of toxicity then watched up to one week
Sub acute toxicity- usually in months
Chronic toxicity not less than a year

42. Formulation
After discovery and pharmacological and toxicological studies, the new drug must be presented in a form that will be most acceptable for consumption
This is the role of the pharmacist
The pharmacokinetics of the drug must be given due consideration in the formulation

43. Clinical trials
This involves the testing of the new herbal drug in humans
Permission must be obtained from regulatory authorities i.e. the national regulatory agency such as NAFDAC, FDA and the appropriate ethics committee
An informed consent must be obtained from all participants

44. Clinical trials involve several phases viz:
Phase I (Clinical pharmacology trial)
Phase II (Exploratory clinical trial)
Phase III (Multicentric clinical trial)
Phase IV (Post marketing surveillance)

45. Clinical trials Phase 1 This is clinical pharmacology phase
Performed in healthy male volunteers
Intended to establish preliminary evaluation of safety data on pharmacodynamic effects including ADRs and initial pharmacokinetic data
Clinical, physiological, biochemical and haematological parameters are monitored by trained investigators
Double blind studies

46. Clinical trials Phase 2 Called the exploratory phase
Aimed to demonstrate activity and assess short-term safety in patients suffering from disease for which the product is intended
Makes use of limited number of patients to establish therapeutic utility, dosage schedule and possible side effects
Additional pharmacokinetic data is also generated
Study usually limited to one or two centers and patients depending on the drug

47. Clinical trials Phase 3
Called multicentric clinical trial/confirmtory trial
Should generate sufficient data about the safety and efficacy in comparison with a standard drug
Spread over several centers and covers larger and varied patient groups (about 500 patients)
Additional studies may be required in special cases such as elderly patients, hepatic, renal or cardiac complications

48. Phase 4 Called post-marketing surveillance
Performed after marketing the new product and based on the product characteristics on which market authorisation was obtained
The same scientific and ethical guidelines are used as in pre-marketing

49. Conclusion
World is going for naturals; herbal medicines/ remedies in health care to fight diseases
There are millions of plants yet unscreened
Research in ethnopharmacology by young pharmacists in the making like YOU is encouraged