TRADITIONAL DRUGS AND HERBAL MEDICINES (PHYTOTHERAPY)

1. TRADITIONAL DRUGS AND HERBAL MEDICINES(PHYTOTHERAPY) Kuswinarti and Muchtan Sujatno Department of Pharmacology & Therapy Medical School , Padjadjaran University

2. History : • Chinese Traditional Medicine  Oriental Traditional • Medicine • Ayurvedic Traditional Medicine from Ayurveda (India) • Western Herbal Medicine • Others : Egypt, Indonesia • 25% of prescribed drugs in America at least one active substance is plant origin • Herbal medicine and CAM (Complementary and Alternative Medicine) used by 42% of American peoples • Users in Indonesia increase • ------------- Development of Herbal Medicine

3. INTRODUCTION • DEFINITION : • Traditional Drugs • Herbal Medicine • TOGA • Phytopharmaca • Herbal preparations : Simplicia, Infusion, decoct, etc.

4. Jamu is a herbal preparation, an Indonesian traditional medicine (Obat Tradisional Indonesia – OTI) Departemen Kesehatan RI divided jamu into 3 cathegories : 1. Jamu 2. Standardized herbal medicine 3. Phytopharmaca Someone was ill. He took a natural substances then he felt better and healed. That substances could be taken from plants, animal, minerals. This herbal medicine is made by dukun, someone or by a special team in a kingdom.

5. Traditional Medicine are substances or preparation consist of plants, minerals, animal, galenic (sari tumbuhan) or mix of those all substances that used from the ancient to heal the illness base on experiences (empiric). These experiences are passed on from old generation to the next generation (turun temurun) Jamu  Home made and industrial product Jamu that produced by manufacture has to give label JAMU in every jamu package and give a special logo of jamu Direction for use  non pharmacological terminology JAMU Direction to use : Traditionally used for relieving headache Dosage : 1 eatspoon in a glass of boiled water LOGO

6. STANDARDIZED HERBAL MEDICINE Herbal medicine can be made from same type of plant, but it found from different area, so the effect is also different  standard simplicia : A. From plant that grow in same area with same treatment and same drying procedure B.PLUS preclinical trial to find the special effect and the safety C. PRODUCED by fulfill the criteria of CARA PEMBUATAN OBAT TRADITIONAL YANG BAIK (CPOTB) A – B – C  STANDARDIZED HERBAL MEDICINE

7. Standardized Herbal Medicine has a special LOGO In BPOM (Badan Pengawasan Obat dan Makanan)- FDA of Indonesia there are 17 SHB : Diabmeneer, Diapet, Fitogaster, Fitolac, Glucogard, Hi-stimuno, Irex-max, Kiranti pegal linu, kiranti sehat datang bulan etc. Obat Herbal terstandar Have a special LOGO Used for increase, decrease, speed up, subside………… The user compliance is better caused by certainty of effect and safety of the medicine LOGO

8. TOGA  Tanaman Obat KeluarGA • Garden plants • Simple preparations • Can be found and planted at home • First aid before going to hospital • JAMU / HERBAL MEDICINE : • Used by Empirical • Simple preparations • Named by traditional terminology : tolak angin, pegel linu, galian singset, lancar haid, gempur batu etc.

9. PHYTOPHARMACAused in formal health facilities • Standardized • Clinical trial • Efficacy and safety (+) • Ruled by Health Ministry : 1995 SP3T • Direction for use by pharmacological terminology : analgesic, diuretic, antipyretic, etc • = modern drugs / orthodox medicine • Preparations : capsule, tablets, ointment, etc • Modern packaging 5 phytopharmaca have to be confessed by BPOM : Nodia, Rheumaneer, Stimuno, Tensigard Agromed and X-gra

10. PACKAGE of PHYTOPHARMACA LOGO PHYTOPHARMACA Indication : Hypertension Dysfunction of erection Immunomodulator, etc. Dosage : 1 tablet in the morning 1 capsule 3 times a day etc.

11. Phytopharmaca are available in formal health care system : hospital or public heath service. It can be prescribed by doctors (Allium sativum L for hypercholesterolemia). It has precaution for person who can directly consumed this drug such as : Only for patient with hypertension that established by doctor If side effect occurred, stop medication and contact the doctor

12. HERBAL MEDICINES (PHYTOTHERAPY) • May have pharmacological actions which affect the patient • Not all herbal medicines are free from adverse effects • May interact with orthodox medicines if they are taken concurrently • In the West  Food Supplement

13. ADVERSE EFFECTS & EFFICACY OF OTI/TM • Adverse effects : rarely, but be careful • SEES (Side effects Eliminating Substances) • Secondary Efficacy Enhancing Substances

14. PREPARATION OF AN ORAL DOSAGE FORM • LIQUID • Medicinal tea • Infusion • Decoction • SOLID • Tablets • Pills • Powder

15. HERBAL MEDICINE BE ORTHODOX MEDICINE/MODERN DRUG ALKALOIDS of Plants The name of the plant Active substance ---------------------------------------------------- • Rauwolfia serpentina  Reserpine (HBP) • Ephedra sp  Ephedrine (Asthma) • Atropa belladonna  Atropine, scopolamine • Pilocarpus jaborandi  Pilocarpine • Vinca rosea  Vincristine, vinblastine (antiviral drugs)

16. ADVERSE EFFECTS OF HERBAL DRUGS Liver cell necrosis has been reported caused by herbal tea from comfrey leaves (Symphytum officinale) • General rule of simplisia tested for microbiological quality and for residues of pesticides and fumigation agents, toxic metals, likely contaminant and adulterants, etc

17. POTENTIAL CONTAMINANTS Type of contaminants Examples ______________________________________________________ Botanicals Atropa belladonna, digitalis, Rauwolfia serpentina Micro-organism Staph. aureus, E. coli, Salmonella, Shigella, Psudomonas aeroginosa Microbial toxins Bacterial endotoxins, aflatoxins Pesticides & fumigants agents Metals Lead, Cadmium, mercury, arsenic Synthetic drugs Analgesic and antiinflammatory agents (aminophenazone, phenylbutazone, indomethacin ), corticosteroids, HCT, diazepam Animals drugs Thyroid hormones

18. Quality specifications of plant materials and preparations • Information for fresh, dried and processed plant materials • Name and characteristics • Latin, native languages, English • Part of the plant used and its condition (Root, leaf, flower, fruit, tuber, seed etc) • A brief description of the distribution and habitat Quality specifications • Authenticity • Purity • Assay • Packaging, labeling and storage

19. Drug dosage form for medicinal preparations of plant materials • Powdered plants materials  traditional powders and pills • Extracts  tablets, granules, ointments and newer types of pills • Purified extracts/pure active constituents isolated from the plants material  injections (phytopharmaca)

20. PHARMACODYNAMIC AND GENERAL PHARMACOLOGICAL STUDIES OF HERBAL MEDICINES • Various pharmacological effects • Animals • Species : mice, rats, guinea pigs, rabbits, dogs, etc Characteristics of the animals : strain, sex, age, holding conditions • Disease models : chemicals & other modalities • Test assays can use : whole animals, isolated organs/tissue, etc • Administration • Route 0f administration : PO (clinic) • Frequency of administration • Control group : • Negative (vehicle only) • Positive ( modern drugs )

21. Toxicity investigation of herbal medicines • Acute toxicity test • Animals species : at least two species (rodents & non rodents) • Sex : males & females • Number of animals : rodents  5 animals/sex non rodents  2 animals/sex • Route of administration= PO • Dose levels : rodents  LD ; non rodents  toxic signs • Frequency of administration : one or more doses /24 hour period • Observation : toxic signs & severity, onset, progression, reversibility of the signs ; at least 7-14 day

22. Long term toxicity test • Animal species • At least two species (rodent & non rodent) • Sex • The same number of male and female • Number of animals • Rodents : at least 10/sex • Non rodents : at least 3/sex • Route of administration • The expected clinical route of administration • Adm. Period • The expected period of clinical use • Dose levels • At least 3 different dose levels • Observations and examination • General signs, body weight , food & water intake • Hematological examination • Renal & hepatic function tests • Recovery from toxicity

23. Expected period of clinical use Adm. period for the toxicity study -------------------------------------------------------------------------- Single adm. or repeated adm. for less 2 weeks to 1 month than one week Repeated adm., between 1 to 4 weeks 4 weeks to 3 months Repeated adm, between 1 to 6 months 3 to 6 months Long-term repeated adm. for more 9 to 12 months than 6 months

24. Local toxicity test & special toxicity tests • Local toxicity tests • Skin sensitization test • Special toxicity tests • Mutagenicity test • Carcinogenicity test • Reproductive and development toxicity test

25. ADULTERATION OF COMMERCIAL PRODUCTS = Mix certain substance into jamu  decrease quality and may be harmful • Replaced by an equivalent related species • To add modern drugs in the herbal medicine • Careless gathering, storage, or distribution of medical plant material

26. ADULTERATION OF ASIAN HERBAL MEDICINES WITH SYNTHETIC DRUG SUBSTANCES Reference Preparations Chemical and clinical details ------------------------------------------------------------------- Itdehaag et al -Chuifong Toukuwan One patient developed (1979) (Hongkong) Cushing’s syndrome from 12 pills/day The pills contained dexa- methasone, indomethacin, HCT, diazepam Tay and Johns- -Dr.Tong Shap Yee’s Theophylline 12 mg ton (1989) asthma pills Bury et al -Powder : colds and One patient gained weight • flu and became moonface Contained prednisolone + paracetamol

27. INTERACTIONS BETWEEN HERBAL MEDICINES AND DRUGS USED IN ORTHODOX MEDICINE Herbal preparation Orthodox medicine Interaction ----------------------------------------------------------------------------------------------------------- • Sedatives : • Sedative prep. Alcohol/antihistamines,hypnotics Potentiation Tropane alkaloids Alcohol/antihistamines,hypnotics Potentiation • Endocrine : • Antidiabetic prep. Antidiabetic agents, insulin Loss of diabetic contr. • Guar gum Penicillin Reduced bioav.of ab Rauwolfia, ginseng Drugs causing gynaecomastia, Potentiation of gynae. phenothiazine comastia, galactorrhea • Antidepressant : • Ginseng Phenelzine Headaches, insomnia, visual hallucinations

28. TERIMAKASIH Pandanglah masalah dengan mata hatimu Bukan sekedar memandang dengan mata di kepalamu