TRADITIONAL DRUGS TRADITIONAL DRUGS AND HERBAL MEDICINESAND HERBAL MEDICINES

(PHYTOTHERAPY)(PHYTOTHERAPY)

Kuswinarti and Muchtan SujatnoKuswinarti and Muchtan Sujatno

Department of Pharmacology & Department of Pharmacology & TherapyTherapy

Medical School , Padjadjaran Medical School , Padjadjaran UniversityUniversity

History :1. Chinese Traditional Medicine Oriental

Traditional

Medicine

2. Ayurvedic Traditional Medicine from Ayurveda (India)

3. Western Herbal Medicine

4. 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

INTRODUCTIONINTRODUCTIONDEFINITION :DEFINITION :

Traditional Drugs Traditional Drugs Herbal MedicineHerbal MedicineTOGATOGA PhytopharmacaPhytopharmaca

Herbal preparations : Herbal preparations :

Simplicia, Infusion, decoct, etc.Simplicia, Infusion, decoct, etc.

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. PhytopharmacaSomeone 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.

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 jamuJAMU

Direction to use : Traditionally used for relieving headache

Dosage : 1 eatspoon in a glass of boiled water

LOGO

Direction for use

non pharmacological terminology

STANDARDIZED HERBAL MEDICINEHerbal 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

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

TOGA TOGA Tanaman Obat KeluarGA Tanaman Obat KeluarGAGarden plantsGarden plantsSimple preparationsSimple preparationsCan be found and planted at homeCan be found and planted at homeFirst aid before going to hospital First aid before going to hospital

JAMU / HERBAL MEDICINE :JAMU / HERBAL MEDICINE :Used by EmpiricalUsed by EmpiricalSimple preparations Simple preparations Named by traditional terminology : tolak Named by traditional terminology : tolak

angin, pegel linu, galian singset, lancar angin, pegel linu, galian singset, lancar haid, gempur batu etc.haid, gempur batu etc.

PHYTOPHARMACAPHYTOPHARMACAused in formal health facilitiesused in formal health facilities

StandardizedStandardized Clinical trial Clinical trial Efficacy and safety (+)Efficacy and safety (+) Ruled by Health Ministry : 1995 SP3TRuled by Health Ministry : 1995 SP3T Direction for use by pharmacological Direction for use by pharmacological

terminology : analgesic, diuretic, terminology : analgesic, diuretic, antipyretic, etcantipyretic, etc

= modern drugs / orthodox medicine= modern drugs / orthodox medicine Preparations : capsule, tablets, ointment, Preparations : capsule, tablets, ointment,

etcetc Modern packagingModern packaging 5 phytopharmaca have to be confessed by 5 phytopharmaca have to be confessed by

BPOM : BPOM : Nodia, Rheumaneer, Stimuno, Nodia, Rheumaneer, Stimuno, Tensigard Agromed and X-graTensigard Agromed and X-gra

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.

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

HERBAL MEDICINES HERBAL MEDICINES (PHYTOTHERAPY)(PHYTOTHERAPY)

May have pharmacological actions May have pharmacological actions which affect the patientwhich affect the patient

Not all herbal medicines are free Not all herbal medicines are free from adverse effectsfrom adverse effects

May interact with orthodox May interact with orthodox medicines if they are taken medicines if they are taken concurrentlyconcurrently

In the West In the West Food Supplement Food Supplement

ADVERSE EFFECTS & EFFICACYADVERSE EFFECTS & EFFICACY OF OTI/TM OF OTI/TM

Adverse effects : rarely, but be carefulAdverse effects : rarely, but be careful SEES (Side effects Eliminating SEES (Side effects Eliminating

Substances)Substances) Secondary Efficacy Enhancing Secondary Efficacy Enhancing

Substances Substances

PREPARATION OF AN ORAL DOSAGE PREPARATION OF AN ORAL DOSAGE FORMFORM

LIQUIDLIQUIDMedicinal teaMedicinal teaInfusionInfusionDecoctionDecoction

SOLIDSOLIDTabletsTabletsPillsPillsPowderPowder

HERBAL MEDICINE HERBAL MEDICINE BE ORTHODOX BE ORTHODOX MEDICINE/MODERN DRUGMEDICINE/MODERN DRUG

ALKALOIDS of PlantsALKALOIDS of Plants

The name of the plant Active substanceThe name of the plant Active substance

-------------------------------------------------------------------------------------------------------- Rauwolfia serpentina Rauwolfia serpentina Reserpine (HBP)Reserpine (HBP) Ephedra sp Ephedra sp Ephedrine (Asthma)Ephedrine (Asthma) Atropa belladonna Atropa belladonna Atropine, scopolamine Atropine, scopolamine Pilocarpus jaborandi Pilocarpus jaborandi Pilocarpine Pilocarpine Vinca rosea Vinca rosea Vincristine, vinblastine Vincristine, vinblastine

(antiviral drugs)(antiviral drugs)

ADVERSE EFFECTS OF HERBAL ADVERSE EFFECTS OF HERBAL DRUGSDRUGS

Liver cell necrosis has been reported Liver cell necrosis has been reported caused by herbal tea from comfrey caused by herbal tea from comfrey leaves (leaves (Symphytum officinaleSymphytum officinale))

General rule of simplisiaGeneral rule of simplisia tested for tested for microbiological microbiological quality and quality and

for for

residues of pesticidesresidues of pesticides and and fumigation fumigation

agents, toxic metals, likely contaminant agents, toxic metals, likely contaminant and and

adulterants, etc adulterants, etc

POTENTIAL CONTAMINANTSPOTENTIAL CONTAMINANTS

Type of contaminantsType of contaminants ExamplesExamples____________________________________________________________________________________________________________BotanicalsBotanicals Atropa belladonna, digitalis, Rauwolfia Atropa belladonna, digitalis, Rauwolfia serpentinaserpentinaMicro-organismMicro-organism Staph. aureus, E. coli, Salmonella, Staph. aureus, E. coli, Salmonella,

Shigella,Shigella, Psudomonas aeroginosaPsudomonas aeroginosa

Microbial toxinsMicrobial toxins Bacterial endotoxins, aflatoxins Bacterial endotoxins, aflatoxinsPesticides & fumigants agentsPesticides & fumigants agentsMetalsMetals Lead, Cadmium, mercury, arsenic Lead, Cadmium, mercury, arsenicSynthetic drugsSynthetic drugs Analgesic and antiinflammatory agents Analgesic and antiinflammatory agents

(aminophenazone, phenylbutazone, (aminophenazone, phenylbutazone, indomethacin ), corticosteroids, HCT, indomethacin ), corticosteroids, HCT,

diazepamdiazepamAnimals drugsAnimals drugs Thyroid hormones Thyroid hormones

Quality specifications of plant Quality specifications of plant materials and preparationsmaterials and preparations

Information for fresh, dried and processed Information for fresh, dried and processed plant materialsplant materials Name and characteristicsName and characteristics

Latin, native languages, EnglishLatin, native languages, EnglishPart of the plant used and its conditionPart of the plant used and its condition (Root, leaf, flower, fruit, tuber, seed etc)(Root, leaf, flower, fruit, tuber, seed etc)A brief description of the distribution and habitatA brief description of the distribution and habitatQuality specificationsQuality specificationsAuthenticityAuthenticityPurityPurityAssayAssay

Packaging, labeling and storagePackaging, labeling and storage

Drug dosage form for Drug dosage form for medicinal preparations of plant medicinal preparations of plant

materialsmaterials

Powdered plants materials Powdered plants materials traditional traditional powders and pills powders and pills

Extracts Extracts tablets, granules, ointments tablets, granules, ointments and newer types of pills and newer types of pills

Purified extracts/pure active Purified extracts/pure active constituents isolated from the plants constituents isolated from the plants material material injections injections

(phytopharmaca)(phytopharmaca)

PHARMACODYNAMIC AND GENERAL PHARMACODYNAMIC AND GENERAL PHARMACOLOGICAL STUDIES OF HERBAL PHARMACOLOGICAL STUDIES OF HERBAL

MEDICINESMEDICINES

Various pharmacological effectsVarious pharmacological effects AnimalsAnimals

Species : mice, rats, guinea pigs, rabbits, dogs, etcSpecies : mice, rats, guinea pigs, rabbits, dogs, etc Characteristics of the animals : strain, sex, age, holding Characteristics of the animals : strain, sex, age, holding

conditionsconditions Disease models : chemicals & other modalitiesDisease models : chemicals & other modalities Test assays can use : whole animals, isolated Test assays can use : whole animals, isolated

organs/tissue, etcorgans/tissue, etc AdministrationAdministration

Route 0f administration : PO (clinic)Route 0f administration : PO (clinic) Frequency of administration Frequency of administration Control group : Control group :

Negative (vehicle only)Negative (vehicle only) Positive ( modern drugs ) Positive ( modern drugs )

Toxicity investigation of herbal Toxicity investigation of herbal medicinesmedicines

Acute toxicity testAcute toxicity test Animals species : at least two species (rodents & non Animals species : at least two species (rodents & non

rodents) rodents) Sex : males & femalesSex : males & females Number of animals : rodents Number of animals : rodents 5 animals/sex 5 animals/sex

non rodents non rodents 2 animals/sex 2 animals/sex Route of administration= PORoute of administration= PO Dose levels : rodents Dose levels : rodents LD ; non rodents LD ; non rodents toxic signs toxic signs Frequency of administration : one or more doses /24 Frequency of administration : one or more doses /24

hour periodhour period Observation : toxic signs & severity, onset, progression, Observation : toxic signs & severity, onset, progression,

reversibility of the signs ; at least 7-14 dayreversibility of the signs ; at least 7-14 day

Long term toxicity testLong term toxicity test Animal speciesAnimal species

At least two species (rodent & non rodent)At least two species (rodent & non rodent) SexSex

The same number of male and femaleThe same number of male and female Number of animalsNumber of animals

Rodents : at least 10/sexRodents : at least 10/sex Non rodents : at least 3/sexNon rodents : at least 3/sex

Route of administrationRoute of administration The expected clinical route of administrationThe expected clinical route of administration

Adm. PeriodAdm. Period The expected period of clinical useThe expected period of clinical use

Dose levelsDose levels At least 3 different dose levelsAt least 3 different dose levels

Observations and examinationObservations and examination General signs, body weight , food & water intakeGeneral signs, body weight , food & water intake Hematological examinationHematological examination Renal & hepatic function testsRenal & hepatic function tests

Recovery from toxicityRecovery from toxicity

Expected period of clinical use Adm. period Expected period of clinical use Adm. period for the for the

toxicity studytoxicity study----------------------------------------------------------------------------------------------------------------------------------------------------Single adm. or repeated adm. for lessSingle adm. or repeated adm. for less 2 weeks to 1 month 2 weeks to 1 monththan one weekthan one week

Repeated adm., between 1 to 4 weeks 4 weeks to 3 Repeated adm., between 1 to 4 weeks 4 weeks to 3 monthsmonths

Repeated adm, between 1 to 6 monthsRepeated adm, between 1 to 6 months 3 to 6 3 to 6 monthsmonths

Long-term repeated adm. for moreLong-term repeated adm. for more 9 to 12 months 9 to 12 monthsthan 6 monthsthan 6 months

Local toxicity test & special toxicity Local toxicity test & special toxicity teststests

Local toxicity testsLocal toxicity testsSkin sensitization testSkin sensitization test

Special toxicity testsSpecial toxicity testsMutagenicity testMutagenicity testCarcinogenicity testCarcinogenicity testReproductive and development toxicity Reproductive and development toxicity

testtest

ADULTERATION OF COMMERCIAL ADULTERATION OF COMMERCIAL PRODUCTSPRODUCTS

= Mix certain substance into jamu = Mix certain substance into jamu decrease quality and may be harmfuldecrease quality and may be harmful

Replaced by an equivalent related Replaced by an equivalent related speciesspecies

To add modern drugs in the herbal To add modern drugs in the herbal medicinemedicine

Careless gathering, storage, or Careless gathering, storage, or distribution of medical plant materialdistribution of medical plant material

ADULTERATION OF ASIAN HERBAL MEDICINES WITH ADULTERATION OF ASIAN HERBAL MEDICINES WITH SYNTHETIC DRUG SUBSTANCESSYNTHETIC DRUG SUBSTANCES

ReferenceReference Preparations Preparations Chemical and clinical details Chemical and clinical details

--------------------------------------------------------------------------------------------------------------------------------------Itdehaag et alItdehaag et al -Chuifong Toukuwan-Chuifong Toukuwan One patient developedOne patient developed(1979) (Hongkong) (1979) (Hongkong) Cushing’s syndrome from Cushing’s syndrome from 12 pills/day12 pills/day

The pills contained dexa-The pills contained dexa- methasone, indomethacin,methasone, indomethacin, HCT, diazepamHCT, diazepam

Tay and Johns-Tay and Johns- -Dr.Tong Shap Yee’s-Dr.Tong Shap Yee’s TheophyllineTheophylline 12 mg12 mgton (1989)ton (1989) asthma pills asthma pillsBury et alBury et al -Powder : colds and-Powder : colds and One patient gained weightOne patient gained weight(1987)(1987) fluflu and became moonfaceand became moonface

Contained prednisolone +Contained prednisolone +paracetamolparacetamol

INTERACTIONS BETWEEN HERBAL MEDICINES AND INTERACTIONS BETWEEN HERBAL MEDICINES AND DRUGS USED IN ORTHODOX MEDICINEDRUGS USED IN ORTHODOX MEDICINE

Herbal preparation Orthodox medicineHerbal preparation Orthodox medicine Interaction Interaction---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Sedatives :Sedatives :

Sedative prep. Alcohol/antihistamines,hypnotics PotentiationSedative prep. Alcohol/antihistamines,hypnotics Potentiation Tropane alkaloids Alcohol/antihistamines,hypnotics Potentiation Tropane alkaloids Alcohol/antihistamines,hypnotics Potentiation

Endocrine :Endocrine : Antidiabetic prep. Antidiabetic agents, insulinAntidiabetic prep. Antidiabetic agents, insulin Loss of Loss of

diabetic contr.diabetic contr. Guar gumGuar gum Penicillin Penicillin Reduced Reduced

bioav.of abbioav.of ab Rauwolfia, ginseng Drugs causing gynaecomastia, Potentiation of Rauwolfia, ginseng Drugs causing gynaecomastia, Potentiation of

gynae.gynae. phenothiazine comastia, phenothiazine comastia,

galactorrhea galactorrhea Antidepressant :Antidepressant :

GinsengGinseng Phenelzine Phenelzine Headaches, Headaches, insomnia,insomnia,

visual hallucinationsvisual hallucinations

TERIMAKASIHPandanglah masalah dengan

mata hatimu

Bukan sekedar memandang dengan mata di kepalamu