E. Yeşilada 1

ADVERSE EFFECTS AND

DRUG INTERACTIONS WITH HERBAL MEDICINES

AND SCIENTIFIC EVALUATION OF

TOXICITY REPORTS ON HMPs

EACH PLANT IS A MIXTURE OF DOZENS OF COMPONENTS

EACH MOLECULE MAY HAVE THERAPEUTICAL or TOXIC or POISONOUS

effectExpressions like

“HERBALS ARE SAFE ??? or

THEY ARE NATURAL THEN NOT TOXIC??? “

are illogical E. Yeşilada 2

Paracelsus (16.century)

“Difference between the therapeutic and poisonous effects of a particular compound is

dose”

E. Yeşilada 3

(WHO)

Adverse effects of drugs:

“Unwanted or toxic effect observed against a drug when administered in

NORMAL DOSAGE for diagnostic purposes, prophylactic or treatment

of diseases or to change a physiological response in human”

4E. Yeşilada

Double-blind clinical studies revealed that;“even through placebo drug administration a wide-range of unwanted/adverse effects may be observed”

In 1228 healthy volunteers, percentages of advers effects after placebo drug administration; Single dose administration; 19% Older ages single dose administration; 26% Repeated administration increased the rate to 28%

Reported advers effects; headache (7%), lethargy (5%) ve anxiety (4%) etc.

Rates may be subjected to change depending on the population and designation of the study

5E. Yeşilada

NOCEBO (negative placebo) EFFECT

Sources of/ Factors inducing

Risks in HMPs

6E. Yeşilada

Due to the ingredients

with toxic effect,

high concentration of plant ingredients with

potent activity,

Falcification/Adulteration:

Addition of wrong plant materials

Intended/Unintended,

Undeclared addition of synthetic active

chemicals to strenghten the activity, 7E. Yeşilada

I. Risks due to insufficient Quality and Standardization of drugs

Contamination with toxic materials;

Environmental wastes,

Heavy metals,

Agricultural agents; pesticides, fumigants,

veterinary drugs etc.,

Microbiological contamination,

8E. Yeşilada

I. Risks due to insufficient Quality and Standardization in drugs

Wrong pharmaceutical formulation design;

Inappropriate excipients selection etc.

Wrong procedures in the preparation of

HMP:

Insufficient denaturation of toxic

ingredients,

Extraction of toxic components

9E. Yeşilada

I. Risks due to insufficient Quality and Standardization in drugs

E. Yeşilada 10

Administration in high doses,

Long-term administration,

Due to a metabolic/physiological

deficiency of the patient,

Due to personal sensitivity or

idiosyncratic reactions,

i.e., allergy, irritation etc.

II. Risks due to individual factors or sensibility

E. Yeşilada 11

Age-dependent increased risks,

Interactions with concurrent therapy,

Delayed risks;

carcinogenity/mutagenity/teratogenity etc.,

II. Risks due to personal factors or sensibility

Commercial competitionSlanderous claims

12E. Yeşilada

III. Fake studies or False interpretation

Multivitamin researchers say "case is closed" after studies find no health benefits

13E. Yeşilada

E. Yeşilada 14

E. Yeşilada 15

Are Vitamins realy

ineffective?

December 2013: CBS News:

16E. Yeşilada

Hypothetical suggestions or warnings are postulated based on the composition of the HMP in some sources were quoted to other documents without notifying as hypothetical, and may be accepted as if it is real by others

17E. Yeşilada

IV. Theoretical/hypothetic adverse effect/toxicity

1. Adverse effects or toxicity due to the high concentration of plant ingredients with potent physiological activity or with toxic effect

18E. Yeşilada

Plants/ingredients with powerful physiological activity; - May have a unique physiological/ therapeutical

effect in very low doses,- In higher doses may be dangerous or fatal;

-Atropine etc. alkaloids [Nightshade-Atropa sp., Henbane-Hyoscyamus sp.],

-Cardioactive components, i.e. digitoxine [Foxglove-Digitalis sp.]

Plant/parts containing toxic components should not be used in phytotherapy:

19E. Yeşilada

A. Direct application may be toxic/ poisonous:

B. Some plant components may have adverse/toxic effect:

Care should be given in Excessive usages Long term applications High concentrations/doses

E. Yeşilada 20

1. Pyrazolidine alkaloids:Hepatic veno-occlusive (HVO) diseaseOcclusion of the centrolobular veins of the

liver,Clinical symptoms in human:

abdominal pain, Water-arrest in abdomen, hepatomegaly,Increase in serum transaminases: AST,

ALT

21E. Yeşilada

E. Yeşilada 22

Plants with Pyrazolidine derivatives are

prohibited/restricted to be used in formulations

Coltfoots; öksürükotu

(Tussilago farfarae)

Senecio sp., kanarya otu, liferootSenecio scandens (unsaturated

pyrazolidine alkaloids) In Traditional Chinese Medicine (Qianbai Biyan Pian); prohibited by EMEA

E. Yeşilada 23

2. Furanocoumarins:

In: Apiaceae (Parsley, celery), Rutaceae (Bergamot, Orange family), Moraceae (mulberry and Fabaceae (beans)

Powerful phototoxic activity; psoralen, bergapten

24E. Yeşilada

In volatile oils; Bergamot essence is used in perfumes

as fixative for a long-lasting scent,Volatile oil contains bergapten, a

furanocoumarin,Due to the phototoxic property,

increase the sensitivity of skin to sunlight and induce dispersed stains on the skin, in fact burns,

This essence was used in some sun-cosmetics for rapid tanning; may induce skin cancer

25E. YeşiladaFuranocoumarins

Sweden; after large amount consumption of

CELERY soup a woman sunbathed under UV-light in a Beauty Center suffered from severe burns.

U.K.; after taken large amount of a soup

containing celery, parsley and wild carrot the patient was subjected to oral photochemotherapy [PUVA; psoralen and UV-A] suffered from severe burns

26E. Yeşilada

Furanocoumarins

Furanocoumarins

Large amount of kantaron (St.John’s wort) consumption may yield photodermatitis only in calves;

Not any report has been found in human

E. Yeşilada 27

St.John’s wort is used in phytotherapy as an effective antidepressant medicine

Individual factors influencing the toxic effect

risks

28E. Yeşilada

29E. Yeşilada

Contact dermatitis; eugenol, L-carvone‘ (mint oil) are

the ingredients of toothpaste may induce inflammatory lips in sensitive people,

Volatile oil ingredients:

Respiratory irritation; We smell the nice fragrance in cosmetics/

lotions/perfumes/soaps etc. without any harmful effect

In Aromatherapists and similar professions continuous /repeated inhalation/exposure may develop intolerence/allergic reactions

30E. Yeşilada

Volatile oil ingredients

Apiol: [in Parsley/maydonoz volatile oil] • Abortifacient• hepatocarcinogenity: in large amounts and

long-term

“It is very rare to see such toxicities with spices when it is consumed in rational quantities”

E. Yeşilada 31

Volatile oil ingredients: in Spices

Camphre/kafur; internally; hepatotoxicity and CNS damage,on skin; neurotoxicity

Ointments with camphre (Vicks, etc.) induced hepatotoxicity when applied to the skin of a 2-month old baby in order to reduce the symptoms of catarhh, however, the symptoms recovered as soon as stop application

32E. Yeşilada

Volatile oil ingredients

Ma Huang (ephedrine) from Ephedra sinicaBronchodilatator in asthma and similar

symptoms (as doping in sports)OTC: Also is used in formulations to loose-

weight or to increase energy in x60 times higher doses.

December 2003: FDA (Federal Drug Administration) prohibited the use of Ephedrin formulations in USA due to the remarkable adrenergic activity; particularly the symptoms of acute hepatit, halucinations and paranoia. 33E. Yeşilada

Alkaloids

Anthrasen derivatives laxatives (i.e., aloe, senna/sinameki, cascara, rheum/ravent)

Used as laxative/purgative in pharmacotherapy (Pursenid®, Bekunis®, Senecod®, Roha®)

Long-term application (over 10 days) increase the risk developping colorectal cancer,

34E. Yeşilada

Kernels/seeds of many edible fruits [apricot/kayısı, bitter almond/acı badem, cherry/kiraz, sour cherry/vişne, peach/şeftali, pear/armut, prune/erik, apple/elma etc. ]contain cyanogenetic glycosides,

35E. Yeşilada

Cyanogenetic glycosides

Cyanogenetic glycosides:

Cyanogentic glycosides are used in food as flavour, in therapy as sedative (2-4 gtt).

Hydrolysed in the stomach to yield HCN (cyanhydric acid) and absorbed readily from the upper gastro-intestinal system and may induce sudden death due to respiratory collapse (suffocation),

Average 50 mg oral HCN or equivalents; 50-60 apricot kernel in adults or 8-10 in children may induce death.

In southeast Anatolia apricot kernels are used as snack after roasted on fire in a pan or in oven until dark color to cleave the toxic principles

36E. Yeşilada

Licorice/Meyan;

Licorice extract from roots has been used widespread as beverage “Meyan Şerbeti” in south Anatolia since centuries.

Licorice extract/saponins are precious drug components with a wide range of therapeutic effects: antiulcer, antiviral, anti-inflammatory, antihepatotoxic, etc.

Have also been added to formulations to increase bioavailability.

Long-term application in high doses induced edema and hypertension in cardiac insufficient patients due to the enzyme inactivation in liver,

Due to the inactivation of enzyme metabolizing the endogenous ACTH secreted from the upper- kidney glands, ACTH accumulated in the body and induced edema and then induced hypertension in-turn.

37E. Yeşilada

38E. Yeşilada

2. Adverse or toxic effects due to falcification or incorrect plant specimen

Botanic identitiy of the plant be problematic with self-controlled plants.

Botanic identitiy of the plant may even be problematic in the prepackaged commercially available materials or formulations

39E. Yeşilada

“Gordolobo” (Verbascum thapsus) case:

Latin Americans use the yellow flowers against cough in children as a safe remedy,

In USA, a Mexican-originated American bought “Gordolobo” from a local Mexican market

The material was obtained from a wrong plant “Senecio longilobus” which is known to possess toxic pyrazolidine alkaloids,

Death was reported due to HVO in the baby.

40E. Yeşilada

Real Ginseng: roots of [Panax ginseng & P. notoginseng];

Effect: increase stamina, physical performance, boost immune system, regulates CNS, regulates metabolism (diabetes, etc.), adaptogen

41E. Yeşilada

Falcification;

- Mandrake (Mandragora

officinarum) or Rauwolfia roots,

contain alkaloids: toxic

- Siberian Ginseng

(Eleuterococcus senticosus), roots;

Possess a completely different

chemical composition,; lignans

Used as adaptogenic, weaker

activity then Ginseng,

In longer administration reported

to induce hypertension, and not

suggested for hypertensives,

42E. Yeşilada

1993: Brussel Patients from a “Chinese Slimming Clinic” applied to “Immergency Centers” in hospitals after using a Chinese slimming formulation with the complaints of;Gradually increasing nonspecific fibrosis,

tubular atrophy And related kidney disturbances

43E. Yeşilada

Among 2000 woman were administered the formulation 100> nephropathy80> connected to dializing unit /or subjected to kidney transplantation

44E. Yeşilada

In TCM drug plants having the same Chinese name were used ;“Ma Tong”;Clematis sp., Stephania tetrandra, Cocculus sp. Akebia sp.’stems and Aristolochia manshuriensis

“Fang-ji”; Stephania tetrandra, Cocculus sp. and Aristolochia fangchi roots 45E. Yeşilada

In the formulation instead of Stephania tetrandra; Aristolochia fangchi or Aristolochia manschuinsis were used.

Aristolochia sp.; contains aristolochic acidNephrotoxic,

carcinogenic and mutagenic

E. Yeşilada 46

(2001) France: 7 nephropathy reports U.K.: 2 severe renal insufficiencyChina: 17 cases and 12 deathJapan: 10 renal failure

47E. Yeşilada

3. Wrong processing applied for the preparation of remedy

Adverse/toxic effect may be shown;Due to the wrong extraction procedures

excessive amount of toxic principle might be extracted,

Due to insufficient denaturation of toxic ingredients.

E. Yeşilada 48

“Burçak”(Vicia sp.) (müdürmük) seed:hypoglycaemic remedy is used

frequently by the diabetics,Contains vasoconstructor proteins,Excess amounts/longer applications may induce

symptoms of having the feeling of pins and needles in limbs, even may lead to gangrene,

Seeds should be roasted for a while before use for denaturation the toxic proteins in a pan on fire.

49E. Yeşilada

Lack of information regarding the preparation of remedy

Soy beans, reddish-colored bean etc. contain toxic lectins, phytohemaglutinins, and

tripsine inhibitors. To remove these components is advised to be boiled

at least 30 min in water before cooking and discard the boiled water.

50E. Yeşilada

Toxic components in foods

Potato tubers With the effect of direct sunlight may be

turned to green in color indicating that poisonous alkaloids (solanin etc.) are synthetised.

These alkaloids have vasocontructor activity, excess amounts may lead to gangreneous symptoms.

Green potatoes should not be used as foodShoots and surrounding parts should be

scraped off/removed before using as food 51E. Yeşilada

Toxic components in foods

52E. Yeşilada

4. Due to insufficient quality control parameters practised in the preparation of formulation or Lack of Standardization

In Hong Kong in a market survey on 14 OTC Ginkgo biloba preparations the level of potential allergenic principle ”ginkgolic acid” was investigated:

In only 1 preparation was found within the limits suggested by WHO,

In 13 prep. Limits were found 16-733 times higher then suggested by WHO.

E. Yeşilada 53

These types of contaminations are observed in drugs uncontrolled by official authorities:

Unintentional: environmental contamination, During the processing; i.e., extraction incopper caldrons,

etc. Intentional:

In order to increase acute physiological response undeclared prescription drugs with potent activity may be added,

In Eastern Traditional Medicines, i.e., Ayurveda, TCM, heavy metals or certain toxins may be intentionaly added as a part of the treatment

54E. Yeşilada

5. Intentional/Unintentional mixing with Heavy metals/toxic elements and/or synthetic drugs

Ginseng Improves the physical capacity and other

physiological effects only after 15 to 20 days of administration;

To provide rapid acute response Caffeine containing extracts [Cola extr., Guarana, Green Tea extr.] or pure caffeine etc. stimulant drugs may be added without any notification on label .

Caffeine intoxication may be observed In longer applications or higher doses In hypertensive and related CV patients:

Hypertension Gastritic & complaints Nervousness: Agitations, Sleep disturbances,

insomnia

55E. Yeşilada

To potentiate the physiological response;

TCM or Ayurvedic formulations may contain as a part of treatment; o Arsenic disulfas (realgar), o mercury chloride (calomel), o mercury sulfas (cinnabaris), o red mercury oxide (hydrargyri

oxydum rubrum) etc.

56E. Yeşilada

Intentional addition of Heavy Metals as a part of treatment

In at least (32%) were found to

possess undeclared

Active constituents; i.e., ephedrine,

chlorpheniramine, phenacetine,

methyltestosterone, etc.) or

Heavy metals;i.e., lead, arsenic, mercury

etc.

57E. Yeşilada

Asian Drugs Imported to USA/Canada/U.K. were examined

In Singapour [1990-1997]; 42 TCM formulations contains high levels of heavy metals,32 prep. 19 different synthetic active drug agents;

berberine, antihistaminics (chlorpheniramine, promethacine, ciproheptadine),NSAIDs (diclofenac, indomethacin, ibuprofen), analgesics-antipyretics (paracetamol, dipyrone), corticosteroids (prednisolone, dexamethasone, fluocinonid), symphatomimetics (ephedrine), broncodilators (teophylline), diuretics (hydrochlorthiazides), antidiabetics (phenphormine) etc.

58E. Yeşilada

In Turkey (2007 - )Slimming formulations

Contains “sibutramin” 3x higher than suggested dose.

Not notified on the label.

59E. Yeşilada

Microbiologic, Insect, Pesticide, Fumigant, Environmental waste, Heavy metals, Radiation etc. lar.

60E. Yeşilada

6. Contamination of plant material

In Pharmacopeias plant materials may contain <102-104 g/CFU aerobic bacteria/ fungi;Infection rate may increase depending upon

the;• Incorrect cultivation/growing conditions, • Wrong harvesting, i.e., in rainy weathers • Inconvenient processing • Inconvenient storage conditions• Composition of the material, i.e., starch,

etc.

CFU: colony forming unit

61E. Yeşilada

Microbiologic Contamination:

E. Yeşilada 62

Dangerous contaminants in HMPs: NOT ALLOWEDPatogenic organisms;

Enterobacter, Enterococcus, Clostridium, Pseudomonas, Shigella, Streptococcus vd.’

Endotoxins and mycotoxins:

Aspergillus flavus; aflatoxins No limit in European Pharmacopeia x10 times difference in Europe and USA

Pesticides:To protect crop from pests;

* Cultivars or * Materials collected nearby to cultivation area;

- Chlorinated hydrocarbons; DDT etc., - Organophosphates, - Carbamates, - Polychlorinated biphenyls, etc.

63E. Yeşilada

LIMIT

S

SHOULD B

E

TESTED

Fumigants:To protect the processed plant material

phosphin, 1,3-dichloropropene, chloropicrin, methyl isocyanate, hydrogen cyanide, sulfuryl fluoride, formaldehyde, iodoform etc.

- Due to the suspected carcinogenic effect of ethylene oxide is forbidden in Europe,

Methyl bromide is restricted due to ozon depleting effect by Montreal Convention.

- Should be controlled for imported products,

64E. Yeşilada

LIMIT

S

SHOULD BE

TESTED

Contamination with Environmental Pollutants/wastes :

Heavy metals: - lead, cadmium, mercury, tallium and

arsenic etc.

Radioactive wastes;

65E. Yeşilada

LIMITS

SHOULD BE

TESTED

DRUG INTERACTIONS

66E. Yeşilada

7. Interaction with the treatment/ concurrent drugs/ and/or food regime of the patient

1. Inhibitory effects on drug metabolizing enzymes

May influence on the enzyme profile of the liver/intestines

Potentiate the effects of drugs metabolized by those isoenzymes,

Creating the potential for an increased risk of side effects; silymarin, licorice, etc.

67E. Yeşilada

Influence on drug metabolism

Grapefruit juice, furanocoumarins Inhibitory effect on Cytochrome p450 3A4 in

the intestinal wall Leading to decreased first-pass metabolism and

increased bioavailability. Metabolism of drugs metabolized through 3A4

enzyme is slowed down Due to the reduced metabolism rate, the rate of

unmetabolised drug absorption increased May induce adverse effect/toxicity E.g. Statins

68E. Yeşilada

Inhibitory effects on drug metabolizing enzymes may potentiate the effect of

pharmacotherapy

2. Upregulation of drug metabolizing enzymes:Accelerate the metabolism rate

and speed of certain drugs, Plasma level of drug has rapidly reduced and

may lead to therapeutic failure; MAY BE DANGEROUS IN PATIENTS NEED

CONTINUOUS MEDICATION, i.e., St.John’s wort

Organ transplantation; In order to prevent organ rejection

immunosupressants like cyclosporine must NOT be used in the rest of the patients’ life,

Reduced level of immunosupressants agent in plasma may lead to organ rejection 69E. Yeşilada

Influence on drug metabolism

Potentiazation in serotonergic effects may be observed concurrent use of Serotonin reuptake-inhibitors (SRI), [centralin, paroxetine etc.]

Concurrent use of MAOI (phenelsine) may induce headache, tremor and mania

70E. Yeşilada

Digoxin should be continuously provided in certain level in the plasma of cardiac patients,

Due to P-glycoprotein induction effect of St.John’s wort, plasma level of digoxin may not be ensured

71E. Yeşilada

3. P-glycoprotein Induction may reduce the intestinal drug absorption

E. Yeşilada 72

Drug name Effect Results of interaction Possible mechanism

Cyclosporine Immuno-suppresant

Decrease in plazma concentration of drug; organ rejection

P-glycoprotein induction

Ethynyl estradiol/Desogestrel

Oral contraseptive

Bleeding Hepatic enzyme induction

Teophylline Antiasthmatic Decrease in plazma concentration of drug

Hepatic enzyme induction

Phenprocoumone

Anticoagulant

Decrease in plazma concentration of drug Decrease in anticoagulant activity

Hepatic enzyme induction

Warfarin Hepatic enzyme induction

Amitriptiline Antidepressant Decrease in plazma concentration of drug

Hepatic enzyme induction

Indinavir Antiviral (AIDS)

Decrease in plazma concentration of drug

Hepatic enzyme inductionP-glycoprotein induction

Digoxine Cardiotonic Decrease in plazma concentration of drug

P-glycoprotein induction

NephazodonSertralineParoxetine

Antidepressant Serotonin syndrome Synergistic SRI inhibition

Effect on GI absorption rate: Impairment of renal excretion,Displacement from plasma protein binding sites,

Competition for receptor sites, resulting in interference with the pharmacological

response.

73E. Yeşilada

Other potential sites of drug interactions;

Synergistic effect:

Prolonged blood coagulation time

(Prothrombine time)

In patients receiving oral anticoagulant therapy (OACT)/antiplatelet agents, due to the narrow therapeutic range interference may lead to a medical emercency 74E. Yeşilada

Plants containing compounds with

coumarin-like activity prolong the coagulation time in higher doses/long term administrations

Concurrent use of agents of Anticoagulants; Warfarin/ NSAIDs/ with plants with antiplatelet activity, i.e., Ginseng, Ginkgo, Garlic, horse chestnut, etc. should be avoided

75E. Yeşilada

Synergistic effect

Hypoglycaemic shock

Plants with Hypoglycaemic activity may potentiate the effect of hypoglycaemic agents;i.e., Ginseng or Garlic, with

glibenclamide or insulin

76E. Yeşilada

Synergistic effect

Concurrent use of plants with known Hypertansive effect, i.e., Siberian Ginseng, or licorice would have a negative effect on the antihypertansive pharmacotherapy

77E. Yeşilada

Antagonistic Effect:

Long term or high dose administration of

herbal diuretics;May increase the diuretic

pharmacotherapy and affect hypotansive/hypertansive treatment

Due to loss of potassium, effect of cardioactive drugs (digoxin etc.) may be potentiated

78E. Yeşilada

Hypokalemia may potentiate the effect of Cardioactive drugs

Antracen derivatives of laxatives, in long term administration;May induce reduction in serum

potassium level,Potentiate the effect of cardiotonic

glycosides (Digoxine, Lanatoside etc.) and antiarythmic agents.

79E. Yeşilada

Hypokalemia may potentiate the effect of Cardioactive drugs

Pre-, Peri- and Post-operative interactions:

May induce severe complications

Even death

80E. Yeşilada

Interactions with surgical operations

Myocardial infarction, Stroke, Paralysis Increase bleeding risk, Insufficient coagulation, Increase in Anesthesia period, Insufficient anesthesia, Interactions with drugs administered

during operation,Tissue rejection in Organ transportions,

81E. Yeşilada

Due to interaction with cyclosporine and St.John’s wort (kantaron); acute tissue rejection in 2 heart transplantation cases

Concurrent administration of Valerian and kava-kava (CNS sedative), with drugs effective on CNS may increase the anesthesia period in surgical operations;

SHOULD BE STOPPED AT LEAST ONE WEEK PRİOR TO SURGICAL OPERATIONS

82E. Yeşilada

Physiologic discomfort/disease,

Genetics, Metabolism rate, Sensitivity, Age, Nutrition, Durability.

83E. Yeşilada

8. Individual factors;

Immune insufficiency patients;

AIDS , tuberculosis, lupus, MS, ALD, leucosis, collagen disease, etc.;

Immune-stimulating HMP may induce deterioration in arhtritis etc. complications due to excessive stimulation of autoimmune system

84E. Yeşilada

Since elimination rates of certain compounds may be affected may lead to severity in symptoms.

85E. Yeşilada

Impaired functions in Kidney/Hepatic;

Oral applications: Sudden Type I hypersensibility reactions;

rhinitis, headache, dermatitis, anaphylactic shock,

Topic applications; Type IV contact dermatitis,

86E. Yeşilada

Allergic /idiosyncratic reactions:

Asteraceae (Daisy family) plants frequent cause of allergic reactions due to sesquiterpene lactones in sensitive people;

- Echinacea prep.: Popular and safe immunostimulants against COLD (Chronic Obtructive Lung Diseases) 2 anaphylaxis were reported in Australia,

-Feverfew: Effective in migrain pain May stimulate pain in allergic individuals

E. Yeşilada 87

9. HMPs during pregnancy and/or nursing

Not allowed to use any Herbal remedy during pregnancy and/or nursing, due to low number of randomized studies and lack of scientific data

E. Yeşilada 88

Possible interactionsTeratogenic, Embryocidal,Carcinogenic, Abortifacient, and other possible adverse effects etc.

89E. Yeşilada

E. Yeşilada 90

Abortive etffect:

Feverfew (Tanacetum parthenium) stimulate menstration, during pregnancy may induce abortion depending on dose

1. Since it is rare to have any information on the effects of an herbal agent on the fetus, their use during pregnancy should be avoided.

2. Little is known about the transfer of active principles in mother’s milk for most herbs, so their use in nursing mothers should be avoided.

3. In the absence of specific knowledge of herbals interactions with prescription medications, concomitant use should be discouraged or monitored closely.

4. Except for agents with known estrogenic or androgenic properties, little is known about the effects of most herbs on fertility.

91E. Yeşilada

The precautionary principles

5. Oral anticoagulant therapy has always been a corcern regarding drug-drug interactions and this is also true regarding herb-drug interactions. Concomitant use of most herbs should be avoided.

6. Generally there is little known about the effects of continued use over long periods of time. A periodic “resting period” is probably a good idea, but how frequently this should occur, and how long it should be, are a matter of pure speculation given the lack of pharmacokinetic data most cases.

7. There is some corcern about the possibility that herbal medicines may create undue risk in the peri-operative period. Withdrawal 7-10 days prior to surgery may be advisable for most herbs, but in some cases, for example Valerian, a gradual reduction in dosage may be necessary.

8. Children generally are not good candidates for herbal therapy. They may have greaer relative exposure, less well-developed biotransforming enzymes, a higher rate of cell division, making them more vulnerable to mutagenesis.

92E. Yeşilada

Many of the adverse effect and toxicity reports are due to Insufficient standardizationScanty controlFalcificationHigh-dose applicationsLong term administrationIndividual factors; sensitivity, function

disorders

93E. Yeşilada

Conclusion remarks