Transcript ADVERSE EFFECTS AND DRUG INTERACTIONS WITH HERBAL MEDICINES AND SCIENTIFIC EVALUATION OF TOXICITY REPORTS ON HMPs E.

ADVERSE EFFECTS
AND
DRUG INTERACTIONS
WITH HERBAL MEDICINES
AND
SCIENTIFIC EVALUATION OF
TOXICITY REPORTS ON HMPs
E. Yeşilada
1
 EACH PLANT IS A MIXTURE OF DOZENS OF
COMPONENTS
 EACH MOLECULE MAY HAVE
 THERAPEUTICAL or


TOXIC or
POISONOUS
effect
Expressions 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 ”
E. Yeşilada
4
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
E. Yeşilada
5
E. Yeşilada
6
 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,
E. Yeşilada
7
 Contamination with toxic materials;
 Environmental wastes,
 Heavy metals,
 Agricultural agents; pesticides, fumigants,
veterinary drugs etc.,
 Microbiological contamination,
E. Yeşilada
8
 Wrong pharmaceutical formulation design;
 Inappropriate excipients selection etc.
 Wrong procedures in the preparation of HMP:
 Insufficient denaturation of toxic ingredients,
 Extraction of toxic components
E. Yeşilada
9
II. Risks due to individual factors or
sensibility
 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.
E. Yeşilada
10
II. Risks due to personal factors or sensibility
 Age-dependent increased risks,
 Interactions with concurrent therapy,
 Delayed risks;
 carcinogenity/mutagenity/teratogenity etc.,
E. Yeşilada
11
 Commercial competition
 Slanderous claims
E. Yeşilada
12
 Multivitamin researchers say "case is closed" after
studies find no health benefits
E. Yeşilada
13
E. Yeşilada
14
Are Vitamins
realy
ineffective?
E. Yeşilada
15
 December 2013:
CBS News:
E. Yeşilada
16
 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
E. Yeşilada
17
E. Yeşilada
18
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., HenbaneHyoscyamus sp.],
-Cardioactive components, i.e. digitoxine [Foxglove-Digitalis sp.]
 Plant/parts containing toxic components
should not be used in phytotherapy:
E. Yeşilada
19
Care should be given in

Excessive usages

Long term applications

High concentrations/doses
E. Yeşilada
20
1. Pyrazolidine alkaloids:
 Hepatic veno-occlusive (HVO) disease
 Occlusion of the centrolobular veins of the liver,
 Clinical symptoms in human:
 abdominal pain,
 Water-arrest in abdomen,
 hepatomegaly,
 Increase in serum transaminases: AST, ALT
E. Yeşilada
21
Plants with Pyrazolidine
derivatives are
prohibited/restricted to be used
in formulations
Coltfoots;
öksürükotu
(Tussilago farfarae)
E. Yeşilada
22
 Senecio sp., kanarya otu, liferoot
 Senecio 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
E. Yeşilada
24
 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
E. Yeşilada
Furanocoumarins
25
 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
E. Yeşilada
26
 Large amount of kantaron
(St.John’s wort) consumption
may yield photodermatitis
only in calves;
 Not any report has been found
in human
St.John’s wort is used in phytotherapy as an effective antidepressant medicine
E. Yeşilada
27
E. Yeşilada
28
Volatile oil ingredients:
Contact dermatitis;
eugenol, L-carvone‘ (mint oil) are
the ingredients of toothpaste may induce
inflammatory lips in sensitive people,
E. Yeşilada
29
 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
E. Yeşilada
30
Volatile oil ingredients: in Spices
 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
Camphre/kafur;
internally; hepatotoxicity and CNS damage,
on skin; neurotoxicity
Ointments with camphre (Vicks, etc.) induced
hepatotoxicity when applied to the skin of a 2month old baby in order to reduce the
symptoms of catarhh,
however, the symptoms recovered as soon as
stop application
E. Yeşilada
32
Alkaloids
 Ma Huang (ephedrine) from Ephedra sinica
 Bronchodilatator 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.
E. Yeşilada
33
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,

E. Yeşilada
34
 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,
E. Yeşilada
35
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 gastrointestinal 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
E. Yeşilada
36
 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.
E. Yeşilada
37
E. Yeşilada
38
 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
E. Yeşilada
39
 “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.
E. Yeşilada
40
 Real Ginseng: roots of [Panax ginseng & P.
notoginseng];
 Effect: increase stamina, physical performance,
boost immune system, regulates CNS, regulates
metabolism (diabetes, etc.), adaptogen
E. Yeşilada
41
 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,
E. Yeşilada
42
 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
E. Yeşilada
43
 Among 2000 woman were administered the
formulation
 100> nephropathy
 80> connected to dializing unit /or
subjected to kidney transplantation
E. Yeşilada
44
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
E. Yeşilada
45
 In the formulation instead of
Stephania tetrandra;
Aristolochia fangchi or
Aristolochia manschuinsis
were used.
 Aristolochia sp.; contains
aristolochic acid
 Nephrotoxic, carcinogenic
and mutagenic
E. Yeşilada
46
 (2001) France: 7 nephropathy reports
 U.K.: 2 severe renal insufficiency
 China: 17 cases and 12 death
 Japan: 10 renal failure
E. Yeşilada
47
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
Lack
of information regarding the preparation of remedy
 “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.
E. Yeşilada
49
Toxic components in foods
 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.
E. Yeşilada
50
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 food
 Shoots and surrounding parts should be scraped
off/removed before using as food
E. Yeşilada
51
E. Yeşilada
52
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
E. Yeşilada
54
 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
E. Yeşilada
55
 TCM or Ayurvedic formulations may contain as
a part of treatment;
Arsenic disulfas (realgar),
o
mercury chloride (calomel),
o
mercury sulfas (cinnabaris),
o
red mercury oxide (hydrargyri oxydum rubrum)
etc.
o
E. Yeşilada
56
 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.
E. Yeşilada
57
 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.
E. Yeşilada
58
 In Turkey (2007 -
)
 Slimming formulations
 Contains “sibutramin” 3x higher than suggested dose.
 Not notified on the label.
E. Yeşilada
59







Microbiologic,
Insect,
Pesticide,
Fumigant,
Environmental waste,
Heavy metals,
Radiation etc. lar.
E. Yeşilada
60
 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
E. Yeşilada
61
Dangerous contaminants in HMPs:
NOT ALLOWED
Patogenic organisms;
Enterobacter, Enterococcus, Clostridium,
Pseudomonas, Shigella, Streptococcus vd.’
Endotoxins and mycotoxins:
Aspergillus flavus; aflatoxins

No limit in European Pharmacopeia

x
10 times difference in Europe and USA
E. Yeşilada
62

Pesticides:
To protect crop from pests;
* Cultivars or
* Materials collected nearby to
cultivation area;
- Chlorinated hydrocarbons; DDT etc.,
- Organophosphates,
- Carbamates,
- Polychlorinated biphenyls, etc.
E. Yeşilada
63
 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,
E. Yeşilada
64
Contamination with Environmental
Pollutants/wastes :
Heavy metals:

-

lead, cadmium, mercury, tallium and arsenic
etc.
Radioactive wastes;
E. Yeşilada
65
DRUG INTERACTIONS
E. Yeşilada
66
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.

E. Yeşilada
67
Inhibitory effects on drug metabolizing
enzymes may potentiate the effect of
pharmacotherapy
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
E. Yeşilada
68
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
E. Yeşilada
69
 Potentiazation in
effects
serotonergic
may be observed concurrent use of
Serotonin reuptake-inhibitors (SRI), [centralin,
paroxetine etc.]
 Concurrent use of MAOI (phenelsine)
may induce headache, tremor and
mania
E. Yeşilada
70
 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
E. Yeşilada
71
Drug name
Effect
Results of interaction
Possible mechanism
Cyclosporine
Immunosuppresant
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
Decrease in plazma
concentration of drug
Decrease in anticoagulant
activity
Hepatic enzyme induction
Phenprocoumone
Warfarin
Anticoagulant
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 induction
P-glycoprotein induction
Digoxine
Cardiotonic
Decrease in plazma
concentration of drug
P-glycoprotein induction
Nephazodon
Sertraline
Paroxetine
Antidepressant
Serotonin syndrome
Synergistic SRI inhibition
E. Yeşilada
72
 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.
E. Yeşilada
73
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
E. Yeşilada
74
Synergistic effect
 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
E. Yeşilada
75
Synergistic effect
 Hypoglycaemic shock
 Plants with Hypoglycaemic activity may
potentiate the effect of hypoglycaemic agents;
 i.e.,
Ginseng
insulin
or
Garlic,
with glibenclamide or
E. Yeşilada
76
 Concurrent use of plants with known
Hypertansive effect, i.e., Siberian Ginseng, or
licorice would have a negative effect on the
antihypertansive pharmacotherapy
E. Yeşilada
77
Hypokalemia may potentiate the
effect of Cardioactive drugs
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
E. Yeşilada
78
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.
E. Yeşilada
79
Pre-, Peri- and Post-operative interactions:
 May induce severe complications
 Even death
E. Yeşilada
80
 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,
E. Yeşilada
81
 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
E. Yeşilada
82







Physiologic discomfort/disease,
Genetics,
Metabolism rate,
Sensitivity,
Age,
Nutrition,
Durability.
E. Yeşilada
83
 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
E. Yeşilada
84
 Since elimination rates of certain
compounds may be affected may lead to
severity in symptoms.
E. Yeşilada
85
Oral applications:
Sudden Type I hypersensibility
reactions;
rhinitis, headache, dermatitis,
anaphylactic shock,
Topic applications;
Type IV contact dermatitis,
E. Yeşilada
86
 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
 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 interactions
 Teratogenic,
 Embryocidal,
 Carcinogenic,
 Abortifacient,
 and other possible adverse
effects etc.
E. Yeşilada
89
Abortive etffect:
Feverfew (Tanacetum
parthenium)
stimulate
menstration,
during pregnancy
may induce abortion
depending on dose
E. Yeşilada
90
1.
2.
3.
4.
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.
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.
In the absence of specific knowledge of herbals
interactions with prescription medications, concomitant
use should be discouraged or monitored closely.
Except for agents with known estrogenic or androgenic
properties, little is known about the effects of most
herbs on fertility.
E. Yeşilada
91
5. Oral anticoagulant therapy has always been a corcern regarding drugdrug 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.
E. Yeşilada
92
Many of the adverse effect and toxicity reports
are due to
 Insufficient standardization
 Scanty control
 Falcification
 High-dose applications
 Long term administration
 Individual factors; sensitivity, function disorders
E. Yeşilada
93