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E. Yeşilada 1
ADVERSE EFFECTS AND
DRUG INTERACTIONS WITH HERBAL MEDICINES
AND SCIENTIFIC EVALUATION OF
TOXICITY REPORTS ON HMPs
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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
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Paracelsus (16.century)
“Difference between the therapeutic and poisonous effects of a particular compound is
dose”
E. Yeşilada 3
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(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
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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
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Sources of/ Factors inducing
Risks in HMPs
6E. Yeşilada
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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
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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
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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
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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
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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
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Commercial competitionSlanderous claims
12E. Yeşilada
III. Fake studies or False interpretation
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Multivitamin researchers say "case is closed" after studies find no health benefits
13E. Yeşilada
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E. Yeşilada 14
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E. Yeşilada 15
Are Vitamins realy
ineffective?
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December 2013: CBS News:
16E. Yeşilada
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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
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1. Adverse effects or toxicity due to the high concentration of plant ingredients with potent physiological activity or with toxic effect
18E. Yeşilada
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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:
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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
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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
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E. Yeşilada 22
Plants with Pyrazolidine derivatives are
prohibited/restricted to be used in formulations
Coltfoots; öksürükotu
(Tussilago farfarae)
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Senecio sp., kanarya otu, liferootSenecio scandens (unsaturated
pyrazolidine alkaloids) In Traditional Chinese Medicine (Qianbai Biyan Pian); prohibited by EMEA
E. Yeşilada 23
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2. Furanocoumarins:
In: Apiaceae (Parsley, celery), Rutaceae (Bergamot, Orange family), Moraceae (mulberry and Fabaceae (beans)
Powerful phototoxic activity; psoralen, bergapten
24E. Yeşilada
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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
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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
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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
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Individual factors influencing the toxic effect
risks
28E. Yeşilada
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29E. Yeşilada
Contact dermatitis; eugenol, L-carvone‘ (mint oil) are
the ingredients of toothpaste may induce inflammatory lips in sensitive people,
Volatile oil ingredients:
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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
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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
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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
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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
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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
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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
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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
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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
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38E. Yeşilada
2. Adverse or toxic effects due to falcification or incorrect plant specimen
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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
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“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
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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
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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
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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
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Among 2000 woman were administered the formulation 100> nephropathy80> connected to dializing unit /or subjected to kidney transplantation
44E. Yeşilada
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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
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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
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(2001) France: 7 nephropathy reports U.K.: 2 severe renal insufficiencyChina: 17 cases and 12 deathJapan: 10 renal failure
47E. Yeşilada
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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
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“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
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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
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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
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52E. Yeşilada
4. Due to insufficient quality control parameters practised in the preparation of formulation or Lack of Standardization
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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
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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
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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;
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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
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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
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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
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In Turkey (2007 - )Slimming formulations
Contains “sibutramin” 3x higher than suggested dose.
Not notified on the label.
59E. Yeşilada
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Microbiologic, Insect, Pesticide, Fumigant, Environmental waste, Heavy metals, Radiation etc. lar.
60E. Yeşilada
6. Contamination of plant material
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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:
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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
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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
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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
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Contamination with Environmental Pollutants/wastes :
Heavy metals: - lead, cadmium, mercury, tallium and
arsenic etc.
Radioactive wastes;
65E. Yeşilada
LIMITS
SHOULD BE
TESTED
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DRUG INTERACTIONS
66E. Yeşilada
7. Interaction with the treatment/ concurrent drugs/ and/or food regime of the patient
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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
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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
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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
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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
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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
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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
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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;
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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
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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
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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
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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:
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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
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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
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Pre-, Peri- and Post-operative interactions:
May induce severe complications
Even death
80E. Yeşilada
Interactions with surgical operations
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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
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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
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Physiologic discomfort/disease,
Genetics, Metabolism rate, Sensitivity, Age, Nutrition, Durability.
83E. Yeşilada
8. Individual factors;
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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
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Since elimination rates of certain compounds may be affected may lead to severity in symptoms.
85E. Yeşilada
Impaired functions in Kidney/Hepatic;
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Oral applications: Sudden Type I hypersensibility reactions;
rhinitis, headache, dermatitis, anaphylactic shock,
Topic applications; Type IV contact dermatitis,
86E. Yeşilada
Allergic /idiosyncratic reactions:
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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
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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
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Possible interactionsTeratogenic, Embryocidal,Carcinogenic, Abortifacient, and other possible adverse effects etc.
89E. Yeşilada
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E. Yeşilada 90
Abortive etffect:
Feverfew (Tanacetum parthenium) stimulate menstration, during pregnancy may induce abortion depending on dose
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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
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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.
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Many of the adverse effect and toxicity reports are due to Insufficient standardizationScanty controlFalcificationHigh-dose applicationsLong term administrationIndividual factors; sensitivity, function
disorders
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Conclusion remarks