1. A Informative Slides On HERB + DRUG Interaction VANDANA JANGHEL Assistant Professor (M. Pharma, Pharmacognosy) (Siddhi Vinayaka Institute of Technology & Sciences, Bilaspur, C.G.) What comes from Nature + What we change in nature + What we don’t want 2. 1. What are Herb-drug interactions? 2. How herbs interact with other co administered drug ? 3. Whether they are diagnoised? 4. Are they neglected? 5. Any reports available ? 6. What is the significance of the study ? 7. Need for the study We will discuss on following points HERB + DRUG Interaction 3. Herb drugs + Allopathic drug = Some Reactions HERB + DRUG Interaction 1. When herbal medicinal products and western drugs administered together may interact each other in body leading to kinetic and dynamic alterations. 2. Herbs are often administered in combination with therapeutic drugs, raising the potential of herb-drug interactions. 3. Herbs or Herbal drugs often taken with the Allopathic drugs with belief that it will have some Beneficial effect. 4. Most of the herbal drugs are taken because of- Availability, Economic consideration and its safety 4. PharmacodynamicPharmacokinetics Herb may causes Additive Synergistic Antagonistic Unidentified Response activity in relation to conventional drug Change the Absorption Distribution Metabolism Protein binding Excretion of the drug thus changing blood level of drug HERB + DRUG Interaction 5. Diagnosis Evidence of Interaction Preclinical Trials Clinical Trials Case studies from pharmacovigilance 1 2 3 6. 1. Drug interaction is the 4th to 6th cause of death in the world. 2. About 70-80 herbs may increase the risk of bleeding. 3. Aristolochic acid from Kidamari (Aristolochia Bracteolata) is toxic. 4. Ephedra (Somlata) caused more than 54 deaths and 1600 cases of adverse reaction. Facts about Herbal Drug Interactions 7. 1. Clinician lack of adequate knowledge about Drug-herb Interaction 2. No quality control and assurance for the purity and safety. 3. No advance research in this field. 4. Blind believe or over believe in Ayurverdic medicine 5. Avoidance of patient history about drug sensitivity 6. Adulteration in herbal drug Reason for Herb-Drug Interaction Less Knowledge No Quality Control No Documentation Mythological Believe Herbal-Drug Interaction 8. PHARMACOKINETIC INTERACTION Parameter Increases Decreases Absorption Ginger Fibers Green tea Mucilage containing herb Black pepper Mucilage containing herb Metabolism Guggul Grape juice Elimination Laxative (Aloe) Liquorices Diuretics herbs 9. ALOE VERA Interferes with drug absorption through Laxative action (Aloe latex) Decrease transit time Decrease Intestinal Fluids GINGKO BILOBA Decrease effectiveness of Alprazolam by decreasing its absorption. Ginkgo decreases absorption of Alprazolam rather than inducing hepatic metabolism of alprazolam. GINGER Enhance the absorption of sulfaguanidine and decreases blood sugar PHARMACOKINETIC INTERACTION Herbal drugs which shows Interaction related to Absorption 1

1. Presented By:
Mahewash Sana A. Pathan.

2.  Drug interactions
 Potential for herb-drug interactions
 Significance to study herbal-drug interactions
 Reasons for herbal drug interactions.
 Types of drug interactions as per Ayurveda.
 Different Ways Of Herbal Preparations Toxicity
 Effects Of Herb-drug Interactions On Various Systems Of
Body
 Mechanism Of Herb-drug Interactions
 Study of drugs & their possible side effects and interactions:
Hypericum, Kava-kava, Ginkgo biloba, Ginseng, Garlic,
Pepper, Ephedra
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3.  Drug interaction is defined as “ alteration in the
pharmacological activity of one drug by the
concomitant use of another drug or other
substances. The concurrent use of herbs may
increase, decrease or mimic the effect of other
drugs.”
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4.  There is no chemical reaction between herb & drug
but components of herb can enhance or diminish
the amount of drug present in bloodstream.
 Herbal drugs may be toxic intrinsically or when
these are taken with combination of other
preparations, toxic effects can be observed.
 Herbal drugs contain contaminants (incorrect
species, pollen grains, insects, allergens, heavy
metals & poisonous drugs, etc) may cause toxic
reactions.
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5.  Herbal drug interactions can affect health &
efficiency of treatments as some herbal therapies
might:
a. Increase the side effects of drugs, leading to
toxicity.
b. Leads to treatment failure due to decrease in
effect of drug.
c. Unexpected complications may occur due to
modification of drug action.
d. Enhance therapeutic effect of drug.
e. Prescription & non prescription drugs can alter
reaction of body to herbal therapies.
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6. 1. Proper information is not available regarding the
contents of herbal product.
2. Product information may be incomplete or
inaccurate.
3. Herbal product contain many phytoconstituents
which are not characterized properly.
4. Lack of adequate knowledge of combinations.
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7. HERB
INTERACTIONS
Herb-herb
interaction Eg.
Piper betal should
not be
administered with
Garcinia morella
Herb-Food
interactions eg.
Sesame seed
with blak cumin
cause
diarrhoea.
Herb & drug of
animal origin eg.
Meat is
contraindicated
with Brassica alba
Interactions
related to
diseases eg.
Haritaki cannot
be administered
in pregnancy.
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8. •Some herbs contain toxic ingredient. E.g.
Mentha pulegium oil contain a potent
abortifacient compound.
1. Toxic ingredients
•Herbal weight reduction e.g. Aristolochia
fangchi causes kidney damage & cancer.
2. Unintentional
addition of toxic
species
•This is done to potentiate the effect of
herbs. Adulteration with steroids etc.
3. Intentional
addition of drugs
•E.g. Heavy metal poisoning
4. Contamination due to
envionmental factors
•Toxicity due to metabolic & physiologic
effects of modern medicines.
5. Toxicity due to
combination with
modern medicines
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9. 1. GIT: Horse chestnut acts as irritant to GIT & can affect
efficacy of anti ulcer drugs. Activity of laxatives may be
enhanced by use of senna.
2. CVS: Antihypersensitive drugs may be adversely
affected by use of ginseng & dandelion. Alfalfa
enhances effect of hypolipidaemic drrugs.
3. CNS: Sedatve herbs react with hypnotic & anxiolytic
drugs. Evening primerose oil can react with
epileptogenic drugs.
4. Endocrine system: Ginseng & red clover can interfere
with activity of sex hormonal treatment & oral
contraceptives.
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10. MECHANISM OF
HERB-DRUG
INTERACTIONS
PHARMACO-
KINETIC
ABSORPTION
DISTRIBUTION
METABOLISM
ELIMINATION
PHARMACO-
DYNAMIC
ADDITIVE
ANTAGONISTIC
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11.  Synonym: St. John’s wort, Amber, Demon chaser,
Amber touch-and-heal, Millepertuis, Goat weed,
Bassant.
 Biological source: Dried aerial plant parts of
Hypericum perforatum L.
 Family: Hypericaceae.
 Geographical source: England, Europe, Australia,
western himalayas.
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12.  MACROSCOPIC
CHARACTERS:
Colour- leaves are green
with black spots
Odour- distinct, balsamic
Taste- astringent & bitter
Shape- leaves are oblong,
entire
Flowers- yellow corolla,
small five petaled.
Capsules- ovoid
Seeds- very small
Stem- 2 edged.
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13.  CHEMICAL CONSTITUENTS:
No. Chemical
class
Constituents present in Hypericum
1 Flavonoids Rutin, Epigallocatechin, Isoquercetin,
quercetin, quercitrin, hyperoside,
amentoflavone, biapigenin, astilbin,
myricetin, kaempferol, luteolin.
2 Naphthodiant
hrones
Hypericin, pseudohypericin,
protohypericin, protopseudohypericin.
3 Phenolic acids Chlorogenic acids, caffeic acid, p-
coumaric acid, ferulic acid, p-
hydroxybenzoic acid, vanillic acid.
4 Alkaloids Vitamins, pectin, beta sitosterol,
hexadecane, caffeine, carotenoids,
kielcorin, norathyriol.
5 Saturated
fatty acids
Isovaleric acid, myristic acid, palmitic
acid, stearic acid.
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14.  STANDARDS:
i. FOM: > 3.0 %
ii. Alcohol soluble extractive: < 13.0 %
iii. Water soluble extractive: <24%
iv. LOD: >10%
v. Total ash: >7%
vi. Acid insoluble ash: >0.8%
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15. 1. Anti depressant
2. In treatment of anxiety, seasonal affective disorders.
3. In the treatment of symptoms of menopause, mental
disorders, premenstrual syndrome.
4. In treatment of fibromyalgia (chronic rheumatic condition),
chronic fatigue syndrome(CFS), burning feelings in the
mouth, maigraine, pain, irritable bowel syndrome,skin
diseases.
5. Food flavour
6. Hypericin reported to have antiviral potential against HIV &
hepatitis C virus.
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16. Hypericum when taken orally upto 12 weeks, it is
considered as safe. Possible side effects are:
 Trouble sleeping
 Vivid dreams
 Restlessness
 anxiety
 Irritability
 Stomach upset
 Fatigue
 Diarrhoea
 Skin rash
 Dizziness
 Dry mouth
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17.  Hypericum interacts with certain antidepressant drugs
leads to serious conditions resulting excess of
serotonin. Symptoms of this interaction are confusion,
fever, hallucinations, nausea, imbalance in muscle
coordination, sweating, & shakiness.
 Decreases metabolism of anti-anxiety drug alprazolam,
hence decrease its effectiveness.
 Decreases efficacy of birth control pills.
 Decreases effect of cardiotonic drug digoxin.
 Decreases effect of anti HIV drugs like imatinib,
irinotecan, ketamine, etc.
 Hypericum with cyclosporin decreases drug
concentration & rejection of transplanted organ by
induction of Cyt P3A4.
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18.  Synonym: Ava pepper, Ava root, Awa.
 B/S: dried roots of plant Piper methysticum, family-
Piperaceae.
 G/S: Melanesia, Micronesia, polynesia.
 M/C: it is shrub & has heart shaped leaves & woody
stem. Stem are green with swollen nodes. The fruits are
berries with one seed.
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19.  Root consist of 12% water, 43% starch, 20% fibers,
sugars & minerals.
 Main phytoconstituents are kavalactones, chalcones,
kawain, 7,8-dihydrokawain, methysticin, yangonin,
demethoxy yanonin.
 Minor constituents are three chalcones flavokavain A,
B & C.
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20.  Kava decreases anxiety, stress, insomnia & post
menopausal symptoms.
 It may used in treatment of cancer, ADHD, epilepsy,
psychosis, depression, CFS & headaches.
 In treatment of common cold, respiratory tract
infection, tuberculosis, muscle pain, UTI, skin diseases
& wounds.
Possible side effects of Kava:
 When taken orally, may cause liver damage.
 Aggregates the symptoms of depression & parkinson’s
disease.
 Not safe during pregnancy & lactation.
 It may cause visual disturbances, GI discomfort,
urinary retention, etc.
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21.  Kava when taken together with alprazolam cause
drowsiness.
 Kava interact with CNS depressants & cause
drowsiness.
 Decrease liver metabolism of some drugs.
 Kava enhances absorption of medications such as
etoposide, paclitaxel, vinblastine, vincristine,
indinavir, nelfinavir, cimetidine, corticosteroids.
 Kava when administered with medicines such as
acetaminophen, amiodarone, isoniazid, methyldopa,
itraconazole, etc can cause hepatotoxicity.
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22.  SYNONYM: Maiden hair tree,
kew tree
 Biological source: Dried leaves
of Ginkgo biloba L.
 Family: Ginkgoaceae.
 Geographical source: China,
USA, Japan, Europe, Australia.
 Macroscopic characters:
Colour: bright yellow flowers.
Leaves: bilobate
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23. Chemical constituents of Ginkgo:
 Ginkgo leaves possess variety of glycosides,
predominantly flavonol, mono, di & tri glycosides of
isorhamnetin, kaempferol & quercetin.
 Bio-flavones present are gingketin, gingkolic acid &
bilobetin.
 Leaves also possess diterpene lactones, mainly
ginkgolides A, B, C, & J.
 Total ash should be 11%.
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24.  Anti-inflammatory & hepatoprotective agent.
 Plant has antilipedemic, antidiabetic & antioxidant
activity.
 It reduces anxiety & treats dementia.
 Also act as anti-allergic, anti viral, anti proliferative, anti
tumorigenic & anti carcinogenic agent.
Adverse effects:
 Stomach upset, headache, dizziness, constipation,
increase in force of heartbeat, allergic skin reactions,
etc.
 High dose of leaf extract may increase risk of liver &
thyroid cancers.
 Ginkgo seeds may cause seizures & death.
 It is not safe in pregnancy & lactation.
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25.  When ginkgo is administered with ibuprofen, it increase
chances of bruising & bleeding.
 Can decrease effect of alprazolam, efavirenz,
carisoprodol, citalopram, diazepam, omeprazole,
haloperidol, olanzepinepropranolol, etc.
 When administered with fluoxetine, may cause
hypomania.
 Ginkgo may slow down the metabolism of certain drugs.
 Decrease the effect of anti diabetic drugs such as
glimeperide, insulin, rosiglitazone, etc.
 Trazodone when taken with ginkgo, may cause serious
side effects.
 Hydrochlorothiazide when administered with ginkgo
cause increase in BP.
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26.  Synonym: Panax ginseng, red berry,
renshen, hong shen.
 B/S: dried roots of Panax Ginseng,
Family- Araliaceae.
 G/S: Manchuria, Chinese tartary,
eastern asia, Korea & Japan.
 Description: it is smooth perennial
herb. Has large, fleshy, spindle
shaped very slow growing root.
 Colour- Pale yellow to brownish
 Odour- odourless
 Taste- mucilagenous with slight
bitterness.
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27.  Steroid like saponin- Ginsenosides. Ginsenosides
Rb1, Rb2, Rc, Rd, R, etc comprise 90% of total
ginsenosides.
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28.  Treat depression, anxiety, general fatigue, chronic
fatigue syndrome, multiple sclerosi, anemia, chronic
bronchitis, swine flu, pre diabetes & diabetes, gastritis,
COPD, fertility problems.
 It has wide applications in treating bleeding disorders,
loss of appetite, vomiting, intestinal problems,
gallstones, bad breath, insomnia, nerve pain, joint pain,
headache, convulasions, disorders of pregnancy, heart
failure, high BP, & as antiaging agent.
Side effects:
 Skin reactions, diarrhoea, insomnia, headache, rapid
heartbeat, increased or decreased BP, loss of appetite,
itching, vaginal bleeding.
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29.  When taken with caffeine, can cause serious
reactions such as increased heart rate & high BP.
 Decreases the effect of estrogen pills, furosemide,
midazolam, nifidipine.
 Decreases metabolism of imatinib, amitriptylene,
clozapine, donepezil, fentanyl, fluoxetine,
methadone, etc.
 Might decrrase the effectiveness of
immunosuppressant drugs.
 Panax slows down blood clotting.
 Ginseng when used with HIV drug like Raltegravir,
can increase chances of liver toxicity.
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30.  Synonym: Allium, Lasun
 B/S: dried bulbs of Allium sativum L,
Family- Liliaceae.
 G/S: Central Asia, Africa, United
states, India & Europe.
 Description: It is a bulbous perennial
plant having height of 4ft. It consist of
several cloves covered with white or
pink membrane. It is hermaphrodite
flowers. Pollinated by bees & insects.
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31.  About 1% volatile oils mainly allicin, responsible for
particular odour.
 Alliin, allixin, allylpolysulfides, diallyltrisulphide, N-
acetylcysteine, S- allylcysteine & thiacremonone.
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32.  It acts as aphrodiasiac, carminative, expectorant,
stimulant.
 Used to treat fever, hyperlipidemia, bronchial asthma,
tuberculosis, GIT disorders, diabetes, infections &
arteriosclerosis.
Possible side effects:
 Allergic reactions such as difficulty in breathing,
swelling of face, lips, tongue or throat, etc.
 Unpleasant breath or body odour, heartburn, burning
in mouth or throat, nausea, vomiting, gas or
diarrhoea, etc.
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33.  Garlic may increase bleeding times with
anticoagulants.
 Garlic may induce hepatic CyP3A4 metabolism of
protease inhibitors like ritonavir, indinavir etc.
 During & after surgery, garlic causes spontaneous
bleeding.
 When co-administered with chlorpropamide,
produces antihyperglycemic effect.
 Minor interactions include changes in paracetamol
pharmacokinetics & hypoglycaemia.
 Decreases effect of anti HIV drugs.
 Decreases effect of calcium channel blockers due to
increase in liver breakdown of such medications.
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34.  Synonym: Black pepper, kali miri,
Pippali
 B/S: dried ripe fruits of Piper
nigrum, Family- Piperaceae.
 G/S: Brazil, Indonesia & India.
 Description: plant grows well in
shade & need support.
Leaves-heart shaped, alternate with
palmate veins.
Fruits- drupe with single seed & red
in color when matured.
Seeds- brown or black, with aromatic
odor & pungent taste.
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35.  1-2.5% volatile oils. Pharmacologically active principle
is pungent alkaloid piperine.
 Other phytoconstituents are Brachyamide B, dihydro-
pipericide, N- formylpiperidine, guineensine,
isobutyl-eicosadienamide, tricholein, piperamide,
piperettine, pipericide, samantine, limonene,
camphene, cinnamic acid, etc.
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36.  Antihypertensive, antiplatelet, antioxidant,
anticancer, antiasthmatic, anti-inflamatory, analgesic,
anti-diarrhoeal, antispasmodic, immunomodulatory,
anticonvulsant, anti-thyroid, hepatoprotective,
antifungal, insecticidal & larvicidal activities.
 It act as a bioenhancers & increase absorption of
many drugs & nutrients.
Adverse effects:
 It is generally safe when given in small doses.
 If get into eyes cause redness & burning.
 In large doses it may cause miscarriage in
pregnancy.
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37.  As pepper has diuretic effect, it decreases clearance
of lithium & increases its concentration in the body
hence cause serious side effects.
 Enhances absorption of various drugs such as
lovastatin, ketoconazole, ITZ by altering their liver
metabolism.
 Enhances the effects & side effects of phenytoin.
 Carbamazepine absorption increases & metabolism
decreases when administered with pepper.
 Piperine increases bioavailability of fexofenadine.
 Piperine slows down blood clotting. Hence with
anticoagulant medications it may increase chances of
bruising & bleeding.
 Can increase sedative side effects of pentobarbital.
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38.  Synonym: Ma-huang, yellow horse,
yellow astringent, pinellia.
 B/S: dried young stem of Ephedra
gerardiana, E. nebrodensis, E. sinica,
E. equisetina, family- Ephedraceae.
 G/S: northern china, mongolia,
southern europe, North Africa, Asia.
It typically grow in dry & desert
regions.
 Description: it is an evergreen shrub
2-3 ft height & no leaves. Stem-
green, jointed, smooth, woody,
branching.
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39.  1% of amino alkaloids such as ephedrine,
pseudoephedrine, norpseudoephedrine,
methylephedrine, including quinoline & 6-
hydroxykynurenic acid & tannis.
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40.  It is used in asthma, bronchitis, bronchospasm,
allergies, nasal congestion, colds, flu, fever & other
breathing problems.
Side Effects:
 Dizziness, restlessness, anxiety, irritability, headache,
loss of appetite, nausea, vomiting, etc.
 It also cause arrythmia & sudden death, myocardial
infarction, stroke, autonomic hyperactivity, seizures,
gastric mucosal injury, etc.
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41.  Ephedra when administered with medications like
amiodarone, disopyramide, dofetilide, ibutilide,
quinidine etc can cause serious side effects like heart
attack.
 Ephedra when taken with methylxanthines might
cause nervousness, fast heartbeats, high BP &
anxiety.
 Effectiveness of dexamethasone may decrease due to
ephedra.
 Decreases efficacy of antidiabetic drugs.
 Can decrease the efficacy of anticonvulsant drugs
such as phenobarbital, primiidone, valproic acid,
gabapentin, phenytoin.
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