HERB – DRUG INTERACTIONS
Dr.Bidhan Mahajon
PG SCHOLAR
V.P.S.V AYURVEDA COLLEGE,KOTTAKKAL

1
Scholar
Dr.Bidhan Mahajon
Guide
Dr. Remadevi.R. MD(AYU)
Professor and H.O.D

2

Department of Dravyaguna Vijnanam
V.P.S.V....
Introduction
• Global Increase
– demand for herbs/herbal formulations
• 25,000 Plant based formulations – Available
• 1.5 ...
• 5 billion/yr industry
• More than 700 therapeutic herbs and
phytomedicines sold in German Pharmacies
• Approximately 70%...
Purpose for use of Herbal Medicine?
Health Benefit

Total
Shoppers
(1000)

Female
(711)

Male
(289)

Ensure overall good h...
6
A MILLION
DOLLAR
QUESTION

SAFETY OF
HERBAL
MEDICINES ?
Answer: Equivocal
7
Facts about drug interactions/herbal
medicine/ herb-drug interactions
• Drug interactions - 4th – 6th Cause of death

• At...
Interactions between Immunomodulatory
herbs and drugs
Herb

Drug/ Class of
drugs

Mechanism of Herb – Drug
Interaction

As...
Ginseng

Digoxin

Increased drug concentrations

Induction of CYP2C9

Opioid
analgesics

Decreased activity of opioids – c...
Interactions between herbs used for
cardiovascular disorders and drugs
• GARLIC
– Antihyperglycemic effect when it was co ...
Cont….
GUM GUGGULU (COMMIPHORA
MUKUL)
– It may produce an additive effect with
anticoagulants
– It is believed to act as a...
Interactions between herbs used for central
nervous system disorders and drugs
Herb

Areca (ARECA
CATECHU)

Drug/Class
of ...
Ginkgo (GINKGO
BILOBA)

Aspirin
Clopidogrel
Ticlopidine

Increased risk of bleeding

Digoxin

Increased bioavailability of...
Green tea
(CAMELIA SINENSIS)

Warfarin

Increased risk of bleeding

Guarana(PAULLINIA
CUPANA)

Caffeine/
Respiratory
stimu...
St.John’s wort
(HYPERICUM
PERFORATUM)

Amitryptyline

Induction of CYP3A4

Cyclosporine

Induction of CYP3A4 and P - gP le...
St.John’s wort
(HYPERICUM
PERFORATUM)

Methadone

Induction of CYP 3A4, 2C8 and CYP 2D6
leading to decrease in drug concen...
St.John’s wort
(HYPERICUM
PERFORATUM)

Theophylline

Induction of CYP1A2 leading to decreased
concentration of drug

Thyro...
Herb – drug interactions due to alteration of
cytochrome P450 enzymes in in - vitro models
Herb

CYP Enzyme

In – vitro mo...
Herb

CYP Enzyme

In – vitro model

Garlic
( ALLIUM
SATIVUM)

Inhibits CYP2C9,
CYP2C19,
Inhibits CYP3A4
Inhibits CYP2E1

H...
Herb

CYP Enzyme

In – vitro model

Liquorice
(GLYCYRRHIZA
GLABRA)

CYP3A4, CYP2C9

Human recombinant enzymes

Schizandra
...
Interactions between other herbs and drugs
• Artemesinin
– Artemisinin, - decreases – omeprazole
bioavailability - inducti...
Cont….
• Liquorice
– Antihypertensive drugs - synergistic effect
(Cumming et al., 2003)
– Hydrocortisone - pseudoaldostero...
Cont….
•

Silymarin
• potentiate the effects of antiarrhythmic drugs
(Gyonos et al., 2001)
2001
• Increases - pharmacologi...
Interactions between herbs and drugs acting on blood

B
L
O
O
D
C
L
O
T
T
I
N
G

ALTERATION OF INR

Herbs containing couma...
PREDICTED - HDI
• Bearberry (ARCTOSTAPHYLOUS UVA URSI)
• Estrogens/Oral contraceptives - May ↓ response to estrogen
• Lipi...
• Chamomile (MATRICARIA RECUTITA) Iron - May inhibit iron absorption
• Chaste tree berry (VITEX AGNUS – CASTUS)
- Dopamine...
• Guarana (PAULLINIA CUPANA)
– Adenosine - May lower response
– Benzodiazepine - Drugs may be less
effective
• Hawthorn (C...
Herbs to be avoided prior to
surgery
•
•
•
•
•
•
•

Ephedrine – 24 hrs
Garlic/Garlic products – 7 days
Ginkgo – 36 hrs
Gin...
THE OTHER SIDE OF HERB –
DRUG INTERACTIONS
• Aromatic herbs such as ginger can be used to
prevent drug-induced nausea
• Mi...
Cont….
• Combination of aqueous extract of
Chinese medicinal plant Tripterygium
wilfordi and cyclosporine significantly
in...
Cont….
• Co – administration of ginkgo with
antipsychotics (haloperidol) in chronic
schizophrenic patients reduces extra
p...
Cont….
Momordica charantia is reported to
augment the hypoglycemic effect of
rosiglitazone which can be used to reduce
the...
Cont….
• Piperine can be used as bioavailability
enhancer for several drugs and studies
bolster that piperine enhances the...
Cont….
• Ginseng is considered to be potent
adjuvant for delivery of vaccines which
have been proven to induce higher or
s...
Cont….
• Rosemary (Rosmarinus officinalis) has
chemopreventive effect as it increases
efflux and intracellular accumulatio...
37
CONCLUSION
We need to bring into lime light about the
herb – drug interactions

38
39
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Hearbs drugs interaction

  1. 1. HERB – DRUG INTERACTIONS Dr.Bidhan Mahajon PG SCHOLAR V.P.S.V AYURVEDA COLLEGE,KOTTAKKAL 1
  2. 2. Scholar Dr.Bidhan Mahajon Guide Dr. Remadevi.R. MD(AYU) Professor and H.O.D 2 Department of Dravyaguna Vijnanam V.P.S.V. Ayurveda College Kottakkal 2
  3. 3. Introduction • Global Increase – demand for herbs/herbal formulations • 25,000 Plant based formulations – Available • 1.5 Million Practioners of Traditional Medicinal system • 25% of all modern medicines – directly /indirectly derived from plants • 60% of antitumour and antimircobial medicines are derived from plants 3
  4. 4. • 5 billion/yr industry • More than 700 therapeutic herbs and phytomedicines sold in German Pharmacies • Approximately 70% Physicians prescribe registered herbal remedies • 7800 Medicinal drug manufacturing Units India 4
  5. 5. Purpose for use of Herbal Medicine? Health Benefit Total Shoppers (1000) Female (711) Male (289) Ensure overall good health 88% 91% 82% Reduce fat intake 81% 84% 72% Doctor’s advice 73% 75% 69% Weight Reduction/Control 73% 76% 67% Reduce cholesterol levels 72% 74% 66% Reduce the risk of a specific condition or illness 66% 69% 59% Improve stamina or energy level 64% 65% 60% Desire to manage or treat specific health condition on their own 63% 65% 56% Cope with food intolerance 48% 50% 43% Manage Stress 46% 46% 44% Manage allergies 41% 45% 33% Slow down the aging process 39% 41% 35% 5
  6. 6. 6
  7. 7. A MILLION DOLLAR QUESTION SAFETY OF HERBAL MEDICINES ? Answer: Equivocal 7
  8. 8. Facts about drug interactions/herbal medicine/ herb-drug interactions • Drug interactions - 4th – 6th Cause of death • At least 100 preoperative fatalities due to herb -drug/surgery interactions • >70 – 80 Herbs - Increase risk of bleeding • >30 – 40 Herbs possibility of causing hepatic failure • Ephedra – 54 deaths , 1600 Adverse events • Aloe vera injection – 4 Deaths • Pennyroyal tea – 2 infants Multiorgan Dysfunction • Aristolochic Acid – Death of 100 Belgian Women 8
  9. 9. Interactions between Immunomodulatory herbs and drugs Herb Drug/ Class of drugs Mechanism of Herb – Drug Interaction Astragalus (ASTRAGALUS MEMBRANACEUS) Azathioprine Cyclosporine Methotrexate Antagonism Borage (BORAGO OFFICINALIS) Hypnotics Potentiation Echinacea (ECHINACEA PURPUREA) Acetaminophen Potentiation of Hepatotoxicity Corticosteroids Cyclosporine Antagonism Fexofenadine Itraconazole Lovastatin Inhibition of CYP3A4 leading to increase in drug concentration 9
  10. 10. Ginseng Digoxin Increased drug concentrations Induction of CYP2C9 Opioid analgesics Decreased activity of opioids – clear mechanism is unknown Phenelzine and MAO inhibitors Increased CNS side effects due to additive effect Warfarin Shankpushpi (CONVOLVULUS PLURICAULIS) Induction of CYP3A4 Hexobarbital (PANAX GINSENG) Amlodipine Alteration of INR value Phenytoin Decreased therapeutic effect 10
  11. 11. Interactions between herbs used for cardiovascular disorders and drugs • GARLIC – Antihyperglycemic effect when it was co – administered with chlorpropamide – Decreases – bioavailabilty of saquinavir – induction of P- glycoprotein (P – gP) 11
  12. 12. Cont…. GUM GUGGULU (COMMIPHORA MUKUL) – It may produce an additive effect with anticoagulants – It is believed to act as a thyroid stimulating agent – avoid the co – administration with thyroid drugs – Guggul - predicted to decrease the absorption of beta blockers and calciumchannel blockers 12
  13. 13. Interactions between herbs used for central nervous system disorders and drugs Herb Areca (ARECA CATECHU) Drug/Class of drugs Procyclidine Mechanism of Herb Drug Interaction Antagonistic effect on drug – leading to extra pyramidal syndrome Capsicum ACE (CAPSICUM inhibitors FRUTESCENCE, CAPSICUM Theophylline ANNUM) Increased risk of developing cough Chasteberry (VITEX AGNUS – CASTUS) Dopamine receptor antagonists Interferes with the activity of drugs Feverfew (TANACETUM PARTHENIUM) Antimigraine Drugs Potentiation of drug effect Warfarin Additive antiplatelet effect due to inhibition of platelet aggregation Enhanced bioavailability can lead to theophylline toxicity 13
  14. 14. Ginkgo (GINKGO BILOBA) Aspirin Clopidogrel Ticlopidine Increased risk of bleeding Digoxin Increased bioavailability of digoxin Diltiazem Increased bioavailability of drug Ibuprofen Intracerebral mass bleeding due to inhibition of platelet aggregation Nicardipine Induction of CYP 3A4 leading to decreased activity of drug Omeprazole Induction of CYP2C9 Thiazide diuretics Increase in blood pressure Trazodone Induction of CYP3A4 Warfarin Increased risk of bleeding 14
  15. 15. Green tea (CAMELIA SINENSIS) Warfarin Increased risk of bleeding Guarana(PAULLINIA CUPANA) Caffeine/ Respiratory stimulants Potentiation of activity Kava (PIPER METHYSTICUM) Alprazolam Potentiation of sedation Anesthetics Prolongation of anesthesia Levodopa Antagonism Lemon balm (MELISSA OFFICINALIS) CNS depressants Additive CNS effects Thyroid hormones Inhibits binding of thyroid hormones to TSH receptors Sage (SALVIA MITILIORRHIZA) Warfarin Increased risk of bleeding Diazepam Induction of enzymes 15
  16. 16. St.John’s wort (HYPERICUM PERFORATUM) Amitryptyline Induction of CYP3A4 Cyclosporine Induction of CYP3A4 and P - gP leading to decrease in drug concentration and rejection of transplanted organ Digoxin Induction of P – gP Fexofenadine Inhibition of P - gP Indinavir, Saquinavir Induction of CYP 3A4 Loperamide Acute delirium – mechanism unknown 16
  17. 17. St.John’s wort (HYPERICUM PERFORATUM) Methadone Induction of CYP 3A4, 2C8 and CYP 2D6 leading to decrease in drug concentration Oral Contraceptives Failure of contraception due to induction of CYP3A4 Piroxicam Photosensitizing drugs Increased risk of phototoxicity Quazepam Induction of CYP 3A4 Sertraline Inhibits vesicular uptake of monoamines leading to serotonergic syndrome Simvastatin Induction of CYP3A4 Tacrolimus Immuno graft rejection due to induction of CYP enzymes 17
  18. 18. St.John’s wort (HYPERICUM PERFORATUM) Theophylline Induction of CYP1A2 leading to decreased concentration of drug Thyroid stimulating hormone Elevation of TSH levels Venlaxafine Serotonin syndrome – Inhibition of serotonin reuptake and MAO Inhibition Verapamil Induction of CYP3A4, leading to decreased bioavailabilty Warfarin Induction of CYP3A4 and CYP2C9 Valerian (VALERIANA OFFICINALIS) Barbiturates Additive sedation Yohimbine (PAUSINYSTALIA YOHIMBE) Clomipramine Increased blood pressure 18
  19. 19. Herb – drug interactions due to alteration of cytochrome P450 enzymes in in - vitro models Herb CYP Enzyme In – vitro model ANGELICA DAHURICA Inhibits CYP3A4 Inhibtis multidrug-resistant and methicillin-resistant strains of Staphylococcus aureus Liver microsomes Devil’s Claw (HARPOGOPHYTUM PROCUMBENS) CYP2C8,CYP2C19, CYP3A4,CYP1A2, CYP2D6 Human kidney (HK-2) proximal tubule cell line Echinacea (ECHINACEA PURPUREA) Inhibits CYP2C19, CYP2D6 Baculovirus expressed CYP enzymes 19
  20. 20. Herb CYP Enzyme In – vitro model Garlic ( ALLIUM SATIVUM) Inhibits CYP2C9, CYP2C19, Inhibits CYP3A4 Inhibits CYP2E1 Human liver microsomes CYP 3A4 Substrates (7Benzyloxyresorufin and 7-ethoxy3 cyanocoumarin Rat iver microsomal cytochrome P450 fractions Ginseng (PANAX GINSENG) Inhibits CYP1A2, CYP2B1, CYP2C9,CYP3A4 c-DNA-expressed cytochrome P450 enzyme catalytic activity Goldenseal (HYDRASTIS CANADENSIS) CYP2D6, CYP3A4, CYP3A5 Caco – 2 cell lines Kava (PIPER METHYSTICUM) Inhibits CYP3A4, CYP1A2, CYP2C9, CYP2C19,CYP2D6 Human liver microsomes 20
  21. 21. Herb CYP Enzyme In – vitro model Liquorice (GLYCYRRHIZA GLABRA) CYP3A4, CYP2C9 Human recombinant enzymes Schizandra (SCHIZANDRA CHINENSIS) Inhibits CYP3A4 Liver microsomes Silymarin (SILYBUM MARIANUM) Inhibits CYP3A4 CYP2C9 Human hepatocytes/ Human recombinant enzymes Valerian (VALERIANA OFFICINALIS) Inhibits CYP3A4, CYP2C9 and CYP2C19 Cytochrome P450 CYP3A4 supersomes Vinca (CATHARANTHUS ROSEUS) Inhibits CYP2D6 Human Liver Microsomes 21
  22. 22. Interactions between other herbs and drugs • Artemesinin – Artemisinin, - decreases – omeprazole bioavailability - induction of CYP2C19 activity (Svensson et al., 1998). 1998 • Foeniculum vulgare – Decrease the rate of absorption of ciprofloxacin chelation of the drug (Zhu et al., 1999). 1999 22
  23. 23. Cont…. • Liquorice – Antihypertensive drugs - synergistic effect (Cumming et al., 2003) – Hydrocortisone - pseudoaldosteronism (Beate et al., 1999) – Oral contraceptives - hypertension, edema and hyperkalemia (Gerty et al., 1997). 23
  24. 24. Cont…. • Silymarin • potentiate the effects of antiarrhythmic drugs (Gyonos et al., 2001) 2001 • Increases - pharmacological activity of cisplatin (Scambia et al., 1996), 1996 • Decreases the blood concentrations of – indinavir (Piscitelli et al., 2002) 2002 – losartan (Han et al., 2009) and 2009 – metronidazole (Chon et al., 2005) 2005 24
  25. 25. Interactions between herbs and drugs acting on blood B L O O D C L O T T I N G ALTERATION OF INR Herbs containing coumarins: Arnica, celery, chlorella, danshen, dong quai, chamomile, fenugreek, goldenseal, guar gum, horse chestnut seeds, papain, passionflower, red clover, sweet clover, boldo Herbs containing vitamin K: Eg: Acerola, agrimony, stinging nettle, plantain INHIBITION OF PLATELET AGGREGATION Bilberry, cayenne, bromelain, capsicum, European mistletoe, feverfew, garlic INHIBITION OF PLATELET ACTIVATING FACTOR (PAF) Garlic, Ginkgo and saw palmetto 25
  26. 26. PREDICTED - HDI • Bearberry (ARCTOSTAPHYLOUS UVA URSI) • Estrogens/Oral contraceptives - May ↓ response to estrogen • Lipid lowering drugs – Possibility of additive effect • Black Cohosh (CIMIFUGA RACEMOSA) – Lipid lowering drugs - Possibility of additive effect • Bladderwrack (FUCUS VESICULOSUS) – Hypoglycemic drugs - Possibility of additive effect • Blue Cohosh (CAULOPHYLLUM THALICTROIDES) - Nitrates and Calcium channel blockers - May antagonize the hypertensive effect 26
  27. 27. • Chamomile (MATRICARIA RECUTITA) Iron - May inhibit iron absorption • Chaste tree berry (VITEX AGNUS – CASTUS) - Dopamine receptor antagonists (Phenothiazines) May antagonize drug effect • Devil’s claw (HARPAGOPHYTUM PROCUMBENS) - Antiarrhythmic drugs - May interfere with drug activity • Echinacea (ECHINACEA PURPUREA) – Corticosteroids/ Cyclosporine – May nullify the effect of drug 27
  28. 28. • Guarana (PAULLINIA CUPANA) – Adenosine - May lower response – Benzodiazepine - Drugs may be less effective • Hawthorn (CRATAEGUS LAEVIGATA, C. MONOGYNA, C. PINNATIFIDA, C.OXYCANTHA) – Anesthetics - May enhance hypotension 28
  29. 29. Herbs to be avoided prior to surgery • • • • • • • Ephedrine – 24 hrs Garlic/Garlic products – 7 days Ginkgo – 36 hrs Ginseng – 7 days Kava – 24 hrs St.Johns Wort – 5 days Valerian – weeks before surgery by tapering 29
  30. 30. THE OTHER SIDE OF HERB – DRUG INTERACTIONS • Aromatic herbs such as ginger can be used to prevent drug-induced nausea • Milk thistle can be used to prevent the liver toxicity associated with drugs • Capsaicin reduces gastric mucosal damage induced by aspirin 30
  31. 31. Cont…. • Combination of aqueous extract of Chinese medicinal plant Tripterygium wilfordi and cyclosporine significantly increases the heart and kidney allograft survival compared to cyclosporine alone • Garlic prevents the formation of toxic metabolites of paracetamol . 31
  32. 32. Cont…. • Co – administration of ginkgo with antipsychotics (haloperidol) in chronic schizophrenic patients reduces extra pyramidal side effects associated with haloperidol • Centella asiatica can also be used as an adjunctive medication for patients with epilepsy due to its additive anticonvulsant activity 32
  33. 33. Cont…. Momordica charantia is reported to augment the hypoglycemic effect of rosiglitazone which can be used to reduce the dose of rosiglitazone to achieve enhance therapeutic effect with minimum side effects 33
  34. 34. Cont…. • Piperine can be used as bioavailability enhancer for several drugs and studies bolster that piperine enhances the bioavailability of propranolol which can be used as a means to achieve better therapeutic control and improved patience compliance 34
  35. 35. Cont…. • Ginseng is considered to be potent adjuvant for delivery of vaccines which have been proven to induce higher or similar antibody titres than vaccines adjuvanted with aluminium hydroxide 35
  36. 36. Cont…. • Rosemary (Rosmarinus officinalis) has chemopreventive effect as it increases efflux and intracellular accumulation of doxorubicin and vinblastine • Silybinin enhances the antitumour activity of cisplatin 36
  37. 37. 37
  38. 38. CONCLUSION We need to bring into lime light about the herb – drug interactions 38
  39. 39. 39
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