Hearbs drugs interaction

HERB – DRUG HERB – DRUG

INTERACTIONSINTERACTIONS

Dr.Bidhan MahajonDr.Bidhan Mahajon

PG SCHOLAR PG SCHOLAR

V.P.S.V AYURVEDA COLLEGE,KOTTAKKALV.P.S.V AYURVEDA COLLEGE,KOTTAKKAL

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ScholarScholar

Dr.Bidhan MahajonDr.Bidhan Mahajon

GuideGuide

Dr. Remadevi.R. MD(AYU) Dr. Remadevi.R. MD(AYU)

Professor and H.O.D Professor and H.O.D

Department of Dravyaguna VijnanamDepartment of Dravyaguna Vijnanam V.P.S.V. Ayurveda CollegeV.P.S.V. Ayurveda College

Kottakkal Kottakkal 2

Introduction• Global Increase Global Increase

– demand for herbs/herbal formulationsdemand for herbs/herbal formulations

• 25,00025,000 Plant based formulations – Available Plant based formulations – Available

• 1.5 Million1.5 Million Practioners of Traditional Practioners of Traditional

Medicinal systemMedicinal system

• 25%25% of all modern medicines – directly of all modern medicines – directly

/indirectly derived from plants/indirectly derived from plants

• 60%60% of antitumour and antimircobial of antitumour and antimircobial

medicines are derived from plantsmedicines are derived from plants

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• 5 5 billionbillion/yr/yr industry industry

• More than More than 700700 therapeutic herbs and therapeutic herbs and

phytomedicines sold in German phytomedicines sold in German

PharmaciesPharmacies

• Approximately Approximately 70%70% Physicians prescribe Physicians prescribe

registered herbal remedies registered herbal remedies

• 78007800 Medicinal drug manufacturing Medicinal drug manufacturing

Units - IndiaUnits - India

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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

A MILLION DOLLAR

QUESTION

SAFETY OF HERBAL

MEDICINES ?Answer: Equivocal

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• 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

Facts about drug interactions/herbal medicine/

herb-drug interactions

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HerbHerb Drug/ Class Drug/ Class of drugsof drugs

Mechanism of Herb – Drug Mechanism of Herb – Drug InteractionInteraction

Astragalus(ASTRAGALUS MEMBRANACEUS)

Azathioprine Cyclosporine Methotrexate

Antagonism

Borage (BORAGO OFFICINALIS)

Hypnotics Potentiation

Echinacea(ECHINACEA PURPUREA)

Acetaminophen

Potentiation of Hepatotoxicity

CorticosteroidsCyclosporine

Antagonism

FexofenadineItraconazole Lovastatin

Inhibition of CYP3A4 leading to increase in drug concentration

Interactions between Interactions between Immunomodulatory herbs and drugsImmunomodulatory herbs and drugs

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Ginseng (PANAX GINSENG)

Amlodipine Induction of CYP3A4

Digoxin Increased drug concentrations

Hexobarbital 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 Alteration of INR value

Shankpushpi(CONVOLVULUS PLURICAULIS)

Phenytoin Decreased therapeutic effect

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Interactions between herbs used Interactions between herbs used for cardiovascular disorders and for cardiovascular disorders and

drugsdrugs

• GARLIC

– Antihyperglycemic effect when it was co –

administered with chlorpropamide

– Decreases – bioavailabilty of saquinavir –

induction of P- glycoprotein (P – gP)

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Cont….GUM GUGGULU (GUM GUGGULU (COMMIPHORA COMMIPHORA

MUKUL)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 - predictedpredicted to decrease the decrease the

absorptionabsorption of beta blockers and

calcium-channel blockers 12

Interactions between herbs used for Interactions between herbs used for central nervous system disorders and central nervous system disorders and

drugsdrugs HerbHerb Drug/Drug/

Class of Class of drugsdrugs

Mechanism of Herb Drug InteractionMechanism of Herb Drug Interaction

Areca (ARECA Areca (ARECA CATECHU)CATECHU)

Procyclidine Antagonistic effect on drug – leading to extra pyramidal syndrome

Capsicum Capsicum (CAPSICUM (CAPSICUM FRUTESCENCFRUTESCENCE, CAPSICUM E, CAPSICUM ANNUM)ANNUM)

ACE inhibitors

Increased risk of developing cough

Theophylline Enhanced bioavailability can lead to theophylline toxicity

Chasteberry Chasteberry (VITEX (VITEX AGNUS – AGNUS – CASTUS)CASTUS)

Dopamine receptor antagonists

Interferes with the activity of drugs

FeverfewFeverfew(TANACETUM (TANACETUM PARTHENIUMPARTHENIUM))

Antimigraine Drugs

Potentiation of drug effect

Warfarin Additive antiplatelet effect due to inhibition of platelet aggregation

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Ginkgo (GINKGO BILOBA)

AspirinClopidogrelTiclopidine

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

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Green tea(CAMELIA SINENSIS)


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)


Diazepam Induction of enzymes

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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

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Methadone Induction of CYP 3A4, 2C8 and CYP 2D6 leading to decrease in drug concentration

Oral Oral ContraceptivesContraceptives

Failure of contraception due to induction Failure of contraception due to induction of CYP3A4of CYP3A4

PiroxicamPhotosensitizing drugs

Increased risk of phototoxicity

Quazepam Induction of CYP 3A4

Sertraline Inhibits vesicular uptake of monoamines leading to serotonergic syndrome

Simvastatin Induction of CYP3A4

TacrolimusTacrolimus Immuno graft rejection due to induction Immuno graft rejection due to induction of CYP enzymesof CYP enzymes

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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

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Herb Herb CYP EnzymeCYP Enzyme In – vitroIn – vitro model model

ANGELICA ANGELICA DAHURICADAHURICA

Inhibits CYP3A4Inhibits CYP3A4 Inhibtis multidrug-resistant and Inhibtis multidrug-resistant and methicillin-resistant strains of methicillin-resistant strains of Staphylococcus aureusStaphylococcus aureusLiver microsomesLiver microsomes

Devil’s Claw Devil’s Claw (HARPOGOPHYTUM (HARPOGOPHYTUM PROCUMBENS)PROCUMBENS)

CYP2C8,CYP2C19, CYP2C8,CYP2C19, CYP3A4,CYP1A2, CYP3A4,CYP1A2, CYP2D6CYP2D6

Human kidney (HK-2) proximal Human kidney (HK-2) proximal tubule cell linetubule cell line

Echinacea Echinacea (ECHINACEA (ECHINACEA PURPUREA)PURPUREA)

Inhibits Inhibits CYP2C19, CYP2C19, CYP2D6CYP2D6

Baculovirus expressed CYP Baculovirus expressed CYP enzymesenzymes

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

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Garlic Garlic ( ALLIUM SATIVUM)( ALLIUM SATIVUM)

Inhibits CYP2C9, Inhibits CYP2C9, CYP2C19, CYP2C19, Inhibits CYP3A4Inhibits CYP3A4Inhibits CYP2E1Inhibits CYP2E1

Human liver microsomesHuman liver microsomesCYP 3A4 Substrates (7-CYP 3A4 Substrates (7-Benzyloxyresorufin and 7-Benzyloxyresorufin and 7-ethoxy-3 cyanocoumarinethoxy-3 cyanocoumarinRat iver microsomal Rat iver microsomal cytochrome P450 fractionscytochrome P450 fractions

Ginseng Ginseng (PANAX (PANAX GINSENG)GINSENG)

Inhibits CYP1A2, Inhibits CYP1A2, CYP2B1, CYP2B1, CYP2C9,CYP3A4CYP2C9,CYP3A4

c-DNA-expressed cytochrome c-DNA-expressed cytochrome P450 enzyme catalytic activityP450 enzyme catalytic activity

Goldenseal Goldenseal (HYDRASTIS (HYDRASTIS CANADENSIS)CANADENSIS)

CYP2D6, CYP3A4, CYP2D6, CYP3A4, CYP3A5CYP3A5

Caco – 2 cell lines Caco – 2 cell lines

Kava Kava (PIPER (PIPER METHYSTICUM)METHYSTICUM)

Inhibits CYP3A4, Inhibits CYP3A4, CYP1A2, CYP2C9, CYP1A2, CYP2C9, CYP2C19,CYP2D6 CYP2C19,CYP2D6

Human liver microsomesHuman liver microsomes

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Liquorice Liquorice (GLYCYRRHIZA (GLYCYRRHIZA GLABRA)GLABRA)

CYP3A4, CYP2C9CYP3A4, CYP2C9 Human recombinant enzymesHuman recombinant enzymes

Schizandra Schizandra (SCHIZANDRA(SCHIZANDRA CHINENSISCHINENSIS))

Inhibits CYP3A4 Inhibits CYP3A4 Liver microsomesLiver microsomes

Silymarin Silymarin (SILYBUM (SILYBUM MARIANUM)MARIANUM)

Inhibits CYP3A4 Inhibits CYP3A4 CYP2C9CYP2C9

Human hepatocytes/ Human Human hepatocytes/ Human recombinant enzymesrecombinant enzymes

Valerian Valerian (VALERIANA (VALERIANA OFFICINALIS) OFFICINALIS)

Inhibits CYP3A4, Inhibits CYP3A4, CYP2C9 and CYP2C9 and CYP2C19CYP2C19

Cytochrome P450 CYP3A4 Cytochrome P450 CYP3A4 supersomessupersomes

VincaVinca(CATHARANTHUS (CATHARANTHUS ROSEUS)ROSEUS)

Inhibits CYP2D6Inhibits CYP2D6 Human Liver MicrosomesHuman Liver Microsomes

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Interactions between other herbs and Interactions between other herbs and drugsdrugs

• Artemesinin

– Artemisinin, - decreases – omeprazole

bioavailability - induction of CYP2C19 activity

(Svensson Svensson et al.,et al., 1998 1998).

• Foeniculum vulgare

– Decrease the rate of absorption of ciprofloxacin

- chelation of the drug (Zhu Zhu et al.,et al., 1999 1999).

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Cont….

• Liquorice

– Antihypertensive drugs - synergistic effect

(Cumming et al., 2003)

– Hydrocortisone - pseudoaldosteronism

(Beate et al., 1999)

– Oral contraceptives - hypertension, edema

and hyperkalemia (Gerty Gerty et al.,et al., 1997). 1997).

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Cont….

• Silymarin

• potentiate the effects of antiarrhythmic drugs

(Gyonos Gyonos et al.,et al., 2001 2001)

• Increases - pharmacological activity of

cisplatin (Scambia Scambia et al.,et al., 1996 1996),

• Decreases the blood concentrations of

– indinavir (Piscitelli Piscitelli et al.,et al., 2002 2002)

– losartan (Han Han et al.,et al., 2009 2009) and

– metronidazole (Chon Chon et al.,et al., 2005 2005)

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ALTERATION OF INRALTERATION OF INRHerbs containing coumarins: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:Herbs containing vitamin K:Eg: Acerola, agrimony, stinging nettle, plantainEg: Acerola, agrimony, stinging nettle, plantain

INHIBITION OF PLATELET INHIBITION OF PLATELET AGGREGATIONAGGREGATION

Bilberry, cayenne, bromelain, capsicum, European mistletoe, feverfew, garlic

INHIBITION OF PLATELET ACTIVATING INHIBITION OF PLATELET ACTIVATING FACTOR (PAF)FACTOR (PAF)

Garlic, GinkgoGarlic, Ginkgo and saw palmettoand saw palmetto

BBLLOOOODD

CCLLOOTTTTIINNGG

Interactions between herbs and drugs acting on Interactions between herbs and drugs acting on bloodblood

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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

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• 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

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• 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

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Herbs to be avoided prior to Herbs to be avoided prior to surgerysurgery

• 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

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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

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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 .

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• 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

Cont….

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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

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• 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

Cont….

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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

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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

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We need to bring into lime light about the herb – drug interactions

CONCLUSION

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Hearbs drugs interaction

Health & Medicine

Transcript of Hearbs drugs interaction