Herb drug & herb-food interactions

Definition of drug interaction, potential of herb-drug interactions,significance of study of herb-drug interactions, reasons for their study, types according to ayurveda, effects & different ways of herb-drug interactions, their mechanism, hypericum, kava lava, ginkgo biloba, ginseng, garlic, pepper, ephedra.

1. HERB-DRUG & HERB-FOOD INTERACTIONS 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 CONTENTS 2

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.” DRUG INTERACTION: 3

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. POTENTIAL FOR HERB-DRUG INTERACTIONS: 4

5. Herbal drug interactions can affect health & efficiency of treatments as some herbal therapies might: Increase the side effects of drugs, leading to toxicity. Leads to treatment failure due to decrease in effect of drug. Unexpected complications may occur due to modification of drug action. Enhance therapeutic effect of drug. Prescription & non prescription drugs can alter reaction of body to herbal therapies. SIGNIFICANCE TO STUDY HERBAL-DRUG INTERACTIONS: 5

6. Proper information is not available regarding the contents of herbal product. Product information may be incomplete or inaccurate. Herbal product contain many phytoconstituents which are not characterized properly. Lack of adequate knowledge of combinations. REASONS FOR HERBAL-DRUG INTERACTIONS: 6

7. TYPES OF DRUG INTERACTION AS PER AYURVEDA: 7

8. DIFFERENT WAYS OF HERBAL PREPARATIONS TOXICITY : 8

9. 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 . CVS: Antihypersensitive drugs may be adversely affected by use of ginseng & dandelion. Alfalfa enhances effect of hypolipidaemic drrugs . CNS: Sedatve herbs react with hypnotic & anxiolytic drugs. Evening primerose oil can react with epileptogenic drugs. Endocrine system: Ginseng & red clover can interfere with activity of sex hormonal treatment & oral contraceptives. EFFECTS OF HERB-DRUG INTERACTIONS ON VARIOUS SYSTEMS OF BODY: 9

10. MECHANISM OF HERB-DRUG INTERACTIONS: 10

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 . HYPERICUM 11

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. 12

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 Naphthodianthrones 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. 13

14. STANDARDS: FOM: > 3.0 % Alcohol soluble extractive: < 13.0 % Water soluble extractive: <24% LOD: >10% Total ash: >7% Acid insoluble ash: >0.8% 14

15. Anti depressant In treatment of anxiety, seasonal affective disorders. In the treatment of symptoms of menopause, mental disorders, premenstrual syndrome. In treatment of fibromyalgia (chronic rheumatic condition), chronic fatigue syndrome(CFS), burning feelings in the mouth, maigraine , pain, irritable bowel syndrome,skin diseases. Food flavour Hypericin reported to have antiviral potential against HIV & hepatitis C virus. Uses of Hypericum 15

16. Hypericum when taken orally upto 12 weeks, it is considered as safe. Possible side effects are: Trouble sleeping Vivid dreams Restlessness anxiety Irritability Possible side effects of Hypericum: Stomach upset Fatigue Diarrhoea Skin rash Dizziness Dry mouth 16

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. Herb-Drug Interactions of Hypericum: 17

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. KAVA KAVA 18

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. C/C of Kava kava : 19

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. Uses of Kava Kava 20

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 . Herb-Drug Interactions of Kava 21

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 GINKGO 22

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%. 23

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. Uses of Ginkgo: 24

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 . Herb-Drug Interactions of Ginkgo: 25

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. GINSENG 26

27. Steroid like saponin - Ginsenosides . Ginsenosides Rb1, Rb2, Rc , Rd, R, etc comprise 90% of total ginsenosides . Chemical constituents of Ginseng: 27

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. Uses of Ginseng: 28

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. Herb-Drug Interactions of Ginseng: 29

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. GARLIC 30

31. About 1% volatile oils mainly allicin , responsible for particular odour. Alliin , allixin , allylpolysulfides , diallyltrisulphide , N- acetylcysteine , S- allylcysteine & thiacremonone . Chemical constituents if garlic: 31

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 . Uses of garlic: 32

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. Herb-Drug Interactions of Garlic: 33

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. PEPPER 34

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. Chemical constituents of pepper: 35

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. Uses of pepper: 36

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. Herb-Drug Interactions of Pepper: 37

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. EPHEDRA 38

39. 1% of amino alkaloids such as ephedrine, pseudoephedrine, norpseudoephedrine , methylephedrine , including quinoline & 6-hydroxykynurenic acid & tannis . Chemical Constituents of Ephedra : 39

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. Uses of Ephedra : 40

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 . Herb-Drug Interactions of Ephedra : 41

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