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    562P ToxicHerbal PDF

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    Tl. Ii. TOXIC HERBAL PRODUCTS Introduction Herbal Medicines and Their Toxic Effects A. Herbs that contain carcinogens B. Herbs that can cause CNS toxicities C. Herbs that can cause cardiac toxicities and respiratory depression D. Herbs that can cause tissue organ damage E. Herbs and related products that cause other toxic effects Mechanisms of Toxicity A. Pennyroyal B. Germander TOXIC HERBAL PRODUCTS. Sid Nelson, Med Chem 525 December 2009 L Introduction n. Herbal Medicines and Their Toxic Effects A. Herbs that contain carcinogens B. Herbs that can cause CNS toxicities C. Herbs that can cause cardiac toxicities and respiratory depression D. Herbs that can cause tissue organ damage E, Herbs and related products that cause other toxic effects III. Mechanisms of Toxicity A. Pennyroyal B. Germander References: 1, B. Bertram, ef al, “Mutagenic and Carcinogenic Constituents of Medicinal Herbs Used in Europe or in the USA” Pharmazie $6:99-120 (2001). 2, _ B, Emst, “The Risk-Benefit Profile of Commonly Used Herbal Therapies: Ginkgo, St. John’s Wort, Ginseg, Echinacea, Saw Palmetto, and Kava” Ann Intern Med 136:42-53 (2002). 3. P.A.G.M, De Smet, “Health Risks of Herbal Medicines: An Update” Clin. Pharmacol. Ther. 76:1-17 (2004), 4, A. Sparreboom, et al., “Herbal Remedies in the United States: Potential Adverse Interactions with Anticancer Agents” J. Clin. Oncol. 22:2489-2503 (2004), 5. PD. Coexeter, et al.,“Herb-Drug Interactions: An Evidance Based Approach” Current Medicinal Chemistry 11:1513-1525 (2004). 6. F.Stickel, et al,,“Herbal Toxicity” J. Hepatol. 43:901-910 (2005). 7. “Herbal Supplements ~ Drug Interactions: Scientific and Regulatory Perspectives” Series: Drugs and The Pharmaceutical Sciences, Vol. 162, (F. Lam et al., eds.) Informa Healtheare, New York (2006). 8. Symposium on Toxicity & Drug Interactions of Herbs & Dietary Supplements Clinical Toxicology 442603 ff (2006) 9. S, Shalansky, et al., “Risk of Warfarin-Related Bleeding Events and Supratherapeutic International Normalized Ratios Associated with Complementary and Alternative Medicine: A Longitudinal Analysis” Pharmacotherapy 27:1237-1247 (2007). 10. S. Chitturi and G.C. Farrell, “Hepatotoxic Slimming Aids and Other Herbal Hepatotoxins” J. Gastroenterol. Hepatol. 23:366-373 (2008). 11, DM. Cato et al, “Use of Prescription and Over-the-counter Medications and Dietary Supplements Among Older Adults in the United States” J. Amer. Med. Assoc. 300:2867-2878 (2008), 12, G, Mazzanti ef al, “Hepatotoxicity from Green Tea: A Review of the Literature and Two Unpublished Cases” Eur. J. Clin. Pharmacol, 65:331-341 (2009), I. Introduction American Herbal Products Association (AHPA) Safety Rating Scale Class 1 - Class 2. - 2a: 2b: 2c: 24: Class 3 - Class 4 - Herbs that can be safely consumed when used appropriately Herbs for which the following use restrictions apply, unless otherwise directed by an expert qualified in their use: For external use only. Not to be used during pregnancy. Not to be used while nursing, Other specific use restrictions as noted. Herbs for which significant data exist to recommend the following labeling: "To be used only under the supervision of an expert qualified in the appropriate use of this substance." Labeling must include proper use information: dosage, contraindications, potential adverse effects, and drug interactions, and any other relevant information related to the safe use of the substance. Herbs for which insufficient data are available to classify. Historically Toxic Herbs: Hemlock (Conium maculatum) ~ Digitalis (Digitalis purpurea) - Belladona (Atropa belladona) - Lily of the Valley (Convallaria majalis) - - Larkspur (Delphinium spp.) - Castor beans (Ricinus communis) - Il. Toxic Herbal Medicines A. Herbs that contain carcinogens 1. Comfrey (Symphytum officinale) - 2. Coltsfoot (Tussilago farfara) - 3. Borage (Borago officinalis) - 4. Life root (Senecio aureus) - 5. Sassafras (Sassafras albidum) - 6. Calamus (Acorus calamus) ~ 7. Chinese herbs containing aristolochic acid, e.g., GuanMuTong (Aristolochia fangchi, Aristolochia manshuriensis) Herbs that can cause CNS toxic effects 1, Ephedra (Ephedra sinica) - 2. Yohimbine (Corynanthe yohimbe) - 3. Camphor (Cinnamomum camphorur) - Herbs that cause cardiotoxicity and respiratory depression 1. Ephedra (Ephedra sinica) - 2. Pokeroot (Phytolacca americana) - 3. Senna (Cassia acutifolia) - 4, Lobelia (Lobelia inflata) - 5. Oleander (Nerium oleander) - Herbs that can cause tissue organ damage Chaparral (Larrea indentata) - 2. Jin Bu Huan (Lycopodium servatum) - 3. Oil of Cloves (Eugenia caryophyllues) - 4. Pennyroyal (Mentha pulegium, Hedleoma pulegoides) - Germander (Teucrium chaemadrys) — 6. Lichen (Usnic Acid) ~ 7. Green Tea Extract (Camelia sinensis) - 8. Oil of Wormwood (Artemesia absinthe) 9. Chinese slimming herbals (Stephania tetrandra; Magnolia officinalis) and Chinese herbals containing aristolochic acid (see IIA.7) E. Herbs and related products that cause other toxic effects 1. Ginkgo (Gingko biloba) - 2. Echinacea - St. John's Wort - 4. Amygdalin - 5. Black Cohosh (Cimicifuga racemosa) - 6. L-Tryptophan - DHEA - 8 GBL- 9, Pau d'Arco plus Sculleap (Tabebuia lapacho or taheebo plus Scutellaria lateriflora) - Contraindications and Drug Interactions of Some Commonly Used Herbal Products Alphabetically by common name of herbal product 1. Black Cohosh (Cimicifuga racemosa)- AHIPA classification (2b,c) not to be used in pregnancy or when nursing; Drug Interactions: has estrogenic effects that can lead to hyperestrogenic effects in patients on estrogens or can counteract the effects of antiestrogens (e.g., patients on tamoxifen for breast cancer), 2. Chamomile (tea) - AHPA classification (1) although generally is contraindicated in pregnancy due to emmenagogue effects; no known drug interactions even though it contains coumarins. 3. Dong Quai Root (Angelica sinensis)- AH'PA classification (2b) not to be used in pregnancy; Drug Interactions: increases the hypoprothrombinemic response to warfarin. 4, Echinacea - AHPA classification (1) but is contraindicated in progressive systemic diseases and autoimmune disorders (e.g., TB, MS, AIDS, cheumatoid arthritis, lupus) and is not to be used with potentially hepatotoxic drugs such as anabolic steroids, methotrexate, amiodarone, ketoconazole, and troglitazone; Drug Interactions: may interfere with immunosuppressive therapy. 5. Evening Primrose Oil (Ocenothera biennis) - AHPA classification (1) but is contraindicated in schizophrenics and patients on phenothiazines. 6. _ Feverfew - AHPA classification (2b) not to be used in pregnancy due to emmenagogue effect; Drug Interactions: May increase the hypoprothrombinemic effects of other anticoagulant drugs. 7. Garlic cloves (Allium sativum) - AHPA classification (2c) contraindicated in patients on anticoagulant or hypoglycemic therapies unless carefully monitored. 8. Ginger (Zingiber officinale) - AHPA classification (1) but is contraindicated in patients with gallstones and some say in pregnancy (maybe only at high dose); Drug Interactions: anticoagulant and hypoglycemic effects at high doses. 9. Ginkgo (Gingko biloba) - AHPA classification (1) but is contraindicated in patients with high blood pressure; Drug Interactions: increases the hypoprothrombinemic effects of warfarin and one report of intracerebral hemorrhage; may diminish the effectiveness of anticonvulsants and tricyclic antidepressants; decreases effect of insulin. 10. Asian Ginseng (Panax ginseng) - AHPA. classification (2d) contraindication in patients with high blood pressure (180/90mm Hg) patients with psychiatric disorders, and in pregnancy; Drug Interactions: may accentuate the effects of stimulant drugs, may have hypoglycemic effects, and may increase the hypoprothrombinemic effect of warfarin; can lead to falsely high readings for digoxin levels in digoxin assays with no digoxin-like effects or toxicity. 1 14, 16. Hawthorn berries (Cratageus species) - AHPA classification (1) but is contraindicated in patients on conventional therapies for hypertension and cardiac disorders. Kava Kava - AHPA classification (2b,c,d1) is contraindicated in pregnancy, nursing mothers, and use no more than three months as it can lead to exfoliative dermatitis. Licorice root (Glycerrhiza glabra) - AHPA classification (2b,d) is contraindicated in pregnancy and in patients who have renal insufficiency or are overweight and hypertensive or with other cardiac problems; Drug Interactions: mineralocorticoid effects lead to potassium loss and sodium and water retention complicating therapy with thiazides and dig meds. ‘Saw Palmetto (Serenoa repens) - AHPA classification (1); Drug Interactions: due to antiandrogenic effects concomitant therapy with hormonal therapy should be avoided. St. John’s Wort (Hypericum perforatum) ~ AHPA classification (24) is contraindicated in pregnancy and nursing and patients subject to photosensitivity or undergoing UV therapy; Drug Interactions: not to be used with prescription antidepressants; CYP3A inducer —> inactivation of CYP3A substrate drugs such as cyclosporin and HIV protease inbibitors; likely P-glycoprotein-inducer + digoxin concentrations. Valerian (Valeriana officinalis) - AHPA classification (1) though it is contraindicated in patients on other sedative therapy or who drink alcohol, and continued use has been associated with melancholia and hysteria, Recommendation for counseling patients Discourage use of herbal products with drugs that have a narrow therapeutic index (e.g., warfarin, digoxin, cyclosporin, theophylline). If a patient uses herbal products with Western medicines, have them watch carefully for evidence of altered drug effect or toxicity. Determine if a female user is pregnant or nursing or planning on becoming pregnant and caution accordingly. Do not recommend a product that contains toxic ingredients. Advise against the use of many herbal remedies at the same time. Advise against the use of herbal products if the patient is taking several prescription or OTC drugs already, unless you are sure of the safety of the product with all of these other medications. Advise against the use of large doses of any herbal product or their long-term, continued use unless carefully monitored. ci [TRADINDICATI! INTERACTION Pregnancy and/or Lactation Gallstones Autoimmune Disorders or use of Immunosuppressive Drug or Potentially Hepatotoxic Drugs Warfarin Hypertension, CHF andior use of Digoxin, Diuretics and other Heart Medications Estrogenic or Androgenic Therapies or Anti-therapies CNS Disorders or use of CNS Medications HERBAL PRODUC Black Cohosh Chamomile Dong Quai Feverfew Ginseng Kava Licorice St. John's Wort Ginger Echinacea Dong Quai Feverfew Garlic Ginkgo Ginseng Danshen Ginseng Hawthorn Licorice Ephedrine-containing Senna Pokeroot Black Cohosh Dong Quai Saw Palmetto Ephedrine-containing Evening Primrose Ginkgo Ginseng Kava St. John's Wort Valerian Yohimbine Seattle Post-Intellingencer Saturday October 26, 1996 Concern over ‘herbal abortion’ Pennyroyal can be toxic if it's used incorrectly, doctors caution By TOM PAULSON 1 REORTER The woman was six weeks pregnant and dant want tobe, gen! aban ke eed oe surgea ‘abortion, sbe eile to éo" evel = ‘etal wing t geal bea brew crated from a member of te mint family, pennyroyal “Within hous, afer {fist saw ber, she was Deeding from every oie" sald De. Sande Suan en shstetnciangynecologt at Group Heals Eastide Hospital “Ive never seen anything lke" “The woman bled profs, then went ino ki sults elesiein nor et, ale by atc respiration Saban sid. The ye Si worst, who adel ot Wty cae Peas Insptized but "recovering. She may sllneed habitation restment for poeta! newsologial damage embed ter omeecn "What happened to tis gil is jst unbelievable” Sultan suid boing that she sl roped 2 Suapical orton Fenryropal, in lea and in concentrated ol form, ic widely wala as an herb or dietary supplement in health food stores and herb shops. Doctors and herbalists alike say they are concerned shout an increased interes in pentyroyal as “natural” etn Sey Naor dean of te! Unies of yr. Sidey Nal aersty of Washingion School of Phamacy ‘and a. haticoaly recognized expert on pentru kis, sid eases of Cet nnyoyalis an aromatic ‘herb in the mint fr Its leaves are useg ‘making tea which sbeteved to relax spasmodi pan, ease Anxiety and relieve abdominal Pressure Its main use has been to stimulate the menstrual brocess and strengthen Uterine contraction. Ithas ‘been use to induce abortions, but most exerts belive fils todo 80 umes taken in Potentatly lethal amounts, Peonyroyal me we Pit rae Pennyroyalindued nes yay re poty document Sorted is “Pennyroyal poisoning continues to occur regularly,” Nelson and his eolngues. reported a te Apel 1666

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