You are in: eMedicine Specialties > Emergency Medicine > TOXICOLOGY Plant Poisoning, HerbsArticle Last Updated: Oct 10, 2006AUTHOR AND EDITOR INFORMATIONAuthor: Fermin Barrueto Jr, MD, Assistant Professor, Department of Surgery, Division of Emergency Medicine, University of Maryland Fermin Barrueto, Jr, is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine Coauthor(s): Jon Mark Hirshon, MD, MPH, Associate Professor, Department of Emergency Medicine, University of Maryland School of Medicine Editors: B Zane Horowitz, MD, FACMT, Professor, Fellowship Director, Department of Emergency Medicine, Oregon Health and Sciences University; Medical Director, Oregon Poison Center; Medical Director, Alaska Poison Control System; John T VanDeVoort, PharmD, ABAT, Director of Pharmacy, Sacred Heart Hospital; Michael Hodgman, MD, Assistant Clinical Professor of Medicine, Department of Emergency Medicine, Bassett Healthcare; John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center; Asim Tarabar, MD, Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital Author and Editor Disclosure Synonyms and related keywords: herbal products, herbal preparations, Atropa belladonna, A belladonna, Datura metel L fastuosa, Datura stramonium, jimson weed, deadly nightshade, Hyoscyamus niger, henbane, Mandragora officinarum, scopolamine-containing mandrake, kava-kava, Piper methysticum, St. John's wort, Hypericum perforatum, Podophyllum emodi, Podophyllum peltatum, mayapple, mandrake, Lobelia inflata, Nicotiana, Strychnos nux-vomica, strychnine, Digitalis lanata, ephedra, Ma Huang, Aconitum, monkshood, wolfsbane, Veratrum, Cinchona bark, Heliotropium, heliotrope, Senecio, gordolobo, Crotalaria, Symphytum, comfrey, Mentha pulegium, pennyroyal oil, squaw mint, germander, creosote bush, greasewood, hediondillo, Jin Bu Huan, Syo-saiko-to, Dai-saiko-to, Aristolochia, birthwort, heartwort, fangji, licorice root, ginkgo biloba INTRODUCTIONBackgroundAlthough most plant exposures are unintentional, many adults ingest herbal products for self-treatment of illness and health maintenance. What constitutes an herbal product is generally ill defined. This article discusses several plants and plant products commonly used to improve health or to treat illness as herbs and herbal products. While many herbal products are innocuous or possess minimal toxicity, some contain toxic ingredients that may not be identified on the label. These unidentified ingredients may be unintentionally included in the product (eg, misidentification of a toxic plant as a desired nontoxic plant) or adulterated for increased effect (eg, addition of a pharmaceutical agent to an herbal preparation). Dietary supplements, including herbal products, are regulated under the Dietary Supplement Health and Education Act (DSHEA) of 1994 as a food product. This Act does not require these products to be efficacious or safe prior to marketing. The Food and Drug Administration (FDA) has little control over which herbal products are marketed, but it may prohibit sales of herbal products containing pharmaceutical agents. The FDA also may prohibit sale of an herbal product proven to have serious or unreasonable risk under conditions of use on the label or as commonly consumed; prohibition of an herbal product generally occurs after marketing and extensive distribution to the public. The burden of proof lies with the FDA and consumer reporting. Previous case reports and studies reveal that herbal products may contain ingredients, sometimes toxic, not listed on the label; also, quantities of ingredients listed on the label can vary greatly, hindering definition of toxic ingredients and unsafe products for public consumption. Herbs and herbal products in this article are discussed because of their reported toxicity and increased use in the general patient population. Many herbal products continue to be available to the public with either ill-defined or unknown toxicity. PathophysiologyHerbal products are generally heterogeneous, may produce multiple effects, and may affect multiple organs systems, including the nervous, cardiovascular, GI, hepatic, renal, and hematologic systems. The following herbal products are divided into specific toxic plants by the system most severely affected. Central nervous system Anticholinergic toxicity may be seen. Atropa belladonna contaminated burdock root tea in the 1970s and 1980s, resulting in anticholinergic toxicity. Datura metel L fastuosa mistakenly has been used in place of Campsis and Paulownia species, producing anticholinergic poisoning. Plants with anticholinergic activity include Datura stramonium (jimson weed), A belladonna (deadly nightshade), and Hyoscyamus niger (henbane). In the 1970s, ginseng contaminated with Mandragora officinarum (scopolamine-containing mandrake) produced anticholinergic toxicity. Kava-kava (Piper methysticum) is an herbal preparation that may be brewed into a beverage and is especially popular among natives of the South Pacific islands. Methysticine and kawain (a local anesthetic) are its main constituents; however, primary effects of kava-kava are anxiolytic, myorelaxant, and sedation. This herbal preparation has been associated with hepatotoxicity. St. John's wort (Hypericum perforatum) is a weak monoamine oxidase inhibitor (MAOI) and serotonin agonist. Concern has been raised regarding initiation of hyperadrenergic MAOI-reactions by mixing adrenergic preparations, such as ephedra and ephedrine-containing preparations, with St. John's wort; however, no cases of serotonin syndrome or MAOI crisis have been linked to the use of St. John's wort. When taken in conjunction with other prescription medications, St. John's wort may decrease systemic bioavailability. Podophyllum emodi and Podophyllum peltatum (mandrake and mayapple, respectively) contaminated herbal preparations (eg, Gentiana and clematis) in the 1980s and 1990s. Podophyllin causes metaphase arrest at the cellular level and altered mental status, peripheral motor and sensory neuropathy, gastroenteritis, and multisystem organ failure. Lobelia inflata and Nicotiana products can cause nicotine toxicity with hypertension, fasciculations, and CNS excitation. Severe cases may progress to neuromuscular paralysis. Older versions of smoking-deterrent tablets contained Lobelia. Strychnos nux-vomica (strychnine) has been found in imported herbal patent medicines and can cause abdominal distress. Although frequently formulated in homeopathic doses, toxic amounts of strychnine cause profound metabolic acidosis, rhabdomyolysis, and generalized "spinal seizures" in fully alert patients. Cardiovascular system Cardiac glycosides and other cardioactive steroid contaminants may cause toxicity. Digitalis lanata was mistaken for plantain and caused severe cardiotoxicity (eg, complete heart block) in 1997 when consumed as an internal cleansing product. An outbreak of digoxinlike deaths occurred in New York City when a Chinese aphrodisiac called Chan-Su was sold. The labeling was in Chinese and stated that the product was meant to be applied topically, but several people ingested it. This product contained an extract from the venom of Bufo toads, which caused the deaths. These types of ingestions can be treated with digoxin-specific Fab. Ephedra and ephedrine-containing products (eg, Ma Huang) may produce cardiac stimulation, hypertension, peripheral vasoconstriction, chest pain, myocardial infarctions, and intracerebral hemorrhage. Ma Huang (ephedra) may produce hypersensitivity myocarditis (case report) and vasculitis. A sufficient public outcry and data collected on adverse effects have enabled the FDA to ban ephedra products from the United States. Aconitum species (ie, monkshood or wolfsbane) contain aconitine; Veratrum species contain veratrum alkaloids. These toxins open sodium channels in cardiac myocytes, resulting in conduction blockade, bradycardia, ventricular dysrhythmias (especially bidirectional tachycardia), and refractory cardiovascular collapse. Aconitine-containing Chinese herbal medicine compounds have been used to treat chronic pain syndromes and unfortunately have also been associated with deaths in Asia and Australia. Cinchona bark ingestion can cause quinine toxicity. Hepatic system Hepatic toxicity with Budd-Chiari syndrome has been reported with pyrrolizidine alkaloids, which are metabolized to alkylating agents that produce hepatic veno-occlusive disease, hepatomegaly, and cirrhosis. These herbal products include Heliotropium (heliotrope), Senecio (gordolobo), Crotalaria, and Symphytum (comfrey). Senecio and Crotalaria have been used in Jamaica to make bush tea. Toxicity can affect the fetus as well. Mentha pulegium (ie, pennyroyal oil, "squaw" mint) teas have been mistaken for other mint teas and have been used intentionally as abortifacients. These teas contain the hepatotoxin, pulegone, which causes hepatocellular necrosis. Pulegone toxicity can result in multisystem organ failure. Germander and kava can cause centrilobular necrosis. In France, germander was marketed as a slimming agent in the 1990s; fatalities were reported. Chaparral (ie, creosote bush, greasewood, hediondillo) can produce periportal injury, inflammatory changes, scarring, cholangitis, and cholestasis. Jin Bu Huan may have varying compositions, but some preparations have caused fatal hepatic injury. Other preparations have caused severe bradycardia. Syo-saiko-to (a mixture of 7 herbs) has been associated with toxic hepatitis. Dai-saiko-to has reportedly produced an autoimmune hepatitis. Kombucha tea is a symbiotic mixture of yeast and bacteria brewed into tea. Case reports describe a syndrome characterized by hepatotoxicity, pulmonary edema, and disseminated intravascular coagulation (DIC) after ingestion. Renal system Aristolochia species (eg, birthwort, heartwort, fangji) can cause interstitial renal fibrosis due to aristolochic acid, a known nephrotoxin. Licorice root may cause profound renal potassium loss (see Plant Poisoning, Licorice). Hematologic system Ginkgo biloba has been reported to increase bleeding times and may have contributed to intracranial hemorrhages. Yohimbine use has been associated with agranulocytosis (probably an idiosyncratic response) and priapism. Dysosma pleianthum (ie, bajiaolian) contains podophyllotoxin and causes thrombocytopenia and leukocytosis. Jui, a Chinese herbal medication, has been associated with thrombocytopenia. A reaction may be triggered by repeat exposure because of sensitization from previous exposure or exposures. Jui contains Sinomeni caulis et rhizoma, Glycyrrhizae radix, Aralia elata, Glechomae herba, and Taxus cuspidata. L-tryptophan has been contaminated with a by-product and associated with 38 deaths. Numerous chronic pulmonary effects are known collectively as eosinophilia-myalgia syndrome. Elevated eosinophil levels are characteristic of the syndrome. Other systems Echinacea and chamomile tea can cause anaphylaxis. Royal jelly and yohimbine can cause allergic reactions. Shiitake mushrooms can cause severe dermatitis. Garlic, chamomile tea, and capsicum may produce contact dermatitis. Some herbal products contain high concentrations of heavy metals, such as lead, mercury, and arsenic (also found in kelp); they can cause heavy metal toxicity. (Use of ayurvedic medications should arouse suspicion of heavy metal contamination). Some herbal preparations are adulterated with undeclared ingredients (eg, caffeine, acetaminophen, indomethacin, hydrochlorothiazide, ephedrine, chlorpheniramine, methyltestosterone, prednisolone, phenacetin). Adulteration with mefenamic acid and cadmium has resulted in acute renal failure. Adulteration with dipyrone and phenylbutazone has resulted in agranulocytosis. Some herbal products have potentially dangerous endocrine effects, despite claims to the contrary, such as the estrogenic PC-SPES (a combination of 8 herbs). Recent incidence of toxicity due to herbal medication with oral sulfonylureas has been reported. FrequencyUnited StatesAccording to a rural Mississippi study, almost three fourths of respondents had used plant-derived remedies during the preceding year. Another study found that one third of US citizens have used herbal medicines. One survey in an urban hospital showed herbal use to be 27% and highest (36%) among the Asian population. A national survey examining trends in alternative medicine found that use of at least 1 of 16 alternative therapies increased from 33.8% in 1990 to 42.1% in 1997. InternationalThe World Health Organization (WHO) has estimated that herbal and other plant-derived remedies are the most frequently used therapies worldwide. WHO estimates that 4 billion people, 80% of the world population, use herbal preparations for primary healthcare. One South Australian survey found that 48.5% of respondents used at least one nonmedically prescribed alternative medicine (including vitamins). Mortality/MorbidityThe FDA noted 2621 adverse drug reactions and 184 deaths due to herbal products over a 5-year period. However, the report relied on voluntary physician reporting, which may substantially underestimate total incidence. Actual mortality and morbidity are difficult to assess due to underreporting. RaceSome ethnic groups are more likely to utilize herbal preparations. One survey in a New York urban hospital showed overall herbal use to be 27% and highest (36%) among the Asian population. CLINICALHistoryThe following questions are necessary to ascertain specific history:
PhysicalEvaluate the patient for possible toxidromes such as anticholinergic syndromes or those consistent with cardiac glycosides or heavy metal poisonings.
CausesAdverse effects from herbal preparations can be categorized by type.
DIFFERENTIALSAnaphylaxis Cholangitis Cholecystitis and Biliary Colic Cholelithiasis Depression and Suicide Encephalitis Gastroenteritis Glomerulonephritis, Acute Heart Block, First Degree Heart Block, Second Degree Heart Block, Third Degree Hepatitis Hyperkalemia Hypertensive Emergencies Hypokalemia Idiopathic Thrombocytopenic Purpura Meningitis Munchausen Syndrome Munchausen Syndrome by Proxy Pediatrics, Anaphylaxis Pediatrics, Child Abuse Pediatrics, Gastroenteritis Pediatrics, Meningitis and Encephalitis Pediatrics, Reactive Airway Disease Pediatrics, Reye Syndrome Pediatrics, Sudden Infant Death Syndrome Plant Poisoning, Glycosides - Cardiac Plant Poisoning, Glycosides - Coumarin Plant Poisoning, Hypoglycemics Plant Poisoning, Licorice Plant Poisoning, Oxalates Plant Poisoning, Phytophototoxins Premature Ventricular Contraction Renal Failure, Acute Rhabdomyolysis Toxicity, Mushroom - Amatoxin Toxicity, Mushroom - Gyromitra Toxin Toxicity, Mushroom - Hallucinogens Toxicity, Mushroom - Orellanine WORKUPLab Studies
Imaging Studies
Procedures
TREATMENTPrehospital Care
Emergency Department Care
ConsultationsConsider consultation with a poison control center and medical toxicologist. They may know of recent similar case presentations in the area and assist with management. MEDICATIONFor toxic ingestions in general, consider activated charcoal. Other care should be based on patient's symptomatology.
Drug Category: GI decontaminationThese agents are used empirically to adsorb toxin in GI tract, thereby limiting systemic absorption. They are most effective if administered within 1 hour of ingestion. In selected cases, repeated doses may be beneficial if the toxin is entero-hepatically metabolized allowing a second opportunity to bind and remove it from the body.
FOLLOW-UPFurther Inpatient Care
Patient Education
MISCELLANEOUSMedical/Legal Pitfalls
REFERENCES
Plant Poisoning, Herbs excerpt Article Last Updated: Oct 10, 2006 |