Download Chapter 164 - Plants, Mushrooms, and Herbal Medications

CHAPTER 164 Plants, Mushrooms, and
Herbal Medications
Richard D. Shih
PERSPECTIVE
BOTANICAL IDENTIFICATION
Botanicals such as plants, herbal products, and mushrooms have
a long-standing and important place in medical history. Their use
as therapeutic agents has been documented in the earliest of
medical writings. The extraction of alkaloids from the opium
poppy in the 1800s was a forerunner of modern pharmacology.
The general public increasingly is using herbal products for
medicinal purposes. Despite the tremendous growth in popularity
of herbal products, data on herbal efficacy and toxicity are limited.
This chapter focuses not on the medicinal use of natural products
but rather on the toxicology related to their exposure or utility.
Identification of the botanical in question is most useful, but
most patients and medical professionals do not have enough
knowledge of botany or plant identification. The name of the
plant or mushroom is often confusing because the scientific name
is not typically known, and common names often overlap. Most
emergency department personnel cannot identify common plants,
such as mistletoe, holly berries, philodendron, and others. Several
resources may be helpful, including plant atlases, CD-ROM plant
databases, a local botanical expert, botanical garden personnel, or
a poison center. Alternatively, a digital photograph of the plant or
mushroom in question can be quickly e-mailed to a local expert
to aid in identification.5 With herbal products, the product name
or herbal plant may be known. Because of the limited Food and
Drug Administration (FDA) regulation, however, the purported
herb might have been harvested from the wrong plant or contaminated with other toxic material.
Epidemiology
Although plants, mushrooms, and herbal products are derived
naturally, they have different but predictable exposure patterns
and epidemiology. Ingestions fall into three common exposure
patterns.
Unintentional Childhood Exposure
Unintentional childhood exposure occurs most commonly
with plants. Approximately 5% of all poison center calls involve
plants. Of these, about 80% involve children younger than 5 years.
Most of these cases involve household plants with a limited
amount of plant material or toxin ingested, resulting in little or
no toxicity.1,2
Misidentification of Botanical
Natural plant and mushroom gathering for personal food ingestion is a popular activity. Mistakes while foraging commonly
occur, with the potential for serious toxicity and death. In contrast
to unintentional childhood exposures, foraging accidents by adults
usually involve the eating of plants or mushrooms and are associated with a much larger toxin burden because a larger quantity of
the botanical is ingested. Another type of botanical misidentification occurs with herbal products when plants used for herbal
manufacture are misidentified by the manufacturer and incorrectly packaged and marketed.
Plants as Drugs of Abuse
Many plants, mushrooms, and herbals are used and abused
for their mind-altering potential. These include hallucinogenic
mushrooms, peyote, kava kava, and anticholinergic plants such as
jimsonweed.3,4
2066
Plants
Among more than 60,000 plant exposures reported to U.S. poison
centers annually, most plant exposures occur in children (younger
than 5 years) and involve household plants. Hospitalization for
plant poisoning is rare, and fatalities occur in less than one in
10,000 exposures. Of thousands of different plant species, only a
few are dangerously toxic.1,2,6 Following is a more detailed discussion of specific plants focusing on plants that are most poisonous
or most commonly implicated in human exposures.1,6
Abrus precatorius
Abrus precatorius (Fig. 164-1), known by several different common
names (jequirity pea, rosary pea, prayer bean, Seminole bean,
Indian bean, and crab’s eye), contains the toxin abrin, which
affects protein synthesis, leading to cell death. The toxin is found
in highest concentration in the seeds, which are used in jewelry or
decoration. Because of their attractiveness, the seeds are often
ingested by children. The hard, shiny coat causes most seeds to
pass through the gastrointestinal tract without being digested. If
the seeds are chewed or do not pass through the bowel rapidly and
become digested, abrin is released, causing nausea, vomiting, and
abdominal pain, which can be severe, and fluid and electrolyte
balance is disturbed.7-11 Systemic absorption of the toxin is limited
because the protein is enzymatically digested in the gastrointestinal tract. Rare parenteral exposure of small amounts is associated
with severe toxicity and possible death. Treatment is supportive,
with attention to fluid rehydration and electrolytes. Symptomatic
Chapter 164 / Plants, Mushrooms, and Herbal Medications 2067
Figure 164-2. Cicuta maculata (water hemlock). (Courtesy Steven
Setzer.)
Figure 164-1. Abrus precatorius (jequirity pea or rosary pea).
(Courtesy Steven Setzer.)
patients should be given activated charcoal to absorb leaking
abrin, and whole-bowel irrigation has not been studied but may
help in moving numerous seeds more rapidly through the gastrointestinal tract.
Brassaia
The Brassaia is a popular indoor plant known as schefflera,
umbrella tree, Australian umbrella tree, dwarf schefflera, rubber
tree, and starleaf. This plant contains calcium oxalate crystals,
which can cause mouth pain, but most ingestions cause mild or
no symptoms.
Capsicum annum
Capsicum annum includes many types of peppers (e.g., chili
pepper, red pepper, bell pepper) and contains the active toxin
capsaicin. This alkaloid releases and depletes selected nerve terminals of substance P, causing a severe local inflammatory response
manifested by swelling, fluid exudation, and pain, which resolves
rapidly as capsaicin depletes substance P. Capsaicin is not absorbed
well through intact skin, but rarely symptoms can occur with
prolonged and intense exposure.12 Ingestions often cause gastrointestinal symptoms, depending on the amount of toxin exposure.
Most capsaicin exposures are from a pepper spray product, causing
chemical conjunctivitis. Keratitis can occur and is assessed with
fluorescein. Treatment consists of local irrigation and analgesics.
Despite their often dramatic appearance, cases resolve rapidly
during several hours without sequelae.13-15 Use of topical antacids
may be effective for dermal exposures. Inhalation of capsaicincontaining powders is less common but can cause severe pulmonary exudation, potential acute respiratory distress syndrome, and
death.16 Treatment is supportive, but extracorporeal membrane
oxygenation has been used in children who have acute respiratory
distress syndrome.
Cicuta maculata
Cicuta maculata (Fig. 164-2), commonly known as water hemlock,
contains the potent neurotoxin cicutoxin.17 Deaths from water
hemlock are among the most commonly reported plant fatalities
in the United States. Water hemlock has small white flowers at the
ends of umbrella-like stems. They resemble Daucus carota (Queen
Anne’s lace) and Heracleum lanatum (cow parsnip). The mistaking
of water hemlock for one of these edible plants is a common cause
of exposure.18 Ingestion of any part of the plant can lead to nausea,
vomiting, and abdominal cramping. Severe toxicity is manifested
by seizures occurring within the first hour, which often are intractable and are a common cause of death. The toxic mechanism may
be due to γ-aminobutyric acid (GABA) receptor antagonism. The
ingestion is highly toxic and may be fatal. Seizures are common
and are initially treated with benzodiazepines (i.e., lorazepam,
1-2 mg intravenously). If response is poor, treatment is as described
for status epilepticus in Chapter 102. Because of the severe toxicity
and lack of effective antidote, activated charcoal may be useful.
Consultation with a regional poison center may be useful in individual cases.
Conium maculatum
Conium maculatum (Fig. 164-3), or poison hemlock, was purported to be used in the execution of Socrates. It is mistaken for
several edible plants, such as Daucus carota (Queen Anne’s lace),
Foeniculum vulgare (sweet fennel), and Heracleum lanatum (cow
parsnip).19 Poison hemlock contains the toxin coniine, which is
similar to nicotine in structure and toxicity. The clinical picture
and management resemble those of tobacco poisoning (see section
on Nicotiana tabacum).20,21
Datura stramonium
Datura stramonium (jimsonweed) (Fig. 164-4) is one of numerous
plants with alkaloids that have anticholinergic effects (see Chapter
150). The fruit is spiny and when opened contains 50 to 100 black
seeds. All parts (including the seeds) contain the toxins atropine,
hyoscyamine, and scopolamine, which are potent anticholinergic
agents.22,23 One hundred seeds approximate 6 mg of atropine.
2068 PART IV ◆ Environment and Toxicology / Section Two • Toxicology
Figure 164-3. Conium maculatum (poison hemlock). (Courtesy Steven
Setzer.)
Figure 164-5. Dieffenbachia. (Courtesy Steven Setzer.)
plant parts are chewed.33,34 Because of the immediate pain, further
exposure typically is limited. Treatment is aimed at pain relief
and local supportive measures, typified by feeding of ice cream
to a symptomatic infant. Analgesics such as nonsteroidal antiinflammatory drugs or opioids may be needed for pain.
Epipremnum aureum
Epipremnum aureum is a common household plant also known as
pothos ivy, devil’s ivy, hunter’s robe, and golden pothos. Toxicity
is due to calcium oxalate crystals,6 the same toxin found in the
Dieffenbachia, and the toxicity and treatment are similar.
Figure 164-4. Datura stramonium (jimsonweed). (Courtesy Steven
Setzer.)
Exposures are most commonly a result of abuse for hallucinogenic
effects, usually by smoking of dried leaves or ingestion of the
seeds.24-26 The clinical picture is that of the anticholinergic toxidrome.27,28 The symptoms can last for several days if the overdose
is due to ingestion of seeds. It is unclear if activated charcoal and
gastric emptying measures are effective at decreasing the course
of toxicity and are not routinely recommended. Consultation with
a regional poison center may be useful in individual cases.24 Treatment is as for anticholinergic poisoning29,30 (see Chapter 150).
Dieffenbachia
Dieffenbachia (Fig. 164-5) has more than 30 different common
names, including dumb cane, mother-in-law’s tongue, dumb
plant, and tuft root. Some of these names refer to the inability to
talk that can occur after biting into parts of this plant. Typically,
the mucous membranes of the mouth are affected immediately
with severe pain, swelling, and the sensation of biting into glass.
Most cases are limited to the mucous membranes of the oropharynx, but rare cases of airway compromise have been reported.31
The local effects are due to calcium oxalate crystals, packaged into
bundles called raphides, that are found in cellular structures called
idioblasts.32 These idioblasts also contain proteolytic enzymes that
are ejected out of the idioblasts with the oxalate crystals when
Eucalyptus
Eucalyptus plants have common names, such as the silver dollar,
lemon-scented gum, cider gum, and blue gum. These plants are
not toxic but are implicated in frequent plant exposures.35 The
plants are used, however, to produce concentrated (approximately
70%) eucalyptus oil. Ingestion of small amounts (1-3 mL) has
been reported to cause severe toxicity.36 The predominant symptoms are neurologic, including mental status alteration, headache,
ataxia, and seizures. Treatment of severe toxicity is symptomatic
supportive, except for seizures, which are treated as described in
Chapter 102.
Euphorbia pulcherrima
Euphorbia pulcherrima (poinsettia) is a popular ornamental plant
that is frequently implicated in plant exposures. It has a false reputation for being extremely poisonous. Ingestions are benign or
cause minimal toxicity. However, contact dermatitis is relatively
common with skin exposure and can be treated with steroids or
antihistamines. Further discussion is found in Chapter 120.
Ilex
Ilex (holly) contains more than 400 different species and is frequently implicated in plant exposures. The plant’s red and black
berries are attractive to children and contain numerous toxins that
are potent gastrointestinal irritants. Symptoms include nausea,
vomiting, abdominal cramping, and diarrhea. Treatment is supportive and may require intravenous fluids and antiemetics.
Chapter 164 / Plants, Mushrooms, and Herbal Medications 2069
Figure 164-6. Nerium oleander. (Courtesy of Steven Setzer.)
Figure 164-7. Phytolacca americana (pokeweed). (Courtesy Steven
Setzer.)
Nerium oleander
Nerium oleander (Fig. 164-6), or oleander, is one of many plants
that contain toxic cardiac glycosides37,38 structurally similar to
digoxin. Ingestion of several leaves is unlikely to cause serious
symptoms.39,40 Large exposures from suicide attempts or misidentification of plants used for teas or herbal products can lead to
severe toxicity or death. The cardiac glycosides are potent sodiumpotassium–adenosine triphosphatase inhibitors, and the symptoms they cause are similar to those of digoxin poisoning (see
Chapter 152). Measurement of an abnormal digoxin level is only
qualitative proof of exposure because the serum digoxin test can
falsely measure nondigoxin cardiac glycosides. Conversely, a
normal digoxin measurement does not rule out exposure because
the level of cardiac glycoside cross-reactivity varies. Treatment of
dysrhythmias and hypotension includes multidose activated charcoal (50 g every 6 hours for 3 days) and digoxin-specific Fab
antibodies (see Chapter 152).39-44 However, larger doses of Fab
fragments generally are needed than for comparable digoxin poisonings. The initial empirical dose of digoxin-specific Fab fragments is 10 vials. If response to therapy is poor, repeated
administration of an additional 10 vials is recommended.
Nicotiana tabacum
Nicotiana tabacum is widely grown in the southeastern United
States as a source for cigarette and cigar tobacco. Several Nicotiana
species contain nicotine as their major toxin, which activates
and subsequently blocks acetylcholine receptors in the central
nervous system (CNS) and peripheral autonomic nervous system.
Most exposures are the ingestion of cigarettes or cigars by young
children. Dermal exposure to workers harvesting plants and ingestion of wild plants mistaken for edible plants also have led to
poisoning.45,46
The ingestion of one or two cigarettes has the potential to cause
moderate poisoning in children, but most children ingesting cigarettes do not manifest toxicity. Patients without nausea and vomiting do not seem to progress to more severe toxicity.47 Dermal
exposure in tobacco workers has been called green tobacco sickness.48 Nicotine is absorbed through the skin and occurs most
severely when the skin or plant is wet. Exposure can be avoided
by wearing of proper protective equipment.
Symptoms begin shortly after absorption. Nausea, vomiting,
salivation, lacrimation, diarrhea, hypertension, tachycardia, diaphoresis, agitation, and fasciculation are seen initially. More severe
toxicity is manifested by seizures, respiratory depression (muscle
weakness), and hyperthermia.49 Activated charcoal may be useful
to limit absorption. Other treatments are supportive in nature
because no specific antidote for nicotine is available. If seizures
occur, initial treatment is with a benzodiazepine (i.e., lorazepam,
1-2 mg intravenously). If response is poor, treatment is as described
for status epilepticus in Chapter 102. If severe salivation and lacrimation occur, atropine in 1-mg doses may be repeated until
symptoms improve.
Phytolacca americana
Found in the eastern United States, Phytolacca americana (Fig.
164-7) is commonly known as pokeweed, poke, pokeberry, inkberry, scoke, American cancer, garget, phytolacca, and pigeonberry. Although the plant is poisonous, it can be detoxified by
boiling it in water twice before use in salads or other recipes.
Toxicity is seen when the plant is inadequately detoxified or raw
parts of the plant are eaten.50 Symptoms begin shortly after ingestion and include severe nausea, vomiting, abdominal cramping,
and diarrhea. Treatment is supportive.
Pyracantha
Pyracantha, commonly known as the firethorn, has small red,
orange, or yellow fruit attractive to and commonly ingested by
children. The plant is not toxic, but the thorny parts can penetrate
skin deeply and may be difficult to remove.
Rhododendron
Rhododendron includes more than 1000 species of azaleas and
rhododendrons, including mountain laurel, dwarf laurel, rose bay,
western Labrador tea, and Japanese pieris. Numerous structurally
related toxins (diterpene polyalcohols) have been identified from
these plants, including grayanotoxin, rhodojaponin, asebotoxin,
and others.51-53 These toxins bind to sodium channels and increase
2070 PART IV ◆ Environment and Toxicology / Section Two • Toxicology
Figure 164-8. Taxus (yew). (Courtesy Steven Setzer.)
permeability (sodium channel openers), causing cardiovascular
(e.g., bradycardia and hypotension) and gastrointestinal (e.g.,
nausea, vomiting, and abdominal pain) effects. Although ingestion of a few leaves is unlikely to cause symptoms, larger exposures
can cause severe toxicity. In addition, these plant toxins can be
concentrated in honey, so large honey ingestions, “mad honey,”
can also lead to toxicity.52,54 However, no deaths have been reported.
Treatment is supportive; atropine and cardiac pacing are used for
bradycardia. For ventricular dysrhythmias, sodium channel–
blocking agents, such as quinidine and procainamide, are used.
However, limited efficacy data are available for these therapies. If
response is poor, treatment with standard advanced cardiovascular life support (ACLS) protocol is warranted.
Spathiphyllum
Spathiphyllum includes the peace lily, Mauna Loa, white anthurium, and snowflower. These plants contain calcium oxalates and
have toxicity and treatment similar to those of Dieffenbachia.
Taxus
Taxus (yew trees) (Fig. 164-8) have a hard seed surrounded by a
fleshy red cup (the aril). The aril portion is not poisonous, and
the seed has a hard coat that limits toxin release in the gastrointestinal tract so that most ingestions are nontoxic. If the seed
is chewed or leaves are ingested, cardiac (e.g., bradycardia and
hypotension) and gastrointestinal (e.g., nausea, vomiting, and
abdominal pain) symptoms may occur. Deaths from this
plant have been reported, usually in the setting of a suicide and
secondary to cardiac manifestations. Bradycardia is treated with
atropine. Wide-complex tachydysrhythmias are not responsive to
sodium bicarbonate and should be treated per standard ACLS
guidelines.55,56
HERBAL MEDICINES
Herbal products have gained an extraordinary amount of popularity in the past several decades. Although the highest use is
among immigrants and patients with difficult-to-treat diseases,
such as advanced cancer and acquired immunodeficiency syndrome (AIDS), these products are used by approximately 30%
of the general population.57-59 Consumers often perceive herbals
as more “natural” and thus “safer” and “harmless” despite many
examples of toxicity associated with their use. This is coupled with
medical practitioners’ having limited knowledge about herbal
medications. In addition, herbals are widely marketed as safe and
effective, especially on the Internet.60 One study of pregnant
patients documented 45% herbal medicine use during some point
of the pregnancy.61 Emergency department patients are also frequent users of herbal products.62-64
Herbal products are classified as dietary supplements and are
not regulated as medications, even though they are used for their
medicinal value.58,64,65 Regulation of dietary supplements is limited.
Safety, quality, and efficacy for medicines are the responsibility of
manufacturers. For herbal products used as dietary supplements,
of which there are thousands to hundreds of thousands of potential products, the burden of proving efficacy and safety lies with
the FDA.65-68
Studies looking at the efficacy of herbal products are limited,
with few randomized, controlled studies. The National Institutes
of Health sponsored several high-profile randomized placebocontrolled studies assessing the efficacy of several well-known
herbals: St. John’s wort for depression, hawthorne extract for congestive heart failure, echinacea for the common cold, glucosamine–
chondroitin sulfate for arthritis of the knee, saw palmetto for
benign prostatic hypertrophy, and ginko biloba for dementia
onset. Unfortunately, none of these trials has shown the herbal
treatment to be effective.69-74 In addition, herbal manufacturers are
not required to conduct efficacy studies. Studies evaluating side
effects, drug interactions, and toxicity are even less available.
Most herbal products have some direct pharmacologic action.
The potency of these agents is usually limited, however. As a result,
toxicity and side effects from the direct actions of herbal products
are relatively uncommon.69-76
The lack of manufacturing quality control accounts for most
toxicologic problems associated with their use. Four major types
of toxicologic problems are associated with herbal product use:
the misidentification of an herbal plant and toxicity resulting from
a substituted plant, contamination with nonherbal toxic material,
direct toxicity or overdose of the herbal product (Table 164-1),
and drug-herbal interaction (Table 164-2).77
Misidentification of Herbal Plants
Incorrect plant identification and subsequent use in the production of herbal products have occurred on numerous occasions,
leading to epidemic exposures with tragic outcomes. The following examples illustrate this problem.
Herbal Slimming Regimen, 1992
During the early 1990s, the Chinese herb Stephania tetrandra was
used for weight loss in Belgium. More than 100 cases of renal
failure and many cases of urethral dysplasia resulted from toxicity
of this herbal regimen. It was discovered that Aristolochia fangchi,
which contains the nephrotoxin aristolochic acid, was mistakenly
used instead of S. tetrandra.78-81
Paraguay Tea, 1994
The South American herbal tea Paraguay tea is made from Ilex
paraguariensis, used for urinary tract infections, cardiac insufficiency, and “lack of stamina.” In 1994, several individuals had
anticholinergic poisoning from Paraguay tea after the manufacturer had purchased and mistakenly used other plant materials
containing the belladonna alkaloids atropine, scopolamine, and
hyoscyamine directly from farmers before packaging.82
Digitalis lanata, 1997
An herbal dietary supplement used for “internal cleansing” contained 14 herbal ingredients. Two patients had complete heart
Chapter 164 / Plants, Mushrooms, and Herbal Medications 2071
Table 164-1 Common Herbal Medications and Adverse Effects
HERBAL NAME
BOTANICAL NAME
USES
ADVERSE EFFECT
Bee pollen
Apis mellifera
General tonic
Allergic reactions
Betel nut
Areca catechu
Stimulant
Bronchospasm
Blue cohosh
Caulophyllum thalictroides
Menstrual cramps
Nicotinic effects
Astringent, wounds
Dermatitis, GI, hepatic, renal, CNS
Boron
Buckthorn
Rhamnus frangula
Laxative
Diarrhea
Cantharidin
Cantharis
Aphrodisiac
GI, dermatitis, renal
Cat’s claw
Uncaria tomentosa
AIDS, cancer, arthritis
None reported
Chamomile
Matricaria chamomilla
Fever, cough, colds, wounds
Allergic reactions
Chaparral
Larrea tridentata
Cancer, aging, general tonic
Hepatotoxicity
Comfrey
Symphytum officinale
Contusions and sprains
Hepatotoxicity
Compound Q
Trichosanthes kirilowii
AIDS
Pulmonary, CNS
Dandelion
Taraxacum officinale
Diuretic, appetite stimulant
None reported
Dong quai
Angelica polymorpha
Blood purifier, increase circulation
Anticoagulation, dermatitis
Echinacea
Echinacea purpurea
Common cold
Fever, nausea and vomiting
Ephedra
Ephedra spp.
Stimulant, asthma
Hypertension, tachycardia, CNS, MI
Fennel
Foeniculum vulgare
GI illnesses, cough
Allergic reactions
Fenugreek
Trigonella foenumgraecum
Expectorant, anti-inflammatory
None reported
Feverfew
Tanacetum parthenium
Migraines, antipyretic
Post-feverfew syndrome, rebound migraine
Garlic
Allium sativum
Infection, CAD, hypertension
Dermatitis, GI
Germander
Teucrium chamaedrys
Gout, fever, dietary aid
Hepatotoxicity
Ginger
Zingiber officinale
Motion sickness, GI illness
None reported
Ginkgo
Ginkgo biloba
General tonic, depression, anxiety, memory
GI effects, bleeding effects, drug interactions
Ginseng
Panax ginseng
General tonic, depression, stress, anxiety, fatigue
Ginseng abuse syndrome
Arthritis
None reported
Glucosamine
Goldenseal
Hydrastis canadensis
Cutaneous wounds
GI, CNS, and pulmonary effects in overdose
Gordolobo yerba
Senecio longiloba
URI, fever
Budd-Chiari syndrome
Henbane
Hyoscyamus niger
Sedative, GI discomfort
Anticholinergic toxicity
Jimsonweed
Datura stramonium
Asthma
Anticholinergic toxicity
Juniper
Juniperus communis
UTI, kidney stones, appetite
Renal toxicity
Kava kava
Piper methysticum
Sedative, aphrodisiac
Euphoria, CNS
Kumbucha
Cancer, memory loss
None reported
Larkspur
Delphinium consolida
Diuretic, sedative
Lethargy, muscle paralysis
Licorice
Glycyrrhiza glabra
Cough, GI illnesses
Hypokalemia, drug interactions
Ma huang
Ephedra sinica
General tonic, common cold
Sympathomimetic
Mate
Ilex paraguayensis
Stimulant
None reported
Milk thistle
Silybum marinum
General tonic, GI disorders
None reported
Mistletoe
Viscum album
GI illness, cancer, HIV infection
GI, bradycardia, CNS
Nutmeg
Myristica fragrans
Aphrodisiac, hallucinogen
CNS, GI
Parsley
Petroselinum crispum
UTI, kidney stones
Contact dermatitis
Pennyroyal
Mentha pulegium
Abortifacient, GI illnesses
Hepatotoxicity
Rose hips
Rosa canina
URI, vitamin C
None reported
Rue
Ruta graveolens
Menstrual disorders
Contact dermatitis, GI and CNS effects in overdose
Sage
Salvia officinalis
Antiseptic, wounds
Absinthism
St. John’s Wort
Hypericum perforatum
Depression, anxiety
Drug interactions
Sassafras
Sassafras albidum
GI stimulant
Liver, carcinogen
Saw palmetto
Serenoa repens
Benign prostatic hypertrophy
GI effects
Continued
2072 PART IV ◆ Environment and Toxicology / Section Two • Toxicology
Table 164-1 Common Herbal Medications and Adverse Effects—cont’d
HERBAL NAME
BOTANICAL NAME
USES
ADVERSE EFFECT
Scullcap
Scutellaria lateriflora
Nervous disorders, bitter tonic
Hepatotoxicity
Shepherd’s purse
Capsella bursa pastoris
Hypertension, CHF, headaches, menstrual
disorders
None reported
Siberian ginseng
Eleutherococcus senticosus
General tonic
None reported
Soy
Glycine max
Menopause, CAD
Carcinogen
Tonka bean
Dipteryx odorata
Whooping cough
Anticoagulant effect
T’u-san-chi
Gynura segetum
Stimulant tea
Budd-Chiari syndrome
Valerian
Valeriana officinalis
Sleep, anxiety, general tonic
Hepatotoxicity
Woodruff
Galium odorata
Diuretic, anxiety, menstrual disorders
Anticoagulant effect, CNS effects, hepatotoxicity
Wormwood
Artemisia cina
Worm infection, anxiety
Seizures, CNS effects
Yarrow
Achillea millefolium
Poor appetite, GI illnesses
Allergic reactions
Yew
Taxus baccata
GI illness, cancer
Dizziness, bradycardia
Yohimbine
Pausinystalia yohimbe
Sexual disorders, aphrodisiac
Hypertension, agitation, CNS effects
CAD, coronary artery disease; CHF, congestive heart failure; CNS, central nervous system; GI, gastrointestinal; MI, myocardial infarction; URI, upper respiratory infection; UTI,
urinary tract infection.
Table 164-2 Common Herbal-Drug Interactions
HERBAL
DRUG
TYPE OF INTERACTION
Betel nut
Fluphenazine
Prednisone and salbutamol
Extrapyramidal effects
Bronchospasm
Boldo
Warfarin
Increased INR
Chili pepper
ACE inhibitors
Theophylline
Cough
Increased drug absorption
Curbicin
Warfarin
Increased INR
D-400
Oral hypoglycemics
Increased drug concentration and decreased serum glucose
Danshen
Warfarin
Increased INR
Devil’s claw
Warfarin
Increased INR
Dong quai
Warfarin
Increased INR
Fenugreek
Warfarin
Increased INR
Garlic
Warfarin
Increased INR
Ginkgo
Aspirin
Blood thinners
Thiazide diuretics
Warfarin
Increased platelet inhibition
Bleeding side effects
Hypertension
Increased INR
Ginseng
Warfarin
Ethanol
Decreased INR
Increased ethanol clearance
Green tea
Warfarin
Decreased INR
Guar gum
Many drugs
Digoxin
Decreased absorption of drug
Decreased drug concentration
Karela
Chlorpropamide
Decreased serum glucose
Licorice
Oral contraceptives
Prednisolone
Antihypertensives
Hypertension, edema, hypokalemia
Alteration of pharmacokinetics
Hypokalemia
Lycium
Warfarin
Increased INR
Ma huang
Guanethidine
MAO inhibitors
Sympathomimetic effects
Sympathomimetic effects
Mango
Warfarin
Increased INR
Oat bran
Lovastatin
Decreased drug concentration
Papaya
Warfarin
Increased INR
Chapter 164 / Plants, Mushrooms, and Herbal Medications 2073
Table 164-2 Common Herbal-Drug Interactions—cont’d
HERBAL
DRUG
TYPE OF INTERACTION
PC-SPES
Warfarin
Increased INR
Pectin
Lovastatin
Decreased drug concentration
Psyllium
Lithium
Decreased drug concentration
St. John’s wort
Selective serotonin reuptake inhibitors
Theophylline
Digoxin
Cyclosporine
Indinavir
Irinotecan
Nevirapine
Oral contraceptives
Simvastatin
Warfarin
Serotonin syndrome
Decreased drug concentration
Decreased drug concentration
Decreased drug concentration
Decreased drug concentration
Decreased drug concentration
Decreased drug concentration
Decreased drug concentration
Decreased drug concentration
Decreased INR
Siberian ginseng
Digoxin
Increased digoxin levels
Soy
Warfarin
Decreased INR
Tamarind
Aspirin
Increased drug absorption
Wheat bran
Digoxin
Decreased drug concentration
Yohimbine
Tricyclic antidepressants
Hypertension
ACE, angiotensin-converting enzyme; INR, international normalized ratio; MAO, monoamine oxidase.
block because one of the herbal ingredients, plantain, contained
Digitalis lanata (a cardiac glycoside–containing plant).83
Dandelion Salad, 2004
Dandelion is a commonly ingested herb used as an appetite stimulant and diuretic. Many users grow and harvest their own plants.
A 53-year-old woman who had ingested some home-grown dandelion had persistent nausea, vomiting, and bradycardia with a
heart rate between 30 and 40 beats/minute. Her bradycardia persisted for several days and had associated syncope. Her diagnosis
was unclear until it was discovered that she had mistakenly harvested and ingested foxglove instead of dandelion.84
Contamination with Nonherbal
Toxic Material
Contamination with nonherbal toxic material as a mechanism of
herbal toxicity may be due to contamination of the products at
the time of manufacture or consumer fraud. Because of the limited
FDA regulation of herbal manufacturers, one of the major risks
of herbal use is the use of a product contaminated with a toxic
substance. A study of Asian herbal patent medications sold in
California found that 32% of these products were contaminated
with heavy metals or undeclared pharmaceuticals.85
Lead, mercury, arsenic, cadmium, aluminum, tin, zinc, and
copper have been found in herbal products.86-89 The most common
undeclared pharmaceuticals include ephedrine, chlorpheniramine, methyltestosterone, and phenacetin.90 Metal shavings have
been added to herbal preparations to increase selling price when
the herbals are sold by weight. Some herbal products use the metal
as an active ingredient with a purported medicinal benefit (e.g.,
lead in azarcon or mercury in cinnabar). Other cases involve contamination with the metals during the manufacturing process.89-91
Consumer fraud in the herbal industry has been well documented
on numerous occasions. Typically, an FDA-controlled pharmaceutical product is mixed in with an herbal product, or the label did
not list the pharmaceutical agent.
Chuifong toukuwan, an herbal preparation, was associated with
several cases of agranulocytosis. Analysis revealed that it contained
phenylbutazone, indomethacin, and aminopyrine.92 Gan mao
tong, an herbal product found to contain phenylbutazone, caused
aplastic anemia.93 An undefined herbal preparation that was used
“to avoid taking other medicine” was found to contain triamcinolone. A patient using the product for more than 1 year had several
manifestations of steroid excess: thoracic compression fractures,
proximal muscle weakness, and osteoporosis.94 Tung shueh, an
herbal product that was found to contain mefenamic acid and
diazepam, caused gastrointestinal bleeding and acute interstitial
nephritis.95 Another herbal product was found to contain mefenamic acid, which caused acute renal failure necessitating hemodialysis. Dr. Tong Shap Yee’s asthma pills were found to contain
theophylline.96 Leng Pui Kee herbal cough remedy was found to
contain bromhexine.96
Direct Toxicity of Herbals
and Herbal-Drug Interactions
Some herbal preparations can cause allergic reactions ranging
from contact dermatitis to anaphylactic shock (Box 164-1).97,98
Other herbal products are associated with uncommon idiosyncratic reactions, particularly hepatic toxicity (see Table 164-1).99-104
Herbal products are often taken in overdose. Not controlled by a
prescription system, herbal medicines are seen as natural and safe
so that “if one is good, then two or three is better.” Direct toxicity
is often due to this overuse. Herbs associated with specific toxicities and side effects are listed in Table 164-1.89,96,98,105-107
Concurrent herbal and pharmaceutical use is common and can
cause drug interactions. Of U.S. adults, 18% who take prescription
medications also use an herbal or mineral supplement, and
60% who use alternative therapies are unlikely to report this to
their physicians.108 Individuals often do not consider that herbs
can potentially interact with conventional medicines, and serious
drug reactions associated with an herbal product are less likely
to be reported than are reactions that occur with a conventional
medicine. Common herbal-drug interactions are listed in
Table 164-2.109,110
2074 PART IV ◆ Environment and Toxicology / Section Two • Toxicology
BOX 164-1 Herbals Associated with Allergic Reactions
Agnus castus
Angelica
Aniseed
Apricot
Aristochol
Arnica
Artichoke
Asafetida
Balxum of Peru
Bee pollen
Bee venom
Black cumin oil
Boneset
Camphor
Capsaicin
Cassia
Cedar wood oil
Celery
Chamomile
Chrysanthemum
Cinnamon
Cowslip
Curcumin
Dandelion
Echinacea
Elecampane
Euphorbia
Fennel
Feverfew
French marigold
Fucus
Garlic
Gingko
Gravel root
Guaiacum
Holy thistle
Hops
Hydrangea
Hydrocotyle
Inula helenium
Jasmine
Juniper
Kava
Lady’s slipper
Lavender
Mai-Men-Dong-Tang
Meadowsweet
Motherwort
Paprika
Parsley
Peppermint oil
Pilewort
Plantain
Pulsatilla
Rosemary
Rosewood
Royal jelly
Rue
Slippery elm
Tansy
Tea tree oil
Tung seed
Wild carrot
Yarrow
Ylang-ylang
Table 164-3 Mushroom Groups
GROUP/TOXIN
REPRESENTATIVE
EXAMPLE
CLINICAL EFFECTS
Early Onset of Symptoms
Coprine
Coprinus atramentarius
Disulfiram reaction with
alcohol
GI toxin
Many species
Nausea, vomiting, diarrhea,
abdominal pain
Ibotenic acid
and muscimol
Amanita muscaria
Diverse CNS effects,
including hallucinations,
seizures, delirium, coma,
agitation
Muscarine
Clitocybe dealbata
Peripheral cholinergic
toxidrome
Psilocybin
Psilocybe cubensis
CNS effects, including
hallucinations and euphoria
Late Onset of Symptoms
Cyclopeptides
Amanita phalloides
GI effects followed by
hepatotoxicity
Gyromitrin
Gyromitra esculenta
GI effects followed by
seizures
Orellanine
Cortinarius orellanus
GI effects followed by renal
toxicity
Allenic
norleucine
Amanita smithiana
GI effects followed by renal
toxicity
CNS, central nervous system; GI, gastrointestinal.
and management is most often used to identify the highest risk
ingestions.
MUSHROOMS
Mushroom Groups
U.S. poison center data estimate that five exposures take place for
every 100,000 population per year. These exposures occur in three
types of situations: ingestion of wild mushrooms by young children playing outdoors (which usually results in a small exposure),
mistaken selection of poisonous mushrooms while foraging for
edible wild mushrooms intended for a meal (which leads to a
larger toxin exposure and most of the severe cases of mushroom
poisoning, including deaths), and abuse of certain mushrooms for
their mind-altering potential.3,4 Mushrooms of abuse typically
involve a young population that often abuses other drugs. Most of
these cases do not come to medical attention and often involve
other substances added to the mushrooms. Despite the potential
for severe toxicity and death, most exposures are relatively
benign.2,111,112 Approximately 5% result in moderate poisoning,
with only a few deaths reported per year.
Ten general groupings have been found to be useful for clinical
management (Table 164-3). These groups can be classified into
mushrooms with early onset of symptoms (0-4 hours after ingestion), late onset of symptoms (<6 hours after ingestion), or no
symptoms (edible). Mushrooms with serious toxicity and potential for death have late onset of symptoms. Particular attention
should be paid to the timing of initial symptoms.113-115 Mushroom
species often grow together, and foragers frequently pick and eat
more than one species of mushroom so that the onset of early
symptoms does not preclude the diagnosis of a more serious
poisoning.
Management of Mushroom Exposure
The prognosis depends on the specific species. Identification of
the mushroom is the most helpful factor in deciding on a treatment plan. Techniques for mushroom identification are described
in most mycology and toxicology textbooks. Local mycologists or
a poison center may be helpful. If a specimen is available, it can
be stored in a paper bag at room temperature for delivery. Alternatively, a digital picture can be taken and e-mailed.5 Vomitus can
be collected because mushroom parts may be recovered. Despite
these measures, the species is unknown in more than 90% of
ingestions. Because Amanita species are responsible for most
deaths, a clinical strategy or algorithm for differential diagnosis
Early Onset of Symptoms
Gastrointestinal symptoms of nausea, vomiting, diarrhea, and
abdominal cramps are common among many of the mushroom
groupings (see Table 164-3). These symptoms are most predominant, however, in the gastrointestinal toxin group. This group
contains numerous diverse mushrooms, many with unknown
toxins. They cause symptoms rapidly (0.5-3 hours) after ingestion,
and symptoms typically last 24 hours. Treatment is supportive,
with good outcome expected.
CNS effects are associated with two groups of mushrooms,
ibotenic acid–muscimol and psilocybin.113,114 Psilocybin is structurally related to serotonin and lysergic acid diethylamide (LSD).
Similar to LSD, hallucinations and CNS effects are prominent.
This mushroom is most often used as a drug of abuse and is often
obtained from Internet sources.3,4,116 Ibotenic acid and muscimol
are toxins that are structurally related to glutamic acid and GABA.
Chapter 164 / Plants, Mushrooms, and Herbal Medications 2075
Glutamic acid is an excitatory neurotransmitter, whereas GABA is
an inhibitory one. Lethargy, hallucinations, seizures, or severe agitation begins within 1 to 2 hours after ingestion. Treatment of
seizures and supportive care produce a good outcome.
The cholinergic toxidrome is associated with muscarinecontaining mushrooms. Muscarine is structurally related to acetylcholine. Because of muscarine’s quaternary structure, it does
not cross the blood-brain barrier. Symptoms include salivation,
lacrimation, urination, defecation, gastroenteritis, and emesis
(SLUDGE). Atropine can be used for severe symptoms. Pralidoxime is not indicated because acetylcholinesterase inhibition is not
involved.117
The final mushroom group causes early onset of symptoms
only with simultaneous ingestion of ethanol.118 These coprinecontaining mushrooms cause a disulfiram-like reaction by blocking acetaldehyde dehydrogenase. The symptoms include flushing,
nausea, vomiting, and headache. The onset of this reaction associated with ethanol can occur 30 minutes to several days after mushroom ingestion. Treatment is supportive and similar to that of
disulfiram reactions from other causes.
Late Onset of Symptoms
Four groups of mushrooms cause late onset of symptoms (>6
hours after ingestion): cyclopeptide, gyromitrin, orelline/
orellanine, and allenic norleucine. The orelline/orellanine-containing mushrooms are infrequently found in the United States,
and there have not been any reported cases of toxicity in North
America. The allenic norleucine–containing mushrooms have
involved the Amanita smithiana mushroom located in the Pacific
Northwest. Only a few cases (<20 total cases) have been reported
and have typically involved individuals foraging from that area of
the United States for the edible matsutake or pine mushroom
(Tricholoma magnivelare). The main toxicity is delayed-onset renal
failure. Gastrointestinal symptoms are frequently present and may
be manifested early after ingestion. These symptoms typically
subside, and patients present with renal symptoms 3 to 4 days after
ingestion.119 The cyclopeptide group is responsible for most
mushroom-related deaths in the United States.
The cyclopeptide mushrooms contain many species, of which
Amanita phalloides is the most well known.120 Several cyclopeptide
toxins have been identified (e.g., amatoxins, virotoxins, phallotoxins) that are thought to be responsible for toxicity.121,122 Initial
manifestations, such as severe nausea, vomiting, diarrhea, and
abdominal cramping, begin 6 to 24 hours after ingestion. Hydration and supportive care often lead to initial relief of symptoms
and a relatively quiescent period. Hepatic toxicity followed by
other end-organ involvement may ensue in the next several days
to weeks. Progressive elevation of hepatic transaminases, jaundice,
and hepatic encephalopathy can lead to death.121
Many cases are misdiagnosed as gastroenteritis. Numerous noninvasive therapies have been suggested, including silibinin, silybin,
thioctic acid, activated charcoal, high-dose penicillin, dexamethasone, vitamin C, cytochrome c, cimetidine, N-acetylcysteine,
kutkin, and aucubin.122,123 None of these therapies has been rigorously tested in human-controlled studies. Multidose administration of activated charcoal seems to be reasonable because of its
ability to bind the toxins and its availability and relative safety;
however, its effectiveness is unclear.
Numerous invasive therapies also have been proposed for use
in cyclopeptide poisoning, including forced diuresis, hemodialysis,
hemoperfusion, hemofiltration, plasmapheresis, and hepatic
transplantation.124-127 Similar to the noninvasive modalities, it is
not clear if any of these therapies are effective. There have been
several reports of successful transplantation in severe cases of
poisoning124-127; however, it is uncertain what criteria should be
used for selection of candidates.127-130 Patients with severe hepatic
signs and symptoms should be considered for transfer to a transplant center.
Gyromitrin-containing mushrooms commonly are mistaken
for edible mushrooms as they look like Morchella species (morel)
mushrooms.131 The metabolites of this toxin cause GABA neurotransmitter depletion similar to isoniazid toxicity, leading to
excitatory CNS effects, such as headaches, agitation, and seizures.
Effects also include nausea, vomiting, and possible hepatotoxicity.
The onset of symptoms is at least 6 hours after ingestion. Because
of its similarity to isoniazid toxicity, pyridoxine has been proposed
as an antidote. It is unclear how effective this antidote is, but it is
useful for gyromitrin-induced CNS effects because of its availability and safety profile.
Orelline/orellanine-containing mushrooms (Cortinarius genus)
have been found in North America. There have been no reports
of toxicity associated with cases in the United States, however, with
most reported cases in Europe. Symptoms begin 1 to 2 days after
ingestion, with nausea, vomiting, abdominal pain, and headache.
Renal toxicity is manifested days to weeks after these initial symptoms and can progress to chronic renal failure.132,133
Disposition
Initial management is aimed at ruling out of mushroom groups
associated with early onset of symptoms. If the patient remains
asymptomatic after a 3-hour period of observation, the patient
should be discharged with instructions to return if any symptoms
are manifested during the next 72 hours.
KEY CONCEPTS
■ Plant exposures occur commonly in children and most
commonly involve household plants. Most exposures cause
little or no toxicity.
■ Plants and mushrooms are often ingested for their mindaltering properties.
■ Misidentification of plants and herbal products is a common
cause of plant-induced and herbal product–induced toxicity.
■ Natural plant and mushroom gathering for personal ingestion
is a popular activity. Mistakes while foraging occur
commonly, with the potential for serious toxicity and
numerous fatalities.
■ Herbal medicines increasingly are being used by the general
public. Limited information is available about the efficacy and
toxicity of these products.
■ In the assessment of a patient exposed to a mushroom, the
timing of initial symptoms and the assessment for associated
symptoms constitute the most important data needed to
make a differential diagnosis.
■ A patient who has eaten or been exposed to a wild
mushroom may have another medical condition actually
responsible for the symptoms.
The references for this chapter can be found online by
accessing the accompanying Expert Consult website.
Chapter 164 / Plants, Mushrooms, and Herbal Medications 2075.e1
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