You are in: eMedicine Specialties > Emergency Medicine > TOXICOLOGY Toxicity, Mushroom - Disulfiramlike ToxinsArticle Last Updated: Jun 7, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: C Crawford Mechem, MD, MS, FACEP, Associate Professor, Department of Emergency Medicine, University of Pennsylvania School of Medicine; EMS Medical Director, Philadelphia Fire Department C Crawford Mechem is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, and Society for Academic Emergency 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 Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; 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: coprine-containing mushroom toxicity, Coprinus atramentarius, C atramentarius, alcohol inky, inky cap, Clitocybe clavipes, C clavipes, fat-footed clitocybe, clubfoot funnel cap, disulfiram, Antabuse, mushroom toxicity, mushroom poisoning, disulfiram-like toxins, toxic mushrooms, coprine INTRODUCTIONSection 2 of 10
  BackgroundEdible wild mushrooms often are gathered by foragers and prized for their taste. Occasionally, toxic mushrooms are mistaken for edible species, and human poisoning occurs. In addition, some food aficionados around the globe will intentionally eat certain mushrooms, despite their content of known toxins. For example, Coprinus atramentarius contains the heat-stable toxin, coprine, which only causes toxicity when consumed with ethanol. Because victims of mushroom poisoning will most commonly seek initial medical care in emergency departments, it is important that emergency physicians be familiar with the diverse signs and symptoms of mushroom toxicity. Coprinus atramentarius C atramentarius, a member of Coprinaceae or inky cap family, is known familiarly as alcohol inky or inky cap. This mushroom is found particularly during autumn months in urban regions and along roadsides throughout the Other coprine-containing mushrooms Other Coprinus mushrooms that contain coprine include Coprinus insignis, Coprinus quadrifidus, and Coprinus variegatus. Some Coprinus mushrooms generally are not toxic, such as Coprinus comatus (ie, shaggy mane, lawyer's wig), which is sought for its asparaguslike qualities. Clitocybe clavipes C clavipes, of the family Tricholomataceae, is also associated with disulfiramlike reactions. However, coprine has not been identified in this species. C clavipes tends to grow in conifer trees or mixed woods and fruits in late autumn or winter. Its cap is gray-brown, mostly flat, and 1-3 inches in width. Gill extends down a stem that is club shaped and thickened near the base. C clavipes is commonly called fat-footed clitocybe or clubfoot funnel cap. PathophysiologyC atramentarius contains coprine (N5-1-hydroxycyclopropyl-L-glutamine), a protoxin without intrinsic toxicity. Coprine is metabolized to 1-aminocyclopropanol, which inhibits the enzyme aldehyde dehydrogenase (ALDH). ALDH catalyzes conversion of acetaldehyde to acetic acid. Inhibition of ALDH produces a clinical syndrome similar to disulfiram (Antabuse) alcohol reaction. Disulfiram has been widely used in the manufacture of rubber since the 1800s. In 1937, an American chemical plant physician noted that employees exposed to disulfiram in the workplace developed a constellation of symptoms after drinking ethanol. These included flushing, headache, nausea, palpitations, and dyspnea, and the symptoms were severe enough to promote abstinence from ethanol. In later years, the basis for this effect, the disulfiram-mediated inhibition of ALDH, was discovered. Ethanol usually is metabolized by alcohol dehydrogenase to acetaldehyde, which is then metabolized by ALDH to acetate and carbon dioxide. Accumulation of acetaldehyde leads to the clinical manifestations of the disulfiram-ethanol interaction. Disulfiram has been widely used in the treatment of alcohol dependence, although its benefits are the subject of controversy. After ingestion of coprine-containing mushrooms, ALDH is inhibited and consumption of ethanol results in acetaldehyde accumulation. This inhibition of ALDH takes at least 30 minutes, which is the time required to metabolize inactive coprine to active 1-aminocyclopropanol. Therefore, small volumes of ethanol ingested concomitantly with mushrooms may not cause toxicity. Enzyme inhibition generally persists for approximately 72 hours but may continue for 5 days. Ingestion of ethanol 3 days after mushroom ingestion may produce acetaldehyde toxicity. Unlike disulfiram, coprine does not appear to inhibit dopamine beta-hydroxylase, the enzyme that hydroxylates dopamine to form norepinephrine within storage vesicles of presynaptic neurons. In experimental models, rats exposed to coprine are capable of eliciting a tachycardic response to ethanol challenge; those exposed to disulfiram are not capable of eliciting this response (presumably due to inhibition of dopamine beta-hydroxylase). Whether a similar response occurs in humans is unknown. FrequencyUnited StatesAccording to data gathered by the American Association of Poison Control Centers Toxic Exposure Surveillance System (TESS), coprine-containing mushrooms account for a minority of reported mushroom exposures. Of 7146 mushroom exposures reported to TESS in 2005, only 10 cases were strongly suspected or confirmed to be related to coprine-containing mushrooms. Six of these patients were treated in health care facilities. No deaths were reported.1 InternationalNo adequate database exists to determine frequency of coprine exposure or toxicity internationally, although some sources suggest a 1-3% frequency of all reported mushroom poisonings. Mortality/Morbidity
AgeSince ethanol ingestion precedes toxicity, children generally are not affected. CLINICALSection 3 of 10
HistoryHistory of mushroom ingestion is helpful. Raw and cooked mushrooms and the cooking water are capable of producing toxicity through ALDH inhibition. Symptoms begin within minutes of ethanol ingestion. Patients may relate symptoms to ethanol, not mushrooms. Ascertaining if other species of wild mushrooms were ingested concomitantly and the approximate elapsed time since ingestion is important.
Physical
CausesAn association with ethanol always exists, although ethanol use may be unintentional (eg, cough syrup). DIFFERENTIALSSection 4 of 10
Alcohol and Substance Abuse Evaluation Bulimia CBRNE - Botulism Esophageal Perforation, Rupture and Tears Gastroenteritis Hyperventilation Syndrome Panic Disorders Shock, Hypovolemic Sunburn Toxic Shock Syndrome Toxicity, Mushroom - Amatoxin Toxicity, Mushroom - Gyromitra Toxin Toxicity, Mushroom - Orellanine Toxicity, Organophosphate and Carbamate Toxicity, Scombroid Urticaria
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| Drug Name | Activated charcoal (Actidose-Aqua, Insta-Char, Liqui-Char) |
|---|---|
| Description | Most useful if administered within 4 h of ingestion. Repeat doses may be used, especially with ingestion of sustained release agents. Limited outcome studies exist, especially when administration is more than 1 h after ingestion. Administration of charcoal by itself (in aqueous solution), as opposed to coadministration with a cathartic, is becoming the current practice standard because no studies have shown benefit from cathartics and, while most drugs and toxins are adsorbed within 30-90 min, laxatives take hours to work. Dangerous fluid and electrolyte shifts have occurred when cathartics are used in small children. When ingested dose is known, charcoal may be given at 10 times ingested dose of agent over 1 or 2 doses. |
| Adult Dose | 1 g/kg PO/NG (50-75 g usual dose); may administer 0.5 g/kg PO/NG as repeat dose if desired Cathartic: Not recommended |
| Pediatric Dose | <2 years: Cathartic administration not recommended 1 g/kg PO/NG (12.5-25 g usual dose); may administer 0.5 g/kg PO/NG as repeat dose prn |
| Contraindications | Documented hypersensitivity; poisoning or overdosage of mineral acids and alkalies; unprotected airway with absent gag reflex |
| Interactions | May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; decreased levels occur when given with sherbet, milk, or ice cream |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Protect airway prior to administration in patients with absent gag reflex or a depressed level of consciousness; when considering repeat dosing, monitor for active bowel sounds to minimize risk |
These agents are used to control nausea and vomiting.
| Drug Name | Metoclopramide (Reglan) |
|---|---|
| Description | Prokinetic agent that increases GI motility and accelerates gastric emptying. Works as antiemetic by blocking dopamine receptors in chemoreceptor trigger zone of CNS. |
| Adult Dose | 10 mg IV q2-3h; not to exceed 1 mg/kg |
| Pediatric Dose | <6 years: 0.1 mg/kg IV q2-3h 6-14 years: 2.5 mg IV q2-3h >14 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; pheochromocytoma; GI hemorrhage, obstruction, or perforation; history of seizure disorders; parkinsonism; depression; psychosis; early post-GI surgery |
| Interactions | May antagonize effects of metoclopramide; opiate analgesics may increase metoclopramide toxicity in CNS |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Caution in history of mental illness and Parkinson disease; may cause altered mental status and movement disorders (eg, extrapyramidal syndromes with dystonic reactions, tardive dyskinesia) |
| Drug Name | Prochlorperazine (Compazine) |
|---|---|
| Description | May relieve nausea and vomiting by blocking postsynaptic mesolimbic dopamine receptors through anticholinergic effects and depressing reticular activating system. In addition to antiemetic effects, it has the advantage of augmenting hypoxic ventilatory response, acting as a respiratory stimulant at high altitude. |
| Adult Dose | 10 mg IV, slowly; may repeat once; not to exceed 40 mg/d 25 mg PR q12h |
| Pediatric Dose | <20 lb: Not recommended 20-29 lb: 2.5 mg PR bid 30-39 lb: 2.5 mg PR tid <12 years: 0.06 mg/lb IM |
| Contraindications | Documented hypersensitivity; bone marrow suppression; narrow-angle glaucoma; severe liver or cardiac disease; parkinsonism; depression |
| Interactions | Coadministration with other CNS depressants or anticonvulsants may cause additive effects; coadministration with epinephrine may cause hypotension |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Drug-induced Parkinson syndrome or pseudoparkinsonism occurs frequently; akathisia is most common extrapyramidal reaction in elderly persons; lowers seizure threshold; caution with history of seizures; may cause hypotension, altered mental status, and NMS |
H2-receptor antagonists are reversible competitive blockers of histamine at the H2 receptors, particularly those in the gastric parietal cells where they inhibit acid secretion. The H2-receptor antagonists are highly selective, do not affect the H1 receptors, and are not anticholinergic agents.
| Drug Name | Ranitidine (Zantac) |
|---|---|
| Description | H2-receptor antagonist that may be a useful adjunct in reducing emesis volume. |
| Adult Dose | 50 mg IV q8h |
| Pediatric Dose | 1 mg/kg IV q6-8h |
| Contraindications | Documented hypersensitivity |
| Interactions | May decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Caution in renal or liver impairment; consider adjusting dose or discontinuing treatment if changes in renal function occur during therapy |
These agents are used to treat vomiting and symptomatic nausea resulting from radiation therapy and/or chemotherapy, for postoperative nausea and vomiting, and for general symptomatic relief.
| Drug Name | Ondansetron (Zofran) |
|---|---|
| Description | Selective 5-HT3-receptor antagonist that blocks serotonin both peripherally and centrally. Indicated for nausea and vomiting due to radiation and/or chemotherapy, for postoperative nausea and vomiting, and for general symptomatic relief. While historically an expensive medication, recent availability of a generic form has removed cost as a consideration. |
| Adult Dose | Nausea and vomiting secondary to gastric irritation: 4-8 mg PO q8h; 4-8 mg IV q4h up to 3 doses While not studied specifically in setting of poisoning by mushrooms containing disulfiramlike toxins, dosing similar to other indications seems appropriate |
| Pediatric Dose | Nausea and vomiting secondary to gastric irritation: 4 mg PO q8h; 0.1-0.15 mg/kg IV q4h up to 3 doses While not studied specifically in setting of poisoning by mushrooms containing disulfiramlike toxins, dosing similar to other indications seems appropriate |
| Contraindications | Documented hypersensitivity |
| Interactions | Although potential for cytochrome P-450 inducers (barbiturates, rifampin, carbamazepine, and phenytoin) to change half-life and clearance of ondansetron, dosage adjustment is not usually required |
| Pregnancy | B - Usually safe but benefits must outweigh the risks |
| Precautions | May cause headache |
Toxicity, Mushroom - Disulfiramlike Toxins excerpt
Article Last Updated: Jun 7, 2007
