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Toxicity, Mushroom - Disulfiramlike Toxins: Treatment & Medication
Updated: Jun 1, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Prehospital Care
Supportive care and parenteral rehydration are essential.
Emergency Department Care
Symptomatic treatment (eg, antiemetics) and supportive maneuvers are mainstays of medical management.
- Provide intravenous fluids if GI effects have not abated.
- Hypotension generally responds to volume expansion with normal saline.
- Patients with severe hypotension may require vasopressor agents once volume restoration is ensured.
- Direct-acting vasopressors (eg, norepinephrine) are preferred over indirect-acting agents (eg, dopamine).
- Recommendation is an extension of known pharmacology of disulfiram, which inhibits dopamine beta-hydroxylase, thereby depleting presynaptic catecholamines.
- Activated charcoal may be beneficial if mushrooms were ingested recently.
- Fomepizole (4-methylpyrazole) could theoretically be of benefit by blocking alcohol dehydrogenase and formation of acetaldehyde. Its use in the treatment of methanol and ethylene glycol poisoning is well established. Fomepizole is currently very expensive, and its use is not established in this clinical setting.
- Histamine-2 blockers (cimetidine is best studied) reduce the severity of flush and hypotension in Asian patients who experience these effects following ethanol ingestion. The Asian flush is due in part to a relative deficiency of aldehyde dehydrogenase.
- Antiemetics with alpha-adrenergic blocking properties (eg, aliphatic and piperidine phenothiazines) should be avoided.
Consultations
Consultation with a regional PoisonControlCenter, toxicologist, or mycologist may be helpful.
Medication
The goals of pharmacotherapy are to reduce morbidity, to prevent complications, and to neutralize effects of the toxin.
GI decontaminant
These agents are empirically used to minimize systemic adsorption of the toxin.
Activated charcoal (Actidose-Aqua, Insta-Char, Liqui-Char)
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
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
<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
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
Documented hypersensitivity; poisoning or overdosage of mineral acids and alkalies; unprotected airway with absent gag reflex
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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
Antiemetics
These agents are used to control nausea and vomiting.
Metoclopramide (Reglan)
Prokinetic agent that increases GI motility and accelerates gastric emptying. Works as antiemetic by blocking dopamine receptors in chemoreceptor trigger zone of CNS.
Adult
10 mg IV q2-3h; not to exceed 1 mg/kg
Pediatric
<6 years: 0.1 mg/kg IV q2-3h
6-14 years: 2.5 mg IV q2-3h
>14 years: Administer as in adults
May antagonize effects of metoclopramide; opiate analgesics may increase metoclopramide toxicity in CNS
Documented hypersensitivity; pheochromocytoma; GI hemorrhage, obstruction, or perforation; history of seizure disorders; parkinsonism; depression; psychosis; early post-GI surgery
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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)
Prochlorperazine (Compazine)
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
10 mg IV, slowly; may repeat once; not to exceed 40 mg/d
25 mg PR q12h
Pediatric
<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
Coadministration with other CNS depressants or anticonvulsants may cause additive effects; coadministration with epinephrine may cause hypotension
Documented hypersensitivity; bone marrow suppression; narrow-angle glaucoma; severe liver or cardiac disease; parkinsonism; depression
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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
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.
Ranitidine (Zantac)
H2-receptor antagonist that may be a useful adjunct in reducing emesis volume.
Adult
50 mg IV q8h
Pediatric
1 mg/kg IV q6-8h
May decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal or liver impairment; consider adjusting dose or discontinuing treatment if changes in renal function occur during therapy
Antiemetic, Serotonin Antagonist
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.
Ondansetron (Zofran)
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
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
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
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
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May cause headache
More on Toxicity, Mushroom - Disulfiramlike Toxins |
| Overview: Toxicity, Mushroom - Disulfiramlike Toxins |
| Differential Diagnoses & Workup: Toxicity, Mushroom - Disulfiramlike Toxins |
 Treatment & Medication: Toxicity, Mushroom - Disulfiramlike Toxins |
| Follow-up: Toxicity, Mushroom - Disulfiramlike Toxins |
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References
Malcolm R, Olive MF, Lechner W. The safety of disulfiram for the treatment of alcohol and cocaine dependence in randomized clinical trials: guidance for clinical practice. Expert Opin Drug Saf. Jul 2008;7(4):459-72. [Medline].
Garbutt JC. The state of pharmacotherapy for the treatment of alcohol dependence. J Subst Abuse Treat. Jan 2009;36(1):S15-23; quiz S24-5. [Medline].
Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Heard SE. 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report. Clin Toxicol (Phila). Dec 2008;46(10):927-1057. [Medline].
Tayyareci Y, Acarel E. Acute myocardial infarction associated with disulfiram-alcohol interaction in a young man with normal coronary arteries. Turk Kardiyol Dern Ars. 2009;37(1):48-50. [Medline].
Banys P. The clinical use of disulfiram (Antabuse): a review. J Psychoactive Drugs. Jul-Sep 1988;20(3):243-61. [Medline].
Berger KJ, Guss DA. Mycotoxins revisited: Part II. J Emerg Med. Feb 2005;28(2):175-83. [Medline].
Brent J, McMartin K, Phillips S, Aaron C, Kulig K; Methylpyrazole for Toxic Alcohols Study Group. Fomepizole for the treatment of methanol poisoning. N Engl J Med. Feb 2001;344(6):424-9. [Medline].
Carlsson A, Henning M, Lindberg P, Martinson P, Trolin G, Waldeck B, et al. On the disulfiram-like effect of coprine, the pharmacologically active principle of Coprinus atramentarius. Acta Pharmacol Toxicol (Copenh). Apr 1978;42(4):292-7. [Medline].
Christensen JK, Moller IW, Ronsted P, Angelo HR, Johansson B. Dose-effect relationship of disulfiram in human volunteers. I: Clinical studies. Pharmacol Toxicol. Mar 1991;68(3):163-5. [Medline].
Hender E, May T, Beulke S. Poisoning due to eating fungi in Victoria. Aust Fam Physician. Oct 2000;29(10):1000-4. [Medline].
Ho MP, Yo CH, Liu CM, Chen CL, Lee CC. Refractive hypotension in a patient with disulfiram-ethanol reaction. Am J Med Sci. Jan 2007;333(1):53-5. [Medline].
Kunkel DB, Connor DA. Coprine-containing mushrooms. In: Spoerke DG, Rumack BH. Handbook of Mushroom Poisoning: Diagnosis and Treatment. CRC Press, LLC; 1994:303-7.
Meyer JH, Herlocher JE, Parisian J. Esophageal rupture after mushroom-alcohol ingestion. N Engl J Med. Dec 2 1971;285(23):1323. [Medline].
Michelot D. Poisoning by Coprinus atramentarius. Nat Toxins. 1992;1(2):73-80. [Medline].
Miller NS, Goodwin DW, Jones FC, Gabrielli WF, Pardo MP, Anand MM, et al. Antihistamine blockade of alcohol-induced flushing in orientals. J Stud Alcohol. Jan 1988;49(1):16-20. [Medline].
Suh JJ, Pettinati HM, Kampman KM, O'Brien CP. The status of disulfiram: a half of a century later. J Clin Psychopharmacol. Jun 2006;26(3):290-302. [Medline].
Wright C, Moore RD. Disulfiram treatment of alcoholism. Am J Med. Jun 1990;88(6):647-55. [Medline].
Yilmaz A, Gursoy S, Varol O, Nur N, Ozyilkan E. Emergency room cases of mushroom poisoning. Saudi Med J. Jun 2006;27(6):858-61. [Medline].
Further Reading
Keywords
mushroom toxicity, mushroom poisoning, disulfiram-like toxins, toxic mushrooms, coprine, coprine-containing mushroom toxicity, Coprinus atramentarius, C atramentarius, alcohol inky, inky cap, Clitocybe clavipes, C clavipes, fat-footed clitocybe, clubfoot funnel cap, disulfiram, Antabuse
