sign in sign up
<<
Home , Amanita pantherina, Conocybe, Mushroom poisoning, Panaeolus

Brief managing common in companion animals

❖ PEER-REVIEWED in dogs Rhian B. Cope, BVSc, BSc (Hon 1), PhD, DABT

ushroom poisoning of identification (e.g. the Oregon Poi- companion animals, par- son Center [(800) 222-1222]) or a M ticularly dogs, is a poten- mycologist as needed.9,10 tially underestimated problem in North America. Because of their Cyclopeptides wandering and scavenging na- , , and ture, dogs seem particularly species contain toxic prone to .1-8 cyclopeptides. Amanita species are While there have been sporadic the most commonly documented reports of mushroom poisoning cause of fatal mushroom - in dogs in the veterinary litera- ing in dogs,1,2,4-8 and they account ture,1-8 anecdotal experience in for 95% of mushroom-related fa- the Pacific Northwest suggests it talities in people.9 Amanita phal- is more prevalent than the litera- loides, the death cap mushroom ture indicates. (Figure 1), accounts for more than This article summarizes the 50% of all mushroom-associated clinical effects of the toxicologi- deaths in people and most of the cally important mushrooms in reported fatal cases in dogs.1,2,6,9 North America. Spring, summer, The toxic cyclopeptides in these 1. , the death cap and fall are the principal seasons mushrooms are , phallo- mushroom, is the most common cause of 8,9 for mushroom poisoning in most potentially fatal mushroom poisoning in , and . These pep- 9 of North America. people and dogs. tides are rapidly absorbed from the gut, and their duration of action is IDENTIFICATION AND TREATMENT increased by enterohepatic circulation and active resorp- Toxic mushrooms are divisible into eight groups based on tion of amatoxins from the renal glomerular filtrate. Ama- their type (Table 1).9 Six of these groups are of poten- toxins and are responsible for most of the tial veterinary significance, and representative members of pathologic effects.9 Amatoxins interfere with DNA and these groups are common throughout North America.9 In RNA transcription and, thus, selectively affect the rapidly line with the adage, “There are old mushroom hunters, replicating cells of the gastrointestinal (GI) and renal tubu- there are bold mushroom hunters, but there are no old, lar epithelium and liver. Phallotoxins irreversibly polymer- bold mushroom hunters,” all wild-growing mushrooms ize hepatic actin filaments, triggering hepatic cholestasis.9 should be regarded as toxic until proven otherwise. Typically, 10 to 12 hours pass between consumption Ideally, samples of the ingested mushrooms should and the onset of clinical signs.9 This delay is an impor- be brought in to the clinic along with the affected ani- tant differential diagnostic feature of cyclopeptide inges- mal. Do not place mushrooms for identification in a tion and is probably due to the time required for amatox- plastic bag; instead, wrap them in a moist paper towel ins to bind to intranuclear RNA polymerase II.9 or wax paper or place them in a paper bag. Identifying There are three distinct sequential phases of cyclopep- mushroom species is often complex, so consult a human tide poisoning. The initial gastroenteritis phase is charac- poison information center with experience in mushroom terized by profuse bloody , , nausea, abdominal pain, dehydration, electrolyte imbalance, “Toxicology Brief” was contributed by Rhian B. Cope, BVSc, BSc (Hon 1), fever, tachycardia, and hyperglycemia.9 This phase typi- PhD, DABT, Department of Environmental and Molecular Toxicology, cally lasts about 24 hours. The resolution of clinical signs College of Agricultural Sciences, Oregon State University, Corvallis, OR 97331.The department editor is Petra Volmer, DVM, MS, DABVT, DABT, and subclinical elevations of serum alanine transaminase College of Veterinary Medicine, University of Illinois, Urbana, IL 61802. and aspartate transaminase activities characterize the

Photo ©iStockphoto.com/Tomasz Resiak Photo ©iStockphoto.com/Tomasz Veterinary Medicine February 2007 95 Toxicology Brief PEER-REVIEWED

TABLE 1 Toxicologic Classification of Toxic Mushrooms

Toxin Type Relevant Species Methods of Cyclopeptides Amanita species (death Amatoxins inhibit RNA and DNA transcription, caps, death angels, destroying affecting cells with the highest replication rates. angels, deadly ), Galerina Phallotoxins irreversibly polymerize hepatic species actin filaments, resulting in cholestasis. species (false morels) is converted to monomethyl- hydrazine. Other toxic hydrazines are also

present. They antagonize pyridoxine (vitamin B6), an essential cofactor for the synthesis of GABA. They also directly inhibit the synthesis of GABA. Coprinus atramentarius (ink cap) Hyperacetaldehydemia is triggered if () is consumed within two to 72 hours after consuming the mushrooms. Probably not of veterinary significance. , , , Produces the classical muscarinic cholinergic , Boletus, Hebeloma, clinical signs: SLUD (salivation, lacrimation, , and species urination, and diarrhea). Isoxazole derivatives Amanita species and are psychoactive and generally produce distortions in visual perception. and psilocin , Panaeolus, , The LSD-like compounds cause dysphoria, Gymnopilus, , and , and sympathomimetic effects. species (hallucinogenic or magic mushrooms) GI irritants , Boletus, Chlorophyllum, Most of the agents that trigger acute GI distress Entoloma, Gomphus, Hebeloma, have not been identified. Idiosyncratic and Lactarius, Naematoloma, allergic mechanisms have been proposed. Omphalotus, Paxillus, Ramaria, Many, but not all, of these toxins are inactivated Rhodophyllus, , Scleroderma, by cooking. and Tricholoma species Orelline and species from Europe These species cause irreversible acute renal and Japan failure; often the only effective treatment is renal transplant. onset of the 12- to 24-hour latent phase.9 The final—and gency upper GI decontamination (inducing emesis or gas- often terminal—hepatorenal phase of poisoning begins tric lavage) is probably not beneficial more than four three to four days after .9 Severe hepatic dys- hours after ingestion since phallotoxins and amatoxins function, severe renal failure, cerebral edema, icterus, ele- are rapidly absorbed from the GI tract and do not form vated serum hepatic enzyme activities, hypoglycemia, gastric concretions or delay gastric emptying.9 Induce coagulopathies and hemorrhage, azotemia, metabolic emesis only in asymptomatic animals because of the risks acidosis, and sepsis characterize the hepatorenal phase. associated with this procedure. In addition, neurologic dysfunction including hepatic en- The effectiveness of activated charcoal is unknown, cephalopathy and coma can occur.9 Typically, the animal but its use has been recommended.9 Administer an acti- dies three to seven days after ingestion.9 vated charcoal slurry (1 g/5 ml water) orally at a dose of 2 to 5 ml/kg in combination with a mild cathartic (sor- Treatment. Early aggressive decontamination and bitol 3 mg/kg orally).11 Repeated doses of activated char- enhanced elimination are critical.6,8,9 Performing emer- coal may be administered every four to six hours in an

96 February 2007 Veterinary Medicine attempt to reduce the enterohepatic circulation of ama- verse effects, treatment can be attempted by administer- toxins and may be of value up to 48 hours after inges- ing a loading dose of 140 mg/kg orally followed by 70 tion.9 Adequately hydrate patients treated with multiple mg/kg orally every six hours for as long as the patient doses of activated charcoal to prevent constipation.11 Re- needs it based on clinical judgment. peated doses of sorbitol may cause marked hypotension or hypovolemic shock, particularly in patients with un- Monomethylhydrazine derlying cardiovascular problems or in small patients, so Gyromitra species of mushrooms, often called false morels, monitoring is required if repeated doses of activated vary considerably in their toxicity from year to year and charcoal and sorbitol are administered.11 location to location. Of the several different toxic hy- Enhanced elimination using peritoneal dialysis and drazine compounds found in these mushrooms, gy- other methods of extracorporeal elimination has yielded romitrin is the best known.9 occasional therapeutic successes in people.6,9 Administer- The hydrolysis of gyromitrin in the gut results in the ing parenteral penicillin G benzathine at doses greater formation of monomethylhydrazine, a GI irritant, and than 4,300 U/kg, which subsequent gastroenteritis displaces amatoxins from within six to eight hours plasma protein-binding The final hepatorenal of ingestion. Most cases sites making them more are relatively mild and available for renal excre- phase of cyclopeptide self-limiting; however, ex- tion, has been claimed to treme poisonings charac- improve survival in peo- terized by hepatic damage ple.9 However, a recent 20- poisoning begins have been reported in year retrospective analysis people.9 Monomethyl- has demonstrated that this three to four days hydrazine also directly in- treatment, alone or in com- hibits the synthesis of bination with other agents, after ingestion. gamma-aminobutyric acid has little efficacy.12 (GABA) within the central Supportive care involves administering intravenous (CNS) and antagonizes pyridoxine (vita- crystalloids, glucose, fresh frozen plasma, GI protectants min B6), an essential cofactor for the synthesis of GABA. (e.g. kaolin/pectin 1 to 2 ml/kg orally every six to 12 The net result is uncontrolled CNS electrical activity, anxi- hours), and broad-spectrum parenteral antibiotics to re- ety, restlessness, excitation, and .9 duce the risk of sepsis. Oral supplementation or par- enteral treatment with vitamin K1 (2.5 to 5 mg/kg daily) Treatment. Pyridoxine (25 mg/kg administered as a and packed or whole blood transfusions slow intravenous infusion over 15 to 30 minutes) has may be required if bleeding is severe. been recommended as an for the neurologic ef- Silibinin dihydrogen disuccinate disodium and fects of this type of mushroom poisoning.9 Additional acetylcysteine have been suggested as for cy- treatment consists of upper GI decontamination and clopeptide poisoning.9 Silibinin is a semisynthetic, com- supportive care. Because of the risk of precipitating mercialized, active derivative of silymarin, the hepato- seizures, inducing emesis in severe monomethylhy- protectant and antioxidant mixture of medicinal drazine poisoning cases is potentially risky. Inducing flavonolignans derived from milk thistle (Silybum mari- emesis with due clinical prudence and judgment may be anum). Administering silibinin intravenously (20 to 50 appropriate for milder cases. Activated charcoal admin- mg/kg/day in four doses) substantially increases the istration has been recommended, although its effective- survival rate in people.9 Unfortunately, the injectable ness is unknown.9 Rehydration by using intravenous form of this antidote is not available in the United States, crystalloids is the most commonly required supportive and the poor water solubility and bioavailability of sily- treatment.9 Oral GI protectants may be beneficial. If nec- marin may limit the effectiveness of this potential anti- essary, anxiety, restlessness, and seizures can be con- dote when orally administered. Silipide, a complex of trolled with a benzodiazepine (0.25 to 0.5 mg/kg di- silymarin and phosphatidylcholine (lecithin), is about 10 azepam intravenously or intramuscularly).9 times more bioavailable than silymarin, but its effective- ness as an oral antidote for A. phalloides mushroom poi- Coprine soning has not been investigated. The effectiveness of Coprine, the major fungal toxin associated with Coprinus acetylcysteine for treating mushroom cyclopeptide poi- atramentarius mushroom poisoning, inhibits aldehyde de- soning is questionable. However, given its low risk of ad- hydrogenase, thus inhibiting the conversion of ethanol (al-

Veterinary Medicine February 2007 97 Toxicology Brief PEER-REVIEWED cohol) to acetate and resulting in an accumulation of ac- poisoning from isoxazole derivatives.9 Given the popu- etaldehyde. This effect only occurs if there is an association lar recreational use of these mushrooms by people, it is between the consumption of C. atramentarius mushrooms surprising that poisoning in companion animals is and ethanol.9 If ethanol is not consumed concurrently with poorly documented.9 these mushrooms, the poisoning does not occur. Thus, this Ibotenic acid and muscimol, the principal psychoac- poisoning is unlikely in veterinary medicine. tive isoxazole derivatives present in these mushrooms, alter visual perception rather than cause true hallucina- Muscarine tions in people.9 Ibotenic acid, a CNS glutamate acid re- Muscarine is a muscarinic receptor agonist that pro- ceptor agonist, acts as a CNS stimulant; muscimol, a duces postganglionic parasympathomimetic effects, CNS GABAB agonist, acts as a CNS and seda- such as increased genitouri- tive.9 In people, the primary ef- nary muscle tone, bradycardia, fects are periods of CNS stimu- miosis, and salivation.9 The Do not use the lation and depression that may most common mushrooms in- alternate and may manifest as volved in muscarine poisoning correction of periods of manic excitement include members of the Inocybe followed by periods of somno- and Clitocybe genera.9 Al- miosis to judge lence and deep sleep. Clinical though has signs typically associated with been classically associated the dose. poisoning in people include with muscarine toxicity, it con- , ataxia, euphoria, tains insignificant amounts of this toxin.9 muscle twitches, and initial psychic stimulation fol- Clinical signs usually occur within two hours after in- lowed by dream-filled sleep.9 gestion and are characterized by the acronym SLUD (sali- vation, lacrimation, urination, diarrhea).9 Other common Treatment. Treatment consists of upper GI deconta- clinical signs include bradycardia, hypotension, shock, mination and supportive measures, such as observation, dyspnea and wheezing due to bronchoconstriction and confinement in a dark and quiet cage, and possibly seda- increased respiratory secretions, abdominal pain, miosis, tion. Use all hypnotic drugs with caution because the visual disturbance, and rhinorrhea.9 An alternative isoxazole derivatives potentiate their effects.9 acronym sometimes used to describe the effects of exces- sive muscarine stimulation is DUMBBELS (diarrhea, uri- Psilocybin and psilocin nation, miosis, bronchorrhea, bronchoconstriction, eme- Because of its popularity as a recreational drug, this sis, lacrimation, salivation). group of mushrooms, know as hallucinogenic or magic mushrooms, occasionally causes poisoning in dogs.3 Im- Treatment. Performing early upper GI decontamina- portant genera involved in poisoning include Psilocybe, tion is useful, although spontaneous vomiting may elim- Panaeolus, Copelandia, Gymnopilus, Pluteus, and inate the need for this treatment.9 Activated charcoal ad- Conocybe.9 The principal toxins in these mushrooms are ministration is potentially useful. The specific reversal psilocybin and psilocin, which have LSD-like proper- agent for muscarine poisoning is atropine.9 If clinical ties.9 These compounds typically produce a transient signs of excessive muscarine stimulation are present, ad- (less than 12-hour duration), dysphoric, and sympath- minister atropine (0.2 to 2 mg/kg; 50% of the dose ad- omimetic syndrome. Coingestion of other drugs of ministered intravenously and 50% intramuscularly or abuse such as LSD, PCP, and marijuana is common in subcutaneously) slowly and progressively to effect using people and is a potentially important consideration in the drying of the oral and respiratory secretions as the veterinary patients.9 clinical endpoints.9 Do not use the correction of miosis to Common clinical signs, which develop a half an judge the atropine dose since by the time the pupils re- hour to four hours after ingestion, include anxiety, ag- turn to normal, most patients have received too much at- gression, disorientation, visual hallucinations (e.g. fol- ropine, resulting in potentially adverse cardiovascular ef- lowing and biting at imaginary flies, pointless bark- fects.9 Intravenous crystalloids are usually sufficient to ing), weakness, mydriasis, tachycardia, and control any hypotension that develops.9 hyperreflexia.3,9 Hypertension, hyperthermia, or con- vulsions may occur, and patients may become coma- Isoxazole derivatives tose in cases of extreme overdose. However, trauma Amanita muscaria and are the princi- caused by altered behavior is usually the greatest and pal North American mushroom species associated with most immediate threat to life.3,9 ➢

98 February 2007 Veterinary Medicine Toxicology Brief PEER-REVIEWED

Treatment. Emergency GI de- within 24 hours. If required, sup- contamination in a conscious pa- portive care would consist of sub- tient poisoned by these mushrooms cutaneous or intravenous crystal- may be difficult because of the pa- loids. The administration of oral GI tient’s altered behavior and aggres- protectants could be considered sion. An easier option may be gas- once vomiting has ceased. tric lavage after anesthesia and placement of a cuffed endotracheal Orelline and orellanine tube.9 The main potential difficulty While Cortinarius species exist in associated with anesthesia is the in- North America, no poisoning has duction because of the dysphoric, been recorded to date.9 European and potentially aggressive, mental and Japanese species from this state of the patient. Prior sedation cause acute, irreversible with a benzodiazepine (0.5 to 1 tubulointerstitial nephritis and mg/kg diazepam intravenously or acute renal failure.9 1 to 4 mg/kg rectally) or an alterna- tive induction technique, such as PREVENTION using an induction chamber, may As with most poisonings, the best be required. The use of induction method of controlling mushroom chambers carries with it the in- poisonings is preventing exposure. creased risks associated with de- This means that only those who are creased access to the patient, so knowledgeable about mushroom their use with dysphoric patients identification should collect wild- requires careful clinical judgment. growing mushrooms for consump- Treatment usually consists of tion. Dogs should be prevented supportive care. Since the most im- from consuming mushrooms or mediate concern is preventing acci- roaming when they are being exer- dental trauma, often the most suc- cised. As with most poisonings, cessful supportive care is placing the prompt upper GI decontamination animal in a quiet, dark, padded cage and supportive care are critical ele- in the presence of its owner.9 Warn ments of treatment. ❖ the animal’s owners and handlers of the potential for aggressive behavior. REFERENCES 1. Bernard MA. Mushroom poisoning in a dog. Can Vet J If sedation is required, a benzodi- 1979;20:82-83. azepine (0.5 to 1 mg/kg diazepam 2. Cole FM. A puppy death and Amanita phalloides. Aust Vet J 1993;70:271-272. intravenously or 1 to 4 mg/kg rec- 3. Kirwan AP. ‘Magic mushroom’ poisoning in a dog. Vet tally) can be administered. Rec 1990;126:149. 4. Naude TW, Berry WL. Suspected poisoning of puppies by the mushroom Amanita pantherina. J S Afr Vet Assoc GI irritants 1997;68:154-158. GI 5. Ridgway RL. Mushroom (Amanita pantherina) poisoning. J Numerous mushroom genera are Am Vet Med Assoc 1978;172:681-682. irritants (Table 1).9 For the most part, 6. Tegzes JH, Puschner B. Amanita mushroom poisoning: effi- cacy of aggressive treatment of two dogs. Vet Hum Toxicol the toxic principles involved are un- 2002;44:96-99. known,9 although idiosyncratic and 7. Yam P, Helfer S, Watling R. Mushroom poisoning in a dog. Vet Rec 1993;133:24. allergic mechanisms have been pro- 8. Spoerkem D. Mushroom exposure. In: Peterson ME, Tal- posed. Typically, clinical signs of cott PA, eds. Small animal toxicology. Philadelphia, Pa: WB GI Saunders Co, 2001;571-592. acute upset occur within two 9. Schonwald S, Mushrooms. In: Dart RC, ed. Medical toxi- hours of ingestion and consist of cology. 3rd ed. Philadelphia, Pa: Lippincott Williams and Wilkins, 2004;1719-1735. malaise, weakness, nausea, vomit- 10. Menser GP. Hallucinogenic and poisonous mushroom: field ing, and diarrhea.9 The greatest risk guide. 2nd ed. Berkeley, Calif: Ronin Publishing Inc, 1997;1-115. 11. Peterson M. Toxicologic decontamination. In: Peterson associated with poisoning by these ME, Talcott PA, eds. Small animal toxicology. Philadelphia, mushrooms is fluid and electrolyte Pa: WB Saunders Co, 2001;85-98. 12. Enjalbert F, Rapior S, Nouguier-Soule J, et al. Treatment imbalance. Most cases are mild and of poisoning: 20-year retrospective analysis. J Toxi- usually resolve without treatment col Clin Toxicol 2002;40:715-757.

100 February 2007 Veterinary Medicine