Page 1029 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Mushroom Toxins Chapter | 67 961

VetBooks.ir poisonings in humans in this group (Hall and Hall, 1994). after ingestion of A. pantherina (Ridgway, 1978). After a
brief period of sedation, cats experienced a 4-h-long state
The mushrooms grow from summer to autumn in conifer-
of excitement with pronounced muscle spasms, followed
ous and deciduous forests, and they are abundant in the
Pacific Northwest, where they are often found under by a deep sleep. Cats are expected to fully recover within
Douglas fir trees. Other species containing these toxins 24 h after ingestion, especially if decontamination mea-
include Amanita gemmata, Amanita smithiana, Amanita sures are taken. In dogs, clinical signs observed after
strobiliformis, and Tricholoma muscarium (Lincoff and ingestion of A. pantherina include disorientation, opistho-
Mitchel, 1977c). There are a few reports of poisoning in tonus, paresis, seizures, paddling, chewing movements,
dogs (Naude and Berry, 1997; Beug, 2009) and cats miosis, vestibular signs, respiratory depression, coma, and
(Ridgway, 1978) after ingesting A. pantherina. Ingestion death (Hunt and Funk, 1977; Naude and Berry, 1997).
of A. muscaria presumably resulted in clinical signs in a Recoveries are recorded within 12 24 h after aggressive
horse (Beug, 2009). supportive care measures, including mechanical ventila-
tion during periods of respiratory depression; however,
death was reported in several dogs. Similar clinical signs
Pharmacokinetics/Toxicokinetics
were reported in a dog that survived A. muscaria poison-
Definitive data on the toxicokinetics of muscimol and ibo- ing (Martin, 1956).
tenic acid have not been established. Based on the rapid
onset of clinical signs after oral exposure, rapid absorp- Toxicity
tion of toxins is suspected. Once absorbed, muscimol and
ibotenic acid appear to cross the blood brain barrier by In mice, the oral LD 50 is 22 mg/kg for muscimol and
an active transport system. Ibotenic acid decarboxylates 38 mg/kg for ibotenic acid (Hall and Hall, 1994). In rats,
to form muscimol in the stomach, liver, and brain the oral LD 50 is 45 mg/kg for muscimol and 129 mg/kg
(Nielsen et al., 1985). Muscimol and ibotenic acid can be for ibotenic acid. The intraperitoneal LD 50 of muscimol is
detected in urine within 1 h of exposure (Ott et al., 1975; 2.5 mg/kg in mice and 3.5 mg/kg in rats. In humans, the
Merova et al., 2008). toxic threshold is estimated to be 6 mg of muscimol and
30 60 mg of ibotenic acid (Halpern, 2004). The concen-
tration of ibotenic acid in A. muscaria was estimated at
Mechanism of Action
100 mg/kg fresh weight, whereas the concentration of
The major toxins are muscimol and ibotenic acid, but muscimol was less than 3 mg/kg fresh weight. Thus, an
other active substances have been identified, although average-sized fruit body of A. muscaria weighing
with minor pharmacological activates. Ibotenic acid is 60 70 g can contain a toxic concentration. Toxicity data
known to act on glutamic acid receptors in the central ner- for dogs are not available. However, postmortem exami-
vous system (CNS) and produces an excitatory action nation of puppies indicated that the ingestion of a single
(Cleland, 1996), whereas muscimol is a potent agonist at A. pantherina can be lethal (Hunt and Funk, 1977).
GABA A receptors (Chebib and Johnston, 1999). Although
both muscimol and ibotenic acid are present in mush-
Treatment
rooms, muscimol is produced by spontaneous decarboxyl-
ation of ibotenic acid that can occur during dehydration Treatment of exposed animals is mainly symptomatic and
of the mushroom, digestion in the stomach, or after supportive. Decontamination measures should be consid-
absorption in a variety of tissues. Therefore, muscimol is ered in recent exposures, although emetics are only
mainly responsible for the clinical signs. On activation by recommended in animals that are not at risk for develop-
muscimol, the membrane permeability for anions ing aspiration pneumonia. Specific measures to control
increases, usually resulting in a slight, short-lasting hyper- seizures are not without complication. Benzodiazepines,
polarization and associated decreased excitability of the as GABA agonists, may potentiate any CNS depression.
receptive neuron. Effects on the CNS are similar to those Therefore, when diazepam is used, CNS and respiratory
produced by therapeutic doses of diazepam. depression may be severe and prolonged, necessitating
Clinical signs of muscimol toxicosis begin within the use of mechanical ventilation. As long as ventilation is
30 min to 2 h after ingestion and have been termed the maintained adequately, the prognosis for recovery is good.
“pantherine muscaria” syndrome in humans, which is Diazepam can be given to dogs and cats at 0.5 mg/kg i.v.
characterized by mydriasis, dryness of mouth, ataxia, con- to effect and can be repeated as needed every 10 min for
fusion, euphoria, dizziness, and tiredness. Gastrointestinal up to three doses. Other drugs used to control seizures
signs are not consistently seen in cases of isoxazole poi- include phenobarbital and pentobarbital. Phenobarbital is
soning. Full recovery is expected within 1 or 2 days. In dosed at 6 mg/kg i.v. Pentobarbital is given at 5 15 mg/
cats, clinical signs have been observed within 15 30 min kg i.v. to effect to dogs and cats. These, too, are agonists