Page 1028 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

960 SECTION | XIV Poisonous Plants

VetBooks.ir is 75 150 mg/kg body weight, given i.v., during acute Mechanism of Action
phases of seizure activity. Diazepam is given to dogs and
Muscarine acts in the peripheral nervous system, where it
cats at 0.5 1.0 mg/kg i.v. to effect. Phenobarbital is not
recommended for seizure control because of its cyto- competes with acetylcholine at its receptor binding sites.
The muscarinic cholinergic receptors are found in the
chrome P450-inducing capability. Administration of foli-
heart in both its nodes and its muscle fibers, in smooth
nic acid has been recommended in humans, but controlled
muscles, and in glands. They do not occur in skeletal
studies have not been performed. NAC can be considered.
muscles. Once bound to the receptor, muscarine mimics
The dosing is the same as that given in acetaminophen-
the effect of acetylcholine. Muscarine is unable to inacti-
induced hepatic injury. Hemodialysis has been reported in
vate acetylcholinesterase (Young, 1994), and uncontrolled
the literature, but its role in removing gyromitrin or its
overstimulation of receptors occurs. Clinical signs appear
toxic metabolites is not known.
within a few hours and include salivation, lacrimation,
Diagnosis of gyromitrin toxicosis is aided by identifi-
vomiting, diarrhea, abdominal pain, miosis, and bradycar-
cation of gyromitrin-containing mushrooms in the envi-
dia (Lurie et al., 2009). Clinical signs in the dog eating
ronment of the animal. Identification by a mycologist is
I. phaecocomics were observed 3 h after exposure and
important to distinguish between the true and the false
included salivation, diarrhea, vomiting, depression, and
morels. Detection of gyromitrin, hydrazine analogs, or
collapse (Yam et al., 1993).
metabolites in mushrooms or biological specimens is not
routinely available (Arshadi et al., 2006). Diagnosis is
mainly based on clinical and clinicopathological findings Toxicity
and also mushroom identification.
The i.v. LD 50 of muscarine in mice is 0.23 mg/kg (Waser,
1961). The lethal dose of muscarine in humans is esti-
MUSCARINIC AGENTS mated to be between 180 and 300 mg. Ingestion of a sin-
Inocybe and Clitocybe spp. contain the highest concentra- gle mushroom containing 0.33% muscarine on a dry
tions of muscarine, but lower concentrations are found in weight basis can be lethal (Bresinsky and Besl, 1990a).
many other genera, including Entoloma and Mycena
(Young, 1994). Muscarine was first discovered and char- Treatment
acterized in A. muscaria, but concentrations of muscarine
are only approximately 0.0003% (Eugster and Treatment includes induction of emesis and administra-
Schleusener, 1969). In comparison, Inocybe and Clitocybe tion of activated charcoal in asymptomatic animals. Fluid
species have muscarine concentrations between 0.1 and rehydration to restore fluid balance and electrolytes is a
0.33%. Inocybe and Clitocybe species have worldwide key component of treatment. If life-threatening clinical
distributions and are relatively common. Inocybe species signs are present, atropine should be administered. After
grow in association with either conifers or broad-leaved giving a test dose of 0.04 mg/kg (1/4 i.v. and 3/4 i.m. or
trees. Clitocybe species grow on forest litter or grassland s.c.) to determine its efficacy, atropine can be given
humus. The risk of poisoning remains after cooking repeatedly until symptoms are abolished or until cessation
because of the heat stability of muscarine. There are very of salivation. Doses in dogs and cats given to effect range
few published reports of Inocybe spp. poisonings in dogs from 0.2 to 2.0 mg/kg (1/4 i.v. and 3/4 i.m. or s.c.). Other
(Yam et al., 1993; Seljetun and von Krogh, 2017) and criteria for therapeutic endpoint with atropine include
only one reported death of a dog presumably from ease of respiration and lack of respiratory secretions.
Inocybe sp. exposure (Beug, 2009). Mydriasis is not an indicator of its effectiveness. Because
atropine also competes with acetylcholine at the receptors,
ongoing treatment must be carefully monitored for its
Pharmacokinetics/Toxicokinetics
anticholinergic effects, including tachycardia, gastrointes-
Limited data are available. The naturally occurring form of tinal stasis, severe behavioral changes (e.g., delirium),
muscarine is the (L) 1 form. In general, quarternary and hyperthermia. The dose of atropine should be reduced
ammonium compounds are poorly absorbed after oral or discontinued with these adverse effects.
exposure. Once absorbed, muscarine is quickly distributed
throughout the body, and clinical signs develop within ISOXAZOLES
30 min to 2 h. Because of its quaternary configuration,
muscarine does not cross the blood brain barrier, and its Poisoning in this group is attributed to the heat-stable iso-
cholinergic effects are entirely peripheral. A portion of the xazoles derivatives, ibotenic acid, and muscimol. Amanita
ingested muscarine is eliminated unchanged in urine, but pantherina (panther cap or panther agaric) and A. muscaria
detailed toxicokinetic studies have not been performed. (fly agaric) are most commonly associated with