Page 1026 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

958 SECTION | XIV Poisonous Plants

VetBooks.ir clinical trial was sanctioned by the U.S. Food and toxin concentrations and intestinal reuptake of α-amanitin
do not exist beyond 24 h after poisoning (Thiel et al.,
Drug Administration and is currently being conducted in
California
(http://clinicaltrials.gov/ct2/show/
northern
2011). Therefore, decontamination and interruption of
NCT00915681). In dogs, silibinin was shown to be effec- enterohepatic circulation is most effective within 24 h
tive when given twice at a dose of 50 mg/kg i.v. 5 and after poisoning. In addition, external drainage of the bile
24 h after exposure to A. phalloides (Vogel et al., 1984). through as a more invasive approach for detoxification is
Dosed dogs had better indices of liver function as likely only beneficial within the first 24 h and remains
assessed by serum elevations of AST, ALT, bilirubin, and controversial due to lack of data and risk of procedure in
prolonged PT time. On histopathology, no hepatic lesions veterinary patients. In general, activated charcoal is con-
were found. Side effects of silibinin administration are sidered beneficial and recommended to be given every
rare but include anaphylactic reactions, mild laxative 2 6 h until 2 or 3 days postingestion. Close monitoring,
effects, and interactions with certain phase I and phase II fluid replacement, and supportive care are the essential
metabolism enzymes (Venkataramanan et al., 2000). Oral components of intensive care therapy. Intravenous fluids,
administration of milk thistle preparations is not recom- correction of hypoglycemia and electrolyte imbalances,
mended because they are poorly absorbed. vitamin K 1 , and plasma transfusions should be considered.
Penicillin G was shown to protect against amanitin- In humans, liver transplantation has been used success-
induced cell damage in cultured human hepatocytes fully in patients with fulminant liver failure. Currently,
(Magdalan et al., 2010a). Mice given 1000 mg/kg of peni- liver transplantation is not an option for animals poisoned
cillin G intraperitoneally 8 h after exposure to a lethal with amanitins.
dose 95 (LD 95 ) of amanitin had less morbidity and mor- Diagnosis of amanitin toxicosis is aided by identifica-
tality than did control mice (Floersheim, 1972). In dogs, i. tion of amanitin-containing mushrooms in the environ-
v. administration of 1000 mg/kg of penicillin G at 5 h ment of the animal. Mushroom pieces found in gastric
post A. phalloides exposure was considered an effective contents can confirm exposure. Accurate mushroom iden-
treatment (Floersheim, 1978). tification will require consultation with an experienced
The benefits of several antioxidants in amanitin intoxi- mycologist. Detection of amanitins in biological specimens
cations have been evaluated in humans. Most information is confirmatory, but these tests are not routinely available
is available for NAC, which was shown to be as effective at diagnostic laboratories. A liquid chromatography mass
as silibinin in reducing mortality (Enjalbert et al., 2002) spectrometry method was developed and successfully
and protecting against cell damage (Magdalan et al., applied to confirm amanitin poisonings in animals and
2010a). In mice, NAC administration was not effective humans (Filigenzi et al., 2007). A competitive enzyme-
(Schneider et al., 1992). Although efficacy data of NAC linked immunosorbent assay was constructed that allows
administration in dogs with amanitin poisoning are lack- for the detection of β-amanitin in human serum and urine,
ing, there is no reason not to include the glutathione pre- but this assay is not available in clinical settings
cursor in the treatment regimen. Ascorbic acid may also (Abuknesha and Maragkou, 2004). Rapid confirmation of
be of benefit when managing amanitin poisoning in dogs, amanitins in suspect exposures assists in the early recog-
but specific data are not available. In contrast, cimetidine, nition of exposure, whereas a negative result can prevent
thioctic acid, and steroids are no longer recommended unnecessary hospitalization. The well-known reported
because of poor clinical efficacy. newspaper test of Wieland or the Meixner test should not
With the identification of OATP1B3 as the primary be used alone to identify amanitin-containing mushrooms
hepatic uptake transporter for amatoxins in humans, high- (Beuhler et al., 2004). In suspect cases of aminitin poison-
affinity substrates and inhibitors of OATB1B3 provide ing, serum and urine samples should be collected at vari-
excellent candidates for antidotes (Letschert et al., 2006). ous time points beginning as early after exposure as
Silibinin and penicillin G are in this category, but rifampi- possible. In postmortem presentations, liver and kidney
cin, cyclosporine A, and montelukast must be further samples are suitable for testing to confirm exposure. The
evaluated because they may be superior in preventing suspect mushroom or vomited gastrointestinal contents
amanitin uptake into hepatocytes. should also be saved for further analysis.
Hemodialysis, hemoperfusion, activated charcoal, Differential diagnoses in dogs and cats with a clini-
plasmapharesis, forced diuresis, and nasoduodenal suc- cal presentation that involves gastroenteritis and hepatic
tioning have been used to treat amanitin poisonings. failure include other toxic ingestions, such as microcys-
Controversy remains with regard to the efficacy of decon- tins, cocklebur, cycad palm, aflatoxin, xylitol, ricin,
tamination procedures because specific efficacy data do abrin, gyromitrin, and acetaminophen overdose. The
not exist. Recent studies assessing the kinetics and entero- history and geographic environment of the animal can
hepatic circulation of α-amanitin in pigs demonstrated help to eliminate most of the toxicant differentials on
that clinically relevant systemic plasma and portal plasma the list.