Page 231 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

198 SECTION | II Organ Toxicity

VetBooks.ir TABLE 12.1 Neurotoxicants and Associated Antidotes by the diatom Pseudo-nitzschia spp. The toxin is thought
to exert its excitatory and cytotoxic effects on hippocam-
(Poppenga, 2004; Roder, 2004b,d; Plumb, 2015)
pal cells because of its high affinity for binding to the kai-
Neurotoxicant(s) Antidote(s) nite receptor, which is a glutamate receptor subtype.
21
Cellular excitation ensues, resulting in an influx of Ca
Acetaminophen Acetylcysteine ions, up-regulation of the c-Fos gene, and cell death
Amitraz, brimonidine, Atipamezole, yohimbine (Jeffery et al., 2004). Domoic acid toxicity has been
xylazine responsible for the considerable morbidity and mortality
rate of the California sea lion (Zalophus californianus;
Benzodiazepines Flumazenil
Gulland et al., 2002).
Botulinum toxin Antitoxin
A third example of neuronotoxicosis occurs in large
Coral snake Antivenom animals, such as horses, when they ingest yellow star this-
Ethylene glycol Fomepizole (4-MP), ethanol tle (Centaurea solstitialis). This occurs typically in the
dry summer and fall seasons and results in neurologic
Isoniazid Pyridoxine/vitamin B 6
signs including involuntary lip and tongue movements,
Lactrodectus spp. Antivenin
difficulty in prehending food, tremors, writhing, possible
Lead Succimer, calcium EDTA, circling, persistent slow movements (dystonia), and
D-penicillamine significant weight loss. The disease is also called nigro-
Metronidazole Diazepam pallidal encephalomalacia because of the areas of the
brain that are uniquely affected (the globus pallidus and
Pyrethroids Methocarbamol
the pars reticularis of the substantia nigra). The clinical
Opioids Naloxone
signs manifest in these regions draw a striking similarity
Organophosphorus Pralidoxime (2-PAM), atropine to Parkinson’s disease in people (Burrows and Tyrl, 2013;
insecticides Sanders et al., 2001), which has been associated with the
Scorpion Antivenom selective loss of dopaminergic neurons (van den
Munckhof et al., 2006). Of the guaianolide sesquiterpene
SSRIs/TCAs Cyproheptadine
lactones isolated from Centaurea species, cynaropicrin
Tetanus toxin Antitoxin
and an analog of solstitialin are cytotoxic in primary cul-
tures of rat substantia nigra cells, and thus raise suspicion
about their role in the toxicosis. Aspartic and glutamic
acids, two excitatory amino acid neurotransmitters, are
also present in Centaurea (Burrows and Tyrl, 2013), but
their role, if any, in the mechanism of nigropallidal ence-
phalomalacia has yet to be determined.
TABLE 12.2 Signs Associated With Neurotoxicoses
A final example of a neuronopathic toxicant is cur-
(Podell, 2000)
rently a common drug of abuse called methylenedioxyam-
Stimulatory Depressant phetamine (MDMA) or “Ecstasy.” MDMA selectively
Hyperactivity Obtundation targets serotonergic and dopaminergic cells depending on
the species exposed, and long-term, irreversible effects
Vocalization Stupor
may be seen (Gouzoulis-Mayfrank and Daumann, 2006).
Tremors Coma
Acute physiologic effects in people include tachycardia,
Seizures Ataxia hypertension, euphoria, heightened sexual awareness, uri-
nary urgency, nausea, chills, sweating, hyperthermia,
Hyperesthesia Paresis/Paralysis
among others. Signs consistent with serotonin syndrome
Hypermetria Abasia
(hyperactivity, agitation, mental confusion, hyperthermia,
Other: Disorientation tachycardia and tremors) have been observed in experi-
Paresthesia mentally exposed rats (Easton and Marsden, 2006).
Further research is indicated to define species-specific
SLUDDE (salivation, lacrimation, increased
urination, diarrhea, dyspnea, and emesis effects, particularly the extent to which serotoninergic or
dopaminergic neurons are involved. Veterinary practi-
Cranial nerve deficits (rare)
tioners should be aware of the potential for accidentally
exposing small animals to this toxicant.