Page 235 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

202 SECTION | II Organ Toxicity

VetBooks.ir plants that stimulate these receptors including Nicotiana sp. paralysis which results in death within 3 10 days. Signs
are symmetric and progress from the pelvic limbs toward
(varying types of tobacco), Conium maculatum or poison
the thoracic limbs. Cranial nerves may be affected, possi-
hemlock, and Lobelia or Indian tobacco. The numerous
alkaloids present in these plants as well as the cyano- bly resulting in megaesophagus, decreased jaw tone,
bacterial toxin anatoxin-a, most commonly produced by facial paralysis and/or a decreased gag reflex. Autonomic
Anabaena flos-aquae (Roder, 2004c), exert their neuro- functions may be affected as well (Coleman, 1998). The
toxic effects by initially stimulating nicotinic choliner- disease is called limber neck in affected birds. In human
gic and neuromuscular junction receptors but ultimately patients who have been supported with artificial respira-
result in a persistent neuromuscular blocking effect. tion, the duration of the effect has been documented to
Signs include muscular weakness, tremors, nausea, persist for 6 8 months (Kotsonis et al., 2001).
vomiting, ataxia, tachypnea, tachycardia, hypertension, The prognosis for severely affected animals is at best
mydriasis, staggering, seizures, respiratory failure, and guarded, but more realistically, poor. Treatment can
death (Panter, 2004a,b,c). Treatment is symptomatic and include debridement of wounds, penicillin therapy, and
supportive. Prognosis is good except in cases of large antitoxin (5 mL IV or IM) within the first 5 days of expo-
overdoses. sure. Administration of the antitoxin does not reverse the
Imidacloprid (Advantage) is a chloronicotinyl nitro- clinical signs attributed to neurons already affected by the
guanide insecticide marketed for flea control in pets and toxin. Because of its equine source and antigenicity, an
which exerts its effects via possibly both agonist and intradermal test dose is recommended prior to full admin-
antagonist actions at the nicotinic ACh receptor. Death of istration IV or IM. For individuals already severely
the insect is effected via the same clinical signs as affected, assisted ventilation is indicated until the patient
previously described above, yet imidacloprid has a wide can breathe spontaneously, yet the duration of therapy
margin of safety in mammals due to its poor systemic required may not be practical in veterinary medicine.
absorption when applied dermally (as labeled) (Craig Extreme supportive care, including assisted or parenteral
et al., 2005) and due to the higher affinity of imidacloprid feeding, physical therapy, manual evacuation of the blad-
for insect nicotinic receptors versus mammalian receptors. der and intermittent manipulation of body position to pre-
Acute oral ingestions are usually limited to nausea, saliva- vent hypostatic congestion and formation of decubital
tion, and vomiting (Wismer, 2004). ulcers, is critical. Some laboratories can confirm the diag-
Another mechanism by which ACh can be involved in nosis with analysis of serum, gut contents, and/or feed for
toxicoses is the lack of release of the neurotransmitter the preformed toxin (Roder, 2004b; Bailey, 2006). A
from the presynaptic terminal. Botulinum toxin, produced mouse inoculation assay and type-specific ELISA testing
by the anaerobic bacterium Clostridium botulinum, exerts may also aid in the diagnosis of botulism (Thomas, 1991).
its action via this mechanism. Sources of the toxin include
ingestion of food contaminated with either preformed Catecholamine Neurotransmitters
toxin or clostridial spores, contamination of a puncture
wound with spores, and ingestion of spores from the envi- Catecholamines are “fight or flight” neurotransmitters
ronment. Exposure can be oral, inhaled, or absorbed cuta- that include norepinephrine, epinephrine and dopamine.
neously through devitalized skin (Bailey, 2006). The Their synthesis begins with conversion of the amino acid
toxin consists of a 100 kDa heavy chain and a 50 kDa L-tyrosine to L-dopa. Removal of a carboxyl group from
light chain linked by disulfide and noncovalent bonds. L-dopa forms dopamine which is acted upon by dopamine
Upon ingestion of the toxin, its heavy chain binds synap- β-hydroxylase to form norepinephrine (Spencer, 2000).
totagmin, a presynaptic vesicle protein. Once the toxin is Norepinephrine is also stored in the adrenal medulla and
internalized within the presynaptic terminal, its disulfide released into the blood with sympathetic stimulation
bonds are cleaved, releasing the light chain. The free light (Capen, 2001). N-methylation of norepinephrine forms
chain is then available to cleave proteins that are respon- epinephrine, an adrenal hormone, which is only nominally
sible for the docking and release of ACh vesicles into the present in the brain. Catecholamines are inactivated by
synapse. monoamine oxidase (MAO) and catechol-O-methyltrans-
Seven different botulinum toxins (A G) have been ferase (COMT) enzymes (Beasley, 1999; Spencer, 2000).
described. Types C and D are most commonly associated In addition to its role at postganglionic sympathetic
with veterinary species (type C is most common in dogs); neurons, norepinephrine also mediates effects in the CNS.
types A, B, E and F have caused disease in humans. Adrenergic receptors include α 1 , α 2 , β 1 and β 2 receptors.
Although differences exist regarding which proteins are Stimulation of α 1 adrenergic receptors, present peripher-
cleaved by each toxin type, the end result is the lack of ally, results in vasoconstriction and mydriasis.
ACh in the synaptic cleft of the neuromuscular junction Stimulation of α 2 adrenergic receptors, present in the
(Roder, 2004b). The clinical result is a progressive flaccid CNS, mediates inhibition of norepinephrine, resulting in