Page 239 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

206 SECTION | II Organ Toxicity

VetBooks.ir exert their toxic effects via effects on dopaminergic, sero- changes occur. Nature provides us with several examples
of neurotoxicants which affect the sodium channel.
tonergic, and adrenergic pathways. Successful recovery is
Tetrodotoxin (TTX), present in various genera of puffer
aimed at early diagnosis, when signs such as ataxia and
confusion are reversible, and removal of the contaminated fish, in the venom of the blue-ringed octopus
feed source is possible (Evans et al., 2004). The effects of (Hapalochlaena spp.), the rough-skinned newt (Taricha
the ergoline alkaloids, in particular, can also be seen with spp.), and many other creatures, exhibits a profound bind-
ingestion of the seeds of Ipomoea or morning glory and ing affinity for the sodium channel peptide complex.
1
are very similar to those of the related street drug lysergic Whereas the Na ion normally reversibly binds to the pep-
acid diethylamide, also known as LSD (Burrows and tide complex for just nanoseconds, TTX binds to the exter-
Tyrl, 2013). nal surface of the peptide ion channel, remains bound for
α-Latrotoxin, the toxin in the venom of the black tens of seconds, and halts the action potential. A progres-
widow spider (Latrodectus), causes the release of cate- sion of signs occurs with TTX poisoning in people: (1) ini-
cholamine neurotransmitters as well as ACh, GABA and tial numbness around the mouth with or without nausea;
glutamate. The toxin mediates its catecholamine effects (2) numbness of the tongue, face and skin, early motor
by forming a transmembrane pore through which Ca 21 paralysis, and incoordination manifested as slurred speech;
can influx, allowing release of presynaptic vesicles con- (3) more widespread paralysis resulting in dyspnea, hypo-
taining neurotransmitters. Clinical signs associated with a tension, an inability to speak, and fixed and dilated pupils;
bite from Latrodectus species include abdominal pain, and (4) severe paralysis involving respiratory muscles, hyp-
ataxia, muscle fasciculations, muscle rigidity, and flaccid oxia, hypotension, and cardiac arrhythmias. Consciousness
paralysis, which can ascend to involve the respiratory may be lost followed by death because of respiratory fail-
muscles. Cats are more sensitive than dogs to the effects ure as early as 17 min after ingestion or as late as 24 h. No
of α-latrotoxin, but all mammalian species are suscepti- antidote currently exists. Treatment is aimed at decontami-
ble. Antivenin is commercially available for black widow nation and symptomatic and supportive care (Kaku and
spider bite victims. Like all products derived from equine Meier, 1995; White, 1995).
serum, a test dose should be administered intradermally to Saxitoxin, the causative toxin for paralytic shellfish poi-
determine if hypersensitivity to the product exists. If none soning (PSP), is produced by several dinoflagellates, most
exists, the contents of the antivenin vial (2.5 mL) can be notably Alexandrium and Pyrodinium species, and causes a
diluted 4 20 3 (10 50 mL) with sterile saline and similar clinical picture as that of TTX toxicosis also because
administered slowly intravenously over approximately of binding to the sodium ion channel (Smart, 1995).
15 min. A slow, IV injection of 10% calcium gluconate Local anesthetics exert their pharmacologic effects by
may be given to treat the muscle fasciculations and weak- binding to the fast sodium channel complex when it is inac-
ness as well. Aggressive pain management with opioids tive, inhibiting its recovery after depolarization. Lidocaine,
or benzodiazepines is indicated (Roder, 2004d). as an example, rapidly dissociates from the sodium channel
complex and is also rapidly metabolized in the liver.
Consequently, adverse events associated with therapeutic
ION CHANNELS
dosages are rare. In an overdose situation, however, CNS
The propagation of an impulse along an axon depends on depression, ataxia, seizures, and circulatory collapse can
an electrochemical gradient that is intricately regulated by occur (Welch, 2000; Plumb, 2015). Dibucaine HCl is 10
various ion channels in an excitable membrane. Initiation times more potent than lidocaine and much more likely to
of action potentials, release of neurotransmitters, axonal result in adverse effects as a result. Cats are especially sus-
transport, and healthy muscle activity rely on control of ceptible to the methemoglobinemic potential of local anes-
ions such as sodium, potassium, chloride, and calcium thetics. Treatment of clinical signs is largely symptomatic
(Spencer, 2000). Specific veterinary examples follow and supportive, aimed at maintenance of blood pressure,
regarding the variety of natural and synthetic toxicants addressing cardiac arrhythmias, and management of sei-
that target the ion channels of the nervous system. zures (Welch, 2000). The experimental report of
bupivacaine-intoxicated dogs successfully treated with IV
lipid emulsion (Weinberg et al., 2003) holds promise for
Sodium Channels
future use with local anesthetic toxicoses.
The sodium channel of mammals is made up of three pro- Several toxins affect the sodium ion channel by enhanc-
tein subunits, the largest of which is the transmembrane ing its activity, resulting in repetitive and prolonged neuro-
1
alpha (α) subunit, which contains the Na pore and which transmission. Brevotoxins, produced by the dinoflagellates
is flanked by two smaller β subunits. The pores are Karenia brevis and Gymnodinium breve,prolong theopen-
voltage-gated, allowing sodium ion entrance into the cyto- ing of the sodium ion channels, perpetuating the propaga-
plasm only when charge-dependent conformational tion of the action potential. Bossart et al. (1998) implicated