Page 240 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Nervous System Toxicity Chapter | 12 207

VetBooks.ir the toxin in the death of a minimum of 149 manatees along dogs. Within 12 18 h of application or accidental expo-
sure, affected cats will exhibit hyperesthesia, generalized
the southwest coast of Florida in 1996. Another example
are ciguatoxins, which are produced by dinoflagellates and
tremors, hyperthermia, seizures, and possible death. The
are bioaccumulated by herbivorous, and then piscivorous prognosis for complete recovery, however, is excellent with
1
fish. They enhance Na permeability through the ion chan- appropriate care. Seizures should be controlled with diaze-
nel (Spencer, 2000). The hallmark clinical sign of cigua- pam, barbiturates, inhalant anesthetics or intermittent pro-
tera fish poisoning in people, and presumably in affected pofol (caution regarding including Heinz body formation in
veterinary species, is a paresthesia (tingling sensation) cats with propofol). Tremors should be controlled with slow
in the extremities as well as a perception of heat with IV injection of methocarbamol (55 220 mg/kg) to effect.
cold stimuli (“dry-ice phenomenon”) (Kaplan, 2000). Once severe tremors and seizures have been treated, decon-
The neurologic signs are attributable to edema of the tamination with a warm bath using a liquid dishwashing
adaxonal Schwann cell cytoplasm and can persist for detergent is indicated. Thermoregulation is critical.
weeks. Gastrointestinal pain and diarrhea are also typi- Hyperthermia can arise with continued tremors and seizures
cal, particularly in the early course of the disease and could result in life-threatening disseminated intravascu-
(Glaziou et al., 1995; Spencer, 2000). lar coagulation. Hypothermia can ensue following a bath
Other examples of toxicants that block inactivation of and can enhance or prolong the toxicosis. Supportive care
sodium channels include batrachotoxin, a steroid alkaloid with IV fluids can help protect the kidneys from myoglobi-
isolated from the skin of Phyllobates aurotaenia and other nuric damage. Other species may have dermal hypersensi-
species of South American poison dart frogs (Spencer, tivity reactions or local paresthesia effects from topical
2000); grayanotoxins, diterpene alkaloids from the plants application of pyrethroids. Steady resolution with this clini-
of the Rhododendron, Kalmia, Pieris, Leucothoe and cal picture is expected once the dermal residue is removed
Lyonia genera (Puschner, 2004); aconitine, present in post bathing (Volmer, 2004; Hansen, 2006).
monkshood (Aconitum spp.); and veratridine from
Veratrum album (Spencer, 2000). Both α-scorpion and
1 Potassium Channels
β-scorpion toxins bind to Na channels, albeit different
sites, and enhance nerve conduction. Toxins of the Potassium channels are largely involved with repolariza-
1
Sydney funnel web spider (Atrax robustus and tion of the neuron following Na -induced depolarization.
Hadronyche species; δ-atracotoxin, atraxotoxin, robustox- The opening of these potassium channels is voltage
1
in) also block sodium channel inactivation. Persistent neu- dependent and allows K to leave the cell, thereby restor-
ronal excitation with all of these toxins can result in a ing the resting potential of the axonal membrane. Several
tingling sensation, muscle spasms, agitation, seizures, car- subtypes of potassium channels exist, the details of which
diac arrhythmias and death potentially within an hour of exceed the scope of this text. Clinical effects of potassium
exposure (White et al., 1995; Spencer, 2000). channel-blocking toxicants or adverse effects of similarly
1
Pyrethrins, natural organic esters isolated from the acting therapeutic agents depend on the type of K chan-
flower of the Chrysanthemum cinerariaefolium, have natu- nel and location. A potent example of a potassium chan-
ral insecticidal properties because of their ability to bind to nel blocker in veterinary medicine is 4-aminopyridine
1
Na ion channels and slow their inactivation. These natural (4-AP; Avitrol). Predominantly used as an avicide, 4-AP
insecticides have a rapid knockdown effect on the insect ingestion by birds results in rapid onset of seizures and
followed by recovery. Synthetic analogs, pyrethroids, were death (Schell, 2004). Although its classification as a 1 A
1
developed to increase the insecticidal potency. Because of antiarrhythmic indicates it primarily blocks Na channels,
their relatively rapid metabolism, pyrethrins and pyre- quinidine, derived from the Cinchona tree, also blocks
throids are often marketed with synergists such as MGK- potassium channels. Depression, confusion, and seizures
264 or piperonyl butoxide to inhibit enzymes which are possible with quinidine overdose (Plumb, 2015).
degrade them, thereby prolonging their insecticidal action. Classified as a class III (potassium channel blocker) anti-
Today, pyrethroids are common ingredients in flea and tick arrhythmic, amiodarone also has sodium and calcium
spot-on products and sprays. Examples include permethrin, channel-blocking effects. Adverse effects include brady-
phenothrin, tetramethrin, fenvalerate, cyhalothrin, cyflu- cardia and hypotension and potentially hepatopathy
thrin, cypermethrin, cyphenothrin, and etofenprox (Volmer, but not primary nervous system effects. Sotalol, also a
2004; Merola and Dunayer, 2006). class III antiarrhythmic, exerts its pharmacological effect
Fish and cats represent the most susceptible animals to via the blockade of cardiac potassium channels. It also
pyrethroids. Fish typically die acutely when exposed to pyr- has beta-blocking properties. Like amiodarone, adverse
ethroids. Cats are most commonly presented to the veteri- effects are primarily cardiac (bradycardia and hypoten-
narian because of exposure to the highly concentrated sion), but nervous system effects secondary to hypoglyce-
(45% 65%) spot-on permethrin products labeled for use in mia are also possible (Plumb, 2015).