[yorkiegirl2]

Caffeine
Caffeine is a methylxanthine compound (other related compounds are theophylline, aminophylline, and theobromine) and a CNS stimulant [34]. Methylxanthines enhance catecholamine release and increase calcium entry into cells, and inhibit phosphodiesterase, an enzyme that degrades cyclic AMP (cAMP) [2]. Cardiac acceleration occurs with the increase of cAMP [34]. Intoxication in animals most commonly occurs within several hours following ingestion of chocolate, caffeine-based tablets, or elixirs [1]. One ounce of chocolate contains 5 - 10 mg of caffeine and 35 - 50 mg of theobromine, while baking chocolate is approximately 10 times more toxic [2]. Signs of toxicity in dogs and cats may include vomiting, restlessness, hyperactivity, ataxia, muscle tremors, tachycardia, cardiac arrhythmias, seizures, hyperthemia, polydipsia/polyuria, cyanosis, and coma [1,35,209]. There are usually no histological lesions found in the CNS [2]. Treatment is symptomatic and supportive, including anticonvulsants, antiarrythmic agents, activated charcoal, and fluids.

Chlorhexidine
Chlorhexidine is commonly used as an antiseptic and disinfectant. There have been reports of vestibular dysfunction following use of chlorhexidine (0.5%) or chlorhexidine (1.5%)/cetrimide (15%) in treating otitis externa in dogs and cats with perforated tympanic membranes [36]. Pathological findings included loss of sensory epithelium and fibrosis, and degeneration of afferent nerve terminals and the hair cells in the organ of Corti [1,36]. There is no specific treatment for this toxicosis although immediate flushing of the middle ear with saline may be beneficial [36]. Interestingly, a solution containing 0.2% chlorhexidine did not induce vestibular or cochlear neurotoxicity following installation (over a 3-week period) into the external ear canals of dogs with intact and surgically perforated tympanic membranes [37].

Chlorinated Hydrocarbon Toxicity
Chlorinated hydrocarbon compounds (e.g., endrin, aldrin, dieldrin, heptachlor, lindane, DDT) are used for prevention and control of insect infestations around farms, homes, and on animals, although regulatory agencies have banned the use of may of these insecticides because of accumulating tissue residues and environmental persistence [11]. Dogs and cats may be poisoned by ingestion, inhalation, or absorption through the skin when the insecticide is applied topically [38]. Endosulfan is presently used for garden or farm use and is highly toxic to cats and has been used maliciously to kill dogs [11]. Chlorinated hydrocarbon insecticides are considered to be non-specific stimulants of the central nervous system [38]. Clinical signs can include anxiety, hysteria, facial muscular spasms, jaw champing, spastic gait, ataxia, mydriasis, salivation, and severe generalized seizures. External stimuli may precipitate seizures. Body temperature will usually increase significantly as a result of the seizures. Death may occur within minutes or hours, after several days, or not at all. Neuropathological changes are usually absent [39].
A presumptive diagnosis is based on historical data of recent exposure to the toxin and clinical signs. Prognosis is guarded. Signs of acute toxicosis usually abate in 1 to 2 days. Complete recovery may take weeks. Treatment is symptomatic since there is no known antidote. Seizures may be controlled using intravenous anesthetic barbiturates, given to effect. Purgatives and/or gastric lavage will help remove residual toxin ingested, but maximum benefit is to be expected only during the initial 2 hours after exposure. Soap and water scrubs are indicated for animals exposed by the dermal route. Hyperthermic animals may be bathed in cool water. Forced diuresis with 5% mannitol in 0.9% sodium chloride can enhance urinary excretion.

Closantel
Closantel, a salicylanide derivative and potent uncoupler of mitochondrial oxidative phosphorylation, is primarily used as an anthelmintic against nematodes, trematodes and some arthropods in ruminants. It has also been used in treating dogs infected with demodectic mange and ancylostoma caninum. Acute closantel intoxication has been reported in a 13 month old dog that accidentally received 6 times the normal recommended dosage (normal dosage is 5 mg/kg subcutanously followed by 2.5 mg/kg every week until cessation of clinical signs) [210]. Clinical signs of intoxication included depression, blindness, bilateral mydriatic pupils unresponsive to light stimulation, hearing deficit, pelvic limb weakness, hypotonicity, hypersalivation, emesis, diarrhea, and polydipsia/polyuria. Fundic exam revealed markedly swollen optic disks, small papillary/peripapillary hemorrhages, and tapetal hyperreflectivity. Biochemical serum studies revealed marked increase in liver enzymes, muscle CK, and total bilirubin, but decrease in total protein and albumin. The results of clinical and diagnostic findings suggested optic neuritis, myopathy, retinal degeneration, and hepatotoxicosis. Initial supportive treatment included fluid therapy, forced feeding a semifluid diet (Canine/Feline a/d ®, Hills), and prednisolone 2 mg/kg PO bid (followed by alternate day therapy for 1 week and progressive reduction over the ensuing 2 weeks) for the optic neuritis. In order to bind any free closantel (the toxic fraction, since most closantel is bound to plasma proteins, and almost exclusively to albumin), a daily intravenous infusion of 20% albumin was administered (1 ml/kg/day). The dog responded over several weeks and biochemical values returned to normal. Three months after intoxication, the dog appeared clinically normal, although blindness persisted. The histopathology associated with closantel poisoning in dogs is uncertain; however, in sheep with closantel intoxication, spongiform changes are commonly found in the brain, including optic tracts/fasciculi, and neuronal loss in the ganglion cell layer and outer layer of the retina. The chances of chronic toxicity developing in dogs receiving closantel over several months appears to be quite low.

Cyanogenic Plants
Seizures and semicoma, accompanied by bradycardia, pale and cyanotic mucous membranes, pulmonary congestion, vomiting, and frequent defecation were observed in an 11-week-old puppy after consumption of leaves and stems from the cyanogenic shrub, heavenly bamboo (Nandina domestica) [40]. Treatment was supportive, including intubation and oxygenation, epinephrine (1:10,000, IM), prednisolone sodium succinate (100 mg, IV), furosemide (12.5 mg, IV), and ampicillin trihydrate (50 mg, SC). The following morning, the puppy appeared normal.

Cycad Palms
Cycad palms occur in dry sandy soils of tropical and subtropical regions. Ingestion of cycads (also known as sago palms) can result in toxicosis in animals. In a recent survey of 60 dogs with evidence of cycad ingestion, approximately 90% of the dogs were from the southern United States, 39% ingested seeds, 95% developed liver and gastrointestinal tract problems, and 53% had abnormal neurologic signs, including weakness, ataxia, depression, proprioceptive deficits, coma, or seizures [41]. It is not known if the neurological signs were secondary to liver damage or to neurotoxins. High serum bilirubin concentration and alkaline phosphatase and alanine aminotransferase activities were the most common serum biochemical abnormalities. Although clinical signs were observed within 1 day, laboratory values did not change for 24 to 48 hours after cycad ingestion. Mortality rate was 32%, with the remaining dogs responding well to treatment and supportive care such as, emesis, repeated doses of activated charcoal, fluid therapy (e.g., 5% dextrose IV), and seizure control. Sucralfate at 0.5 - 1.0 g, PO, tid, may be used if vomiting is severe or if GI ulceration develops. Dogs ingesting seeds were likely to develop more serious problems.