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Ethylene Glycol Toxicity
Ethylene glycol (EG) is a commercial antifreeze automotive product with limited toxicity, but its metabolites, including glycolic acid are extremely toxic to dogs and cats. In a recent report from the ASPCA National Animal Poison Control Center, exposures were commonly (57%) from container spill, engine flush, or engine leak and were in or around the home (66%) [42]. Interestingly, among cases with a known final outcome, 59% did not show clinical signs and death/euthanasia was reported in 28%. In an earlier study, a mortality rate of 43% was reported in dogs and cats [43]. As little as 1 tablespoonful of 50:50 radiator fluid can be lethal in cats, while 4.5 ounces may be lethal in a 20-pound dog [11]. Signs of depression, vomiting, knuckling, ataxia, seizures, and coma may be observed within a few hours of exposure. Affected animals may be hypothermic. The condition is associated with severe metabolic acidosis, serum hyperosmolality, and eventually, renal failure with polydipsia, polyuria, calcium oxalate monohydrate and dihydrate crystalluria, and isosthenuria [44]. Glycolic acid is metabolized to formic acid, oxalic acid and oxalate. The oxalate combines with calcium to form oxalate crystals in renal tubules (especially proximal), urine, and within the lumen or perivascular space of cerebral capillaries [39]. Microscopically, the crystals appear pale yellow and there is evidence of nephrosis with attenuated epithelial cells and dilated tubules [39]. The birefringent crystals may be found in urine after 3 hours in cats and after 5 hours in dogs. Anion gaps > 40 - 50 mEq/L may be diagnostic. A moderate hypocalcemia may be found in serum. Ultrasonographic changes vary from mild to marked increases in renal cortical echogenicity [45]. Ethylene glycol colorimetric spot tests are available for use with urine and serum. A test for rapid (10 min) analysis of biological fluids for EG and glycolic acid also has recently been reported [46].
Treatment consists of administration of activated charcoal and sodium sulfate, correction of dehydration and acidosis, and maintaining fluid therapy. Fomepizole (4-methylpyrazole), an alcohol dehydrogenase inhibitor, is considered safe and effective for dogs if started within 8 hours of exposure [44,47]. The dose is 20 mg/kg, IV, initially as a loading dose, followed by doses of 15, 15, and 5.0 mg/kg at 12, 24, and 36 hours. This drug is not recommended for cats [48]. Instead, 20% ethanol (also an inhibitor of EG metabolism) is given at 5 mL/kg in saline IV, and 5% sodium bicarbonate at 6 mL/kg IV every 6 hours for 5 treatments, then every 8 hours for 4 treatments [11]. For dogs, the ethanol dosage is 5.5 mL/kg in saline IV, together with 8 mL/kg of 5% sodium bicarbonate, IP, each given every 4 hours for 5 treatments, then every 6 hours for 4 treatments. In cases of severe renal failure, peritoneal dialysis and hemodialysis may be options to ameliorate the azotemia, fluid, electrolyte, and acid-base abnormalities [49,50]. Prognosis is guarded. In one study in which EG intoxication was confirmed in 37 dogs, 21 were azotemic or became azotemic within 18 hours after admission, and only 1 of the 21 survived [47]. However, dogs treated with Fomepizole within 8 hours of EG ingestion had a good prognosis. Note that ultrasonographic detection of the "halo" sign (a pattern of greater than normal cortical and medullary echogenicity with persistence of areas of lesser echo intensity at the corticomedullary junction and central medullary regions) in anuric animals with EG intoxication was considered to warrant a grave prognosis.

5-Fluorouracil
5-Fluorouracil (5-FU) is a pyrimidine analog and an antimetabolite. It destroys rapidly dividing cells and is used to treat many neoplastic conditions. 5-FU creams and solutions are used for topical treatment of solar and actinic keratoses and some skin tumors in people [1,51]. In a report of 26 cases of accidental 5-FU ingestions by dogs reviewed from phone calls to the Illinois Animal Poison Information Center from January 1, 1987 to December 31, 1988, 12 were classified as "toxicosis", 13 as "suspected toxicosis", and one as "exposure" [51]. Dogs were the only species involved in 5-FU cases received during this time. Ingestion of more than 20 mg/kg of 5-FU was associated with the development of toxicosis. None of the 12 dogs that ingested oral doses in excess of 43 mg/kg (estimated) survived. Clinical signs associated with 5-FU poisoning in the dog were death, seizures, vomiting (with and without blood), tremors, diarrhea (with and without blood), ataxia, and depression. Cardiac arrhythmias, and respiratory depression have also been noted [51]. Clinical signs generally developed within 45 to 60 minutes after exposure, and deaths occurred 6 to 16 h after ingestion. Hyperesthesia, hyperexcitability, nervousness, muscle tremors, and cerebellar ataxia have also been reported in dogs and cats following intravenous 5-FU treatment or accidental ingestion [1]. Treatment should include dermal decontamination, GI tract decontamination/protection (e.g., sucralfate 0.5 - 1.0 gm, PO, tid), fluid therapy, anticonvulsants (e.g., pentobarbital sodium 3 - 15 mg/kg IV slowly to effect, or phenobarbital 3 - 30 mg/kg IV slowly to effect), and GI protectants. It is recommended that induction of emesis or administration of activated charcoal be delayed until seizures are controlled and the airway protected so as to avoid aspiration [51].

Griseofulvin
Griseofulvin treatment of ringworm in pregnant cats has resulted in multiple congenital malformations in kittens [52]. Malformations of the brain included exencephaly, malformed prosencephalon, caudal displacement, and hydrocephalus. Skeletal malformations included cranium bifidium, spina bifida (C1 through C4, and sacral), abnormal atlantooccipital articulation, cleft palate, absence of maxillae, and lack of tail vertebrae. Cyclopia and anophthalmia with absence of optic nerves and rudimentary optic tracts were also observed. Atresia ani, atresia coli, lack of atrioventricular valves in the heart, and absence of external nares and soft palate were other abnormalities present.