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Hexachlorophene Toxicity
Hexachlorophene (pHisoHex ®) is used as a germicide in soaps, shampoos and disinfectant solutions. Dogs and cats may be exposed by percutaneous absorption of hexachlorophene following skin application, or dogs may eat soap containing hexachlorophene [53-57]. Nursing puppies have been poisoned following hexachlorophene application to the mammary glands of the bitch [55]. Clinical signs in dogs are usually characterized by acute onset of tremors, especially of the head, that can increase with excitement. Tremors may disappear during inactivity or sleep. Neuromuscular twitchings, spasms, opisthotonus, severe seizures, and death have been reported in some affected animals [56]. Irreversible visual impairment and permanent mydriasis were reported in Beagles following dermal application of an ointment containing 3% and 10% hexachlorophene over a 12-week period [58]. In cats, dilated pupils, vomiting, weakness, ataxia and spastic or flaccid paralysis, along with signs of hypovolemic shock (hypothermia, pale mucous membranes, tachycardia, tachypnea, and dyspnea) have been reported [53,59]. Significant elevations in cerebrospinal fluid pressure have been recorded in cats following experimental hexachlorophene toxicity [59].
Grossly, mild brain edema has been reported associated with flattening of the cerebral gyri and prolapse of a portion of the cerebellum through the foramen magnum [54,56]. Microscopically, the toxin produces spongiform changes, seen as a vacuolar myelinopathy, in the white matter of the brain, cerebellum and spinal cord, along with astrocytosis and microgliosis [53,56]. Comparative studies have shown that the vacuoles are associated with intramyelinic edema with splitting of myelin sheaths at the intraperiod line [60,62]. Neuronal cell bodies appear to be unaffected. Vacuolar lesions may also be seen in peripheral nerves [39,63]. Lesions in the CNS may regress after exposure to hexachlorophene is stopped [63].
Prognosis is guarded. Some animals recover spontaneously within a few weeks following removal of the exposure to hexachlorophene [55]. Paralyzed cats that have not reached the stage of severe central nervous system depression usually recover if exposure is stopped; however, clinical recovery may take 4 to 6 weeks. Gastric lavage or saline cathartic treatment may help animals that have ingested the toxin. In experimental studies with cats, hexachlorophene toxicosis has been reversed by slow intravenous injection of 30% urea (2 gm/kg) in a 10% aqueous glucose solution [59]. Cats are especially sensitive to phenol intoxication because of their inability to conjugate glucuronic acid with phenolic compounds. Since hexachlorophene is a polychlorinated biphenol, its use in cats should be contraindicated [53]. Barbiturates reportedly are ineffective in controlling seizures in dogs with experimental hexachlorophene toxicity [56].

5-Hydroxytryptophan
5-Hydroxytryptophan (5-HTP) is sold as an over-the-counter dietary supplement. Within target cells of the CNS, cardiovascular system, GI tract and respiratory tract, 5-HTP is rapidly converted to serotonin. In a recent survey involving 21 dogs with evidence of accidental 5-HTP ingestion, clinical signs of toxicosis, resembling serotonin syndrome in humans, developed in 19 of 21 (90%) dogs. Neurologic signs included seizures, depression, tremors, hyperesthesia, and ataxia. Gastrointestinal tract signs included vomiting or diarrhea, signs of abdominal pain, and hypersalivation. Other clinical signs were hyperthermia and transient blindness. Three dogs died. No important clinical laboratory or necropsy findings were reported. The doses of 5-HTP ingested ranged from 2.5 to 573 mg/kg of body weight; the minimum toxic dose reported was 23.6 mg/kg, and the minimum lethal dose was 128 mg/kg. Onset of signs ranged from 10 minutes to 4 hours after ingestion, and signs lasted up to 36 hours. Of 17 dogs with clinical signs of toxicosis that received prompt and aggressive treatment, 16 recovered. Treatment consisted of decontamination, seizure control, thermoregulation, fluid therapy, and supportive care. Cyproheptadine, a serotonin antagonist, is also recommended at 1.1 mg/kg, PO or rectally, every 1 to 4 hours until signs resolve [64,65].

Ivermectin
Ivermectin, approved for the prevention of canine heartworm infection (at 6 mg/kg, monthly), and believed to be a gamma-aminobutyric acid (GABA) agonist, can produce severe CNS dysfunction in some dogs. In mammals, GABA acts as an inhibitory neurotransmitter at pre- and postsynaptic neurons within the CNS. Signs include depression/disorientation, muscle fasciculations, ataxia, dilated pupils, drooling, rarely seizures, and coma. Mydriasis, depressed menace response, and apparent blindness (reversible with time) may also be observed, along with vomiting, diarrhea, hyperthermia, bradycardia, and sinus arrhythmia [1]. Collies appear idiosyncratically sensitive to the drug [66-68], although toxicosis has been seen in other breeds [69], perhaps associated with the blood-brain barrier acting as an ineffective ivermectin barrier [1]. Treatment is supportive, including activated charcoal and a saline cathartic, fluids, shock doses of corticosteroids (in severely affected dogs), and picrotoxin and physostigmine only in comatose dogs [1]. It has been reported that ivermectin and milbemycin commercial formulations have similar margins of safety and that milbemycin toxicosis appears to be dose-dependent in Collies with a demonstrated sensitivity to ivermectin [70].