5-Fluorouracil Toxicosis in the Dog

Twenty-six cases of accidental 5-fluorouracil (5-FU) ingestions by dogs were reviewed from phone calls to the Illinois Animal Poison Information Center. Cases were collected from January 1, 1987 to December 31, 1988. Of the 26 calls involving 5-FU exposures, 12 were classified as "toxicosis," 13 as "suspected toxicosis," and one as "exposure." Dogs were the only species involved in 5-FU cases received during this time. Accurate estimates of the amount of 5-FU ingested by dogs could be made in 17 cases. 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. Clinical signs generally developed within 45 to 60 minutes after exposure, and deaths occurred 6 to 16 hours after ingestion.     

Clinical observations in collies given ivermectin orally

An oral liquid form of ivermectin was administered to 14 purebred Collies (12 rough coated, 2 smooth coated). All Collies were given ivermectin at dosages of 100 and then 200 micrograms/kg of body weight. Three of the dogs developed mild clinical signs of toxicosis (salivation, vomiting, confusion, ataxia, and tremors) with the 100 micrograms/kg dosage. After the 200 micrograms/kg dosage, 7 dogs (including 1 smooth-coated Collie) developed severe toxicosis (seizure-like activity, recumbency, nonresponsiveness, and coma). Because dogs that developed severe toxicosis were not retreated, only the 7 remaining dogs were given ivermectin at 600 micrograms/kg. Severe toxic signs were not observed in the dogs given the 600 micrograms/kg dosage, and only 1 of these 7 dogs developed severe toxicosis when given ivermectin at 2,500 micrograms/kg. Dogs that developed severe toxicosis were given supportive care while in the comatose state. All dogs recovered completely. The results indicated that Collies (including the smooth-coated Collies) have a wide range of sensitivity to ivermectin-induced toxicosis.     

Fenvalerate/N,N-diethyl-m-toluamide (Deet) toxicosis in two cats

Toxicosis attributable to fenvalerate and N,N-diethyl-m-toluamide (Deet) exposure was suspected in 2 cats. Clinical signs of toxicosis developed within 4 to 6 hours of dermal application of the pesticide. Clinical signs of toxicosis seen in both cats included hypersalivation, ataxia, and depression. In addition, seizures were seen in 1 cat. Both cats died. Analysis of skin, kidney/urine, liver, and brain tissues confirmed the presence of fenvalerate and Deet. The pyrethroid fenvalerate and the insect repellent Deet are used for the control of fleas and ticks on cats. Suspected fenvalerate/Deet toxicosis in cats is associated with tremors, hypersalivation, ataxia, vomiting, depression, and seizures.     

Proliferative glomerulonephritis and chronic active hepatitis with cirrhosis associated with Corynebacterium parvum immunotherapy in a dog

Ivermectin, a broad-spectrum antiparasitic agent, was believed responsible for signs of CNS dysfunction in a dog. Within 2 hours of oral administration of ivermectin, the dog had hind limb ataxia. Neurologic signs progressed rapidly until the dog was in a semicomatose state at admission 20 hours later. The dog improved gradually under supportive care. The ivermectin had been given for suspected endoparasitism. Clinical signs were similar to those reported in dogs with clinical and experimental exposure to ivermectin.     

Neurotoxic effects of ivermectin administration in genetically engineered mice with targeted insertion of the mutated canine ABCB1 gene

Objective-To develop in genetically engineered mice an alternative screening method for evaluation of P-glycoprotein substrate toxicosis in ivermectin-sensitive Collies. Animals-14 wild-type C57BL/6J mice (controls) and 21 genetically engineered mice in which the abcb1a and abcb1b genes were disrupted and the mutated canine ABCB1 gene was inserted. Procedures-Mice were allocated to receive 10 mg of ivermectin/kg via SC injection (n = 30) or a vehicle-only formulation of propylene glycol and glycerol formal (5). Each was observed for clinical signs of toxic effects from 0 to 7 hours following drug administration. Results-After ivermectin administration, considerable differences were observed in drug sensitivity between the 2 types of mice. The genetically engineered mice with the mutated canine ABCB1 gene had signs of severe sensitivity to ivermectin, characterized by progressive lethargy, ataxia, and tremors, whereas the wild-type control mice developed no remarkable effects related to the ivermectin. Conclusions and Clinical Relevance-The ivermectin sensitivity modeled in the transgenic mice closely resembled the lethargy, stupor, disorientation, and loss of coordination observed in ivermectin-sensitive Collies with the ABCB1-1Δ mutation. As such, the model has the potential to facilitate toxicity assessments of certain drugs for dogs that are P-glycoprotein substrates, and it may serve to reduce the use of dogs in avermectin derivative safety studies that are part of the new animal drug approval process.     

Clinical presentation and management of moxidectin toxicity in two dogs

Moxidectin is a macrocyclic lactone related to ivermectin used in horses and dogs for endoparasite treatment and prophylaxis. The clinical and neurological presentation of moxidectin toxicity in two dogs following inadvertent poisoning with a moxidectin-containing equine de-worming medication is reported here. In both the dogs, the predominant clinical signs were generalised tremors and ataxia. Moxidectin exerts its neurotoxic effects in mammals by potentiating the effect of gamma-aminobutyric acid and, consistent with this, both the dogs demonstrated a poor response to treatment with diazepam. It would be more appropriate to avoid gamma-aminobutyric acid agonists, such as benzodiazepines and barbiturates, in dogs with moxidectin toxicity and consider using anaesthetic agents with a different mode of action, such as propofol. The prognosis in dogs accidentally exposed to moxidectin-containing equine de-worming medication appears to be excellent if the cause of the neurotoxicity is correctly identified and the case is appropriately managed.     

Macrocyclic lactone toxicity due to abamectin in farm dogs without the ABCB1 gene mutation

Abstract

CASE HISTORY: A 5-year-old entire female Huntaway from a sheep and beef farm was one of four dogs that developed clinical signs including hypersalivation, depression, blindness and ataxia after the death of another dog. A 4-year-old female Huntaway farm dog from a second farm was observed to be sitting down more often than usual on the day after being fed part of a calf carcass that had been treated with an abamectin pour-on.

CLINICAL FINDINGS: The first dog was ataxic and depressed but did respond to sound. The second dog presented with an acute onset of blindness, mydriasis, absence of a menace response, hypersalivation, gait abnormalities (e.g. high stepping gait and ataxia), and depression. Other presenting signs included muscle tremors, dehydration and difficulty eating. No abnormalities were detected from routine haematology and biochemistry. Analysis of samples of plasma from both dogs revealed concentrations of abamectin of 0.149 mg/L and 0.260 mg/L for the first and second dogs, respectively. Buccal swabs taken from the first dog for DNA testing for the ABCB1 gene mutation, gave a negative result.

DIAGNOSIS: In addition to the presenting signs which suggested a toxicosis, both dogs had measurable concentrations of abamectin in plasma confirming exposure.

CLINICAL RELEVANCE: Farm dogs exposed to concentrated pour-on products containing abamectin have been poisoned and recover or die. The product labels do not carry any warnings as to the risk of poisoning to dogs. This paper discusses two incidents affecting six farm dogs, but the authors are aware of more toxicoses in farm dogs exposed to abamectin.     

Effects of an insecticidal dip containing d-limonene in the cat

A study was undertaken to determine the effects of a single dermal application of a commercial insecticidal dip containing 78.2% d-limonene in cats. At the manufacturer's recommended concentration of 1.5 oz/gal of water, no clinical signs or lesions of toxicosis were seen. At 5 times the recommended concentration, clinical signs were mild and consisted of hypersalivation of short duration, ataxia, and muscle tremors resembling shivering. At 15 times the recommended concentration, clinical signs included hypersalivation lasting 15 to 30 minutes, moderate-to-severe ataxia lasting 1 to 5 hours, muscle tremors resembling shivering lasting 1 to 4 hours, and severe hypothermia beginning soon after treatment and lasting 5 hours. Gross lesions were confined to excoriation of the scrotal and perineal areas of the treated male cats at the 15 X concentration. No deaths or other lasting effects were seen at any dosage.     

Acute toxicity of paraherquamide and its potential as an anthelmintic.

Paraherquamide, an oxindole alkaloid metabolite of Penicillium paraherquei and P charlesii, is a new anthelmintic with potential broad-spectrum use. In initial trials, it had an excellent safety profile in cattle and sheep at doses efficacious against a dozen or more helminths, but recently it produced unexpected and severe toxicosis in dogs at doses far below those that were safe in the ruminants. To provide data on which to build rational safety tests in the future, we tested the acute toxicity of paraherquamide administered PO to male CD-1 mice and compared its profile with the most potent anthelmintic known, ivermectin. The estimated doses lethal to 50% of a group of mice were 14.9 and 29.5 mg/kg of body weight for paraherquamide and ivermectin, respectively. The no-effect doses were 5.6 and 18.0 mg/kg for paraherquamide and ivermectin, respectively. Signs of intoxication in paraherquamide-treated mice, if they developed, emanated within 30 minutes of administration, irrespective of dose, and consisted of either mild depression with complete recovery or a 5- to 10-minute period of breathing difficulty followed by respiratory failure and death by 1 hour after treatment. Gross necropsy findings in paraherquamide-treated mice that died in the high-dose group were normal. Ivermectin-related toxicity was slower and more predictable, taking place over a 3-day period, with dose-dependent signs of intoxication consisting of tremors, ataxia, recumbency, coma, and death. Necropsy of ivermectin-treated mice that died in the high-dose group revealed dehydration, a condition most likely resulting from the coma-induced state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nasopharyngeal turbinates in brachycephalic dogs and cats

This retrospective study reports the presence and incidence of nasal turbinates in the nasopharynx (nasopharyngeal turbinates) in a population of brachycephalic dogs and cats exhibiting signs of upper respiratory disease. Medical records were reviewed for 53 brachycephalic dogs and 10 brachycephalic cats undergoing upper airway endoscopy. Nasopharyngeal turbinates were identified in 21% of brachycephalic animals, including 21% of dogs and 20% of cats. Pugs accounted for 32% of all dogs in the study population and 82% of dogs with nasopharyngeal turbinates. The presence of nasopharyngeal turbinates may play a role in upper airway obstruction in the brachycephalic airway syndrome.     

Assessment of toxicosis induced by high-dose administration of milbemycin oxime in collies

Fifteen Collies, previously having mild reactions to ivermectin challenge (120 micrograms/kg of body weight; 20 times the recommended dosage level), were studied to evaluate the effects of milbemycin oxime administration at 5 and 10 mg/kg (10 and 20 times the manufacturer's recommended dosage). Five replicates, comprising 3 dogs each, were formed on the basis of body weight. Within replicates, each dog was randomly allocated to treatment with 5 or 10 mg of milbemycin/kg or served as a untreated control. Dogs were examined repeatedly for signs of toxicosis for 4 days after treatment and daily thereafter. Two of 5 dogs treated at 5 mg/kg (10x) developed signs of mild depression on the day of treatment, but were normal 24 hours after treatment. All 5 dogs treated at 10 mg/kg (20x) developed signs of mild depression and ataxia by 6 hours. Signs persisted for 24 hours in 3 dogs. Two of these dogs also had mydriasis, whereas 3 salivated excessively. All dogs recovered completely by day 2 after treatment. The results of this study demonstrated that Collies sensitive to the effects of 120 micrograms of ivermectin (20x)/kg show similar sensitivity to the effects of milbemycin oxine administered at 10 mg/kg (20x). We conclude 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.     

Clinical syndrome associated with zolpidem ingestion in dogs: 33 cases (January 1998-July 2000)

Zolpidem is a nonbenzodiazepine hypnotic of the imidazopyridine class that is used to treat insomnia in humans. Zolpidem binds selectively to the benzodiazepine omega-1 receptor and increases the frequency of chloride channel opening, which results in inhibition of neuronal excitation. A retrospective study was conducted of zolpidem ingestion in dogs that were reported to the ASPCA Animal Poison Control Center (APCC) between January 1998 and July 2000. Data analysis included amount ingested, clinical effects, and time of onset of signs. Thirty-three reports of zolpidem ingestion in dogs (ranging in age from 5 months to 16 years) were evaluated. Approximate ingested dosages ranged from 0.24 to 21 mg/kg. Clinical signs reported included ataxia (18 dogs; 54.5%), hyperactivity (10 dogs; 30.3%), vomiting (7 dogs; 21.2%), and lethargy (5 dogs; 15.2%), as well as panting, disorientation, nonspecific behavior disorder, and hypersalivation (4 dogs each sign; 12.1%). Other signs reported include tachycardia, tremors, apprehension, vocalization, hypersalivation, weakness, and hyperesthesia. In 85% percent of reports, clinical signs developed within 1 hour and usually resolved within 12 hours. Although central nervous system (CNS) depression is reported as a primary effect of zolpidem in humans and would also be expected in dogs, information obtained from this study indicates that some dogs may exhibit a paradoxical excitation reaction. This effect appears to vary among individual dogs.     

Clinical, clinicopathologic, and electroencephalographic features of lead poisoning in dogs.

Eleven dogs with signs of lead poisoning were examined. The principal clinical signs were neurologic and included ataxia, tremors, clonic-tonic seizures, amaurosis, and deafness. Basophilic stippling and circulating nucleated red cells were not common findings in blood films. Blood lead values varied from 0.22 ppm to 0.63 ppm before treatment. Electroencephalographic changes in nonsedated dogs were marked by intermittent high-amplitude slow wave activity.     

Polioencephalomyelitis in cats.

Six cats with chronic progressive neurologic signs of ataxia, paresis, tremors, pupillary abnormalities and seizures had polioencephalomyelitis of probable viral origin. Lesions were most severe in the spinal cord. The uniformity in distribution and nature of the lesions in all six cats strongly suggested a common cause. The condition was compared with other viral infections of known and unknown cause.     

Clinical features therapy and epidemiology of tiger snake bite in dogs and cats

SUMMARY Snake bite was diagnosed in 125 dogs and 115 cats over 10 years. Young sporting dogs and young cats were mainly affected. More dogs (48%) were seen in contact with tiger snakes than cats (7%). One hundred and four (84%) dogs and 89 (76%) cats were bitten in the warmer months of the year (October to March). As the incidence rose in September /October, dogs were bitten on days when the temperature was near 20°C or over. The commonest presenting signs were dilated pupils and absences of pupillary light reflex. Dyspnoea, hypothermia, hindleg ataxia and glycosuria were common features in cats. Vomiting, tachypnoea, hyperthermia and complete flaccid paralysis were often seen In dogs. The overall recovery rate after administering antivenene was 90% for cats and 83% for dogs. Death from anaphylaxis as a result of giving antivenene occurred in 3 cats and one dog. Dogs treated soon after being bitten recovered more rapidly. There was no correlation between the bite-to-treatment period and the treatment-to-recovery period for cats.     

Neuronal-Visceral GM1 Gangliosidosis in Portuguese Water Dogs

Three female siblings in a litter of seven Portuguese Water dogs (PWDs) showed clinical signs of ataxia and/or lameness at 5 months of age. Signs of cerebellar dysfunction (intention tremors, ataxia, widebased stance, dysmetria, and/or nystagmus) and mild limb weakness developed rapidly. Results of hemograms (three dogs), blood chemistry profiles (two dogs), urinalyses (two dogs), electroencephalograms (two dogs), and radiographs of the limbs or pelvis (three dogs), vertebrae (two dogs), and skull (one dog) were unremarkable except for an absolute lymphocytosis in one dog. Routine cerebrospinal fluid (CSF) analyses were normal in all three dogs. However, the CSF creatine kinase concentration was elevated in the one dog in which it was measured. Mucopolysacchariduria was present in all three dogs. Due to the rapid progression of clinical signs and a poor prognosis, all three dogs were euthanatized between 6 and 7 months of age. Histopathologic and electron microscopic studies showed neuronal cytoplasmic inclusions, vacuolated hepatocytes, and vacuolated renal tubular epithelial cells, compatible with the diagnosis of a storage disease. Beta-galactosidase activities in leukocytes, serum, and brain homogenates were reduced when compared with that in normal dogs and the stored product was identified as GM1 ganglioside, confirming GM1 gangliosidosis.     

Toxicity in three dogs from accidental oral administration of a topical endectocide containing moxidectin and imidacloprid

Three dogs were presented with a history of oral administration of a topical endectocide containing imidacloprid and moxidectin. They were diagnosed with imidacloprid and moxidectin intoxication, having ingested doses ranging from 7.5 to 1.4 mg/kg of imidacloprid and 1.9 to 2.8 mg/kg of moxidectin. The three dogs were affected to different degrees of severity, but all displayed signs of ataxia, generalised muscle tremors, paresis, hypersalivation and disorientation. Temporary blindness occurred in two cases. The three dogs were tested for the presence of the multi-drug resistance 1 gene deletion, which can cause an increased sensitivity to the toxic effects of moxidectin, and were found to be negative. Treatment included gastrointestinal decontamination, intravenous fluid therapy and benzodiazepines to control muscle tremors. All three dogs made a complete recovery within 48 h of ingestion.     

Association between neurologic and cognitive dysfunction signs in a sample of aging dogs

In human neurology, patients with Alzheimer's disease show seizures and signs of motor deficits, such as movement disorders (i.e., restlessness, slowness, impaired gait, and, rarely, resting tremors). Because canine Cognitive Dysfunction Syndrome (CDS) is considered an Alzheimer-like disease in dogs, it might be possible to document concurrent behavioral and neurologic signs in aging canine patients as well. Twenty-one dogs (14 dogs with CDS-related signs, 7 normal dogs) greater than 7 years of age were studied. Owners completed a behavioral questionnaire and the dogs underwent a neurologic evaluation. Dogs with CDS were twice as likely to show neurologic deficits as dogs without CDS. However, based on this pilot study, a sample of 187 dogs affected with CDS are required to show statistically significant differences between the proportions of dogs with CDS and with neurologic signs and the proportions of control dogs without any of these disorders.     

Alpha-chloralose poisoning in dogs and cats: a retrospective study of 33 canine and 13 feline confirmed cases

Alpha-chloralose (AC) is an anaesthetic compound also used as a rodenticide, and has dose-dependent central nervous system mixed effects of excitation and depression. The objectives of this study were to detail the clinical and clinicopathological characteristics, as well as the treatment and prognosis, of AC toxicosis in dogs and cats. Medical records were retrospectively reviewed for AC poisoning between the years 1989 and 2004, and 33 dogs and 13 cats were included in the study. The most common clinical signs were seizures, muscle tremor, hyperaesthesia, hypothermia, salivation, myosis, stupor, coma and ataxia. Coma was more common, while salivation and ataxia were less common in cats compared to dogs. Although hypothermia was very common, especially in cats (90.9%), hyperthermia was frequently observed in dogs (21%). Treatment in all patients was supportive and symptomatic, and the most commonly used anticonvulsants were diazepam and barbiturates; however, severe unresponsive seizures in three dogs had to be controlled with inhalant gas anaesthesia. The hospitalisation period was 1-3 days, and the overall mortality rate was 6.5%. Alpha-chloralose poisoning seems to have a favourable prognosis in dogs and cats.     

Neurological diseases of rottweilers: Neuroaxonal dystrophy and leukoenceph- alomalacia

Neuroaxonal dystrophy (NAD) and leukoencephalomalacia (LEM) are two neurological disorders of the rottweiler that initially present as ataxia of all four limbs. Disorders to be included in the differential diagnosis are caudal cervical spondylomyelopathy, canine distemper virus meningoencephalomyelitis, other nervous system infections or inflammations and spinal cord neoplasia. All diagnostic tests including myelography, cerebrospinal fluid analysis, electrodiagnos-tic testing and serum and cerebrospinal fluid titres for canine distemper virus are normal in NAD and LEM. There is no treatment for either disease and neurological signs progressively deteriorate. Eventually neurological deficits develop besides ataxia and these help differentiate NAD from LEM. Dogs with NAD develop head tremors and nystagmus while dogs with LEM develop conscious proprioceptive deficits and quadriparesis; the short term prognosis for NAD is better than LEM. Most dogs with LEM are euthanased because of non-ambulatory tetraparesis within one year. The histopathological lesions associated with NAD include axonal spheroids in many spinal cord and caudal brainstem nuclei and reduced numbers of Purkinje cells in the cerebellum, while in LEM, multifocal areas of demyelination and malacia of the spinal cord and brainstem are the primary histopathological lesions. Both NAD and LEM are suspected to have an autosomal recessive genetic transmission.