Electroretinographic changes after intravenous lipid emulsion therapy in a dog and a foal with ivermectin toxicosis

This case report describes ivermectin‐induced blindness in a dog and a foal with normal ophthalmic fundic examinations and attenuated electroretinography (ERG). Subsequent recovery in ERG was noted following intravenous lipid emulsion (ILE) therapy. A dog and a foal were evaluated for ivermectin‐induced blindness. Clinical signs included dull mentation, absent pupillary light reflexes (PLRs), and absent menace on presentation. The animals had normal fundoscopic examinations; however, in both cases ERG was consistent with neurosensory retinal dysfunction. Following ILE therapy for ivermectin toxicosis, return of menace, PLRs, and normal mentation were noted, as was improvement in ERG and serum ivermectin levels. These are the first documented cases of ivermectin‐induced blindness in a dog and a foal with normal fundic examinations and attenuated ERG. ERG improved in both animals after ILE therapy. ERG may assist in the diagnosis of ivermectin toxicosis in dogs and horses. ILE therapy may hasten recovery in treatment of ivermectin‐induced blindness.     

Detection of levamisole and ivermectin in organ samples from a dead collie.]

A collie, known for its breed-dependent adverse reaction to ivermectin, was without any clinical signs. The dog was prophylactically treated with 3 mg/kg KG (s.c.) of levamisole. Within 15 minutes, the dog showed convulsions, vomitus, and dyspnea, and perished 2.5 hours after injection of the drugs. The pathological findings were not informative as to the cause of death, and with regard to the adverse reactions, additional application of ivermectin was not excluded. Therefore, organ samples were submitted for toxicological analysis of both levamisole and ivermectin. For detection of levamisole and ivermectin, modified GC/MS and HPLC procedures were developed. Concentrations up to 535 micrograms levamisole and up to 26 ng ivermectin were found per g tissue. Both analytical methods are sensitive enough to detect these drugs after application of low doses. This study elucidates that combination of low-dosed ivermectin and levamisole is no recommendable means against adverse effects of ivermectin, with respect to collies. Moreover, the synergistic effects of ivermectin and levamisole suggests the same drug incompatibility in other dog breeds and animal species.     

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.     

Safety of moxidectin in avermectin-sensitive collies

OBJECTIVE: To evaluate the safety of moxidectin administration at doses of 30, 60, and 90 microg/kg of body weight (10, 20, and 30 times the manufacturer's recommended dose) in avermectin-sensitive Collies. ANIMALS: 24 Collies. PROCEDURE: Collies with mild to severe reactions to ivermectin challenge (120 mg/kg; 20 times the recommended dose for heartworm prevention) were used. Six replicates of 4 dogs each were formed on the basis of body weight and severity of reaction to ivermectin test dose. Within replicates, each dog was randomly allocated to treatment with oral administration of 30, 60, or 90 microg of moxidectin/kg or was given a comparable volume of placebo tablet formulation. Dogs were observed hourly for the first 8 hours and twice daily thereafter for 1 month for signs of toxicosis. RESULTS: Signs of toxicosis were not observed in any control group dog throughout the treatment observation period. Likewise, signs of toxicosis were not observed in any dog receiving moxidectin at 30, 60, or 90 microg/kg. CONCLUSIONS AND CLINICAL RELEVANCE: The moxidectin formulation used in the study reported here appears to have a wider margin of safety than ivermectin or milbemycin in avermectin-sensitive Collies.     

Retinopathy associated with ivermectin toxicosis in two dogs

CASE DESCRIPTION: 2 dogs (dogs 1 and 2) were examined for sudden onset of blindness. Both dogs had mild obtundation and mydriasis in both eyes. It was thought that dog 1 may have ingested ivermectin; dog 2 had been treated with ivermectin for demodectic mange. CLINICAL FINDINGS: On initial examination, both dogs had mydriasis and decreased pupillary light reflexes in both eyes. Dog 1 had an absent menace response bilaterally. Fundic examination of both eyes in both dogs revealed regions of multifocal retinal edema and folds with low-lying retinal separation. The electroretinogram was extinguished in dog 1 and attenuated in dog 2. Ivermectin was detected in serum samples from both dogs. TREATMENT AND OUTCOME: Both dogs made a complete clinical recovery following cessation of exposure to ivermectin; electroretinographic findings improved, and retinal edema resolved with some residual chorioretinal scarring. CLINICAL RELEVANCE: To our knowledge, this is the first report of resolution of retinal edema and electroretinographic changes associated with ivermectin toxicosis in dogs. In dogs that develop blindness suddenly, fundic examination, electroretinography, and assessment of serum ivermectin concentration are diagnostically useful, even if exposure to ivermectin is unknown.     

Increased toxicity of P-glycoprotein-substrate chemotherapeutic agents in a dog with the MDR1 deletion mutation associated with ivermectin sensitivity

Lymphoma was diagnosed in a 4-year-old spayed female Collie, and treatment with a combination chemotherapy protocol incorporating prednisone, L-asparaginase, vincristine, vinblastine, doxorubicin, and cyclophosphamide was initiated. The dog had signs of gastrointestinal tract toxicosis and myelosuppression after treatment with P-glycoprotein-substrate drugs (vincristine, vinblastine, and doxorubicin) even when dosages were reduced, but did not have signs of toxicosis after treatment with cyclophosphamide, a non-P-glycoprotein-substrate drug, even when administered at the full dosage. It was postulated that a deletion mutation in the canine MDR1 gene (deltaMDR1 295-298) could be responsible for the drug toxicoses in this dog. This mutation has been identified as the cause of a functional P-glycoprotein defect in Collies susceptible to the toxic effects of ivermectin, another P-glycoprotein-substrate drug. The MDR1 genotype of this dog consisted of 1 normal and 1 mutant MDR1 allele. Because P-glycoprotein contributes to renal, biliary, and intestinal excretion of P-glycoprotein-substrate drugs, it is possible that drug excretion was delayed in this patient, resulting in clinical signs of toxicosis.     

Topical (pour-on) ivermectin in the treatment of chronic generalized demodicosis in dogs

Twelve privately owned dogs with chronic generalized demodicosis were treated topically along the dorsal midline with 1.5 mg kg⁻¹ of 0.5% pour-on ivermectin for cattle three times per week for 3–6 months. All 12 dogs had a substantial reduction in clinical signs and in the number of Demodex canis mites found on skin scrapings. Only two dogs, however, became skin-scrapings negative after 3 and 5 months of treatment, respectively. In these two dogs treatment was prolonged for an additional 4 weeks past the negative scrapings. One dog relapsed 2 months after cessation of therapy; the other is still free of symptoms 1.5 years later. The cure rate, based on the lack of recurrence of clinical signs for 12 months after discontinuation of ivermectin administration, was 1 of 12 dogs (8%). Adverse reactions were not seen.     

Evaluation of the safety of ivermectin administered in a beef-based formulation to ivermectin-sensitive Collies

Twenty-four Collies sensitive to the toxic effects of ivermectin, when administered at high dosages, were studied to evaluate the effects of repeated monthly treatment with an ivermectin beef-based formulation at amounts up to 10 times the dosage recommended for heartworm prevention in dogs. Collies were treated 3 times at 30-day intervals at rates of 12, 36, or 60 micrograms of ivermectin/kg of body weight, or with vehicle. Complete physical and neurologic examinations were performed on all dogs prior to the first treatment and after the final treatment. Clinical observations and ivermectin reaction scores were recorded daily for each dog throughout the study. Clinical or neurologic signs characteristic of ivermectin toxicosis were not observed for any dog during the study. Single episodes of vomiting were recorded for 2 vehicle-treated dogs and 2 dogs treated with ivermectin at 12 micrograms/kg from 6 to 21 days after treatment. At the end of the study, all dogs were challenge-exposed with ivermectin at 120 micrograms/kg to reconfirm their sensitivity to this class of compounds. All dogs developed signs typical of ivermectin toxicosis during the subsequent 48- to 72-hour period. Results of this study demonstrated that ivermectin can be administered repeatedly without adverse effects at rates up to 60 micrograms/kg (10 times the recommended use level) to Collies known to be sensitive to this drug.     

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.     

Mechanical Ventilation of a Dog with Pentobarbital Intoxication

A 9-year old spayed female American bulldog presented 5 hours after ingesting a portion of a recently euthanized sheep carcass. The dog was comatose, intubated and manually ventilated on arrival. On physical examination, the dog had stable cardiovascular parameters but was hypothermic. Cranial nerve reflexes were absent and spinal reflexes were depressed. Mechanical ventilation was initiated and maintained for 18 hours before spontaneous respiration returned. Elevated serum pentobarbital concentration (19.1 mg/ml) confirmed pentobarbital intoxication as the cause of neurological signs. This is the first report of a dog with pentobarbital toxicity that was successfully managed with mechanical ventilation. Neurologic and functional recovery was complete and the dog was discharged 48 hours after admission. (J Vet Emerg Crit Care 2001; 11(1):33–37)     

Ivermectin plasma concentrations in collies sensitive to ivermectin-induced toxicosis

Five Collies sensitive to toxic effects of ivermectin and 7 nonsensitive Collies were given 100 micrograms of ivermectin/kg of body weight, PO. Blood samples were collected from each dog before treatment; at posttreatment hours 1, 2, 3.5, 5, and 8; and at posttreatment days 1, 2, 4, 7, 14, and 21. Each sample was assayed for ivermectin concentration, and statistical analyses were performed on the resulting plasma concentration data to determine differences in absorption and clearance of drugs between the 2 groups. Variables measured were area under the curve (using the trapezoidal rule), peak plasma concentration, and the time to peak concentration. Differences between sensitive and nonsensitive Collies for variables analyzed were not significant (P greater than 0.05).     

米尔贝肟对自然感染疥螨病犬的治疗效果

为了评价米尔贝肟对临床自然感染疥螨犬的治疗效果,选用自然感染疥螨犬65例,随机选择5条服用伊维菌素,另外60条随机分为3组,分别服用高剂量(2g/kg体重)、中剂量(1g/kg体重)、低剂量(0.5g/kg体重)的米尔贝肟。给药后2、14、28、42d和56d,刮取皮屑,检查螨虫和虫卵,同时观察临床症状。试验结束时米尔贝肟高剂量组、伊维菌素组的无螨虫犬的比例和螨虫的下降率均为100%,临床症状如红疹、结痂、过度角化等现象均消失,所有动物毛发都开始大范围重生;米尔贝肟中、低剂量组结果稍差。米尔贝肟按2g/kg体重剂量,每周1次,连续用药3周,给药对自然感染疥螨病犬有很好的治疗效果。     

Hematologic abnormalities associated with chronic acetaminophen administration in a dog

Large numbers of eccentrocytes (erythrocytes with hemoglobin contracted to one side of the cell) were seen on a stained blood smear from a Dachshund with compensated hemolytic anemia. The 7-kg dog had been given 325 mg of acetaminophen orally once daily for 6 weeks by the client, because the dog exhibited signs attributed to abdominal pain. More than half of the erythrocytes contained small Heinz bodies visualized after methyl violet staining. The methemoglobin content was 6.4% (normal less than 2%) when measured 16 hours after the last acetaminophen tablet was given. High serum alanin transaminase and alkaline phosphatase activities and hyperbilirubinuria were measured. All abnormal laboratory findings were attributable to acetaminophen-induced oxidative damage to erythrocytes and hepatocytes.     

A comparison between ethanol-induced chemical ablation and ivermectin plus prednizolone in the treatment of symptomatic esophageal spirocercosis in the dog: a prospective study on 14 natural cases

This study included a total of 14 dogs with spontaneous esophageal spirocercosis. Historical and clinical evidence of esophageal dysphagia, detection of parasitic ova in fecal samples and endoscopic documentation of esophageal nodules were the inclusion criteria. The animals were randomly assigned into two groups: group A (n = 6 ) dogs received two intranodular injections of absolute ethanol (96%) via a through-the-endoscope injector, at weekly intervals; group B (n = 8) dogs were put on ivermectin (600 microg/kg BW, subcutaneously, twice, 14 days apart) and oral prednisolone (0.5mg/kg BW, every 12h, for a total of 3 weeks, tapering the dose accordingly). Clinical and fecal examination as well as endoscopy, were performed on admission and at 20, 60 and 180 days from the beginning of the treatment. One group A dog responded poorly and died of pyothorax during the trial and another developed esophagitis due to accidental intraluminal ethanol infusion, only to experience an uneventful recovery. At different times during the 6-month follow-up period, there was a complete disappearance of the clinical signs in 4/6 group A dogs. However, full nodular regression was achieved only in one dog, and parasitic ova were still found in the feces of 4/6 dogs. At the same period of time in five group B dogs still available for evaluation, resolution of the clinical signs and complete nodular regression were seen in four and five animals, respectively, while negative fecal results were obtained in all dogs (8/8) of the same group 2 months from the beginning of the treatment. No significant difference was found between the groups, regarding the resolution of clinical signs, though group B dogs demonstrated a significantly higher rate of regression of esophageal nodules as well as negative fecal results, compared to group A dogs. The combination of ivermectin and prednizolone may be considered an effective treatment in the symptomatic and evidently asymptomatic esophageal spirocercosis of the dog.     

Presumptive Intramural Gastric Hemorrhage Secondary to Rodenticide Intoxication in a Dog

A dog being treated for demodicosis with ivermectin was presented for intermittent vomiting. The vomiting progressed to hematemesis and an underlying coagulopathy was diagnosed. The etiology of the coagulopathy was determined to be ingested brodifacoum. Ultrasound evaluation of the abdomen revealed thickened gastric wall that was suspected to be intramural hemorrhage. Most likely, the intramural hemorrhage and resulting thickening of the stomach wall led to the clinical signs and metabolic alkalosis. This case represents an typical presentation of hemorrhage secondary to rodenticide intoxication. (J Vet Emerg Crit Care 2001; 11(1):27–31, 2001).     

Baclofen intoxication in a dog successfully treated with hemodialysis and hemoperfusion coupled with intensive supportive care

Objective: To describe a case of confirmed baclofen intoxication in a dog that was successfully treated with hemodialysis and hemoperfusion (HD/HP) and to report the serum baclofen kinetics. Case summary: A 2.5‐year‐old, 23 kg, spayed female Brittany Spaniel‐mix was treated after ingesting 21‐52 mg/kg of baclofen. The dog was comatose and was receiving manual ventilation at the time of presentation. Extracorporeal HD/HP was started 10 hours after admission. Within 3 hours of starting HD/HP the dog began initiating breaths and was extubated 18 hours after admission. Serial serum samples that were obtained during the first 24 hours of hospitalization were later analyzed for baclofen concentrations. The dog had elevated creatine phosphokinase and liver enzymes that correlated with an agitated recovery period. The dog had thrombocytopenia that resolved by 10 days after presentation. New or unique information provided: HD/HP shortened the baclofen serum elimination half‐life from 5 to 1.5 hours in the initial 2 hours of treatment. The intrinsic elimination rate constant (K_intr) for this dog was 0.138/hour and the total elimination rate constant (K_tot) during the first 2 hours of HD/HP treatment was 0.458/hour. In this dog, HD/HP was an effective method for rapidly decreasing serum baclofen concentration after an acute overdose.     

A case of dumb rabies and trypanosomiasis in an eight-week-old puppy

An eight-week-old male puppy affected with trypanosomiasis and dumb rabies was presented at the University of Nigeria Veterinary Hospital. The dog had a septic wound on the side of the face. The clinical signs suggested trypanosomiasis and this diagnosis was confirmed by laboratory examination. After treatment with Berenil and antibiotics, the puppy apparently recovered, but a week later became anorectous and recumbent. Dumb rabies was suspected and the dog died in a quarantine kennel less than 24 hours later. Negri bodies were detected in brain smears from the dog and a mouse inoculation test was performed to confirm the diagnosis. Dumb rabies poses serious public health hazards to dog owners and their families, as well as to those occupationally exposed to dogs.     

Comparative effects and safety of ivermectin in pregnant mares

Mares (n=20) approaching 3 months of pregnancy were assigned randomly to 1 of 4 treatment groups. Treatments were (a) an IM injection of ivermectin at 600 mcg/kg, (b) various conventional anthelmintic drugs at the manufacturers' recommended dose, (c) and IM injection of the ivermectin vehicle (placebo) and (d) no anthelmintic treatment during the trial. All anthelmintic treatments were administered at 60-day intervals up to and including the date of parturition. Fecal egg counts, arginase, hemoglobin and packed cell volume values were determined at bi-weekly intervals during the trial and there were no statistically significant differences determined between the treatment groups for these parameters. None of the mares showed any adverse clinical signs during the course of this study and all 20 mares delivered live foals which remained on the research farm until they were sold as year-lings. Mares treated with ivermectin had significantly (P<0.01) lower egg per gram counts than mares in the conventional treatment group. Multiple hematological and clinical chemistry values were determined for all mares and resulting foals within 12 hours post-parturition. A one-way analysis of variance showed no clinically relevant statistically significant differences between treatment groups in either mares or foals at 12 hours post-parturition. This study suggests that ivermectin at 600 mcg/kg is safe and highly efficacious when administered to pregnant mares.     

Neurological dysfunction in three dogs and one cat following attenuation of intrahepatic portosystemic shunts

Neurological dysfunction is an uncommon complication following extrahepatic portosystemic shunt ligation. Three dogs and one cat are described that developed neurological signs within 21 to 42 hours of attenuation of intrahepatic portosystemic shunts. None of these cases had biochemical evidence of hepatic encephalopathy postoperatively. Two dogs died during management of status epilepticus following aspiration of food. One dog died six months postoperatively. The cat had persistent neurological dysfunction at discharge, but was alive and had recovered most of its neurological function at the time of writing, 37 months after surgery. This report demonstrates the potential for animals with intrahepatic portosystemic shunts to develop postoperative neurological signs and highlights the difficulty of managing such cases. Two dogs had both intrahepatic and extrahepatic portosystemic shunts. Large intestinal malrotation (partial situs inversus) may have been linked to the development of a portosystemic shunt in the remaining dog.     

Use of cyclosporine to treat granulomatous meningoencephalitis in three dogs

Use of cyclosporine to treat granulomatous meningoencephalitis in three dogs Three dogs with a presumptive diagnosis of granulomatous meningoencephalitis were treated with orally administered cyclosporine. In 2 dogs, cyclosporine administration replaced initial corticosteroid administration, and in 1 dog, cyclosporine was the only treatment used. One dog had the focal form of the disease in the brainstem, 1 dog had the focal form in the forebrain associated with a concurrent ocular form, and 1 dog had the disseminated form of disease. At 12-month follow-up, the 2 dogs with the focal form of the disease had no clinical signs. The dog with the disseminated form improved only partially, and euthanasia was performed 3 weeks after initial evaluation. Cyclosporine was considered effective at an initial dosage of 6 mg/kg (2.7 mg/lb) every 12 hours. Adverse effects associated with cyclosporine administration included transient lymphopenia, excessive shedding, and focal symmetric hair discoloration.