Pharmacokinetics of Cannabidiol Following Intranasal, Intrarectal, and Oral Administration in Healthy Dogs.

The therapeutic potential of cannabidiol (CBD), a non-psychtropic component of the Cannabis sativa plant, is substantiated more and more. We aimed to determine the pharmacokinetic behavior of CBD after a single dose via intranasal (IN) and intrarectal (IR) administration in six healthy Beagle dogs age 3-8 years old, and compare to the oral administration route (PO). Standardized dosages applied for IN, IR and PO were 20, 100, and 100 mg, respectively. Each dog underwent the same protocol but received CBD through a different administration route. CBD plasma concentrations were determined by ultra-high performance liquid chromatography-tandem mass spectrometry before and at fixed time points after administration. Non-compartmental analysis was performed on the plasma concentration-time profiles. Plasma CBD concentrations after IR administration were below the limit of quantification. The mean area under the curve (AUC) after IN and PO CBD administration was 61 and 1,376 ng/mL*h, respectively. The maximal plasma CBD concentration (Cmax) after IN and PO CBD administration was 28 and 217 ng/mL reached after 0.5 and 3.5 h (Tmax), respectively. Significant differences between IN and PO administration were found in the Tmax (p = 0.04). Higher AUC and Cmax were achieved with 100 mg PO compared to 20 mg IN, but no significant differences were found when AUC (p = 0.09) and Cmax (p = 0.44) were normalized to 1 mg dosages. IN administration of CBD resulted in faster absorption when compared to PO administration. However, PO remains the most favorable route for CBD delivery due to its more feasible administration. The IR administration route is not advised for clinical application.

Primary orthostatic tremor and orthostatic tremor-plus in dogs: 60 cases (2003-2020).

BACKGROUND: Orthostatic tremor (OT) is a rare movement disorder characterized by high-frequency (>12 Hz) involuntary, rhythmic, sinusoidal movements affecting predominantly the limbs while standing. OBJECTIVE: To describe the signalment, presenting complaints, phenotype, diagnostic findings, treatment, and outcome of a large sample of dogs with OT. ANIMALS: Sixty dogs diagnosed with OT based on conscious electromyography. METHODS: Multicenter retrospective case series study. Dogs were included if they had a conscious electromyography consistent with muscle discharge frequency >12 Hz while standing. RESULTS: Fifty-three cases were diagnosed with primary OT (POT). Giant breed dogs represented most cases (83%; 44/53). Most dogs (79%; 42/53) were younger than 2 years of age at onset of signs, except for Retrievers which were all older than 3.5 years of age. The most common presenting complaints were pelvic limb tremors while standing (85%; 45/53) and difficulty when rising or sitting down (45%; 24/53). Improvement of clinical signs occurred in most dogs (85%; 45/53) treated medically with phenobarbital, primidone, gabapentin, pregabalin or clonazepam, but it was mostly partial rather than complete. Orthostatic tremor-plus was seen in 7 dogs that had concurrent neurological diseases. CONCLUSIONS AND CLINICAL IMPORTANCE: Primary OT is a progressive disease of young, purebred, giant/large-breed dogs, which appears to begin later in life in Retrievers. Primary OT apparently responds partially to medications. Orthostatic tremor-plus exists in dogs and can be concomitant or associated with other neurological diseases.

Phenotypic characterization of paroxysmal dyskinesia in Maltese dogs.

BACKGROUND: Paroxysmal dyskinesias (PDs) are a group of central nervous system diseases characterized by episodes of abnormal involuntary hyperkinetic movement without altered consciousness that increasingly have been recognized in dogs. OBJECTIVES: To present the phenotypical characterization, treatment, and outcome of a PD observed in Maltese dogs. ANIMALS: Client-owned Maltese dogs (n = 19) with presumed diagnosis of PD. METHODS: Data were collected retrospectively from medical records (2014-2019), and supporting information was added prospectively by using a questionnaire directed to the owners of the affected dogs. RESULTS: The episodes were characterized mainly by sudden dystonia of ≥1 limbs and generalized body tremors with preserved consciousness. The mean age of clinical onset was 5.4 years. Episode frequency varied widely both among and within individuals. Median episode duration was 4.5 minutes. Most episodes were stress- or exercise-induced. Acetazolamide was administered to 6 dogs, and 4 dogs experienced a decrease in episode frequency. In 7 dogs that received a gluten-free diet, 6 dogs became episode-free. In 4 dogs, the episodes stopped spontaneously and in 2 dogs no medication or specific diet was given and the episodes continued at the same frequency. CONCLUSIONS AND CLINICAL IMPORTANCE: Given the breed predisposition and regional distribution of the disease, additional research should focus on elucidating the underlying genetic cause doing so might advance both our understanding of the pathophysiology and treatment of this disease, not only in dogs, but also in humans. Regardless of the treatment protocol selected, prognosis appears fair to good.

Análise do líquido cérebro-espinhal de três doenças do sistema nervoso central de cães / Analysis of cerebral-spinal fluid of three central nervous system diseases of dogs

Foi realizado um estudo retrospectivo do líquido cérebro-espinhal de cães (LCE), atendidos pelo Serviço de Neurologia do Hospital Veterinário da Instituição, de 2004 a 2015, com o objetivo de analisar os resultados de cães com sinais neurológicos, comparar as alterações encontradas em dois locais de colheita no mesmo paciente e verificar se esse exame auxiliou o clínico em reforçar a suspeita clínica das principais doenças do sistema nervoso central. A pleocitose linfocítica esteve presente em 78,3% (29/37) das amostras de cães com cinomose e em 23,2% (10/43) de cães com DDIV. Houve dissociação albuminocitológica (DAC) em 73% (19/26) das amostras de cães com tumores IC e em 64,3% (9/14) de cães com tumores envolvendo a ME. Em cães com DDIV, houve significância estatística (p<0,05) entre o grau de disfunção neurológica e o total de células nucleadas (TCN) e total de proteínas (TP). Em 29 cães, houve a colheita do LCE da cisterna magna e da cisterna lombar e em 12 (41,4%) os resultados foram diferentes entre as duas amostras colhidas do mesmo cão, onde dois (6,9%) apresentaram alteração na amostra colhida cranial à lesão. Pode-se concluir que a pleocitose linfocítica foi a principal alteração encontrada no LCE de cães com cinomose e DDIV e DAC nas neoplasias, IC e ME, cães acometidos pela DDIV apresentaram sinais neurológicos mais severos conforme o TCN e o TP aumentaram e o LCE sofreu alteração, mesmo colhido cranial ao local da lesão e auxiliou o clínico em reforçar a suspeita clínica, mas não confirmou, as principais doenças neurológicas em cães.(AU)

A retrospective study including the analysis of the cerebrospinal fluid (CSF) of dogs neurologically affected was conducted by the Neurology Service of the Veterinary Hospital at the Institution, between 2004 and 2015. The aim of this study was to analyze the results of the CSF of dogs with neurological signs, and compare the changes in the CSF in two sampling sites in the same patient and see if this test helped the clinician to strengthen clinical suspicion of the major diseases of the central nervous system. Lymphocytic pleocytosis was present in 78.3% (29/37) of samples from dogs with distemper and in 23.2% (10/43) of samples from dogs with IVDD. The albumin cytologic dissociation (ACD) was found in 73% (19/26) of samples from dogs with IC tumors and in 64.3% (9/14) from dogs with tumors involving the SC. For dogs with IVDD, there was statistical significance (p<0.05) between the degree of neurological dysfunction and the total nucleated cells (TNC) and total protein (TP). In 29 dogs, CSF was collected from the cistern magna and the lumbar and in 12 (41.4%) the results were different between the samples of the same dog, where two cases (6,9%) showed alterations in the sample collected cranial to the injury. It can be concluded that the lymphocytic pleocytosis was the main alteration found in the CSF of dogs with distemper and IVDD and ACD in tumors. Dogs affected by IVDD had more severe neurological signs as TNC and TP increased and the CSF was altered even collected cranial to the lesion site and helped the clinician to strengthen the clinical suspicion, but not confirm, the major neurological diseases in dogs.(AU)

Efeitos adversos da morfina, metadona e tramadol no pós-operatório de cães submetidos à cirurgia da coluna vertebral: 180 casos (2011-2016) / Adverse effects of morphine, methadone and tramadol in the postoperative period of dogs undergone vertebral surgery: 180 cases (2011-2016)

A dor pós-operatória em cães que são submetidos a cirurgias da coluna vertebral é considerada severa e seu manejo inadequado pode influenciar no tempo de recuperação do paciente, na qualidade de vida e no resultado cirúrgico. Dentre os analgésicos indicados para uso no pós-operatório dessas cirurgias tem-se os opioides, que podem apresentar inúmeros efeitos adversos que requerem atenção. Devido à escassez de estudos clínicos acerca desse assunto em se tratando do pós-operatório de cães, objetivou-se com o presente estudo retrospectivo apresentar os efeitos adversos da morfina, metadona e tramadol utilizados no pós-operatório de cirurgias da coluna vertebral. Foram revisadas e avaliadas as fichas de 180 cães e anotadas as alterações observadas no pós-operatório e decorrentes do uso de opioides. Os principais efeitos adversos observados foram anorexia, hiporexia, vômito, salivação, vocalização, bradicardia, hipotermia, ofegação e sedação. Também foi observada persistência da dor em alguns cães mesmo com o uso de analgésicos. Houve diferença na ocorrência de anorexia nos cães tratados com morfina e nos tratados com metadona em relação aos tratados com tramadol. Ocorreu diferença também entre a observação de dor dos grupos morfina e tramadol. A associação de dipirona com morfina e com metadona não revelou diferença com relação à ocorrência de efeitos adversos, bem como a variação de doses. Conclui-se que a morfina, a metadona e o tramadol apresentam efeitos adversos quando empregados para tratamento da dor pós-operatória em cães submetidos à cirurgia da coluna vertebral; a anorexia, a hiporexia e o vômito foram os efeitos adversos frequentes com o uso de morfina e de metadona e, mesmo que o tramadol apresente menor ocorrência desses efeitos, seu uso, na dose estudada, pode não ser vantajoso quando se leva em consideração o grau de dor para cirurgias da coluna vertebral.(AU)

Postoperative pain in dogs undergone vertebral surgery is classified as severe and it's important an adequate approach to it, because it can influence recovery time, quality of life and surgery outcome. Opioids are indicated for postoperative pain treatment in these surgeries. Opioids may have adverse effects that may require attention. There are few clinical studies that present the adverse effects of these analgesics in canine postoperative period. The aim of this retrospective study was to present the adverse effects of morphine, methadone and tramadol in canine vertebral surgery postoperative period. There were revised the postoperative records of 180 dogs and the changes resulted from the opioids use were noted. The adverse effects observed were anorexia, hyporexia, vomiting, vocalization, bradycardia, hypothermia, panting, sedation. Pain was also observed in some dogs. A significant difference was found in anorexia between dogs treated with morphine and tramadol and methadone and tramadol. Significant difference was also found in pain between dogs treated with morphine and tramadol. The association of metamizole and morphine or metamizole and methadone was not different in relation to the adverse effects. There was also no difference with the dosage variation and the adverse effects. In conclusion, morphine, methadone and tramadol have adverse effects when used for pain control in the postoperative period of dogs submitted to vertebral surgery. Anorexia, hypophagia and emesis were frequent the adverse effects observed with morphine and methadone and, despite tramadol presented less adverse effects, its use may be not beneficial in the studied doses when we consider the degree of pain, however more controlled studies with clinical situation are needed to confirm this.(AU)

Neuromiopatia isquêmica em cinco cães (2008-2016) / Ischemic neuromyopathy in five dogs (2008-2016)

O objetivo deste estudo foi apresentar dados epidemiológicos, clínicos e anatomopatológicos de cinco cães com neuromiopatia isquêmica secundária a trombose ou tromboembolismo aórtico. Os cães eram fêmeas, com idade ≥11 anos, que apresentavam paraplegia (80%) ou monoplegia (20%) de membro pélvico. Em 40% dos casos (n=2) foi relatada claudicação previamente à disfunção motora. Os principais achados clínicos foram ausência de pulso femoral uni ou bilateral, extremidade de membros pélvicos frias, dor muscular acima da articulação do joelho e ausência de nocicepção (dor profunda) nos dígitos dos membros pélvicos. Quatro cães foram submetidos à eutanásia devido ao prognóstico desfavorável e um veio a óbito em menos de 24 horas de internação. Na necropsia foi encontrada alteração cardíaca em três cães, neoplásica em um e, sem causa determinante em outro caso. Os trombos estavam localizados na aorta abdominal e se estendiam até as artérias ilíacas. Mesmo sendo baixa a incidência, a neuromiopatia isquêmica deve ser incluída no diagnóstico diferencial de cães com claudicação, paraparesia ou paraplegia uni ou bilateral, quando os sinais neurológicos são compatíveis com lesão de neurônio motor inferior (L4-S3) e de evolução aguda ou crônica. A avaliação do pulso femoral digital e/ou por doppler vascular deve ser empregada e pode auxiliar no diagnóstico da doença evitando que os animais iniciem tratamento para outras afecções.(AU)

This study aimed to present epidemiological, clinical and anatomopathological data of five dogs with ischemic neuromyopathy secondary to aortic thrombosis or thromboembolism. The dogs were females, with eleven years of age or more, that had paraplegia (80%) or hind limb monoplegia (20%). Forty percent of the cases (n=2) had lameness previously the motor disfunction. The main clinical findings include absence of unilateral or bilateral femoral pulse, cool hind limbs extremities, muscle pain above the knee joint and absence of nociception (deep pain) on the hind limbs digits. Four dogs were euthanized due to the poor prognosis, and the last one died within 24 hours of hospital admission. The necropsy findings were cardiac lesions in three dogs, neoplastic disease in one, and unknown cause on the other. The thrombi were located on the abdominal aorta, extending to the iliac arteries. Even with low incidence, the ischemic neuromyopathy should be included in the differential diagnosis of dogs with lameness, paraparesis, or unilateral or bilateral paraplegia, when neurological signs are compatible with lower motor neuron lesion (L4-S3) and acute or chronic progression. The digital and/or vascular doppler evaluation of the femoral pulse must be used and can assist on the disease diagnosis, avoiding treatments for other illnesses.(AU)

Avaliação clínica de cães com doença do disco intervertebral (Hansen tipo I) submetidos à descompressão cirúrgica: 110 casos / Clinical evaluation of dogs with intervertebral disc disease (Hansen type I) submitted to surgical decompression: 110 cases

O objetivo deste estudo foi identificar cães com doença do disco intervertebral toracolombar (Hansen tipo I) submetidos ao tratamento cirúrgico em um serviço de rotina em neurologia de um hospital veterinário universitário no período de 2006 a 2014, e obter informações a respeito da idade, do sexo, da raça, local da extrusão, interpretação da mielografia, avaliação dos graus de disfunção neurológica, recuperação funcional desses cães e observar a ocorrência de recidiva dos sinais clínicos da doença. A raça mais frequente foi Dachshund (69%), seguida dos cães sem raça definida (14,5%). Os locais mais afetados foram entre T12-T13 (31,9%) e L1-L2 (19,1%). Dos 110 cães, 74 (67,3%) tiveram melhora dos sinais clínicos após o procedimento cirúrgico, sendo 54 (49,1%) considerados satisfatórios e 20 (18,2%), parcialmente satisfatórios. Destes cães, seis (8,1%) cães estavam em grau II, 19 (25,7%) em grau III, 35 (47,3%) em grau IV e 14 (18,9%) em grau V. Pode-se concluir que o tratamento cirúrgico promove recuperação funcional satisfatória na maioria dos cães com extrusão de disco toracolombar. O prognóstico para recuperação funcional após o tratamento cirúrgico é tanto melhor quanto menor for o grau de disfunção neurológica e o percentual de recidiva é baixo em animais submetidos a este tipo de terapia.(AU)

The aim of this study was to identify dogs with thoracolumbar intervertebral disc disease (Hansen type I) submitted for surgical treatment on a routine service in neurology in a university veterinary hospital in 2006-2014, and to get information about age, sex, breed, site of extrusion, interpretation of myelography, evaluation of the degree of neurological dysfunction, functional recovery of these dogs, and to verify the recurrence of clinical signs of disease. The most common breed was Dachshund (69%), followed by mixed breed (14.5%). The most affected sites were between T12-T13 (31.9%) and L1-L2 (19.1%). Of the 110 dogs, 74 (67.3%) improved clinical signs after surgery, 54 (49.1%) satisfactory and 20 (18.2%), in part satisfactory. From these dogs, six (8.1%) dogs were in grade II, 19 (25.7%) in grade III, 35 (47.3%) in grade IV, and 14 (18.9%) in grade V. It can be concluded that satisfactory surgical treatment promotes functional recovery in most dogs with thoracolumbar disk extrusion. The prognosis for functional recovery after surgical treatment is better the lower the degree of neurological dysfunction and the recurrence percentage is lower in dogs subjected to this type of therapy.(AU)

Doença do disco intervertebral cervical em cães: 28 casos (2003-2008) / Cervical intervertebral disk disease in dogs: 28 cases (2003-2008)

O objetivo deste estudo foi identificar cães com doença do disco intervertebral (DDIV) cervical atendidos no Hospital Veterinário Universitário (HVU) da Universidade Federal de Santa Maria (UFSM) entre janeiro de 2003 e outubro de 2008 e obter informações a respeito de raça, sexo, idade, sinais neurológicos, resposta ao tratamento cirúrgico, complicações, tempo de recuperação funcional após a cirurgia e ocorrência de recidiva. Hiperestesia cervical foi observada em todos os cães (n=28). Quanto ao grau de disfunção neurológica foram verificados: grau I (8/28[28,5 por cento]), grau II (3/28 [10,7 por cento]), grau III (5/28[17,8 por cento]) e grau V (12/2 [42,8 por cento]). A duração dos sinais neurológicos antes da cirurgia em sete cães (25 por cento) permaneceu por até 15 dias, em 14 cães (50 por cento) entre 15 e 30 dias e nos outros sete cães (25 por cento) por mais de 30 dias. A recuperação satisfatória e sem recidiva foi observada em todos os cães submetidos ao tratamento cirúrgico e que sobreviveram (n=21). Pode-se concluir que a DDIV cervical em nossa rotina acomete principalmente cães adultos, machos, de raças condrodistróficas e não condrodistróficas, incluindo as de grande porte; a hiperestesia cervical é a principal manifestação clínica; a técnica de fenda ventral promove recuperação funcional satisfatória e sem recidiva; as principais complicações trans-operatórias são a hemorragia do plexo venoso, a bradicardia e a hipotensão; e a duração dos sinais clínicos não interfere no tempo de recuperação pós-operatória dos cães.

The aim of this study was to evaluate the medical records of dogs with cervical intervertebral disk disease (IDD), submitted to surgical treatment at the Hospital Veterinário Universitário of Universidade Federal de Santa Maria (HVU-UFSM), between January 2003 and October 2008. The animal data included breed, sex, age, neurological signs and their durations, response to surgical treatment, complications, time for functional recovery after surgery, and recurrence. All dogs showed cervical hyperaesthesia confirmed by the neck movement test. Regarding the degree of neurological dysfunction, the following were verified: degree I (eight dogs, 28.5 percent), degree II (three dogs, 10.7 percent), degree III (five dogs, 17.8 percent), and degree V (twelve dogs, 42.8 percent). In relation to the duration of neurological signs prior to surgery, seven dogs (25 percent) showed neurological deficits for up to 15 days, fourteen dogs (50 percent) for 15 to 30 days and the other seven dogs (25 percent) showed signs of neurological deficiencies for more than 30 days. All dogs (n=21) showed satisfactory recovery and no recurrence. It can be concluded that most affected dogs are middle aged, males and condrodystrophic and noncondrodystrophic breeds including large-breed dogs and the main neurological sign is cervical hyperaesthesia. The surgical treatment promotes satisfactory functional recovery and no recurrence, the main complications intraoperative are venous plexus hemorrhage, bradycardia and hypotension and the duration of clinical signs prior to surgery do not interfere with the recovery time of the dogs.

Modificação da técnica de abordagem ventral à articulação atlantoxial sem a secção do músculo esternotireóideo / Modification of ventral technique approach to the articulation atlantoxial with no section of the muscle sternothyreoid

O objetivo deste trabalho foi apresentar uma variação na técnica de acesso ventral à articulação atlantoaxial para tratamento da instabilidade atlantoaxial sem a secção do músculo esternotireóideo. Foram utilizados 15 cães, pesando entre oito e 12kg, sem raça definida, independente do sexo, distribuídos aleatoriamente em três grupos iguais de acordo com o período pós-operatório (PO) denominados de I (30 dias), II (60 dias) e III (90 dias) para avaliações clínicas diárias. A articulação atlantoaxial foi submetida à artrodese por meio do acesso ventral utilizando pinos de Steinmann associados à resina acrílica autopolimerizável. O acesso e a exposição da articulação atlantoaxial sem a secção do músculo esternotireóideo foram realizados sem complicações ou limitações adicionais. Nenhum cão desta pesquisa apresentou tosse, dispnéia, regurgitação, paralisia laríngea ou Síndrome de Horner. Pode-se concluir que a secção do músculo esternotireóideo é um procedimento desnecessário e que não interfere na exposição da articulação atlantoaxial e na realização da artrodese em cães por meio do acesso ventral.

The aim of this research was to present a variation of the ventral technique access to the atlantoaxial joint, for treatment of atlantoaxial instability with no section of sternothyreoid muscle. Fifteen dogs, with weight between 8 and 12kg, were randomly distributed in three groups denominated one (30 days), two (60 days) and three (90 days) for daily clinical evaluations. The atlantoaxial joint was submitted to the arthrodesis through the ventral access using pins of Steinmann associated to acrylic resin. The access and exhibition of the atlantoaxial joint with no section of the sternothyreoid muscle was obtained without complications or additional limitations. No dog of this research presented coughing, dyspnea, regurgitation, laryngeal paralysis or Horner's syndrome. It can be concluded that the section of sternothyreoid muscle is an unnecessary procedure and that there is is no interference in the exhibition of atlantoaxial joint and arthrodesis approach of dogs through ventral access.