Effects of clomipramine hydrochloride on heart rate and rhythm in healthy dogs

OBJECTIVE: To determine the effects of clomipramine hydrochloride on heart rate and rhythm in dogs. ANIMALS: 17 healthy Beagles. PROCEDURES: In experiment 1, 8 dogs received placebo or clomipramine (20 mg/kg of body weight, q 24 h, PO) for 7 days in a 2-way crossover design. In experiment 2, 9 dogs were evaluated for 48 hours before and 24 hours after oral administration of clomipramine (4 or 12 mg/kg) in a 2-way crossover design. Electrocardiogram and heart rate were monitored continuously by use of telemetry. RESULTS: A significant diurnal rhythm in heart rate was detected; minimum values were recorded at night. Administration of 20 mg of clomipramine/kg induced a significant reduction in heart rate, with peak effect achieved approximately 12 hours after dosing. Administration of 4 or 12 mg of clomipramine/kg did not result in significant changes in heart rate. Sinoatrial and second-degree atrioventricular block and ventricular escape beats were observed during periods of slow heart rate in more dogs that received clomipramine (3 to 4 of 8 dogs), compared with dogs that received placebo (1 to 2 of 8 dogs), but this difference was not significant. CONCLUSIONS AND CLINICAL RELEVANCE: Short-term administration of clomipramine induced benign cardiovascular effects in dogs rather than the potentially dangerous arrhythmias or tachycardia reported following administration of tricyclic antidepressants to humans. Precautions regarding cardiovascular effects may not be needed for the use of clomipramine in healthy dogs.     

Biology of aggression in dogs

The science of ethology is concerned with the way external stimuli and internal events cause animals to fight in a particular way. The classification of dog breeds with respect to their relative danger to humans makes no sense, as both, the complex antecedent conditions in which aggressive behaviour occurs, and its ramifying consequences in the individual dog's ecological and social environment, are not considered. From a biological point of view, environmental and learning effects are always superimposed upon genetic influences. Based on the recent developments in the study of ethology, aggression of wolves (Canis lupus L.) and domesticated dogs (Canis lupus f. familiaris) was put into context with respect to other aspects of the lifestyle of wild and domestic canids. Aggressive behaviour does not occur in a biological vacuum. This is also true for domestic dogs and their relationship to human partners. Individual dogs can become highly aggressive and dangerous. Their development and social situation will be presented and discussed in case studies. Finally, there is the question about defining "normal aggression" versus symptoms for maladaptive aggression resp. danger to humans as conspecifics. It is possible to protect the safety of the public and at the the same time practise animal care. Effective animal control legislation must focus on responsible ownership and socialisation of pups f.e. Problems are not unique to some breeds.     

Effects of tetracycline hydrochloride on pleurae in dogs with induced pleural effusion

Pleural effusion was induced in 12 dogs by ligation of the cranial vena cava. Pleurodesis was attempted by injecting a solution of tetracycline hydrochloride into the pleural space of 8 dogs (4 dogs, 25 mg/kg of body weight; 4 dogs, 50 mg/kg) via bilateral thoracostomy tubes. In both groups, tetracycline was diluted in 40 ml of normal saline solution and 10 ml of 1% lidocaine before injection. Half of the solution (25 ml) was instilled in each hemithorax. Four control dogs were treated in the same manner with a solution of normal saline and lidocaine. Daily pleural fluid production was measured after the attempted pleurodesis. Thirty days after administration of the solution, each dog was euthanatized and necropsied. Surface area of pleural adhesions was measured. Tissues from regions of pleural adhesions and areas of parietal and visceral pleura not involved in adhesions were analyzed histologically. Formation of pleural fluid stopped in all but 1 control dog within 48 hours after injection of solution. This dog effused throughout the study. The resolution of effusion was not significantly (P less than 0.05) different between the tetracycline-treated dogs and the control group. Although diffuse pleural adhesions were not induced in any of the dogs, significantly (P less than 0.0027) more surface area of lung was adhered in dogs treated with the higher dose of tetracycline.     

Effect of clomipramine on monoamine metabolites in the cerebrospinal fluid of behaviorally normal dogs.

The tricyclic antidepressant, clomipramine, is an effective treatment for canine compulsive disorder (canine CD). This disorder is a clinical syndrome of abnormal conflict behaviors and its pathophysiology is unknown. However, because clomipramine is an effective treatment, information about the drug's neurochemical effect could enhance the understanding of canine CD. The following experiment used 6 behaviorally normal dogs to assess the effect of clomipramine (3 mg/kg, q24h, PO) on the central turnover of 3 monoamines (serotonin, dopamine, and norepinephrine) as measured by the concentrations of their respective metabolites in cerebrospinal fluid (CSF). In a randomized, placebo-controlled, AB-BA crossover experiment, cisternal CSF was taken after 1, 2, 4, and 6 wk on each treatment. No effect of clomipramine was detected. This contrasts with human studies that have suggested that clomipramine affects the concentrations of monoamine metabolites in lumbar CSF. However, those papers do not address methodological assumptions, such as (i) metabolites in CSF originate only from the brain, and (ii) concentrations of metabolites in cisternal/lumbar CSF reflect the concentrations in local areas of the brain. Notwithstanding the small sample size, our results suggest that more localized sampling techniques (e.g. microdialysis) are needed when examining the effect of drugs on central monoamine metabolites. Clomipramine's efficacy for canine CD indicates the need for neurobiological research and, to our knowledge, our study is the first of its kind in dogs. The resulting data are preliminary but they can inform optimal neurobiological studies of canine CD.     

麻醉药盐酸赛拉嗪对犬肝肾功能的影响

旨在研究临床上常用麻醉药盐酸赛拉嗪对犬肝肾功能指标的影响。选择成年健康杂种犬8只,按常规推荐剂量2.4 mg/kg体重股四头肌注射盐酸塞拉嗪进行麻醉。分别在麻醉前、麻醉后0.5 h、1 h、1.5 h、2 h、24 h、48 h、72 h颈静脉采血2 m L,分离血清。采用全自动生化分析仪检测血清肝肾功能相关指标。结果显示,与试验开始相比,各试验采血点血清天门冬氨酸氨基转移酶和γ-谷氨酰转移酶的活性及血清总蛋白、直接胆红素、肌酐、尿酸、尿素氮的含量均无显著变化(P0.05)。各试验采血点之间相比,肝肾功能指标无显著性差异(P0.05)。研究结果说明,盐酸赛拉嗪用于犬麻醉时对其肝肾功能均无明显影响。     

Differential diagnosis and management of human-directed aggression in dogs.

Canine aggression directed to human beings is a common presenting complaint and requires attention to safety issues and behavior modification to minimize the risks of future aggression. Dogs may bite familiar people, including family members, or unfamiliar people for a variety of reasons. Anxiety plays an important role in aggression regardless of its target or circumstances. Effective management of aggression may include education and safety counseling for owners, lifestyle changes for dogs and owners, avoidance of provocations when possible, and behavior modification to minimize the risk of future bites. Drug therapy may be indicated to facilitate behavior modification or to reduce reactivity in the dog.     

Hypocholesterolaemia in dogs with dominance aggression

Serum lipids and lipoprotein concentrations have been associated with dominance aggression in humans. The aim of this study was to investigate the link between serum lipids, including cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) to HDL-C ratio and dominance aggression in dogs. Levels of serum TC, triglyceride and HDL-C were significantly lower in dogs with dominance aggression compared with non-aggressive dogs (P < 0.001). These results suggest that a relationship exists between serum lipid profile and dominance aggression in dogs, and hypocholesterolaemia exists in dogs with dominance aggression.     

Effect of lenperone hydrochloride on gastroesophageal sphincter pressure in healthy dogs.

Treatment of healthy dogs with the butyrophenone derivative, lenperone hydrochloride, at two different doses significantly decreased gastroesophageal sphincter pressure (GESP). No dose-related effect was identified. Individual variation in the response to lenperone hydrochloride was noted which was consistent on a day-to-day basis. Lenperone hydrochloride is unsuitable for chemical restraint of dogs undergoing esophageal manometry because it decreases GESP and because the magnitude of the decrease varies considerably between dogs.     

Pharmacokinetics of procainamide hydrochloride in dogs

Pharmacokinetics of procainamide hydrochloride were studied in 2 groups of dogs. In a group of 6 dogs, procainamide was administered IV at a small dose of 8 mg/kg (group 1), and blood samples were obtained for 3.5 hours. In another group of 6 dogs, procainamide was administered IV and orally at an average dose of 25.5 mg/kg (group 2) in a crossover manner. Blood samples were obtained for 48 hours. In 2 dogs (previously used in part II), N-acetylprocainamide (NAPA) was administered IV at a dose of 10 mg/kg. Plasma samples were assayed for procainamide by fluorescence polarization immunoassay, and NAPA samples were assayed by high-performance liquid chromatography. In group 1, the elimination of procainamide was described by a 1-compartment, open pharmacokinetic model. The elimination half-life was 2.43 hours, the apparent volume of distribution was 1.44 L/kg, and the systemic clearance was 0.412 L/kg/hr. In group 2, 2 of the 6 dogs were described by a 1-compartment model, and 4 of the 6 dogs were described with a 2-compartment pharmacokinetic model. The elimination half-life for the IV dosage was 2.85 hours, the apparent volume of distribution was 2.13 L/kg, and the systemic clearance was 0.519 L/kg/hr. For the orally administered dose, the bioavailability was 85%, and the absorption half-life was 0.5 hours. There was no evidence of acetylation of procainamide to NAPA or deacetylation of NAPA to procainamide. The estimated elimination half-life of NAPA was 4.7 hours.     

Pharmacokinetics of clomipramine in dogs following single-dose and repeated-dose oral administration

OBJECTIVE: To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs following single-dose and repeated-dose oral administration at various dosages. ANIMALS: 9 male and 9 female Beagles. PROCEDURES: Clomipramine was administered orally at a dose of 1, 2, or 4 mg/kg to 3 male and 3 female dogs, first as a single dose and then, after an interval of 14 days, twice daily for 10 days. Plasma clomipramine and desmethylclomipramine concentrations were measured by use of a gas chromatography with mass-selection method. RESULTS: Dose-related accumulation was detected following repeated-dose administration. Accumulation ratios after administration of clomipramine at dosages of 1, 2, and 4 mg/kg twice daily were 1.4, 1.6, and 3.8, respectively, for clomipramine and 2.1, 3.7, and 7.6, respectively, for desmethylclomipramine. Terminal half-life increased slightly (1.6-fold for clomipramine and 1.2-fold for desmethylclomipramine) with repeated-dose administration but remained short in all groups (< or = 4 hours). Steady state was reached within 4 days in all animals. Ratios of the areas under the concentration versus time curves from time 0 to 12 hours for clomipramine and desmethylclomipramine were 3.9, 3.1, and 1.5 after repeated administration at dosages of 1, 2, and 4 mg/kg every 12 hours, respectively. Areas under the concentration versus time curve, mean residence times, and terminal half-lives were not significantly different between male and female dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Repeated administration of clomipramine results in higher concentrations of clomipramine than desmethylclomipramine in dogs.     

Pharmacokinetics of clomipramine in dogs following single-dose intravenous and oral administration

OBJECTIVE: To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs after IV or oral administration of a single dose. ANIMALS: 6 male and 6 female Beagles. PROCEDURES: Clomipramine was administered IV (2 mg/kg), PO (4 mg/kg) after food was withheld for 15 hours, and PO (4 mg/kg) within 25 minutes after dogs were fed. Plasma clomipramine and desmethylclomipramine concentrations were measured by use of a gas chromatography with mass-selection method. RESULTS: Time to peak plasma concentrations of clomipramine and desmethylclomipramine following oral administration was 1.2 hours. For clomipramine, after IV administration, elimination half-life was 5 hours, mean residence time was 3 hours, and plasma clearance was 1.4 L/h/kg. Values for mean residence time and terminal half-life following oral administration were similar to values obtained following IV administration, and systemic bioavailability was approximately 20% for clomipramine and 140% for desmethylclomipramine, indicating fast absorption of clomipramine from the gastrointestinal tract and extensive first-pass metabolism. Administration of clomipramine with food did not alter the area under the concentration versus time curve for desmethylclomipramine but resulted in a 25% increase for clomipramine. Clomipramine and desmethylclomipramine were extensively bound (> 96%) to serum proteins. There were no significant differences in area under the concentration versus time curve between male and female dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that there should not be any clinically important differences in efficacy regardless of whether clomipramine is administered with or without food.     

Effects of xylazine hydrochloride on urine in cattle.

Urine volume, urine pH, and urine glucose concentration were monitored for up to 24 hours after physiological saline or one of two dosage levels (0.22 mg/kg or 0.44 mg/kg) of xylazine was administered to cows. During the first 2 hours after xylazine was given, urine output was greatly increased (relative to the control animals), with the high dosage group having more output than the low dosage group. The influence of the drug on urine volume had ended by 5 hours after injection when urine output in both dosage groups had returned to that of the control group. Glucose was detected in the urine of xylazine treated animals, beginning at 15 to 30 minutes after injection, reached a maximum at 2 hours, and was undetectable at 5 to 6 hours. Urine pH decreased in control and treated animals, but in treated animals the pH began to increase 2 hr after treatment.     

Pharmacokinetics of hydromorphone hydrochloride in healthy dogs

ObjectiveTo assess the pharmacokinetics of hydromorphone administered intravenously (IV) or subcutaneously (SC) to dogs.Study designRandomized experimental trial.AnimalsSeven healthy male neutered Beagles aged 12.13 ± 1.2 months and weighing 11.72 ± 1.10 kg.MethodsThe study was a randomized Latin square block design. Dogs were randomly assigned to receive hydromorphone hydrochloride 0.1 mg kg⁻¹ or 0.5 mg kg⁻¹ IV (n = 4 dogs) or 0.1 mg kg⁻¹ (n = 6) or 0.5 mg kg⁻¹ (n = 5) SC on separate occasions with a minimum 14-day washout between experiments. Blood was sampled via a vascular access port at serial intervals after drug administration. Serum was analyzed by mass spectrometry. Pharmacokinetic parameters were determined with computer software.ResultsSerum concentrations of hydromorphone decreased quickly after both routes of administration of either dose. The serum half-life, clearance, and volume of distribution after IV hydromorphone at 0.1 mg kg⁻¹ were 0.57 hours (geometric mean), 106.28 mL minute⁻¹ kg⁻¹, and 5.35 L kg⁻¹, and at 0.5 mg kg⁻¹ were 1.00 hour, 60.30 mL minute⁻¹ kg⁻¹, and 5.23 L kg⁻¹, respectively. The serum half-life after SC hydromorphone at 0.1 mg kg⁻¹ and 0.5 mg kg⁻¹ was 0.66 hours and 1.11 hours, respectively.Conclusions and clinical relevanceHydromorphone has a short half-life, suggesting that frequent dosing intervals are needed. Based on pharmacokinetic parameters calculated in this study, 0.1 mg kg⁻¹ IV or SC q 2 hours or a constant rate infusion of hydromorphone at 0.03 mg kg⁻¹ hour⁻¹ are suggested for future studies to assess the analgesic effect of hydromorphone.     

Pain-related aggression in dogs: 12 clinical cases

The aim of this retrospective study was to describe the main features of pain-related aggression in dogs. Twelve dogs presented for aggressive problems at the Veterinary Hospital of the Autonomous University of Barcelona, Spain, were included, and a questionnaire was used to gather information on the context of the aggression, body posture during the attack, impulsiveness, and aggressive behavior before the onset of the pain-eliciting condition. The most common cause of pain was hip dysplasia (66.7%), but no relationship was found between the cause of pain and the characteristics of the aggressive behavior. Dogs were classified as having been aggressive before or after the onset of painful condition. Dogs that had not been aggressive before the onset of the pain-eliciting condition were more impulsive (df = 1, χ² = 5.3, P = 0.0209), showed aggression as a result of manipulation context more frequently (df = 1, χ² = 6, P = 0.0143), and adopted a defensive body posture more frequently (df = 1, χ² = 3.733, P = 0.0533) than dogs that had been aggressive before the onset of pain. These results suggest that previous expression of aggressive behavior has a major effect on the pattern of pain-related aggression in dogs.     

The effects of clomipramine hydrochloride in cats with psychogenic alopecia: a prospective study

A double-blind, placebo-controlled clinical trial was conducted to determine the efficacy of clomipramine hydrochloride in cats with psychogenic alopecia. Twenty-five cats were randomly assigned to receive clomipramine hydrochloride (0.5 mg/kg orally q 24 hours) or placebo for 56 days. Eleven cats in each group completed the trial. The results of this study showed that clomipramine hydrochloride failed to demonstrate significant changes in the number of grooming bouts, hair regrowth, and the area of alopecia in cats with psychogenic alopecia when compared to a placebo. It was uncertain whether these results reflected a lack of drug efficacy, insufficient treatment duration, or an insufficient number of cases enrolled.