Cardiopulmonary effects of a tiletamine-zolazepam combination in sheep

To assess the effects on heart and lung function, a tiletamine-zolazepam (TZ) anesthetic combination was evaluated in 10 Dorset-type ewes. Ewes were randomly allotted to 2 equal groups. Ewes of groups 1 and 2 were given a single bolus of TZ (12 and 24 mg/kg of body weight, IV, respectively) at time zero. Hemodynamic, pulmonary, and ventilation variables were measured at 15-minute intervals to 120 minutes. Blood gas variables were evaluated at 5-minute intervals for the first 30 minutes, then at 15-minute intervals to 120 minutes. In all sheep, TZ administration induced rapid, smooth induction, with gradual and unremarkable recovery. Anesthesia duration was not significantly different between groups (mean +/- SD, 39 +/- 5 and 40 +/- 14 minutes for groups 1 and 2, respectively). Immediate drug effects included apnea, decreased mean arterial blood pressure, and arterial hypoxemia. Cardiac output was significantly decreased in both groups at all times after drug administration. Significant changes in group-1 ewes included increased pulmonary and systemic vascular resistances and decreased inspired minute ventilation, tidal volume, and respiratory airflow. Significant changes in group-2 ewes included increased systemic vascular resistance and decreased pulmonary arterial pressure, inspired minute ventilation, and respiratory airflow. Both drug dosages induced apneustic breathing patterns and caused significant changes in arterial and venous blood hemoglobin concentrations and PCV. Tiletamine-zolazepam is useful for intermediate-duration anesthesia in sheep.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chemical restraint and anaesthetic effects of a tiletamine-zolazepam/ketamine/detomidine combination in cattle

The immobilisation and anaesthesia of free-ranging cattle requires the administration of appropriate drugs in small volume via rifle or dart. The objective of this randomised controlled study was to test the capacity of a concentrated combination of tiletamine-zolazepam (TZ), ketamine (K) and detomidine (D) (TZKD) to immobilise/anaesthetise calves. Following administration of low, medium and high doses of TZKD to six healthy animals IM, the time-of-onset and duration of anaesthesia were recorded, in addition to standard cardio-respiratory parameters. Two noxious stimuli were applied to assess the analgesic effect of the combination. TZKD produced a dose-dependent anaesthetic action associated with respiratory depression and moderate hypoxaemia. Total recumbency lasted from 1h (with low dose) to 2h (with medium and high doses). The findings indicate that TZKD induces anaesthesia in calves, suitable not only for animal immobilisation, but also to carry out minor surgical procedures with or without additional local analgesia. Respiratory depression was the most severe side-effect and careful patient monitoring is recommended when using this drug combination.     

Effect of low dose rate ketamine infusions on thermal and mechanical thresholds in conscious cats

ObjectiveTo determine the thermal and mechanical antinociceptive effects of two different subanesthetic constant rate infusions of racemic ketamine in cats.Study designProspective, randomized, blinded, experimental study.AnimalsEight healthy adult domestic shorthair cats (two intact females and six neutered males).MethodsThe thorax and the lower thoracic limbs of each cat were shaved for thermal (TT) and mechanical threshold (MT) testing and a cephalic catheter was placed. Three intravenous treatments of equivalent volume were given as loading dose (LD) followed by an infusion for 2 hours: (K5) 0.5 mg kg^?1 ketamine followed by 5 μg kg^?1 minute^?1 ketamine infusion, (K23) 0.5 mg kg^?1 ketamine followed by 23 μg kg^?1 minute^?1 ketamine infusion or (S) 0.9% saline solution. Effects on behavior, sedation scores, MT and TT were obtained prior to drug treatment and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.25, 2.5 2.75, 3 hours then every 0.5 hours for 7 hours and 10, 12, 14 and 26 hours after loading dose administration.ResultsKetamine induced mild sedation for the period of the infusion, no adverse behavioral effects were observed. Thermal threshold was significantly higher than baseline (K5: 44.5 ± 0.7 °C; K23: 44.5 ± 0.5 °C) at 15 minutes in the K5 group (46.8 ± 3.5 °C) and at 45 minutes in the K23 group (47.1 ± 4.1 °C). In the K23 group TT was significantly increased compared to S and K5 at 45 minutes. In K5 at 15 minutes MT (9.6 ± 4.0 N) was different to baseline (6.1 ± 0.8 N) and to the S group (5.9 ± 2.3 N).Conclusion and clinical relevanceLow dose rate ketamine infusions minimally affect thermal and mechanical antinociception in cats. Further studies with different nociceptive testing methods are necessary to assess whether ketamine could be a useful analgesic in cats.     

Pharmacokinetics of ivermectin in cats receiving a single subcutaneous dose

Ivermectin is effective against ecto- and endoparasites. It is included in a plan of the Filariasis Division, Thailand for filariasis control and prevention by interrupting transmission of Brugia malayi-microfilariae from cat reservoirs to humans via mosquitoes. The pharmacokinetics of ivermectin in eight healthy cats receiving a single subcutaneous dose of 0.2mg/kg was investigated. Jugular blood samples were collected periodically for up to 30days after dosing. The serum ivermectin concentrations were measured by high performance liquid chromatography with fluorescence detection. The pharmacokinetic parameters (mean+/-S.D.) derived from one-compartment model analysis were as follows: T(max) 1.22+/-0.49day, C(max) 16.75+/-4.04ng/mL, k(ab) 2.62+/-1.86day(-1), t(1/2)(ab) 0.27+/-0.25day, k(el) 0.27+/-0.14day(-1), t(1/2)(el) 2.53+/-2.24day, V(d)/F 9.81+/-5.41L/kg, Cl/F 2.21+/-0.69L/kg/day and AUC(0-->infinity) 98.31+/-30.52ngday/mL. In conclusion, the pharmacokinetics of ivermectin in cats receiving a single dose of 0.2mg/kg by subcutaneous injection revealed a rapid absorption, high distribution, slow elimination and high possibility for the elimination of B. malayi-microfilariae from currently endemic regions.     

Use of a tiletamine-zolazepam mixture to immobilise wild grey seals and southern elephant seals

A mixture of tiletamine and zolazepam at a combined dose of 1 mg/kg was a reliable and safe agent for immobilising wild grey seals (Halichoerus grypus) and southern elephant seals (Mirouga leonina). The agent had a number of advantages over all the other agents used previously.     

Clinical and antiviral effect of a single oral dose of famciclovir administered to cats at intake to a shelter

Although famciclovir is efficacious in feline herpesvirus type 1 (FHV-1)-infected cats, effects of a single dose early in disease course have not been reported. In this two part, randomized, masked, placebo controlled study, cats received a single dose of 125 mg famciclovir (n = 43) or placebo (n = 43; pilot study), or 500 mg famciclovir (n = 41) or placebo (n = 40; clinical trial) on entering a shelter. FHV-1 PCR testing was performed, bodyweight and food intake were recorded, and signs of respiratory disease were scored prior to and 7 days following treatment. FHV-1 DNA was detected in 40% of cats in both parts at study entry. In the pilot study, ocular and nasal discharge scores increased from days 1 to 7 in famciclovir and placebo treated cats. Sneezing scores increased and bodyweight decreased in famciclovir-treated cats. The proportion of cats in which FHV-1 DNA was detected increased over time in all cats in the pilot study. In the clinical trial, food intake and median clinical disease scores for nasal discharge and sneezing increased from days 1 to 7 in both groups and demeanor scores worsened in famciclovir-treated cats. The proportion of cats shedding FHV-1 DNA was greater on day 7 than on day 1 in cats receiving 500 mg famciclovir. A single dose of famciclovir (125 or 500 mg) administered at shelter intake was not efficacious in a feline population in which 40% were already shedding FHV-1.     

Cardiovascular effects of a high dose of romifidine in propofol-anesthetized cats

OBJECTIVE: To determine the hemodynamic effects of IM administration of romifidine hydrochloride in propofol-anesthetized cats. ANIMALS: 15 adult domestic shorthair cats. PROCEDURE: Cats were randomly assigned to receive romifidine (0, 400, or 2,000 microg/kg, IM). Cats were anesthetized with propofol and mechanically ventilated with oxygen. The right jugular vein, left carotid artery, and right femoral artery and vein were surgically isolated and catheterized. Heart rate; duration of the PR, QRS, and QT intervals; mean pulmonary artery pressure; mean right atrial pressure; systolic, diastolic, and mean arterial pressures; left ventricular systolic pressure; left ventricular end-diastolic pressure; and cardiac output were monitored. Systemic vascular resistance, rate of change of left ventricular pressure, and rate pressure product were calculated. Arterial and venous blood samples were collected anaerobically for determination of pH and blood gas tensions (Po2 and Pco2). RESULTS: Administration of romifidine at 400 and 2,000 microg/kg, IM, decreased heart rate, cardiac output, rate of change of left ventricular pressure, rate pressure product, and pH. Arterial and pulmonary artery pressures, left ventricular pressure, left ventricular end-diastolic pressure, and right atrial pressure increased and then gradually returned to baseline values. Arterial blood gas values did not change, whereas venous Pco2 increased and venous Po2 decreased. Significant differences between low and high dosages were rare, suggesting that the dosages investigated produced maximal hemodynamic effects. CONCLUSIONS AND CLINICAL RELEVANCE: Romifidine produces cardiovascular effects that are similar to those of other alpha2-agonists. High dosages of romifidine should be used with caution in cats with cardiovascular compromise.     

Single dose pharmacokinetics of piroxicam in cats

Piroxicam (PIRO) is a nonsteroidal anti-inflammatory drug (NSAID) recognized for its value as a chemopreventative and anti-tumor agent. Eight cats were included in this study. PIRO was administered in a single oral (p.o.) and intravenous (i.v.) dose of 0.3 mg/kg. The study was designed as a randomized complete crossover with a 2-week washout period. Serial blood samples were collected after each dose and plasma was analyzed for PIRO. Pharmacokinetic parameters of PIRO were determined using noncompartmental analysis. PIRO is well absorbed in the cat with a median bioavailability (F) of 80% (range 64-124%). The median i.v. t1/2 was 12 h (range 8.6-14 h). The median Cmax was 519 ng/mL with a corresponding Tmax of 3 h. PIRO appears to be rapidly absorbed following p.o. administration in cats with a higher Cmax and AUC than in dogs.     

Single dose pharmacokinetics of terbinafine in cats

The pharmacokinetics of terbinafine was studied in six healthy fasted cats following a single intravenous and oral administration at a dose of 10 mg/kg and 30 mg/kg, respectively, according to a two-period crossover design. Plasma terbinafine concentrations were determined using a reverse phase liquid chromatographic method. The pharmacokinetic parameters were calculated by non-compartmental analysis with WinNonlin 5.2.1 software. After intravenous administration, the terminal half-life and area under the curve from time 0 to infinity were 10.40 ± 4.56 h, 15.20 ± 3.61 h·μg/ml, respectively. After oral dosing, the mean maximum concentration was 3.22 ± 0.60 μg/ml, reached at 1.33 ± 0.41 h. The terminal half-life, area under the curve from time 0 to infinity and apparent volume of distribution were 8.01 ± 3.46 h, 13.77 ± 4.99 h·μg/ml, 25.63 ± 6.29 l/kg, respectively. The absolute bioavailability of terbinafine hydrochloride tablets after oral administration was 31.00 ± 10.85%. Although bioavailability was low, excellent penetration at the site of infection and low minimum inhibitory concentrations values provided terbinafine with good efficacy against dermatophyte infections.     

Clinical improvement in feline herpesvirus 1 infected cats by oral low dose of interleukin-12 plus interferon-gamma

Feline herpesvirus 1 (FHV-1) is a widespread cat pathogen inducing rhinitis, conjunctivitis and corneal ulcers. To alleviate acute FHV-1-induced disease, antiviral agents are used often with antibiotics. But sometimes, these treatments, as well as conventional doses of cytokines have moderate efficacy and/or collateral effects. Herein we have investigated the effects of low dose interleukin (IL)-12 plus interferon (IFN)-gamma, prepared by Sequential Kinetic Activated (SKA), on the treatment of FHV-1 infection. Twenty-five, unvaccinated FHV-1-positive cats were recruited into a prospective, randomized, placebo-controlled, double-blinded clinical trial. Fifteen cats were treated for 6 months with oral low doses of SKA IL-12 plus IFN-gamma and 10 cats were treated with placebo. At 1, 6 and 12 months (follow-up) after the beginning of treatment, clinical assessment, PCR assay and blood count were carried out. At follow-up, in treated group, we observed significant (p < 0.05) improvements in clinical signs and PCR became negative in 12/15 cats (80%). In placebo, 10/10 cats were PCR-positive, with improvements (30%) or worsening (70%) in clinical signs. Blood values were normal in both groups.Our results show that the low dose therapy, based on activated solutions of IL-12 plus IFN-gamma, represents a novel approach to treat FHV-1 infection in cats.     

Sedative effects of two doses of alfaxalone in combination with methadone and a low dose of dexmedetomidine in healthy Beagles

ObjectiveTo evaluate the sedative effects of two doses of alfaxalone when added to a combination of dexmedetomidine and methadone injected intramuscularly (IM) in healthy Beagles.Study designRandomized, blinded, crossover, experimental study.AnimalsA group of six adult Beagles.MethodsDogs were sedated on three different occasions with IM dexmedetomidine (3 μg kg^–1) and methadone (0.3 mg kg^–1) combined with two doses of alfaxalone (0.5 and 1 mg kg^–1; A0.5 and A1, respectively) or saline (A0). Quality of sedation, response to tail clamping and rectal temperature were recorded at baseline, 5, 15, 25, 35 and 45 minutes. Pulse and respiratory rates, oxygen saturation of haemoglobin (SpO₂) and noninvasive blood pressure (NIBP) were recorded every 5 minutes. Onset of sedation and duration of recumbency, response to venous catheterization and recovery quality were assessed. Physiological variables (analysis of variance) were analysed between treatments and within treatments compared with baseline (Student t test). Nonparametric data were analysed using Friedman and Cochran’s Q tests. Significance was p < 0.05.ResultsSedation scores were significantly higher when alfaxalone was co-administered (area under the curve; p = 0.024, A0.5; p = 0.019, A1), with no differences between doses. Onset of sedation was similar, but duration of recumbency was longer in A0.5 than in A0 [median (minimum–maximum), 43 (35–54) versus 30 (20–47) minutes, p = 0.018], but not in A1. Response to venous catheterization and tail clamping, and quality of recovery (acceptable) presented no differences between treatments. A decrease in all physiological variables (compared with baseline) was observed, except for NIBP, with no differences between treatments. All dogs required oxygen supplementation due to reduced SpO₂.Conclusions and clinical relevanceAdding alfaxalone to methadone and dexmedetomidine enhanced sedation and duration of recumbency. Although cardiopulmonary depression was limited, oxygen supplementation is advisable.     

Cardiopulmonary effects of a halothane/oxygen combination in healthy cats.

The effects of a halothane/oxygen combination on the cardiopulmonary function of 11 healthy cats were studied. Test parameters included cardiac output, measured via thermo-dilution, heart rate, respiratory rate, arterial blood pressure (systolic, diastolic and mean) and blood gas analysis. Values for systemic vascular resistance, cardiac index and stroke volume were calculated from these data. Cardiac output, cardiac index, heart rate, stroke volume, arterial blood pressure (systolic, diastolic and mean) and arterial blood pH were significantly decreased (p less than 0.001). Respiratory rate was also significantly decreased (p less than 0.007) with arterial CO2 tension being significantly increased (p less than 0.001). Statistically significant changes, where seen, persisted for the duration of the anesthetic period. Arterial O2 tension and systemic vascular resistance remained unchanged. All parameters returned to near pretest values within 30 minutes following cessation of halothane anesthesia.     

Cardiopulmonary effects of a ketamine/acepromazine combination in hypovolemic cats.

The cardiopulmonary effects of a ketamine/ acepromazine combination was studied in ten cats subjected to a 25% whole blood volume loss. Test parameters included cardiac output, measured via thermodilution, heart rate, respiratory rate, arterial blood pressure (systolic, diastolic and mean) and blood gas analysis. Values for cardiac index, stroke volume and systemic vascular resistance were calculated from these data. Posthemorrhage, cardiac output, cardiac index, stroke volume, heart rate and measurements of arterial blood pressure were significantly decreased (p less than 0.05). Following the induction of ketamine/ acepromazine anesthesia, cardiac output, cardiac index, stroke volume and heart rate showed mild but statistically insignificant declines and were above their respective posthemorrhage values 120 min into ketamine/ acepromazine anesthesia. Measurements of arterial blood pressure showed further declines from their respective posthemorrhage values that were statistically significant (p less than 0.05). Following hemorrhage, respiratory rate increased significantly (p less than 0.05), associated with a fall in arterial CO2 tension. During ketamine/ acepromazine anesthesia, respiratory rate showed a dramatic and significant decline (p less than 0.05) with arterial CO2 tension rising to prehemorrhage values. Systemic vascular resistance, arterial O2 tension and pH remained essentially unchanged throughout the experimental period.     

Cardiopulmonary effects of a halothane/oxygen combination in hypovolemic cats.

The cardiopulmonary effects of a halothane/oxygen combination were studied in eight cats subjected to a 25% whole blood volume loss. Test parameters included cardiac output measured via thermodilution, heart rate, respiratory rate, arterial blood pressure (systolic, diastolic and mean) and blood gas analysis. Values for cardiac index, stroke volume and systemic vascular resistance were calculated from these data. Posthemorrhage cardiac output, cardiac index, stroke volume and measurements of arterial blood pressure were significantly decreased (p less than 0.05). Heart rate remained unchanged. Following induction of halothane anesthesia the above parameters experienced a further significant decline (p less than 0.05) from their immediate preanesthetic (i.e. posthemorrhage) values. Heart rate also significantly decreased (p less than 0.05). Thirty minutes following the cessation of halothane anesthesia these values returned to near-hemorrhage levels, being above their respective preanesthetic values. Systemic vascular resistance initially rose, peaking ten minutes into halothane anesthesia, before gradually falling to prehemorrhage values at the end of halothane anesthesia. Following hemorrhage, respiratory rate demonstrated a transient increase, associated with an arterial CO2 tension fall, before returning to initial values at the preanesthetic time. During halothane anesthesia respiratory rate remained unchanged whereas arterial CO2 tension rose significantly (p less than 0.05) and pH declined slightly from preanesthetic readings. These returned to prehemorrhage values 30 minutes following the cessation of halothane anesthesia.     

Single and multiple dose pharmacokinetics of a novel mirtazapine transdermal ointment in cats

Single and multiple dose pharmacokinetics (PK) of mirtazapine transdermal ointment applied to the inner ear pinna of cats were assessed. Study 1 was a randomized, cross‐over single dose study (n = 8). Cats were treated once with 0.5 mg/kg of mirtazapine transdermal ointment applied topically to the inner ear pinna (treatment) or administered orally (control) and then crossed over after washout. Plasma was collected predose and at specified intervals over 96 hr following dosing. Study 2 was a multiple dose study (n = 8). Cats were treated daily for 14 days with 0.5 mg/kg of mirtazapine transdermal ointment applied topically to the inner pinna. Plasma was collected on Day 13 predose and at specified intervals over 96 hr following the final dose. In Study 1, single transdermal administration of mirtazapine resulted in mean T_max = 15.9 hr, C_max = 21.5 ng/mL, AUC_0‐24 = 100 ng*hr/mL, AUC_0‐∞ = 260 ng*hr/mL and calculated half‐life = 26.8 hr. Single oral administration of mirtazapine resulted in mean T_max = 1.1 hr, C_max = 83.1 ng/mL, AUC_0‐24 = 377 ng*hr/mL, AUC_0‐∞ = 434 ng*hr/mL and calculated half‐life = 10.1 hr. Mean relative bioavailability (F) of transdermal to oral dosing was 64.9%. In Study 2, daily application of mirtazapine for 14 days resulted in mean T_max = 2.1 hr, C_max = 39.6 ng/mL, AUC_0‐24 = 400 ng*hr/mL, AUC_0‐∞ = 647 ng*hr/mL and calculated half‐life = 20.7 hr. Single and repeat topical doses of a novel mirtazapine transdermal ointment achieve measurable plasma concentrations in cats.     

Administration of Duddingtonia flagrans chlamydospores to goats to control gastro-intestinal nematodes: dose trials

The ability of the nematophagous fungus Duddingtonia flagrans to reduce the number of infective nematode larvae in coproculture was investigated in goats using different doses of chlamydospores (0, 1.25 x 10(5), 2.5 x 10(5), 5 x 10(5) chlamydospores/kg BW/day) given by oral administration or by voluntary consumption in feed during natural or experimental infections with nematodes. The kinetics of excretion of D. flagrans chlamydospores in the faeces was also determined using a dose of 5 x 10(5) chlamydospores/kg BW/day for five days. For all the trials, the faecal nematode egg outputs were determined by a modified McMaster method and standard coprocultures were set up (14 days, 25 degrees C) to determine the number of larvae emerging from culture in fungus treated and control faeces. When chlamydospores were orally administered, the number of larvae were reduced by 50 to 97% when compared to control cultures. No difference in the level of larval emergence from the culture was seen for experimental or natural infections at the different chlamydospore dose rates. In contrast, when chlamydospores were distributed in the feed, a dose-dependent relationship was observed 10 days after the start of administration, the larval development being 2.0%, 14.0% and 86.9% for 5 x 10(5), 2.5 x 10(5) and 0 spores/kg BW/day, respectively. In addition, the kinetic study showed that the larval emergence from coproculture in the fungus group was statistically lower than in the control group from the second day of administration of the chlamydospores and remained lower until the second day after the last administration (p < 0.05). The results indicate that, for goats in farm conditions, a minimum daily dose of 5 x 10(5) chlamydospores/kg BW must be used to ensure a high treatment efficacy and that daily administration is preferable for maintenance of efficacy over time.     

Cardiopulmonary effects of a ketamine hydrochloride/acepromazine combination in healthy cats.

The effect of a ketamine hydrochloride/acepromazine combination on the cardiopulmonary function of 11 healthy cats was studied. Test parameters included cardiac output, measured by thermodilution, heart rate, respiratory rate, arterial blood pressure (systolic, diastolic and mean) and arterial blood gas analysis. Values for systemic vascular resistance, cardiac index and stroke volume were calculated. The cardiac output, cardiac index, stroke volume, arterial blood pressure and arterial blood pH decreased significantly (p less than 0.006). The arterial CO2 increased significantly (p less than 0.006). All changes occurred during the five to 45 minute postinduction time period. The heart rate, respiratory rate, arterial O2 and systemic vascular resistance were not significantly altered. The anesthetic regime maintained an adequate plane of surgical anesthesia for 30-45 minutes.