The impact of MK‐467 on plasma drug concentrations,sedation and cardiopulmonary changes in sheep treated with intramuscular medetomidine and atipamezole for reversal

The effect of MK‐467, a peripheral α₂‐adrenoceptor antagonist, on plasma drug concentrations, sedation and cardiopulmonary changes induced by intramuscular (IM) medetomidine was investigated in eight sheep. Additionally, the interactions with atipamezole (ATI) used for reversal were also evaluated. Each animal was treated four times in a randomized prospective crossover design with 2‐week washout periods. Medetomidine (MED) 30 μg/kg alone or combined in the same syringe with MK‐467 300 μg/kg (MMK) was injected intramuscular, followed by ATI 150 μg/kg (MED + ATI and MMK + ATI) or saline intramuscular 30 min later. Plasma was analysed for drug concentrations, and sedation was subjectively assessed with a visual analogue scale. Systemic haemodynamics and blood gases were measured before treatments and at intervals thereafter. With MK‐467, medetomidine plasma concentrations were threefold higher prior to ATI, which was associated with more profound sedation and shorter onset. No significant differences were observed in early cardiopulmonary changes between treatments. Atipamezole reversed the medetomidine‐related cardiopulmonary changes after both treatments. Sedation scores decreased more rapidly when MK‐467 was included. In this study, MK‐467 appeared to have a pronounced effect on the plasma concentration and central effects of medetomidine, with minor cardiopulmonary improvement.     

Common dolphins,common in neritic waters off southern Israel,demonstrate uncommon dietary habits

1. During the last decade, the common dolphin (Delphinus delphis) has become the second most sighted species in Israeli coastal waters, after the common bottlenose dolphin. Documentation mostly relies on opportunistic, photo and/or video-backed second-party reports, delimited within a 10 km near-shore strip.
2. Sightings occur year round, are confined to the southern part of the Israeli coast and typically comprise relatively large groups (mean ± SD: 21.5 ± 13.3), often with young calves.
3. Strandings are relatively scarce, typically one per year, and have so far yielded five upper digestive tract contents for diet analysis.
4. Cephalopods comprised 1.2% of the estimated number of prey items in the combined content. Surprisingly, by far the most abundant and prevalent prey item found (57% of pooled prey items; present and dominant in four out of five tracts) was the Balearic eel (Ariosoma balearicum), a sand burrower which is also a major dietary component of the common bottlenose dolphins.
5. Bottlenose dolphins in Israel are known to forage in association with bottom trawlers, leading to the notion that common dolphins also make use of this foraging mode. Indeed, in addition to their association with purse seiners, they have been documented accompanying bottom trawlers, by both day and night. The slender Balearic eels are frequently found protruding from the net's eyes, presumably making easy prey for both dolphin species.
6. Information gaps on common dolphins include range extension to the south/south-west, abundance estimation and genetic flow/isolation. Even so, its unusual diet and the fact that the closest known populations to the north/north-west are from the Aegean Sea, were major considerations in the recent designation of the ‘Coastal Shelf Waters of the South-east Levantine Sea’ as a Mediterranean Important Marine Mammal Area.

     

Sublingual administration of detomidine to calves prior to disbudding: a comparison with the intravenous route

ObjectiveTo study the effects of oromucosal detomidine gel administered sublingually to calves prior to disbudding, and to compare its efficacy with intravenously (IV) administered detomidine.Study designRandomised, prospective clinical study.AnimalsTwenty dairy calves aged 12.4 ± 4.4days (mean ± SD), weight 50.5 ± 9.0 kg.MethodsDetomidine at 80 μg kg^?1 was administered to ten calves sublingually (GEL) and at 30 μg kg^?1 to ten control calves IV (V. jugularis). Meloxicam (0.5 mg kg^?1) and local anaesthetic (lidocaine 3 mg kg^?1) were administered before heat cauterization of horn buds. Heart rate (HR), body temperature and clinical sedation were monitored over 240 minutes. Blood was collected from the V. cephalica during the same period for drug concentration analysis. Pharmacokinetic variables were calculated from the plasma detomidine concentration-time data using non-compartmental methods. Statistical analyses compared routes of administration by Student’s t-test and linear mixed models as relevant.ResultsThe maximum plasma detomidine concentration after GEL was 2.1 ± 1.2 ng mL^?1 (mean ±SD) and the time of maximum concentration was 66.0 ± 36.9 minutes. The bioavailability of detomidine was approximately 34% with GEL. Similar sedation scores were reached in both groups after administration of detomidine, but maximal sedation was reached earlier in the IV group (10 minutes) than in the GEL group (40 minutes). HR was lower after IV than GEL from 5 to 10 minutes after administration. All animals were adequately sedated, and we were able to administer local anaesthetic without resistance to all of the calves before disbudding.Conclusions and clinical relevanceOromucosally administered detomidine is an effective sedative agent for calves prior to disbudding.     

Plasma drug concentrations and clinical effects of a peripheral alpha‐2‐adrenoceptor antagonist,MK‐467, in horses sedated with detomidine

ObjectiveTo investigate plasma drug concentrations and the effect of MK-467 (L-659′066) on sedation, heart rate and gut motility in horses sedated with intravenous (IV) detomidine.Study designExperimental randomized blinded crossover study.AnimalsSix healthy horses.MethodsDetomidine (10 μg kg^?1 IV) was administered alone (DET) and in combination with MK-467 (250 μg kg^?1 IV; DET + MK). The level of sedation and intestinal sounds were scored. Heart rate (HR) and central venous pressure (CVP) were measured. Blood was collected to determine plasma drug concentrations. Repeated measures anova was used for HR, CVP and intestinal sounds, and the Student's t-test for pairwise comparisons between treatments for the area under the time-sedation curve (AUC_sed) and pharmacokinetic parameters. Significance was set at p < 0.05.ResultsA significant reduction in HR was detected after DET, and HR was significantly higher after DET + MK than DET alone. No heart blocks were detected in any DET + MK treated horses. DET + MK attenuated the early increase in CVP detected after DET, but later the CVP decreased with both treatments. Detomidine-induced intestinal hypomotility was prevented by MK-467. AUC_sed was significantly higher with DET than DET + MK, but maximal sedations scores did not differ significantly between treatments. MK-467 lowered the AUC of the plasma concentration of detomidine, and increased its volume of distribution and clearance.Conclusions and clinical relevanceMK-467 prevented detomidine induced bradycardia and intestinal hypomotility. MK-467 did not affect the clinical quality of detomidine-induced sedation, but the duration of the effect was reduced, which may have been caused by the effects of MK-467 on the plasma concentration of detomidine. MK-467 may be useful clinically in the prevention of certain peripheral side effects of detomidine in horses.     

Use of ketoprofen as an antipyretic in cats.

The antipyretic effectiveness of Ketoprofen, a non-steroidal anti-inflammatory drug, was investigated in pyretic cats with a variety of bacterial and viral infections. Cats were randomly assigned to receive either a broad-spectrum antibiotic or a broad-spectrum antibiotic plus ketoprofen. Body temperature was monitored 3 times daily, and attitude and appetite were evaluated once daily. The treatment groups were compared with respect to mean body temperatures, using a one-way analysis of variance. Mean temperatures were significantly different (P < 0.05) during the 4 and 8 h post-treatment observations, with a reduction to normal temperatures in the ketoprofen group compared with no change in the group treated with antibiotics alone. The antipyretic effect of ketoprofen was rapid and persisted for at least 8 h, but for less than 24 h. The overall recovery period from pyrexia, depression, and inappetance was also shorter in cats treated with antibiotics and ketoprofen (3 d) than in cats treated only with antibiotics (5 d). Ketoprofen was a useful adjunct in the treatment of pyretic cats.