Behaviour and respiratory rate after administration of methadone and methadone in combination with detomidine in horses

Background: In treatment of nociceptive pain with opioids the full μ-agonists have highest efficacy. Methadone is a synthetic full μ-agonist and also an N-methyl-d-aspartate (NMDA) receptor antagonist used in horses. Opioids might also cause excitement in the horse and respiratory depression especially when used together with other drugs affecting the respiration. The α2-agonists are used in horses for sedation and analgesia both separately and in combination with opioids. A combination of methadone and the α2-agonist detomidine may be useful in pain management but may also cause effects on behaviour and respiratory rate. Objectives: The aims were to investigate the effects on behavior and respiratory rate after treatment with methadone IV or methadone IV in combination with detomidine IM in order to evaluate and possibly diminish adverse effects in the treatment of horses. Materials and methods: The study was randomized, blinded and placebo controlled with cross-over design. Eight Standardbred horses were treated with (1) methadone IV (0.2 mg/kg) in a total volume of 20 mL over 5 min together with placebo (saline) IM or (2) 20 mL methadone IV (0.1 mg/kg) over 5 min together with detomidine IM (0.01 mg/kg) or (3) equivalent volumes saline IV and IM. The effects on behavior and respiratory rate were examined. Results: After methadone administration the horses displayed behavioral changes such as staggering for a short period, head tremors and looking vigilantly around. The behaviors licking, nodding head, picking hay, tail flapping, skin twitching and scraping with front leg were more frequent after treatment with methadone compared to the control. There were no differences in respiratory rate between methadone and saline treatments. After methadone/detomidine administration the horses showed drowsiness, snored, stood with dropped head or head supported by the wall or the crib during the first one to three hours. In addition, a few horses were sweating. The respiratory rate was lowered between one and three hours after administration of the drug combination compared with placebo (P = 0.02). Conclusions: When the horses were treated with methadone they showed drug-related agitation which has been described in horses treated with different opioids. The combination of methadone/detomidine seems to prevent excitement caused by opioid exposure. A lowered respiratory rate is also a known non-wanted effect of opioids but in this study no such adverse effect was observed after solely methadone administration but the combination methadone/detomidine induced decreased respiratory rate. Acknowledgements: Supported by The Swedish-Norwegian Foundation for Equine Research

Воздействие менталитета белорусов на интеграционные процессы Беларуси на культурно-цивилизационной оси "Восток-Запад"

BACKGROUND: Clinical practice guidelines are important for transmitting research findings into practice and facilitating the application of evidence-based practice (EBP). There is a paucity of knowledge about the impact of guideline implementation strategies in primary care physical therapy. The aim of this study was to evaluate the effect of a guideline implementation intervention in primary care physical therapy in western Sweden. METHODS: An implementation strategy based on theory and current evidence was developed. A tailored, multi-component implementation intervention, addressing earlier identified determinants, was carried out in three areas comprising 28 physical therapy practices including 277 physical therapists (PTs) (intervention group). In two adjacent areas, 171 PTs at 32 practices received no intervention (control group). The core component of the intervention was an implementation seminar with group discussions. Among other components were a website and email reminders. Data were collected at baseline and follow-up with a web-based questionnaire. Primary outcomes were the self-reported awareness of, knowledge of, access to, and use of guidelines. Secondary outcomes were self-reported attitudes toward EBP and guidelines. Analyses were performed using Pearson's χ2 test and approximative z-test. RESULTS: 168 PTs (60.6%) in the intervention group and 88 PTs (51.5%) in the control group responded to the follow-up questionnaire. 186/277 PTs (67.1%) participated in the implementation seminars, of which 97 (52.2%) responded. The proportions of PTs reporting awareness of (absolute difference in change 20.6%, p = 0.023), knowledge where to find (20.4%, p = 0.007), access to (21.7%, p < 0.001), and frequent use of (9.5%, NS) guidelines increased more in the intervention group than in the control group. The proportion of PTs reporting frequent guideline use after participation in the implementation seminar was 15.2% (p = 0.043) higher than the proportion in the control group. A higher proportion considered EBP helpful in decision making (p = 0.018). There were no other significant differences in secondary outcomes. CONCLUSIONS: A tailored, theory- and evidence-informed, multi-component intervention for the implementation of clinical practice guidelines had a modest, positive effect on awareness of, knowledge of, access to, and use of guidelines, among PTs in primary care in western Sweden. In general, attitudes to EBP and guidelines were not affected

Drugs in horses

In this thesis the fate and effect of some drugs have been examined in horses. Studies have also been performed to explore some factors which may affect the pharmacokinetics and the pharmacodynamics of drugs in horses. Investigations on the drug metabolising enzyme cytochrome P450 3A (CYP3A) in the intestines of horses showed high gene expression and metabolic activity in the proximal parts of the intestines. The results indicate that CYP3A in the intestines of horse plays a major role in the first-pass metabolism of drugs which are substrates for CYP3A. There is a need for an antihistamine for oral therapy of horses. The oral bioavailability of the antihistamine fexofenadine was found to be low, and this drug is therefore unsuitable for oral use in horses. In contrast oral administration of the antihistamine cetirizine resulted in a sufficient uptake. This drug was also found to have a potent antihistaminic effect in horses. Cetirizine may therefore be a suitable antihistamine in equine medicine. The passage of antihistamines, such as fexofenadine and cetirizine, as well as several other xenobiotics, over cell-membranes in various tissues is partly regulated by transport proteins. Studies in this thesis showed that pre-treatment of horses with the antiparasitic agent ivermectin affects the oral bioavailability of fexofenadine and cetirizine. The effect of ivermectin is probably related to interference in the function of the transport proteins. Acute adverse reactions may occur following treatments of horses with procaine benzylpenicillin or potassium or sodium benzylpenicillin. Analysis of adverse reactions reported in 59 horses indicates that allergy may underlie a few of the cases. However, most reactions may be due to toxic effects of procaine. Several mechanisms may contribute to the procaine toxicity. It was shown that the ability of plasma esterases to hydrolyze procaine to non-toxic metabolites was lower in reacting horses compared to non-reacting control horses. Low plasma esterase activity may increase the likelihood for procaine toxicity and constitute one risk factor

Improved Oral Health and Adaptation to Treatment in Dogs Using Manual or Ultrasonic Toothbrush or Textile of Nylon or Microfiber for Active Dental Home Care

Poor oral health is a common problem in dogs causing pain and impaired welfare. The gold standard to maintain good oral health and prevent periodontitis is daily tooth brushing. However, many dog owners find it difficult, and dogs often show aversive behavior. There are several different tools available, and in this intra-subject study, four different active dental home care treatment options were examined: manual and ultrasonic toothbrush, a nylon glove, and a microfiber finger cloth. The treatments were evaluated for efficacy against gingivitis, plaque, and calculus in beagle dogs. Each dog received two treatments on the buccal sides of the teeth once daily, either two types of toothbrushes (N = 10) or two types of textiles (N = 11), on separate sides of the mouth. The dogs’ teeth were assessed before and after the five-week treatment period, with the assessor blinded by additional, similar dogs (N = 7). The study also assessed the dogs’ stress levels during treatment using a fear, anxiety, stress (FAS) protocol. All four treatments improved dog oral health, reducing gingivitis and plaque. Furthermore, the amount of calculus also decreased in some individuals. Adaptation to dental care occurred in the dogs over time. This information can be used to encourage dog owners to brush their dogs’ teeth

Physiological and Clinical Responses in Pigs in Relation to Plasma Concentrations during Anesthesia with Dexmedetomidine, Tiletamine, Zolazepam, and Butorphanol

Simple Summary Reliable protocols are needed for short-term anesthesia in pigs. The study's aim is to identify an anesthetic procedure that, without the use of sophisticated equipment, ensures an acceptable depth and length of anesthesia, a regular spontaneous breathing pattern, and a stable hemodynamic condition for the animal. A total of 12 pigs were given a single intramuscular injection of dexmedetomidine, tiletamine, zolazepam, and butorphanol. To investigate the possibility of prolonging the anesthesia, six of the pigs also received an intravenous dose of the drug combination after one hour. Physiological and clinical responses and drug plasma concentrations were examined. The main results suggest that intramuscular administration of the drug combination provides up to two hours of anesthesia with stable physiological parameters and an acceptable level of analgesia. An intravenous administration of one-third of the original dosage prolonged the anesthesia for another 30 min. Since the pigs were able to breathe spontaneously, none of them were intubated. The study also provides new information about each drug's plasma concentrations and the impact of the drug combination in pigs. This technique can be used to perform nonsurgical operations or transports when short-term anesthesia is required. Reliable protocols for short-term anesthetics are essential to safeguard animal welfare during medical investigations. The aim of the study was to assess the adequacy and reliability of an anesthetic protocol and to evaluate physiological and clinical responses, in relation to the drug plasma concentrations, for pigs undergoing short-term anesthesia. A second aim was to see whether an intravenous dosage could prolong the anesthesia. The anesthesia was induced by an intramuscular injection of dexmedetomidine, tiletamine zolazepam, and butorphanol in 12 pigs. In six of the pigs, a repeated injection intravenously of one-third of the initial dose was given after one hour. The physiological and clinical effects from induction to recovery were examined. Plasma concentrations of the drugs were analyzed and pharmacokinetic parameters were calculated. Each drug's absorption and time to maximal concentration were rapid. All pigs were able to maintain spontaneous respiration. The route of administration did not alter the half-life of the drug. The results suggest that intramuscular administration of the four-drug combination provides up to two hours of anesthesia with stable physiological parameters and an acceptable level of analgesia while maintaining spontaneous respiration. A repeated intravenous injection may be used to extend the time of anesthesia by 30 min

Bioavailability of subcutaneous and intramuscular administrated buprenorphine in New Zealand White rabbits

Background Buprenorphine is one of the most used analgesics for postoperative pain in rabbits. The recommended dose in rabbits (0.01-0.05mg/kg) is the same for intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration, despite lack of pharmacokinetic data. Five male and five female New Zealand White rabbits (meanSD body weight 3.10.3kg) were administered 0.05mg/kg buprenorphine by the IV, IM and SC routes and 0.1mg/kg by the SC route, in a cross-over design with two-week wash-out periods between treatments. Blood was collected before, and up to 8h post buprenorphine injection, for determination of serum levels by UPHLC-MS/MS.Results The area under the time concentration curve (AUC(0-t)) was lower after SC (398 +/- 155ng/mL/min) than IM (696 +/- 168ng/mL/min, p < 0.001) and IV (789 +/- 189ng/mL/min, p < 0.001) administration. The maximum serum concentration was lower after SC (2.2 +/- 1.4ng/mL) than after IM (11 +/- 3.2ng/mL) administration (p < 0.001). The bioavailability was lower after SC (50 +/- 19%) than after IM (95 +/- 21%) administration (p=0.006). The elimination half-life was longer after SC (260 +/- 120min) than after IM (148 +/- 26min, p=0.002) as well as IV (139 +/- 33min) injection (p < 0.001). An increase in the SC dose from 0.05 to 0.1mg/kg resulted in an increase in the area under the time concentration curve of 50% in female (p=0.022) and 165% in male rabbits (p < 0.001). The bioavailability did not change in the females (36 +/- 14%, p=0.6), whereas it increased in the males (71 +/- 23%, p=0.008).Conclusions The lower bioavailability of 0.05mg/kg buprenorphine after SC administration could explain the lack of efficacy seen in clinical pain studies in rabbits, using this route. For immediate pain relief, IV or IM administration is therefore be recommended, whereas SC administration may be useful to sustain analgesic serum levels, once efficient pain relief has been achieved. The current data do not support an increase in dose to compensate for the lower SC bioavailability