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Pharmacokinetics,pharmacodynamics and clinical use of trazodone and its active metabolite m‐chlorophenylpiperazine in the horse
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J. L. Davis J. Schirmer E. Medlin 《Journal of veterinary pharmacology and therapeutics》2018,41(3):393-401
Trazodone is a serotonin receptor antagonist and reuptake inhibitor used extensively as an anxiolytic in human and small animal veterinary medicine. The aims of this study were to determine the pharmacokinetics of oral trazodone in experimental horses and to evaluate the effect of oral trazodone in clinical horses. Six experimental horses were administered trazodone at 7.5 or 10 mg/kg. Plasma concentrations of trazodone and its metabolite (m‐CPP) were determined via UPLC‐MS/MS. Noncompartmental pharmacokinetic analysis, sedation and ataxia scores were determined. Trazodone was rapidly absorbed after oral administration with a maximum concentration of 2.5–4.1 μg/ml and half‐life of the terminal phase of approximately 7 hr. The metabolite was present at low levels in all horses, representing only 2.5% of the total area under the curve. In experimental horses, concentration‐dependent sedation and ataxia were noted, lasting up to 12 hr. For clinical cases, medical records of horses treated with trazodone for various abnormal behaviours were reviewed and data were summarized. Trazodone was successful in modifying behavioural problems to some degree in 17 of 18 clinical cases. Tolerance and subsequent lack of drug effect occurred in two of 18 clinical cases following 14 or 21 days of use. In both populations of horses, adverse effects attributed to trazodone include oversedation, muscle fasciculations and transient arrhythmias. 相似文献
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《Veterinary anaesthesia and analgesia》2023,50(3):255-262
ObjectiveTo investigate the sedative and cardiorespiratory effects of intranasal atomization (INA) of alfaxalone using a mucosal atomization device in Japanese White rabbits.Study designRandomized, prospective, crossover study.AnimalsA total of eight healthy female rabbits, weighing 3.6–4.3 kg and aged 12–24 months.MethodsEach rabbit was randomly assigned to four INA treatments administered 7 days apart: Control treatment, 0.15 mL 0.9% saline in both nostrils; treatment INA0.3, 0.15 mL 4% alfaxalone in both nostrils; treatment INA0.6, 0.3 mL 4% alfaxalone in both nostrils; treatment INA0.9, 0.3 mL 4% alfaxalone in left, then right, then left nostril. Sedation was scored 0–13 using a composite measure scoring system for rabbits. Simultaneously, pulse rate (PR), respiratory rate (fR), noninvasive mean arterial pressure (MAP), peripheral hemoglobin oxygen saturation (SpO2) and arterial blood gases were measured until 120 minutes. The rabbits breathed room air during the experiment and were administered flow-by oxygen when hypoxemia (SpO2 <90% or PaO2 <60 mmHg; 8.0 kPa) developed. Data were analyzed using the Fisher's exact test and the Friedman test (p < 0.05).ResultsNo rabbit was sedated in treatments Control and INA0.3. All rabbits in treatment INA0.9 developed loss of righting reflex for 15 (10–20) minutes [median (25th–75th percentile)]. Sedation score significantly increased from 5 to 30 minutes in treatments INA0.6 and INA0.9 with maximum scores of 2 (1–4) and 9 (9–9), respectively. fR decreased in an alfaxalone dose-dependent manner and one rabbit developed hypoxemia in treatment INA0.9. No significant changes were observed in PR and MAP.Conclusions and clinical relevanceINA alfaxalone resulted in dose-dependent sedation and respiratory depression in Japanese White rabbits to values considered not clinically relevant. Further investigation of INA alfaxalone in combination with other drugs is warranted. 相似文献
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Reasons for performing study: Detomidine hydrochloride is used to provide sedation, muscle relaxation and analgesia in horses, but a lack of information pertaining to plasma concentration has limited the ability to correlate drug concentration with effect. Objectives: To build on previous information and assess detomidine for i.v. and i.m. use in horses by simultaneously assessing plasma drug concentrations, physiological parameters and behavioural characteristics. Hypothesis: Systemic effects would be seen following i.m. and i.v. detomidine administration and these effects would be positively correlated with plasma drug concentrations. Methods: Behavioural (e.g. head position) and physiological (e.g. heart rate) responses were recorded at fixed time points from 4 min to 24 h after i.m. or i.v. detomidine (30 μg/kg bwt) administration to 8 horses. Route of administration was assigned using a balanced crossover design. Blood was sampled at predetermined time points from 0.5 min to 48 h post administration for subsequent detomidine concentration measurements using liquid chromatography‐mass spectrometry. Data were summarised as mean ± s.d. for subsequent analysis of variance for repeated measures. Results: Plasma detomidine concentration peaked earlier (1.5 min vs. 1.5 h) and was significantly higher (105.4 ± 71.6 ng/ml vs. 6.9 ± 1.4 ng/ml) after i.v. vs. i.m. administration. Physiological and behavioural changes were of a greater magnitude and observed at earlier time points for i.v. vs. i.m. groups. For example, head position decreased from an average of 116 cm in both groups to a low value 35 ± 23 cm from the ground 10 min following i.v. detomidine and to 64 ± 24 cm 60 min after i.m. detomidine. Changes in heart rate followed a similar pattern; low value of 17 beats/min 10 min after i.v. administration and 29 beats/min 30 min after i.m. administration. Conclusions: Plasma drug concentration and measured effects were correlated positively and varied with route of administration following a single dose of detomidine. Potential relevance: Results support a significant influence of route of administration on desirable and undesirable drug effects that influence case management. 相似文献
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The prophylactic use of a dry-cow antibiotic for reducing the incidence of mastitis due to Streptococcus uberis was studied in four seasonally calving dairy herds involving 378 cows. The treatment was a long-acting dry-cow antibiotic preparation administered immediately after the last milking of lactation. New intramammary infections were identified by comparing the bacteriological status of quarters at drying off with that after calving, or through manual udder palpation during the dry period. The administration of dry-cow antibiotic to uninfected quarters at drying off reduced the overall incidence of new infections with Streptococcus uberis from 12.3% for untreated quarters to 1.2% of quarters (p<0.01). The reduction was significant (p<0.01) for both dry-period and post-calving infections. The susceptibility of uninfected quarters to new infection by Streptococcus uberis appeared to be unrelated to the infection status of a cow at drying off. Clinical infections during the dry period were most prevalent (97%) in quarters identified as having open teat canals. Fewer open teat canals (p<0.05) were observed among antibiotic treated quarters over the first 4 weeks of the dry period. Treated quarters had a lower (p<0.05) incidence of new clinical infection during the ensuing lactation and lower somatic cell counts. This did not affect production levels of milk, milk fat or protein. The results clearly indicated a prophylactic benefit for the dry cow antibiotic treatment against new Streptococcus uberis infections during the dry period. 相似文献
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《Journal of Exotic Pet Medicine》2014,23(1):6-20
This article reviews advances in the pharmacokinetics and pharmacodynamics of therapeutic agents used in avian medicine. There has been a significant body of work published within the last 5 years that has helped provide a scientific basis for drug treatment in avian patients. This concise article of different studies on antibacterial, antifungal, analgesic, sedative and anesthetic, hormone (e.g., deslorelin), psychotropic, antiepileptic, and cardiovascular drugs provides evidence of the advancements in this area of companion exotic animal medicine. 相似文献
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黄花败酱化学成分及镇静、抑菌作用研究 总被引:5,自引:0,他引:5
通过对黄花败酱化学成分进行分析及对黄花败酱不同溶剂提取物进行了镇静作用和体外抑菌作用试验 ,结果表明 ,黄花败酱的主要化学成分是三萜皂苷和甾体皂甙、酚类物质和糖类物质、挥发油和有机酸。黄花败酱醇提取液对小白鼠具有明显的镇静的作用 ,其镇静作用的持续时间为 (5 1± 1.93) m in。黄花败酱水蒸馏液对金黄色葡萄球菌和链球菌具有明显的抑菌作用 ,其抑菌直径 (mm)分别为 2 1.2 1± 0 .34及 2 0 .2 0± 1.13。 相似文献
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Steve C. Haskins DVM MS DACVECC 《Journal of Veterinary Emergency and Critical Care》2006,16(4):300-328
Objective: To integrate and compare the effects of tranquilizer/sedatives and anesthetic drugs on various parameters of cardiovascular function in normal dogs and in dogs stressed by hypovolemia, anemia, and endotoxemia, and to discuss the relative merits and appropriate precautions of anesthetic drugs with respect to specific patient physiologic complications. Data sources: Personal data and experiences in conjunction with veterinary and human clinical and research studies. Human and veterinary data synthesis: Drugs that produce calming, sedation, muscle relaxation, analgesia, and loss of consciousness have the potential to produce marked cardiorespiratory effects particularly in hemorrhaged, hypovolemic‐traumatized animals. Acute but key cardiovascular components that are affected by sedative and anesthetic drugs include heart rate and rhythm, venous return (preload), systemic vascular resistance (afterload), and myocardial contractile (inotropic) and relaxation (lusitropic) properties. In addition, all sedative and anesthetic drugs alter or depress normal baroreceptor reflex activity, thereby inhibiting or eliminating the animal's normal physiologic response to decreases in arterial blood pressure and predisposing to tissue hypoperfusion, decreased oxygen delivery, and oxygenation. Oxygen delivery needs to be adequate to meet the metabolic (oxygen) requirements of the patient. Decreases in oxygen delivery to tissues increases oxygen extraction, thereby maintaining tissue oxygenation (supply‐independent oxygen consumption phase) until compensatory processes reach their limit and any further decrease in oxygen delivery causes a decrease in oxygen consumption (supply‐dependent oxygen consumption phase). The critical oxygen delivery that defines the transition between these 2 phases is generally higher in the anesthetized state than in the awake state. The effect of anesthetics on critical oxygen delivery at comparable anesthetic dosages is pentobarbital=ketamine>alfentanil>etomidate=propofol>inhalational anesthetics. Anesthetics generally decrease oxygen consumption from the awake, baseline state; exceptions are ketamine and ether. Ketamine, however, increases oxygen delivery and oxygen extraction. Conclusions: The transition from the awake to the anesthetized state is a huge imposition on the physiology of animals and, therefore, should be accomplished with great care and proper vigilance. Rapid, ‘crash’ induction of anesthesia should be avoided in hypotension‐prone animals and slow, prolonged induction should be avoided in animals with respiratory disorders. It is not recommended to implement an unfamiliar protocol in critical patients, even if it might be pharmacologically preferable. Familiarity with an anesthetic drug is a very important reason for its selection. 相似文献