Topic:Benzodiazepines
Benzodiazepines are a class of psychoactive drugs that act on the central nervous system by enhancing the effect of the neurotransmitter gamma-aminobutyric acid (GABA). In horses, benzodiazepines are used primarily for their sedative, muscle relaxant, and anxiolytic properties. They are often administered during medical procedures to facilitate handling and reduce stress. Common benzodiazepines used in equine medicine include diazepam and midazolam. These drugs can influence the behavior and physiological responses of horses, making them useful in various clinical settings. This page compiles peer-reviewed research studies and scholarly articles that investigate the pharmacokinetics, therapeutic applications, and safety profiles of benzodiazepines in equine practice.
Kinetic disposition of diazepam and its metabolites after intravenous administration of diazepam in the horse: Relevance for doping control. In horses, the benzodiazepine diazepam (DIA) is used as sedative for pre-medication or as an anxiolytic to facilitate horse examinations. As the sedative effects can also be abused for doping purposes, DIA is prohibited in equine sports. DIA is extensively metabolized to several active metabolites such as nordazepam, temazepam and oxazepam (OXA). For veterinarians, taking into account the detection times of DIA and its active metabolites is needed for minimizing the risk of an anti-doping rule violation. Therefore, a pharmacokinetic study on 6 horses was conducted using a single intravenous (...
The effects of flumazenil on ventilatory and recovery characteristics in horses following midazolam-ketamine induction and isoflurane anaesthesia. Flumazenil antagonises the actions of benzodiazepines. There has been no prior research specifically investigating this anaesthetic reversal agent for horses. Objective: To determine the effects of flumazenil administration in horses on (a) ventilatory parameters after midazolam-ketamine induction and maintenance with isoflurane in oxygen and on (b) the characteristics of recovery from general anaesthesia. Methods: Blinded, randomised, crossover experiment. Methods: Six horses were randomly assigned to receive high-dose flumazenil (F , 20 µg/kg), low-dose flumazenil (F , 10 µg/kg) and sali...
Metabolism and excretion of the benzodiazepine analogue etizolam in the horse. Etizolam is a benzodiazepine analogue that is approved for use in Japan, Italy and India but has recently appeared as a nonapproved product on the illicit drug market in Europe and North America. Etizolam was identified in a crystalline material seized at a Kentucky racetrack, raising concerns that this drug may have been used in racing. The aim of this study was to characterize the metabolism and excretion of etizolam in horses to generate information on its disposition and to incorporate the correct urinary and serum target analytes into anti-doping screening procedures. Etizolam was adminis...
Arterial oxygenation in anesthetized horses placed in a 5-degree reverse Trendelenburg position. Low arterial oxygen is a common complication in anesthetized horses and placing the animal in reverse Trendelenburg (RT) position may treat hypoxemia. The objective of this study was to assess the arterial partial pressure of oxygen (PaO) in horses placed in a 5-degree RT compared to horizontal (H) position. Client-owned healthy horses (n = 60) undergoing elective surgeries were enrolled in a randomized controlled clinical study. Horses were sedated with butorphanol, an α-adrenoceptor agonist, ± acepromazine and induced with ketamine combined with a benzodiazepine, propofol, or guaifenesin...
Intrathecal Immunoglobulin for treatment of adult patients with tetanus: A randomized controlled 2×2 factorial trial. Despite long-standing availability of an effective vaccine, tetanus remains a significant problem in many countries. Outcome depends on access to mechanical ventilation and intensive care facilities and in settings where these are limited, mortality remains high. Administration of tetanus antitoxin by the intramuscular route is recommended treatment for tetanus, but as the tetanus toxin acts within the central nervous system, it has been suggested that intrathecal administration of antitoxin may be beneficial. Previous studies have indicated benefit, but with the exception of one small trial n...
Role of the equine CYP3A94, CYP3A95 and CYP3A97 in ketamine metabolism in presence of medetomidine, diazepam and methadone studied by enantioselective capillary electrophoresis. The anesthetic ketamine is often combined with analgesics and benzodiazepines in equine medicine. Therefore, drug-drug interactions are possible. Enzyme kinetics for ketamine N-demethylation were determined using equine CYP3A94, CYP3A95 and CYP3A97, and the effect of medetomidine, diazepam and methadone on the ketamine metabolism was studied in vitro. Ketamine was incubated with the CYPs or equine liver microsomes (ELM) alone or in presence of medetomidine, diazepam and/or methadone for different times. Norketamine levels were determined using enantioselective capillary electrophoresis (CE) wi...
Oxygen supplementation before induction of general anaesthesia in horses. Hypoventilation or apnoea, caused by the induction of general anaesthesia, may cause hypoxaemia. Preoxygenation may lengthen the period before this happens. No scientific studies are published on preoxygenation in equine anaesthesia. Objective: To determine whether supplementation of oxygen at a flow rate of 15 l/min for 3 min via a nasal cannula before induction of general anaesthesia is effective in elevating the arterial partial pressure of oxygen (PaO ) directly after induction. Methods: Randomised, prospective clinical trial. Methods: A total of 18 American Society of Anesthesiologists ph...
Pharmacokinetics and physiologic effects of alprazolam after a single oral dose in healthy mares. The objective of this study was to evaluate the pharmacokinetic properties and physiologic effects of a single oral dose of alprazolam in horses. Seven adult female horses received an oral administration of alprazolam at a dosage of 0.04 mg/kg body weight. Blood samples were collected at various time points and assayed for alprazolam and its metabolite, α-hydroxyalprazolam, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of alprazolam was analyzed by a one-compartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single-dose administration of ...
Evaluation of risk factors, including fluconazole administration, for prolonged anesthetic recovery times in horses undergoing general anesthesia for ocular surgery: 81 cases (2006-2013). OBJECTIVE--To determine risk factors for prolonged anesthetic recovery time in horses that underwent general anesthesia for ocular surgery. DESIGN--Retrospective cohort study. ANIMALS--81 horses that underwent general anesthesia for ocular surgery between 2006 and 2013. PROCEDURES--Descriptive information recorded included the ocular procedure performed, concurrent fluconazole treatments, analgesic and anesthetic agents administered, procedure duration, use of sedation for recovery, and recovery time. Data were analyzed for associations between recovery time and other variables. RESULTS--81 ho...
In vitro diazepam metabolism in horses. There is little information about drug metabolism and pharmacokinetics in horses. Therefore, it is necessary to characterize the profiles of drug metabolites for the safe use of drugs. In this study, we focused on cytochrome P450 enzymes (CYPs), which represent an important enzyme group to determine pharmacological effects of drugs. We chose diazepam as the drug of choice for this study. The aim of this study was to elucidate the metabolic pathway of diazepam in horses in comparison with rats, and to clarify CYP subfamilies responsible for diazepam metabolism in horses. Our results showed tema...
Pharmacokinetics of midazolam after intravenous administration to horses. Midazolam is used to control seizures in horses and to enhance muscle relaxation, but its pharmacokinetics are unknown. Objective: To determine the pharmacokinetics and sedative effects of midazolam in horses. Methods: Blinded, randomised, crossover design. Methods: Midazolam was administered i.v. at either 0.05 or 0.1 mg/kg bwt to 6 horses on 2 occasions at least 7 days apart using a crossover design. Blood samples were collected before and at predetermined times through 24 h after administration. Serum midazolam concentrations were determined by a liquid chromatography tandem-mass spectromet...
Balanced anesthesia and constant-rate infusions in horses. Balanced anesthetic techniques are commonly used in equine patients, and include the combination of a volatile anesthetic with at least one injectable anesthetic throughout the maintenance period. Injectable anesthetics used in balanced anesthesia include the α2-agonists, lidocaine, ketamine, and opioids, and those with muscle-relaxant properties such as benzodiazepines and guaifenesin. Administration of these injectable anesthetics is best using constant-rate infusions based on the pharmacokinetics of the drug, which allows steady-state concentrations and predictable pharmacodynamic actions....
Effect of butorphanol administration on cardiovascular parameters in isoflurane-anesthetized horses – a retrospective clinical evaluation. To determine cardiovascular responses to administration of butorphanol in isoflurane-anesthetized horses. Methods: Retrospective evaluation of anesthetic records. Methods: Seventy-six horses anesthetized for a variety of clinical surgical procedures. Methods: Anesthetic records of clinical equine patients anesthetized between January 1999 and December 2003 were searched. The records were reviewed for horses in which anesthesia was induced with ketamine and a benzodiazepine and maintained with isoflurane, and horses that received butorphanol intraoperatively. Exclusion criteria included horses ...
Anesthetic and cardiopulmonary effects of total intravenous anesthesia using a midazolam, ketamine and medetomidine drug combination in horses. The anesthetic and cardiopulmonary effects of midazolam, ketamine and medetomidine for total intravenous anesthesia (MKM-TIVA) were evaluated in 14 horses. Horses were administered medetomidine 5 microg/kg intravenously as pre-anesthetic medication and anesthetized with an intravenous injection of ketamine 2.5 mg/kg and midazolam 0.04 mg/kg followed by the infusion of MKM-drug combination (midazolam 0.8 mg/ml-ketamine 40 mg/ml-medetomidine 0.1 mg/ml). Nine stallions (3 thoroughbred and 6 draft horses) were castrated during infusion of MKM-drug combination. The average duration of anesthesia wa...
Effects of midazolam on equine innate immune response: a flow cytometric study. Benzodiazepines (BDZ) are among the most frequently used class of psychotropic drugs employed in veterinary medicine in Brazil and worldwide due to their anxiolytic, muscle relaxant and anticonvulsant effects [J. Clin. Pharmacol. 33 (1993) 124]. Peripheral benzodiazepine receptor (PBR) sites were described in peripheral organs, endocrine steroidogenic tissues and immune organs and cells. Midazolam is a mixed-type agonist of PBRs. The present study is focused on the effects of midazolam on equine peripheral blood neutrophils, peritoneal macrophages and cortisol levels in plasma. Adult horses we...
Detection of diazepam in horse hair samples by mass spectrometric methods. A method for the detection of diazepam in horse hair samples by low resolution gas chromatography-mass spectrometry (GC-MS) was developed. Two other techniques, gas chromatography-high-resolution mass spectrometry (GC-HRMS) and high-performance liquid chromatography-atmospheric pressure chemical-ionisation mass spectrometry (HPLC-APCI-MS-MS) were applied on some selected samples. Sample preparation was performed according to a technique previously described for human hair, involving incubation with Sorensen buffer and solvent extraction. Hair samples from different sites such as coat on the ne...
Alpha 2 agonists and antagonists. The alpha 2 agonists can produce reliable dose-dependent sedation and analgesia in most species. Nevertheless, they can also produce significant physiological adverse side effects depending on dose, rate, route of administration, and the concurrent use of other CNS depressants. For this reason, it may be best to use a low dose of an alpha 2 agonist as a preanesthetic agent. The alpha 2 agonists are best suited for young, healthy, exercise-tolerant patients. The combining of low doses of alpha 2, opioid, and benzodiazepine agonists results in a synergistic CNS depressant response while minimizi...
Inhibition of pseudocholinesterase activity in a 20-year-old gelding. A 20-year-old Arab crossbred gelding was examined because it had apparently suffered an overstimulation of the parasympathetic nervous system for three hours. The clinical signs consisted of hypersalivation, profuse sweating, maximal miosis, fasciculation of the muscles and lateral recumbency in combination with continuous convulsions without diarrhoea. The horse's plasma pseudocholinesterase activity was approximately 10 per cent of normal. It responded well to 10 mg atropine and 50 mg diazepam administered intravenously.
Prolongation of xylazine/ketamine induced recumbency time with temazepam in horses. Short term anaesthesia induced with xylazine and ketamine was compared to a combination of xylazine, ketamine and temazepam (a benzodiazepine) in six adult horses. Duration of recumbency was significantly prolonged when temazepam was administered with xylazine and ketamine. No significant differences in heart rate, respiratory rate, blood pressure or arterial pH, pCO2 and pO2 were seen between the xylazine and ketamine combination plus temazepam, and xylazine and ketamine combination only treated horses.
Ingestive behavior. In summary, horses spend 60% or more of their time eating when grazing or when feed is available free choice. Grasses are their preferred food, but they supplement the grass with herbs and woody plants. Sweetened mixtures of oats and corn are the most preferred concentrate. Horses can increase or decrease the time spent eating and amount eaten to maintain caloric intake. Their intake is stimulated by drugs such as diazepam and by the presence of other horses. Horses stop eating when gastric osmolality increases; increases in plasma osmolality, protein, and glucose accompany digestion. Foals ea...
Halothane-sparing effect of benzodiazepines in ponies. The halothane-sparing effect of 2 benzodiazepines, diazepam and temazepam, were investigated in ponies by measuring the minimum alveolar concentration (MAC) for halothane before and after drug administration. The MAC value for halothane decreased 29% and 16% when either 0.044 mg/kg of diazepam or 0.044 mg/kg of temazepam, respectively, was administered intravenously. Heart rate, respiratory rate, systolic and mean arterial blood pressure, and expired CO2 were also measured. No differences were present in these variables before and after drug administration nor were differences noted between th...
[Anesthesia by injection of xylazine, ketamine and the benzodiazepine derivative climazolam and the use of the benzodiazepine antagonist Ro 15-3505]. 25 horses which entered the clinic for minor surgery, received ketamine (2.2 mg/kg i.v.) for induction of anesthesia after previous sedation with xylazine (1.1 mg/kg i.v.). As soon as the horses were in the lateral recumbency, the benzodiazepine derivate climazolam was administered at a dose of 0.1 mg/kg i.v. (10 horses) or 0.2 mg/kg i.v. (15 horses). The anesthesia was maintained with repeated injections of ketamine (1.1 mg/kg i.v. every 9-12 minutes). At the end of the surgery, 20 minutes after the last ketamine injection, Ro 15-3505, a benzodiazepine antagonist, was injected at a dose of 0....
Pharmacological manipulation of sexual behaviour in stallions. Series of experiments and clinical trials were conducted to evaluate the effects of psychoneurotropic agents on sexual behaviour of stallions. The benzodiazepine derivative, diazepam (Valium), effectively reversed experimentally suppressed precopulatory arousal and response. Diazepam treatment also blocked the negative effect of novel environment on sexual response. The dibenzazepines imipramine and clomipramine induced erection, masturbation, and ejaculation in the absence of a sexual stimulus.
Novel environment suppression of stallion sexual behavior and effects of diazepam. Pony stallions were given sexual behavior trials in experimental "home" and "novel" environments, similar in all major features except location. In the novel environment, erection latency was increased and erection time decreased. Treatment with an anxiolytic benzodiazepine derivative (diazepam) appeared to block these effects.
Conditioned suppression of sexual behavior in stallions and reversal with diazepam. Sexual behavior dysfunction unaccompanied by detectable physical or endocrine abnormality is an important cause of reproductive failure among domestic stallions. Several authors have suggested that such dysfunction may be psychogenic, related to negative experience associated with intense handling and training. An experimental model of experience-related dysfunction was developed by exposing pony stallions to erection-contingent aversive conditioning. This resulted in rapid, specific suppression of sexual arousal and response similar to spontaneously occurring dysfunction. Subsequently, treatm...
Stimulation of food intake in horses by diazepam and promazine. In two adult horses doses of 0.02-0.03 mg/kg diazepam, intravenously, increased 1 hr intake 54-75% above control levels. Intake was stimulated when the diet was a high grain, calorically dense one and also when the diet was a high fiber, calorically dilute one. Two young rapidly growing weanling horses showed an even more pronounced stimulation of intake. Following diazepam 1 hr intake was increased 105-240% above control lelvels. Promazine at a dose of 0.5 mg/kg also stimulated intake in adult horses, but not as markedly as did diazepam. A transquilizer and a neuroleptic appear to have a stim...
[Effect of tranquilizer doping on the muscular activity of the sport horse. II. — Diazepam (author’s transl)]. The practise of repeated doping of the sport horse led us to examine its effects on the health of the animal, and particularly on muscular activity. The main doping agent used at present (acepromazine) has already been studied (COURTOT et al., 1974). In this paper, we study the secondary effects of diazepam, a derivative of the benzodiazepine series, which is being used more and more frequently on horses. In treated animals as compared to controls, we observe: -- a slight respiratory depression related solely to effort, -- an increase in seric creatine phosphokinase rate with no apparent relat...