Chemical restraint of coatis by the association of Detomidine, Tiletamine and Zolazepam, in allometrically scaled dosages / [Contenção farmacológica de quatis pela associação de detomidina, tiletamina e zolazepam, em doses calculadas por extrapolação alométrica]

Ten free-living adult coatis (two males and eight females) were chemically restrained with "ZAD-50", a concentrated formulation prepared with the dehydrated content of a Zoletil/50® vial diluted with 0.25mL of 1% atropine, 0.265mL of Dormiun-V®, and 2.2mL of distilled water, being exactly 3.0mL. The formula was administered to each animal previously captured and physically contained with a net. The loss of righting reflex (RR) occurred at 2.3±0.8 minutes post-injection (MPI), with anesthesia beginning at 4.4±2.7 MPI. Myorelaxant and analgesia were considered excellent at all moments of the evaluation. Conscious reactions were observed at 78.7±22.2 MPI, the return of the RR occurred at 101 ± 18 MPI, and normal ambulation was acquired at 137.0±31.0 MPI. The mean values ​​of physiological parameters measured every 10 minutes between 10 and 50 MPI were 152.2 heartbeats per minute for heart rate, 66.4 respiratory movements per minute for respiratory rate, 39.2oC for rectal temperature, 86.2% for SpO2 and 14.6 mmHg for systolic blood pressure. In the same times, the EEG registered sinus rhythm. No adverse reactions were observed, and the assessed vital parameters remained compatible with the state of chemical restraint.(AU)

Dez quatis adultos de vida livre (dois machos e oito fêmeas) foram contidos empregando-se a formulação denominada "ZAD-50". A fórmula foi preparada a partir do conteúdo desidratado de um frasco de Zoletil/50® diluído em 0,25mL de atropina a 1%, 0,265mL de Dormiun-V® e 2,2mL de água destilada, obtendo-se volume final de 3,0mL. A associação foi administrada, por via intramuscular, a cada animal capturado e contido fisicamente com puçá, em dose calculada por meio de extrapolação alométrica interespecífica. A perda da reação postural de endireitamento (RPE) ocorreu aos 2,3±0,8 minutos pós-injeção (MPI), observando-se início da anestesia aos 4,4±2,7 MPI. Miorrelaxamento e analgesia foram considerados excelentes em todos os momentos da avaliação. Reações conscientes foram observadas aos 78,7±22,2 MPI, o retorno da RPE ocorreu aos 101±18 MPI, e os animais voltaram à ambulação normal aos 137,0±31,0 MPI. Os valores médios dos parâmetros fisiológicos mensurados a cada 10 minutos entre 10 e 50 MPI foram 152,2 batimentos por minuto para frequência cardíaca, 66,4 movimentos por minuto para frequência respiratória, 39,2oC para temperatura retal, 86,2% para saturação parcial de oxigênio e 14,6mmHg para pressão arterial sistólica. Nesses tempos, observou-se ritmo sinusal no eletrocardiograma, e não foram observadas reações adversas.(AU)

Identification of Tiletamine, Zolazepam and Their Metabolites in Drug Facilitated Sexual Assault by GC-QTOF-MS.

ABSTRACT: Objective To identify tiletamine, zolazepam and their metabolites in samples from drug facilitated sexual assault by gas chromatography-quadrupole time of flight mass spectrometry （GC-QTOF-MS）. Methods Urine samples of victims were collected, and detected by GC-QTOF-MS after liquid-liquid extraction and concentration. The molecular formula of fragments ions was identified by determination of accurate mass numbers, to detect related substances. Results Tiletamine, zolazepam, three metabolites of tiletamine and two metabolites of zolazepam were identified in urine samples from actual cases. Conclusion GC-QTOF-MS provides abundant and accurate information of fragment ions mass numbers, which can be used for qualitative identification of tiletamine, zolazepam and their metabolites in drug facilitated sexual assault.

Avaliação do perfil eletrocardiográfico pré e trans-anestesia em lobos-guará / Evaluation of electrocardiographic profile pre and trans-anesthesic in maned wolves

O presente estudo tem como objetivo avaliar o efeito da administração do Zolazepam/Tiletamina nas funções cardiorrespiratórias e eletrocardiográficas em lobos-guará (Chrysocyon brachyurus) mantidos em cativeiro. Foram utilizados dez lobos-guará clinicamente saudáveis (seis machos e quatro fêmeas), com média de peso 23,5±3,5kg, e idade de 6,5±2,8 anos. Os lobos eram mantidos em cativeiro e foram capturados pelos tratadores, proporcionando o mínimo de estresse possível para avaliação dos parâmetros pré-anestésicos. Foram avaliadas frequência cardíaca e respiratória, temperatura retal, pressão arterial média e eletrocardiografia. Após coleta dos parâmetros fisiológicos e eletrocardiográficos pré-anestesia, foi administrada a dose de 5,1±0,7mg/kg de Zolazepam/Tiletamina intramuscular. Depois da anestesia, colocaram-se os eletrodos do eletrocardiograma nos membros torácicos e pélvicos. Os animais eram monitorados durante uma hora, sendo que, a cada 10 minutos, era realizado o registro dos valores eletrocardiográficos, assim como os valores dos parâmetros fisiológicos e cardiorrespiratórios. Os resultados mostraram alteração significativa na amplitude da onda P entre 10 a 50 minutos pós-anestesia. Frequência cardíaca (153±20bmp), frequência respiratória (29±6mpm), temperatura corporal (38,4±1oC), pressão arterial média (114±20mmHg) e as outras variáveis eletrocardiográficas não apresentaram alterações. O aumento da amplitude da onda P nos animais deste trabalho sugeriu um aumento atrial, oriundo de doenças cardíacas ou simplesmente pelo aumento da frequência cardíaca durante a contenção.

The aim of this study was to assess the effects of the anesthetic combination of Tiletamine/Zolazepam on the cardiorespiratory function and electrocardiographic profile in captive maned wolves (Chrysocyon brachyurus). Ten maned wolves were used in this study (6 males and 4 females). All animals were healthy, with an average body weight of 23.5±3.5kg, and age of 6.5±2.8years. The wolves were conditioned to be physically restrained by their keepers in order to minimize stress during assessment of pre-anesthetic parameters. Data on heart and respiratory rates, rectal temperature, mean arterial blood pressure and electrocardiography were collected. Pre-anesthetic physiological an eletrocardiographic parameters were collected before the administration of 5.1±0.73mg/kg Tiletamine/Zolazepam intramuscularly. Under anesthesia, electrocardiogram electrodes were placed on thoracic and pelvic limbs and eletrocardiographic data was recorded every 10 minutes for approximately one hour, totaling 6 electrocardiograms. Heart rate 153±20bmp, respiratory rate 29±6mpm, rectal temperature 38,4±1oC, mean arterial blood pressure 114±20mmHg, and the other electrocardiographic parameters did not change; however, the P wave amplitude changed from 10 to 50 minutes after anesthesia. The increase in the P wave on the animals in this study suggested an atrial increase, probably due to cardiac disease or just by increasing the heart rate during the capture.

Determination of constituents of Telazol--tiletamine and zolazepam by a gas chromatography/mass spectrometry-based method.

Tiletamine and zolazepam injection (Telazol) is used in veterinary surgical practice to induce short-term anesthesia and also to immobilize wild animals. The present work describes a sensitive method to measure tiletamine and zolazepam concentrations in plasma by means of GC/EI-MS on a 5% phenyl/95% methylpolysiloxane column. A simple liquid extraction procedure with ethyl acetate was used to isolate the two compounds and the same were separated and analyzed by GC/MS without derivatization. A formal validation of the assay demonstrated good accuracy and precision for both tiletamine (98-100.8%; C.V.total < 6.7%) and zolazepam (98.3-103.4; C.V.total < 13.2%). With 500 microl of plasma, the limits of quantification for both tiletamine and zolazepam were found to be 10 ng/ml. Both compounds were stable after three freeze-thaw cycles. The assay was used to analyze plasma samples collected from a pig after intramuscular administration of 10 mg/kg of Telazol. The plasma concentration-time profile of tiletamine and zolazepam from this representative pig is also provided.

Pharmacokinetics and tissue residues of Telazol in free-ranging polar bears.

A pharmacokinetic and tissue residue study was conducted to assess the risks associated with human consumption of polar bears in arctic Canada that have been exposed to the immobilizing drug Telazol, a mixture of tiletamine hydrochloride and zolazepam hydrochloride. Twenty-two bears were remotely injected with about 10 mg/kg of Telazol. Following immobilization, serum samples were collected serially at regular intervals until the bears awakened. Sixteen of the bears were relocated and killed under permit by local hunters at various times from 0.5 to 11 days after dosing. Serum, kidney, muscle and adipose tissue samples were collected immediately after death. All samples were stored at -70 C until analysis by HPLC. The concentration-time data of tiletamine and zolazepam in serum during the immobilization period were fitted to curves by computer and the pharmacokinetic parameters assessed. In addition, the serum and tissue samples collected at the time of death were analyzed for both parent drugs, for one metabolite of tiletamine (CI-398), and for three metabolites of zolazepam (metabolites 1, 2 and 4). A one-compartment model with first-order absorption and elimination best fit the time-series data for the drugs in serum during the immobilization period. This model gave half-lives (mean +/- SE) for tiletamine and zolazepam of 1.8+/-0.2 h and 1.2+/-0.08 h, respectively, clearance values of 2.1+/-0.3 l x h(-1) x kg(-1) and 1.1+/-0.1 l x h(-1) x kg(-1), and volumes of distribution of 5.2+/-0.6 l/kg and 1.8+/-0.2 l/kg. The concentrations of both drugs and their metabolites declined rapidly to trace levels by 24 h post-dosing, although extremely low concentrations of some metabolites were encountered sporadically over the entire sampling period. In particular, zolazepam metabolite 2, remained detectable in fat and muscle tissue at the end of the study, 11 days after dosing. It was concluded that during immobilization, both tiletamine and zolazepam levels decline rapidly in a monoexponential fashion, and their pharmacokinetic parameters in polar bears are similar to those observed in other species. Tissue levels of the drugs and their metabolites declined sufficiently rapidly that individuals eating meat from exposed bears would be unlikely to experience pharmacological effects from the drugs. Nevertheless, slight exposure to the drugs and/or their metabolites might be possible for an indeterminate time after dosing.

A fatality related to the veterinary anesthetic telazol.

A 45-year-old male veterinarian was found dead in bed. Police investigation showed no evidence of trauma or other suspicious circumstances. Autopsy was unremarkable except for cardiomegaly and hepatosplenomegaly. Toxicological analysis revealed the presence of Telazol and ketamine. Telazol is a veterinary anesthetic agent that is composed of equal parts of tiletamine and zolazepam. Tiletamine is a disassociative anesthetic similar to ketamine and phencyclidine, and zolazepam is a diazepine derivative tranquilizer used to minimize the muscle hypertonicity and seizures associated with tiletamine. Quantitation of tiletamine and zolazepam was performed using gas chromatography-mass spectrometry in the selected ion monitoring mode following a solid-phase extraction. Postmortem blood, urine, and liver concentrations of tiletamine were 295 ng/mL, 682 ng/mL, and 196 ng/g, respectively, whereas postmortem concentrations of zolazepam for the same tissues were 1.71 microg/mL, 1.33 microg/mL, and 15.5 microg/g, respectively. Blood and urine ketamine levels were 37 ng/mL and 381 ng/mL, respectively. The cause of death was ruled an acute mixed drug intoxication of tiletamine, zolazepam, and ketamine with the manner of death ruled as unclassified.