Made available in DSpace on 2014-06-11T19:31:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-03-06Bitstream added on 2014-06-13T19:20:12Z : No. of bitstreams: 1 mendes_mc_dr_jabo.pdf: 1115485 bytes, checksum: e823340e5516e711eac803ea3a0e9a1a (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Com base na ação do amitraz (AMZ) e da romifidina (RMF) em receptores alfa-2 adrenérgicos e nas possíveis vantagens da associação destes fármacos com agentes inalatórios para uma anestesia geral segura, compararamse os efeitos clínicos, cardiocirculatórios e hemogasométricos da infusão contínua (IC) de AMZ ou de RMF associada ao isofluorano. Relacionaram-se os efeitos observados à concentração plasmática do amitraz (CPA) e investigaram-se possíveis efeitos farmacodinâmicos do diluente lipídico (DIL) utilizado na sua formulação. A medicação pré-anestésica (MPA) intravenosa (IV) para cada grupo foi: RMF - 60 μg/kg; AMZ - 0,2 mg/kg; DIL - 60 μg/kg de RMF. Induziu-se a anestesia com midazolam (0,1 mg/kg IV) e cetamina S(+) (0,2 mg/kg IV). A manutenção foi feita com 1,3 V% de isofluorano associado às ICs (RMF - 60 μg/kg.h; AMZ - 0,2 mg/kg.h; DIL - 0,1 mL/kg.h) por 60 minutos. Um minuto após a MPA a CPA média foi 396 ng/mL, aumentando durante a IC (de 93 ng/mL para 257 ng/mL) e diminuindo na recuperação, atingindo 47 ng/mL em 60 minutos. A RMF causou boa sedação e indução, com intubação fácil; manteve a FC estável e aumentou gradualmente a PAM, alterando pouco o CO2; resultou em recuperação ideal. O AMZ causou sedação leve e manteve planos anestésicos mais superficiais do que a RMF, com hipotensão durante a IC; a indução e a intubação foram de boa qualidade; o miorrelaxamento foi maior do que com RMF; a recuperação não teve boa qualidade. O DIL não causou sedação e resultou em recuperação de má qualidade, sendo inerte em relação aos efeitos do AMZ. Concluiu-se que há possibilidade do uso clínico do AMZ, ficando indicados estudos complementares. / Based on the action of amitraz (AMZ) and romifidine (RMF) on alpha-2 adrenergic receptors and in the possible advantages of combining them with inhalation anesthetics for a safe general anesthesia, the clinical, cardiocirculatory and hemogasometric effects of the continuous infusion (CI) of AMZ or RMF in association with isoflurane anesthesia were compared. The observed effects were related to the AMZ plasmatic levels (APL). The existence of pharmacodynamic effects of the lipid vehicle (LV) used for AMZ formulation was also investigated. The intravenous (IV) pre-anesthetic medications (PAM) were: RMF - 60 μg/kg; AMZ - 0.2 mg/kg; LV - 60 μg/kg de RMF. Anesthesia was inducted with midazolam (0.1 mg/kg IV) and S-ketamine (0.2 mg/kg IV) and maintained with 1.3 V% isoflurane, in association with the CIs (RMF - 60 μg/kg.h; AMZ - 0.2 mg/kg.h; LV - 0.1 mL/kg.h) for 60 minutes. One minute after PAM, APL was 396 ng/mL. During the CI, APL increased from 93 to 257 ng/mL. On recovery, APL decreased to 47 ng/mL in 60 minutes. With RMF there were good sedation and induction and the intubation was easy; HR was stable and MAP increased, with little CO2 alterations; the recovery was ideal. AMZ had less sedative effect and reached superficial anesthesia compared to RMF, with hypotension during CI; there were good induction and easy intubation; miorelaxation was greater with AMZ than with RMF; recovery was not good. The LV did not induce sedative effects and resulted in a poor recovery; it did not influence AMZ effects. The clinical use of AMZ is possible, but further studies are indicated.

Orientador: Carlos Augusto Araújo Valadão / Banca: Helenice de Souza Spinosa / Banca: Anderson Farias / Banca: Stelio Pacca Loureiro Luna / Banca: Antonio de Queiroz Neto / Resumo: Com base na ação do amitraz (AMZ) e da romifidina (RMF) em receptores alfa-2 adrenérgicos e nas possíveis vantagens da associação destes fármacos com agentes inalatórios para uma anestesia geral segura, compararamse os efeitos clínicos, cardiocirculatórios e hemogasométricos da infusão contínua (IC) de AMZ ou de RMF associada ao isofluorano. Relacionaram-se os efeitos observados à concentração plasmática do amitraz (CPA) e investigaram-se possíveis efeitos farmacodinâmicos do diluente lipídico (DIL) utilizado na sua formulação. A medicação pré-anestésica (MPA) intravenosa (IV) para cada grupo foi: RMF - 60 μg/kg; AMZ - 0,2 mg/kg; DIL - 60 μg/kg de RMF. Induziu-se a anestesia com midazolam (0,1 mg/kg IV) e cetamina S(+) (0,2 mg/kg IV). A manutenção foi feita com 1,3 V% de isofluorano associado às ICs (RMF - 60 μg/kg.h; AMZ - 0,2 mg/kg.h; DIL - 0,1 mL/kg.h) por 60 minutos. Um minuto após a MPA a CPA média foi 396 ng/mL, aumentando durante a IC (de 93 ng/mL para 257 ng/mL) e diminuindo na recuperação, atingindo 47 ng/mL em 60 minutos. A RMF causou boa sedação e indução, com intubação fácil; manteve a FC estável e aumentou gradualmente a PAM, alterando pouco o CO2; resultou em recuperação ideal. O AMZ causou sedação leve e manteve planos anestésicos mais superficiais do que a RMF, com hipotensão durante a IC; a indução e a intubação foram de boa qualidade; o miorrelaxamento foi maior do que com RMF; a recuperação não teve boa qualidade. O DIL não causou sedação e resultou em recuperação de má qualidade, sendo inerte em relação aos efeitos do AMZ. Concluiu-se que há possibilidade do uso clínico do AMZ, ficando indicados estudos complementares. / Abstract: Based on the action of amitraz (AMZ) and romifidine (RMF) on alpha-2 adrenergic receptors and in the possible advantages of combining them with inhalation anesthetics for a safe general anesthesia, the clinical, cardiocirculatory and hemogasometric effects of the continuous infusion (CI) of AMZ or RMF in association with isoflurane anesthesia were compared. The observed effects were related to the AMZ plasmatic levels (APL). The existence of pharmacodynamic effects of the lipid vehicle (LV) used for AMZ formulation was also investigated. The intravenous (IV) pre-anesthetic medications (PAM) were: RMF - 60 μg/kg; AMZ - 0.2 mg/kg; LV - 60 μg/kg de RMF. Anesthesia was inducted with midazolam (0.1 mg/kg IV) and S-ketamine (0.2 mg/kg IV) and maintained with 1.3 V% isoflurane, in association with the CIs (RMF - 60 μg/kg.h; AMZ - 0.2 mg/kg.h; LV - 0.1 mL/kg.h) for 60 minutes. One minute after PAM, APL was 396 ng/mL. During the CI, APL increased from 93 to 257 ng/mL. On recovery, APL decreased to 47 ng/mL in 60 minutes. With RMF there were good sedation and induction and the intubation was easy; HR was stable and MAP increased, with little CO2 alterations; the recovery was ideal. AMZ had less sedative effect and reached superficial anesthesia compared to RMF, with hypotension during CI; there were good induction and easy intubation; miorelaxation was greater with AMZ than with RMF; recovery was not good. The LV did not induce sedative effects and resulted in a poor recovery; it did not influence AMZ effects. The clinical use of AMZ is possible, but further studies are indicated. / Doutor

En la primera parte se evalúan los efectos sedantes, adversos y sobre el sistema cardiorrespiratorio de la romifidina en la especie felina. Se utilizaron cinco y se realizaron 4 grupos experimentales: romifidina 200, 400 y 600 μg/Kg IM y medetomidina 80 μg/Kg IM. En la segunda parte se evalúa la combinación romifidina/ketamina en la especie felina. Se utilizaron siete gatos. Se realizaron 5 grupos experimentales: Romifidina 100 y 200 μg/Kg con ketamina 7,5 y 10 mg/Kg y romifidina 200 μg/Kg con ketamina 5 mg/Kg. Se monitorizó el grado de relajación muscular, la respuesta al clampado y el sistema cardiorrespiratorio durante 60 minutos. Los resultados obtenidos sugieren que el efecto sedante de la romifidina puede ser útil en premedicación anestésica y en intervenciones no dolorosas. La romifidina potencia la actividad de la ketamina, y su combinación compensa parcialmente los efectos adversos de la misma. / Firstly, the sedative, cardio respiratory and adverse effects produced for the administration of romifidine were evaluated in five cats. Four experimental groups were established: romifidine 200, 400 and 600 μg/Kg in comparison to medetomidine 80 μg/Kg. Secondly, the anaesthetic quality, cardiorespiratory and adverse effects produced by the mixture of romifidine and ketamine were studied in seven cats. Five experimental groups were established: Romifidine 100 μg/Kg and ketamine 7.5 mg/Kg and 10 mg/Kg, romifidine 200 μg/Kg and ketamine 5 mg/Kg, 7.5 mg/Kg, and 10 mg/Kg. The drugs were administred intramuscularly. The results of this experience suggest that romifidine could be a good alternative as a sedative for the development of non-painful procedures, as well as anaesthetic pre-medication. Romifidine enhances the anaesthetic effects of ketamine and the disadvantages of each compound are well remedied in the combination. This mixture in combination wit h opioids could be a chance to perform minor surgery procedures.

Alpha 2 agonists are frequently used in equine medicine. This study focused primarily on α2 agonist-induced changes in PCV and TSP. A secondary aim of this study was to investigate the effects of α2 agonist on selected serum biochemical parameters and splenic size in order to identify potential causes for the changes seen in PCV and TSP. Four healthy adult mares were treated in a blinded, randomized, cross-over design with a single dose of xylazine (0.5 mg/kg), romifidine (0.04 mg/kg) or detomidine (0.01 mg/kg) intravenously, or detomidine (0.02 mg/kg) intramuscularly. A 1-week washout period was allowed between treatments. Haematology, TSP, COP, plasma osmolality, glucose, BUN, serum lactate, electrolytes, venous blood pH, ultrasonographic splenic size and degree of clinical sedation were evaluated at different time points post-injection and compared to baseline values. All treatments induced similar clinical sedation in the mares. A significant change over time in PCV and TSP following each treatment was identified, with overall median (range) maximal reductions compared to baseline of 20.9% (12.9 - 27.3%) and 5.8% (3.0 - 10.3%), respectively. Additionally, changes over time were significant for RBC count, BUN, COP and Ca2+, which decreased; and glucose, plasma osmolality, Na+ and splenic size, which increased, when compared to baseline. There was no significant main effect of treatment on PCV, TSP or any other parameters measured except for glucose. This study concluded that changes in PCV, TSP and other biochemical parameters induced by α2 agonists should be taken into consideration when assessing critically ill horses that received these drugs. There was evidence of splenic RBC sequestration as well as fluid shifts; therefore, the results suggest a multifactorial cause for the changes in PCV and TSP. / Dissertation (MSc)--University of Pretoria, 2011. / Companion Animal Clinical Studies / unrestricted