Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 88
Rev. bras. psiquiatr ; 41(2): 168-178, Mar.-Apr. 2019. tab
Article in English | LILACS | ID: biblio-990820


Objective: Anxiety disorders are highly prevalent and the efficacy of the available anxiolytic drugs is less than desired. Adverse effects also compromise patient quality of life and adherence to treatment. Accumulating evidence shows that the pathophysiology of anxiety and related disorders is multifactorial, involving oxidative stress, neuroinflammation, and glutamatergic dysfunction. The aim of this review was to evaluate data from animal studies and clinical trials showing the anxiolytic effects of agents whose mechanisms of action target these multiple domains. Methods: The PubMed database was searched for multitarget agents that had been evaluated in animal models of anxiety, as well as randomized double-blind placebo-controlled clinical trials of anxiety and/or anxiety related disorders. Results: The main multitarget agents that have shown consistent anxiolytic effects in various animal models of anxiety, as well in clinical trials, are agomelatine, N-acetylcysteine (NAC), and omega-3 fatty acids. Data from clinical trials are preliminary at best, but reveal good safety profiles and tolerance to adverse effects. Conclusion: Agomelatine, NAC and omega-3 fatty acids show beneficial effects in clinical conditions where mainstream treatments are ineffective. These three multitarget agents are considered promising candidates for innovative, effective, and better-tolerated anxiolytics.

Humans , Animals , Anxiety Disorders/drug therapy , Acetylcysteine/pharmacology , Anti-Anxiety Agents/pharmacology , Fatty Acids, Omega-3/pharmacology , Hypnotics and Sedatives/pharmacology , Acetamides/pharmacology , Neuroimmunomodulation/drug effects , Oxidative Stress/drug effects , Disease Models, Animal , Glutamine/drug effects
Acta cir. bras ; 33(4): 314-323, Apr. 2018. tab
Article in English | LILACS | ID: biblio-886285


Abstract Purpose: To evaluate the effects of single intravenous administration of Dexmedetomidine (DEX) on hemodynamics in rabbits. Methods: A total of 32 New Zealand white rabbits were randomly divided into the control group (Group C), Group D1 (2.75 μg/kg), Group D2 (5.5 μg/kg), and Group D3 (8.25 μg/kg) to compare systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), central venous pressure (CVP), left ventricular systolic pressure (LVSP), left ventricular end-stage diastolic pressure (LVEDP), left ventricular developmental pressure (LVDP), +dp/dtmax, -dp/dtmax, and t-dp/dtmax at different time points. Results: The levels of SBP, DBP, HR, LVSP, and LVEDP in Group D1, D2, and D3 were lower than that of Group C from T1 to T5 (P<0.05), but there was no significant difference at T6 and T7 (P>0.05). Compared with T0, the levels of SBP, DBP, HR, LVSP, LVEDP, and left arterial pressure (LAP) from T1 to T7 were decreased (P<0.05), but there was no significant difference in the other indexes (P>0.05). Conclusion: Dexmedetomidine can decrease blood pressure and heart rate in rabbits in a dose-dependent manner, but there is no effect on the myocardial systolic and diastolic function.

Animals , Male , Rats , Dexmedetomidine/pharmacology , Hemodynamics/drug effects , Hypnotics and Sedatives/pharmacology , Reference Values , Time Factors , Random Allocation , Reproducibility of Results , Dexmedetomidine/blood , Heart Function Tests , Heart Ventricles/drug effects , Hemodynamics/physiology , Hypnotics and Sedatives/blood
Rev. bras. anestesiol ; 68(1): 69-74, Jan.-Feb. 2018. tab, graf
Article in English | LILACS | ID: biblio-897807


Abstract Introduction Propofol and Ephedrine are commonly used during anesthesia maintenance, the former as a hypnotic agent and the later as a vasopressor. The addition of propofol to ephedrine or administration of ephedrine before propofol injection is useful for decreasing or preventing propofol related hemodynamic changes and vascular pain. This in vitro study evaluated the antibacterial effect on common hospital-acquired infection pathogens of ephedrine alone or combined with propofol. Material and method The study was performed in two stages. In the first, the Minimum Inhibitory Concentration of propofol and ephedrine alone and combined was calculated for Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Pseudomonas aeruginosa, and a clinical isolate of Acinetobacter spp. at 0, 6, 12 and 24 h, using the microdilution method. In the second stage, the same drugs and combination were used to determine their effect on bacterial growth. Bacterial solutions were prepared at 0.5 MacFarland in sterile 0.9% physiological saline and diluted at 1/100 concentration. Colony numbers were measured as colony forming units.mL-1 at 0, 2, 4, 6, 8, 10 and 12th hours. Results Ephedrine either alone or combined with propofol did not have an antimicrobial effect on Escherichia coli, Enterococcus faecium, or Pseudomonas aeruginosa and this was similar to propofol. However, ephedrine alone and combined with propofol was found to have an antimicrobial effect on Staphylococcus aureus and Acinetobacter species at 512 mcg.mL-1 concentration and significantly decreased bacterial growth rate. Conclusion Ephedrine has an antimicrobial activity on Staphylococcus aureus and Acinetobacter species which were frequently encountered pathogens as a cause of nosocomial infections.

Resumo Introdução Propofol e efedrina são fármacos comumente usados durante a manutenção da anestesia, o primeiro como agente hipnótico e o segundo como vasopressor. A adição de propofol à efedrina ou a administração de efedrina antes da injeção de propofol é útil para diminuir ou prevenir alterações hemodinâmicas e dor vascular relacionadas ao propofol. Este estudo in vitro avaliou o efeito antibacteriano de efedrina, isolada ou em combinação com propofol, em patógenos comuns implicados em infecção hospitalar. Material e método O estudo foi feito em duas etapas. Na primeira, a concentração inibitória mínima (CIM) de propofol e de efedrina isolada e em combinação foi calculada para Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Pseudomonas aeruginosa e um isolado clínico de Acinetobacter spp às 0, 6, 12 e 24 horas, com o método de microdiluição. Na segunda etapa, o mesmo fármaco e sua combinação foram usados para determinar seus efeitos no crescimento bacteriano. As soluções bacterianas foram preparadas em soro fisiológico a 0,9% em 0,5 McFarland e diluídas a uma concentração de 1/100. Os números das colônias foram medidos como ufc.mL-1 às 0, 2, 4, 6, 8, 10 e 12 horas. Resultados Efedrina isolada ou em combinação com propofol não apresentou efeito antimicrobiano sobre E. coli, E. faecium ou P. aeruginosa, um resultado semelhante ao de propofol. Porém, efedrina isolada e em combinação com propofol apresentou efeito antimicrobiano sobre Staphylococcus aureus e Acinetobacter spp, em concentração de 512 mcg.mL-1, e redução significativa da taxa de crescimento bacteriano. Conclusão Efedrina tem atividade antimicrobiana em S. aureus e Acinetobacter spp, patógenos frequentemente identificados como causa de infecções nosocomiais.

Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Vasoconstrictor Agents/pharmacology , Acinetobacter/drug effects , Propofol/pharmacology , Enterococcus faecium/drug effects , Ephedrine/pharmacology , Hypnotics and Sedatives/pharmacology , Vasoconstrictor Agents/administration & dosage , Microbial Sensitivity Tests , Propofol/administration & dosage , Ephedrine/administration & dosage , Escherichia coli/drug effects , Hypnotics and Sedatives/administration & dosage , Anti-Bacterial Agents
Braz. j. med. biol. res ; 51(4): e6803, 2018. graf
Article in English | LILACS | ID: biblio-889059


Propofol is an intravenous sedative hypnotic agent of which the growth-inhibitory effect has been reported on various cancers. However, the roles of propofol in endometrial cancer (EC) remain unclear. This study aimed to explore the effects of propofol on EC in vitro and in vivo. Different concentrations of propofol were used to treat Ishikawa cells. Colony number, cell viability, cell cycle, apoptosis, migration, and invasion were analyzed by colony formation, MTT, flow cytometry, and Transwell assays. In addition, the pcDNA3.1-Sox4 and Sox4 siRNA plasmids were transfected into Ishikawa cells to explore the relationship between propofol and Sox4 in EC cell proliferation. Tumor weight in vivo was measured by xenograft tumor model assay. Protein levels of cell cycle-related factors, apoptosis-related factors, matrix metalloproteinases 9 (MMP9), matrix metalloproteinases 2 (MMP2) and Wnt/β-catenin pathway were examined by western blot. Results showed that propofol significantly decreased colony numbers, inhibited cell viability, migration, and invasion but promoted apoptosis in a dose-dependent manner in Ishikawa cells. Moreover, propofol reduced the expression of Sox4 in a dose-dependent manner. Additionally, propofol significantly suppressed the proportions of Ki67+ cells, but Sox4 overexpression reversed the results. Furthermore, in vivo assay results showed that propofol inhibited tumor growth; however, the inhibitory effect was abolished by Sox4 overexpression. Moreover, propofol inhibited Sox4 expression via inactivation of Wnt/β-catenin signal pathway. Our study demonstrated that propofol inhibited cell proliferation, migration, and invasion but promoted apoptosis by regulation of Sox4 in EC cells. These findings might indicate a novel treatment strategy for EC.

Animals , Female , Apoptosis/drug effects , Endometrial Neoplasms/drug therapy , Hypnotics and Sedatives/pharmacology , Propofol/pharmacology , SOXC Transcription Factors/metabolism , beta Catenin/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Cell Survival/drug effects , Endometrial Neoplasms/pathology , Mice, Inbred BALB C , Neoplasm Invasiveness , Propofol/administration & dosage , Tumor Stem Cell Assay , Wnt Proteins/metabolism , Xenograft Model Antitumor Assays
Rev. bras. anestesiol ; 67(6): 600-606, Nov.-Dec. 2017. graf
Article in English | LILACS | ID: biblio-897789


Abstract Background and objectives Dexmedetomidine (DEX) has demonstrated the preconditioning effect and shown protective effects against organize injury. In this study, using A549 (human alveolar epithelial cell) cell lines, we investigated whether DEX preconditioning protected against acute lung injury (ALI) in vitro. Methods A549 were randomly divided into four groups (n = 5): control group, DEX group, lipopolysaccharides (LPS) group, and D-LPS (DEX + LPS) group. Phosphate buffer saline (PBS) or DEX were administered. After 2 h preconditioning, the medium was refreshed and the cells were challenged with LPS for 24 h on the LPS and D-LPS group. Then the malondialdehyde (MDA), superoxide dismutase (SOD), Bcl-2, Bax, caspase-3 and the cytochrome c in the A549 were tested. The apoptosis was also evaluated in the cells. Results Compare with LPS group, DEX preconditioning reduced the apoptosis (26.43% ± 1.05% vs. 33.58% ± 1.16%, p < 0.05) in the A549, which is correlated with decreased MDA (12.84 ± 1.05 vs. 19.16 ± 1.89 protein, p < 0.05) and increased SOD activity (30.28 ± 2.38 vs. 20.86 ± 2.19 protein, p < 0.05). DEX preconditioning also increased the Bcl-2 level (0.53 ± 0.03 vs. 0.32 ± 0.04, p < 0.05) and decreased the level of Bax (0.49 ± 0.04 vs. 0.65 ± 0.04, p < 0.05), caspase-3 (0.54 ± 0.04 vs. 0.76 ± 0.04, p < 0.05) and cytochrome c. Conclusion DEX preconditioning has a protective effect against ALI in vitro. The potential mechanisms involved are the inhibition of cell death and improvement of antioxidation.

Resumo Justificativa e objetivos Dexmedetomidina (DEX) demonstrou ter efeito pré-condicionante e também efeitos protetores contra lesão organizada. Neste estudo, com células A549 (células epiteliais alveolares humanas), investigamos se o pré-condicionamento com DEX proporcionaria proteção contra lesão pulmonar aguda (LPA) in vitro. Métodos Células A549 foram aleatoriamente distribuídas em quatro grupos (n = 5): controle, DEX, lipopolissacarídeos (LPS) e D-LPS (DEX + LPS). Administramos solução de PBS (tampão fosfato-alcalino) ou DEX. Após 2 h de pré-condicionamento, o meio foi renovado e as células desafiadas com LPS por 24 h nos grupos LPS e D-LPS. Em seguida, malondialdeído (MDA), superóxido dismutase (SOD), Bcl-2, Bax, caspase-3 e em A549 foram testados. Apoptose também foi avaliada nas células. Resultados Em comparação com o grupo LPS, o pré-condicionamento com DEX reduziu a apoptose (26,43% ± 1,05% vs. 33,58% ± 1,16%, p < 0,05) em células A549, o que está correlacionado com a diminuição de MDA (12,84 ± 1,05 vs. 19,16 ± 1,89 de proteína, p < 0,05) e aumento da atividade de SOD (30,28 ± 2,38 vs. 20,86 ± 2,19 de proteína, p < 0,05). O pré-condicionamento com DEX também aumentou o nível de Bcl-2 (0,53 ± 0,03 vs. 0,32 ± 0,04, p < 0,05) e diminuiu o nível de Bax (0,49 ± 0,04 vs. 0,65 ± 0,04, p < 0,05), caspase-3 (0,54 ± 0,04 vs. 0,76 ± 0,04, p < 0,05) e citocromo c. Conclusão O pré-condicionamento com DEX tem efeito protetor contra LPA in vitro. Os potenciais mecanismos envolvidos são inibição da morte celular e melhoria da antioxidação.

Humans , Lipopolysaccharides/adverse effects , Dexmedetomidine/pharmacology , Alveolar Epithelial Cells/drug effects , Hypnotics and Sedatives/pharmacology , Random Allocation , Cells, Cultured , Lipopolysaccharides/antagonists & inhibitors
Bol. latinoam. Caribe plantas med. aromát ; 16(6): 547-555, nov. 2017. tab, graf
Article in English | LILACS | ID: biblio-914928


Species of the genus Tabebuia are used in traditional medicine and are reported in the literature for their properties against various diseases. The objective of this study was to evaluate the antipyretic, sedative and hypnotic activities of methanol extract of Tabebuia hypoleuca stems (THME) using the Brewer's yeast induced pyrexia, Open field and Sodium thiopental-induced sleeping time tests, respectively. In the Brewer's yeast induced pyrexia test, THME at 500 mg/kg produced a significant (p<0.001) decrease of the fever as from the first hour after administration and was sustained for 4 h. In the Open-field test, THME did not cause any significant change in the number of crossings, rearing, preening and defecation, and either in the time of immobility. Moreover, THME did not produce changes in neither the sleeping latency nor the sleeping time induced by sodium thiopental. These results showed that THME administered orally at 500 mg/kg exerts antipyretic activity, probably mediated by the inhibition of the enzyme cyclooxygenase-2. This study also showed that THME does not exert sedative and hypnotic effects at the doses tested.

Especies del género Tabebuia se utilizan en la medicina tradicional y se reportan en la literatura por sus propiedades contra diversas enfermedades. El objetivo de este estudio fue evaluar la actividad antipirética, sedante e hipnótica del extracto metanólico de los tallos de Tabebuia hypoleuca (THME) utilizando las pruebas de pirexia inducida por levadura de cerveza, campo abierto y tiempo de sueño inducido por tiopental sódico respectivamente. En el ensayo de pirexia inducida por levadura de cerveza, THME a 500 mg/kg produjo una reducción significativa (p<0.001) de la fiebre a partir de la primera hora después de la administración y se mantuvo durante cuatro horas. En el ensayo de campo abierto, THME no causó ningún cambio significativo en el número de cruces, levantamientos, acicalamientos y defecación, ni en el tiempo de inmovilidad. Además, THME no produjo cambios ni en la latencia de sueño, ni en el tiempo de sueño inducido por tiopental sódico. Estos resultados mostraron que THME administrado oralmente en dosis de 500 mg/kg posee actividad antipirética, mediado probablemente a la inhibición de la enzima ciclooxigenasa-2. Este estudio también demostró que THME no posee actividad sedante e hipnótica en las dosis ensayadas.

Animals , Male , Rats , Antipyretics/pharmacology , Hypnotics and Sedatives/pharmacology , Plant Extracts/pharmacology , Tabebuia/chemistry , Methanol , Rats, Sprague-Dawley
Rev. bras. psiquiatr ; 39(3): 228-236, July-Sept. 2017. graf
Article in English | LILACS | ID: biblio-899351


Objective: Sedation/somnolence are major side effects of pharmacotherapies for depression, and negatively affect long-term treatment compliance in depressed patients. Use of mirtazapine (MIR), an atypical antidepressant approved for the treatment of moderate to severe depression with comorbid anxiety disorders, is associated with significant sedation/somnolence, especially in short-term therapy. Nonetheless, studies with human subjects suggest that MIR-induced sedation is transient, especially when high and repeated doses are used. The purpose of this study was to explore the effects of acute and chronic administration of different doses of MIR on sedation in the rat. Methods: Assessment of sedation was carried out behaviorally using the rotarod, spontaneous locomotor activity, and fixed-bar tests. Results: A 15-mg/kg dose of MIR induced sedative effects for up to 60 minutes, whereas 30 mg/kg or more produced sedation within minutes and only in the first few days of administration. Conclusion: These results suggest that 30 mg/kg is a safe, well-tolerated dose of MIR which generates only temporary sedative effects.

Animals , Male , Hypnotics and Sedatives/pharmacology , Locomotion/drug effects , Mianserin/analogs & derivatives , Antidepressive Agents, Tricyclic/pharmacology , Time Factors , Trazodone/administration & dosage , Trazodone/pharmacology , Body Weight/drug effects , Rats, Wistar , Rotarod Performance Test/methods , Dose-Response Relationship, Drug , Mirtazapine , Mianserin/administration & dosage , Mianserin/pharmacology , Antidepressive Agents, Tricyclic/administration & dosage
Rev. bras. anestesiol ; 67(2): 193-198, Mar.-Apr. 2017. tab, graf
Article in English | LILACS | ID: biblio-843384


Abstract Background and objectives: Sevoflurane is often used in pediatric anesthesia and is associated with high incidence of psychomotor agitation. In such cases, dexmedetomidine (DEX) has been used, but its benefit and implications remain uncertain. We assessed the effects of DEX on agitation in children undergoing general anesthesia with sevoflurane. Method: Meta-analysis of randomized clinical and double-blind studies, with children undergoing elective procedures under general anesthesia with sevoflurane, using DEX or placebo. We sought articles in English in PubMed database using the following terms: Dexmedetomidine, sevoflurane (Methyl Ethers/sevoflurante), and agitation (Psychomotor Agitation). Duplicate articles with children who received premedication and used active control were excluded. It was adopted random effects model with DerSimonian-Laird testing and odds ratio (OR) calculation for dichotomous variables, and standardized mean difference for continuous variables, with their respective 95% confidence interval (CI). Results: Of 146 studies identified, 10 were selected totaling 558 patients (282 in DEX group and 276 controls). The use of DEX was considered a protective factor for psychomotor agitation (OR = 0.17; 95% CI 0.13-0.23; p < 0.0001) and nausea and vomiting in PACU (OR = 0.49; 95% CI 0.35-0.68; p < 0.0001). Wake-up time and PACU discharge time were higher in the dexmedetomidine group. There was no difference between groups for extubation time and duration of anesthesia. Conclusion: Dexmedetomidine reduces psychomotor agitation during wake-up time of children undergoing general anesthesia with sevoflurane.

Resumo Justificativa e objetivos: Sevoflurano é frequentemente usado em anestesia pediátrica e está associado à alta incidência de agitação psicomotora ao despertar. Nesses casos a dexmedetomidina (dex) tem sido usada, porém permanecem incertos seus benefícios e suas implicações. Foram avaliados os efeitos da dex sobre a agitação no despertar de crianças submetidas à anestesia geral com sevoflurano. Método: Metanálise de ensaios clínicos randomizados e duplamente encobertos, com crianças submetidas a procedimentos eletivos sob anestesia geral com sevoflurano, que usaram dex ou placebo. Buscaram-se artigos em língua inglesa na base de dados Pubmed com termos como Dexmedetomidine, sevoflurane (Methyl Ethers/sevoflurane) e agitation (Psychomotor Agitation). Artigos duplicados, com crianças que receberam medicação pré-anestésica e que usaram controle ativo foram excluídos. Adotou-se modelo de efeitos aleatórios com testes de DerSimonian-Laird e cálculo de odds ratio (OR) para variáveis dicotômicas e diferença de média padronizada para variáveis contínuas, com seus respectivos intervalos de confiança de 95% (IC). Resultados: Dos 146 estudos identificados, 10 foram selecionados, com 558 pacientes (282 no grupo dex e 276 controles). O uso da dex foi considerado fator de proteção para agitação psicomotora (OR = 0,17; 95% IC 0,13-0,23; p < 0,0001) e para náuseas e vômitos na SRPA (OR = 0,49; 95% IC 0,35-0,68; p < 0,0001). Tempo para despertar e para alta da SRPA foram maiores no grupo dexmedetomidina. Não houve diferença entre os grupos para tempo de extubação e duração da anestesia. Conclusão: A dexmedetomidina reduz a agitação psicomotora no despertar de crianças submetidas à anestesia geral com sevoflurano.

Humans , Child , Psychomotor Agitation/prevention & control , Dexmedetomidine/administration & dosage , Methyl Ethers/adverse effects , Psychomotor Agitation/etiology , Randomized Controlled Trials as Topic , Anesthetics, Inhalation/administration & dosage , Anesthetics, Inhalation/adverse effects , Postoperative Nausea and Vomiting/prevention & control , Dexmedetomidine/pharmacology , Sevoflurane , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/pharmacology , Anesthesia, General/adverse effects , Anesthesia, General/methods , Methyl Ethers/administration & dosage
An. acad. bras. ciênc ; 89(1): 203-212, Jan,-Mar. 2017. tab, graf
Article in English | LILACS | ID: biblio-886624


ABSTRACT Linalool is the main compound of many essential oils and occurs in two isomeric forms: S-(+)- and R-(-)-linalool. This study aimed to determine if linalool isomers have different antimicrobial and anesthetic properties in fish. For this purpose, these compounds were previously isolated from Lippia alba (Mill.)N. E. Brown and Ocimum americanum L. essential oils. Antimicrobial effects were evaluated through the microdilution test against Aeromonas hydrophila, an important fish disease etiologic agent. Induction time until sedation, anesthesia and recovery time were determined in silver catfish (Rhamdia quelen) through bath exposure (60, 180, 300 or 500 μL L-1). The results showed different biological properties for the isomers being S-(+)-linalool the only active against A. hydrophila at 3.2 mg mL-1. The sedation was induced without differences between the compounds, however R-(-)-linalool promoted faster anesthesia. There were no differences regarding the recovery time of the animals exposed to the linalool isomers. Although both S-(+)- and R-(-)-linalool can be used for sedative purposes, their use in A. hydrophila infection is inadvisable due to the high effective concentration. Considering anesthesia as the main objective, the R-(-)-linalool demonstrated clear advantages at lower concentration.

Animals , Catfishes , Aeromonas hydrophila/drug effects , Monoterpenes/pharmacology , Hypnotics and Sedatives/pharmacology , Anesthetics/pharmacology , Anti-Bacterial Agents/pharmacology , Reference Values , Stereoisomerism , Time Factors , Oils, Volatile/chemistry , Microbial Sensitivity Tests , Reproducibility of Results , Ocimum/chemistry , Lippia/chemistry , Monoterpenes/isolation & purification , Monoterpenes/chemistry , Acyclic Monoterpenes
Rev. bras. anestesiol ; 66(5): 456-464, Sept.-Oct. 2016. tab, graf
Article in English | LILACS | ID: lil-794812


Abstract Background: Intra-arterial injection of medications may cause acute and severe ischemia and result in morbidity and mortality. There is no information in the literature evaluating the arterial endothelial effects of sugammadex and dexmedetomidine. The hypothesis of our study is that sugammadex and dexmedetomidine will cause histological changes in arterial endothelial structure when administered intra-arterially. Methods: Rabbits were randomly divided into 4 groups. Group Control (n = 7); no intervention performed. Group Catheter (n = 7); a cannula inserted in the central artery of the ear, no medication was administered. Group Sugammadex (n = 7); rabbits were given 4 mg/kg sugammadex into the central artery of the ear, and Group Dexmedetomidine (n = 7); rabbits were given 1 µg/kg dexmedetomidine into the central artery of the ear. After 72 h, the ears were amputated and histologically investigated. Results: There was no significant difference found between the control and catheter groups in histological scores. The endothelial damage, elastic membrane and elastic fiber damage, smooth muscle hypertrophy and connective tissue increase scores in the dexmedetomidine and sugammadex groups were significantly higher than both the control and the catheter groups (p < 0.05). There was no significant difference found between the dexmedetomidine and sugammadex groups in histological scores. Conclusion: Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. To understand the histological changes caused by sugammadex and dexmedetomidine more clearly, more experimental research is needed.

Resumo Justificativa: A injeção intra-arterial de medicamentos pode causar isquemia aguda e grave e resultar em morbidade e mortalidade. Não há informações na literatura que avaliem os efeitos endoteliais arteriais de sugamadex e dexmedetomidina. A hipótese de nosso estudo foi que dexmedetomidina e sugamadex causariam alterações histológicas na estrutura endotelial arterial quando administrados por via intra-arterial. Método: Os coelhos foram randomicamente divididos em quatro grupos: grupo controle (n = 7), sem intervenção; grupo cateter (n = 7), uma cânula foi inserida na artéria central da orelha e medicamentos não foram administrados; grupo sugamadex (n = 7), receberam 4 mg/kg de sugamadex na artéria central da orelha; grupo dexmedetomidina (n = 7), receberam 1 µg/kg de dexmedetomidina na artéria central da orelha. Após 72 horas, as orelhas foram amputadas e histologicamente examinadas. Resultados: Não houve diferença significativa entre os grupos controle e cateter referente aos escores histológicos. Os escores do dano causado ao endotélio e à membrana e fibra elásticas, da hipertrofia do músculo liso e do aumento do tecido conjuntivo foram significativamente maiores nos grupos dexmedetomidina e sugamadex do que nos grupos controle e cateter (p < 0,05). Não houve diferença significativa entre os grupos dexmedetomidina e sugamadex nos escores histológicos. Conclusão: A administração de sugamadex e dexmedetomidina a coelhos por via intra-arterial causou danos arteriais histológicos. Para entender as alterações histológicas causadas por sugamadex e dexmedetomidina com mais clareza, estudos experimentais adicionais são necessários.

Animals , Male , Endothelium, Vascular/drug effects , Dexmedetomidine/pharmacology , gamma-Cyclodextrins/pharmacology , Hypnotics and Sedatives/pharmacology , Arteries/anatomy & histology , Arteries/drug effects , Rabbits , Endothelium, Vascular/anatomy & histology , Dexmedetomidine/administration & dosage , gamma-Cyclodextrins/administration & dosage , Ear, External/blood supply , Sugammadex , Hypnotics and Sedatives/administration & dosage , Injections, Intra-Arterial , Muscle, Smooth, Vascular/anatomy & histology , Muscle, Smooth, Vascular/drug effects
Braz. j. biol ; 76(3): 757-763, tab, graf
Article in English | LILACS | ID: lil-785047


Abstract The effectiveness of menthol as anesthetic and sedative for fat snook (Centropomus parallelus) was tested at different salinities. In the first experiment, the fish were exposed to different concentrations of menthol (25, 37 and 50 mg L–1) in water at different salinities (0, 17 and 36 ppt). In the second experiment, the fish were transported for 10 hours in water with menthol at concentrations of 0, 3.7 and 7.4 mg L–1 under different salinities. Na+ and K+ ions from fish body and water were analyzed after transport. The optimal concentrations of menthol for a short handling period and surgical induction was 37 and 50 mg L–1, respectively, and these values were independent of salinity. After transport, neither mortality nor significant changes in ammonia or dissolved oxygen were observed between treatments at the different salinities. The nitrite levels were lower in freshwater than in brackish and saltwater, but did not change with mentol. The total body levels of Na+ increased with the salinity increase. Menthol is an effective anesthetic for handling of juvenile fat snook at different salinities. Menthol did not influence the measured water parameters and body ions, and it is not necessary for the transport of fat snook.

Resumo A eficácia de mentol como anestésico e sedativo para o robalo peva (Centropomus parallelus) foi testada em diferentes salinidades. No primeiro experimento, os peixes foram expostos a diferentes concentrações de mentol (25, 37 e 50 mg L–1) em diferentes salinidades na água (0, 17 e 36 ppt). No segundo experimento, os peixes foram transportados por 10 horas em água com mentol nas concentrações de 0, 3,7 e 7,4 mg L–1 sob diferentes salinidades. O Na+ e K+ do corpo do peixe e a água foram analisados após o transporte. As concentrações ideais de mentol para um período curto de manipulação e indução cirúrgica foi 37 e 50 mg/L, respectivamente, sendo esses valores independentes da salinidade da água. Após o transporte, não foi verificado mortalidades e nem alterações significativas nos níveis da amônia e oxigênio dissolvido entre os tratamentos para as diferentes salinidades. Os níveis de nitrito foram mais baixos em água doce do que em água salobra e água salgada, mas não se alterou com o mentol. Os níveis corporais de Na+ e K+ aumentaram com o aumento da salinidade. Mentol é um eficaz anestésico para manipulação de robalo peva juvenil em diferentes salinidades. Mentol não influenciou os parâmetros de medição de água e íons do corpo, e não é necessário para o transporte de robalo peva.

Animals , Transportation/methods , Perciformes/surgery , Perciformes/metabolism , Salinity , Menthol/pharmacology , Brazil , Dose-Response Relationship, Drug , Hypnotics and Sedatives/pharmacology , Anesthetics/pharmacology
Rev. bras. anestesiol ; 66(3): 231-236, May.-June 2016. tab
Article in English | LILACS | ID: lil-782881


ABSTRACT Colonoscopy is one of the most common procedures. Sedation and analgesia decrease anxiety and discomfort and minimize risks. Therefore, patients prefer to be sedated when undergoing examination, although the best combination of drugs has not been determined. The combination of opioids and benzodiazepines is used to relieve the patient's pain and discomfort. More recently, propofol has assumed a prominent position. This randomized prospective study is unique in medical literature that specifically compared the use of propofol and fentanyl with or without midazolam for colonoscopy sedation performed by anesthesiologists. The aim of this study was to evaluate the side effects of sedation, discharge conditions, quality of sedation, and propofol consumption during colonoscopy, with or without midazolam as preanesthetic. The study involved 140 patients who underwent colonoscopy at the University Hospital of the Federal University of Juiz de Fora. Patients were divided into two groups: Group I received intravenous midazolam as preanesthetic 5 min before sedation, followed by fentanyl and propofol; Group II received intravenous anesthesia with fentanyl and propofol. Patients in Group II had a higher incidence of reaction (motor or verbal) to the colonoscope introduction, bradycardia, hypotension, and increased propofol consumption. Patient satisfaction was higher in Group I. According to the methodology used, the combination of midazolam, fentanyl, and propofol for colonoscopy sedation reduces propofol consumption and provides greater patient satisfaction.

RESUMO A colonoscopia é um dos procedimentos mais feitos. Sedação e analgesia diminuem a ansiedade e o desconforto e minimizam riscos. Em razão disso, os pacientes preferem que o exame seja feito sob anestesia, embora não tenha sido determinada a melhor combinação de fármacos. A associação de benzodiazepínicos com opioides é usada para aliviar a dor e o desconforto do paciente. Mais recentemente, o propofol assumiu posição de destaque. Este estudo, prospectivo e randomizado, é único na literatura médica e especificamente comparou o uso do propofol e fentanil associado ou não ao midazolam na sedação para colonoscopia feita por anestesiologistas. Os objetivos do estudo foram avaliar os efeitos colaterais da sedação, as condições de alta, a qualidade da sedação e o consumo de propofol durante a colonoscopia, com ou sem o midazolam como pré-anestésico. Envolveu 140 pacientes submetidos à colonoscopia, no Hospital Universitário da Universidade Federal de Juiz de Fora. Os pacientes foram divididos em dois grupos. O Grupo I recebeu, por via endovenosa, midazolam como pré-anestésico, cinco minutos antes da sedação, seguido do fentanil e propofol. O Grupo II recebeu, por via endovenosa, anestesia com fentanil e propofol. Os pacientes do Grupo II apresentaram maior incidência de reação (motora ou verbal) à introdução do colonoscópio, bradicardia, hipotensão arterial e maior consumo de propofol. A satisfação dos pacientes foi maior no Grupo I. De acordo com a metodologia empregada, a associação de midazolam ao propofol e fentanil para sedação em colonoscopia reduz o consumo de propofol e cursa com maior satisfação do paciente.

Humans , Male , Female , Midazolam/pharmacology , Propofol/pharmacology , Fentanyl/pharmacology , Colonoscopy , Analgesics, Opioid/pharmacology , Hypnotics and Sedatives/pharmacology , Pain/prevention & control , Double-Blind Method , Prospective Studies , Patient Satisfaction/statistics & numerical data , Drug Therapy, Combination/methods , Middle Aged
Braz. j. med. biol. res ; 49(1): e4872, 2016. tab, graf
Article in English | LILACS | ID: biblio-951644


(+)-Dehydrofukinone (DHF) is a major component of the essential oil of Nectandra grandiflora (Lauraceae), and exerts a depressant effect on the central nervous system of fish. However, the neuronal mechanism underlying DHF action remains unknown. This study aimed to investigate the action of DHF on GABAA receptors using a silver catfish (Rhamdia quelen) model. Additionally, we investigated the effect of DHF exposure on stress-induced cortisol modulation. Chemical identification was performed using gas chromatography-mass spectrometry and purity was evaluated using gas chromatography with a flame ionization detector. To an aquarium, we applied between 2.5 and 50 mg/L DHF diluted in ethanol, in combination with 42.7 mg/L diazepam. DHF within the range of 10-20 mg/L acted collaboratively in combination with diazepam, but the sedative action of DHF was reversed by 3 mg/L flumazenil. Additionally, fish exposed for 24 h to 2.5-20 mg/L DHF showed no side effects and there was sustained sedation during the first 12 h of drug exposure with 10-20 mg/L DHF. DHF pretreatment did not increase plasma cortisol levels in fish subjected to a stress protocol. Moreover, the stress-induced cortisol peak was absent following pretreatment with 20 mg/L DHF. DHF proved to be a relatively safe sedative or anesthetic, which interacts with GABAergic and cortisol pathways in fish.

Animals , Sesquiterpenes/pharmacology , Stress, Physiological/drug effects , Catfishes/metabolism , Hydrocortisone/metabolism , Oils, Volatile/administration & dosage , Lauraceae/chemistry , Hydrocortisone/blood , Plant Extracts/chemistry , Flumazenil/pharmacology , GABA Modulators/pharmacology , Diazepam/pharmacology , Flame Ionization , Hypnotics and Sedatives/pharmacology , Anesthetics/pharmacology , Gas Chromatography-Mass Spectrometry
Rev. bras. anestesiol ; 65(5): 326-332, Sept.-Oct. 2015. tab, graf
Article in English | LILACS | ID: lil-763133


ABSTRACTBACKGROUND AND OBJECTIVE: Sedation in dialysis dependent end-stage renal disease patients requires caution as a result of performing high doses of sedatives and its complications. Multidrug sedation regimens might be superior and advantage on lesser drug consumption and by the way adverse events which occur easily in end-stage renal disease patients. We evaluated the effects of dexmedetomidine premedication on propofol consumption, sedation levels with Observer's Assessment of Alertness and Sedation scores and the bispectral index and the hemodynamic changes, potential side effects in geriatric patients with end-stage renal disease who underwent hip fracture surgery under spinal anesthesia.METHOD: In this randomized, controlled, double-blind study 60 elderly patients (age ≥ 65 years) with end-stage renal disease and hip fracture scheduled for anterograde femoral intramedullary nailing were assigned to groups that received either intravenous saline infusion (Group C) or dexmedetomidine 0.5 g/kg/10 min infusion for premedication (Group D). All the patients received propofol infusion after the induction of the spinal anesthesia.RESULTS: Total propofol consumption, propofol dose required for targeted sedation levels according to Observer's Assessment of Alertness and Sedation scores and bispectral index levels, recovery times were significantly lower in Group D (p < 0.001). The time to reach to Observer's Assessment of Alertness and Sedation score 4 and to achieve bispectral index ≤ 80 was significantly lower in Group C compared with Group D (p < 0.001). Adverse events were similar in both groups.CONCLUSION: Dexmedetomidine premedication lowers intraoperative propofol consumption to maintain targeted level of sedation. Therefore low dose dexmedetomidine premedication in addition to propofol infusion might be an alternative in geriatric patients with end-stage renal disease for sedation.

RESUMOJUSTIFICATIVA E OBJETIVO: A sedação em paciente dependente de diálise com doença renal em estágio terminal (DRET) requer cautela como resultado da administração de altas doses de sedativos e suas complicações. Os regimes de sedação com múltiplas drogas podem ser superiores e vantajosos em relação ao consumo menor de drogas e aos eventos adversos que ocorrem facilmente em pacientes com DEET. Avaliamos os efeitos da pré-medicação com dexmedetomidina sobre o consumo de propofol, os níveis de sedação com os escores da Observer's Assessment of Alertness and Sedation (OAA/S) e do índice bispectral (BIS), as alterações hemodinâmicas e os potenciais efeitos colaterais em pacientes geriátricos com DRET submetidos à cirurgia para fratura de quadril sob raquianestesia.MÉTODO: Neste estudo randômico, controlado e duplo-cego, 60 pacientes idosos (idade ≥ 65 anos), com DRET e fratura de quadril, agendados para fixação intramedular de haste femoral anterógrada foram designados para grupos para receberam infusão intravenosa de solução salina (Grupo C) ou pré-medicação com infusão de 0,5 mg kg/10 min de dexmedetomidina (DEX) (Grupo D). Todos os pacientes receberam infusão de propofol após a indução da raquianestesia.RESULTADOS: O consumo total de propofol, a dose de propofol necessária para os níveis-alvo de sedação de acordo com os escores da OAA/S, os valores do BIS e os tempos de recuperação foram significativamente menores no Grupo D (p < 0,001). O tempo para atingir o escore 4 na OAA/S e valores BIS ≤ 80 foi significativamente inferior no Grupo C em comparação com o Grupo D (p < 0,001). Os eventos adversos foram semelhantes em ambos os grupos.CONCLUSÃO: A pré-medicação com dexmedetomidina reduz o consumo de propofol no intraoperatório para manter o nível-alvo de sedação. Portanto, a pré-medicação com DEX em dose baixa em combinação com infusão de propofol pode ser uma opção para sedação em pacientes geriátricos com DRET.

Humans , Male , Female , Aged , Preanesthetic Medication , Propofol/administration & dosage , Anesthetics, Intravenous/administration & dosage , Dexmedetomidine/pharmacology , Hypnotics and Sedatives/pharmacology , Kidney Failure, Chronic/metabolism , Double-Blind Method , Dexmedetomidine/administration & dosage , Hypnotics and Sedatives/administration & dosage
Yonsei Medical Journal ; : 1408-1414, 2015.
Article in English | WPRIM | ID: wpr-39975


PURPOSE: Sedatives must be carefully titrated for patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) as oversedation may lead to disastrous respiratory outcomes. This study aimed to investigate the relations between the effect-site concentration (Ce) of propofol and sedation and airway obstruction levels in patients with OSAHS. MATERIALS AND METHODS: In 25 patients with OSAHS, sedation was induced by 2% propofol using target-controlled infusion. Sedation and airway obstruction levels were assessed using the Observer's Assessment of Alertness/Sedation Scale and a four-category scale, respectively. The relationships between propofol Ce and sedation and airway obstruction were evaluated using a sigmoid Emax model. Pharmacodynamic modeling incorporating covariates was performed using the Nonlinear Mixed Effects Modeling VII software. RESULTS: Increased propofol Ce correlated with the depth of sedation and the severity of airway obstruction. Predicted Ce50(m) (Ce associated with 50% probability of an effect> or =m) for sedation scores (m> or =2, 3, 4, and 5) and airway-obstruction scores (m> or =2, 3, and 4) were 1.61, 1.78, 1.91, and 2.17 microg/mL and 1.53, 1.64, and 2.09 microg/mL, respectively. Including the apnea-hypopnea index (AHI) as a covariate in the analysis of Ce50(4) for airway obstruction significantly improved the performance of the basic model (p<0.05). CONCLUSION: The probability of each sedation and airway obstruction score was properly described using a sigmoid Emax model with a narrow therapeutic range of propofol Ce in OSAHS patients. Patients with high AHI values need close monitoring to ensure that airway patency is maintained during propofol sedation.

Adult , Aged , Airway Obstruction/drug therapy , Anesthesia , Anesthetics, Intravenous/blood , Female , Humans , Hypnotics and Sedatives/pharmacology , Male , Middle Aged , Probability , Propofol/pharmacology , Sleep Apnea, Obstructive/physiopathology
Bol. latinoam. Caribe plantas med. aromát ; 12(5): 446-456, sept. 2013. ilus, tab
Article in English | LILACS | ID: lil-726545


Many plant substances are known for their interference with the central nervous system (CNS). Dioclea grandiflora Mart. Ex. Benth (Fabaceae) is a plant used in folk medicine to treat prostate disorders and kidney stones whose extracts from its seeds and root barks were reported to have a significant activity on the CNS and analgesic effect in rodents. In this study, the psychopharmacological activities of D. grandiflora were investigated, using the pods of this plant. Swiss mice were submitted to acute treatments with ethanol extract from the pods of D. grandiflora (EDgP) at doses of 75, 150 and 300 mg/kg by intraperitoneal administration followed by the evaluation of anxiety, depressant and anticonvulsant-related responses. The treatment with EDgP produced a depressant activity on the CNS and a sedative effect in mice. These findings suggest that EDgP has a central activity in mice, indicating an anxiogenic effect.

Varias sustancias de plantas son conocidas por su acción en el sistema nervioso central (SNC). La Dioclea grandiflora Mart. Ex. Benth (Fabaceae) es una planta utilizada en la medicina popular para tratar enfermedades en la próstata y piedras en los riñones, cuyos extractos de sus semillas y de las cáscaras de sus raíces presentan una actividad significativa sobre el SNC y efecto analgésico en roedores. En este estudio, las actividades psicofarmacológicas de D. grandiflora fueron investigadas, utilizando la vaina de la planta. Camudongos Swiss fueron sometidos a tratamientos agudos por la administración intraperitoneal del extracto etanólico de la vaina de D. grandiflora (EDgP) en dosis de 75, 150 y 300 mg/kg administrados intraperitonealmente seguida por la evaluación de respuestas relacionadas con la ansiedad, depresión y anticonvulsivo. El tratamiento con EDgP produjo una actividad depresora sobre el sistema nervioso central y un efecto sedante en camundongos. Estos resultados sugieren que EDgP tiene una actividad central en camundongos, indicando un efecto ansiogénico.

Animals , Mice , Analgesics/pharmacology , Dioclea/chemistry , Plant Extracts/pharmacology , Hypnotics and Sedatives/pharmacology , Central Nervous System , Ethanol
Braz. j. med. biol. res ; 46(9): 771-779, 19/set. 2013. tab, graf
Article in English | LILACS | ID: lil-686577


This study evaluated the sedative and anesthetic effects of the essential oils (EO) of Hyptis mutabilis (Rich.) Briq. and their isolated components on silver catfish (Rhamdia quelen). Quantitative chemical differences between the EOs obtained from leaves and inflorescences were verified, and a new chemotype rich in globulol was described. Although there were no significant differences in the time of induction for sedation and anesthesia between the EOs, only the leaf EO at 344 mg/L anesthetized all fish without side effects. Fractionation of the leaf EO was carried out by column chromatography. The isolated compounds [(+)-1-terpinen-4-ol and (-)-globulol] showed different activity from that detected for the leaf EO in proportional concentrations and similar sedation to a eugenol control at 10 mg/L. However, fish exposed to 1-terpinen-4-ol (3 and 10 mg/L) did not remain sedated for 30 min. Anesthesia was obtained with 83-190 mg/L globulol, but animals showed loss of mucus during induction and mortality at these concentrations. Synergism of the depressor effects was detected with the association of globulol and benzodiazepine (BDZ), compared with either drug alone. Fish exposed to BDZ or globulol+BDZ association showed faster recovery from anesthesia in water containing flumazenil, but the same did not occur with globulol. In conclusion, the use of globulol in aquaculture procedures should be considered only at sedative concentrations of 10 and 20 mg/L, and its mechanism of action seems not to involve the GABAA-BDZ system.

Animals , Anesthetics/pharmacology , Catfishes , Hypnotics and Sedatives/pharmacology , Hyptis/chemistry , Oils, Volatile/pharmacology , Analysis of Variance , Anesthetics/isolation & purification , GABA Agents/metabolism , Gas Chromatography-Mass Spectrometry , Hypnotics and Sedatives/isolation & purification , Inflorescence/chemistry , Mortality , Oils, Volatile/isolation & purification , Plant Leaves/chemistry , Statistics, Nonparametric , Sesquiterpenes/isolation & purification , Sesquiterpenes/pharmacokinetics , Terpenes/isolation & purification , Terpenes/pharmacology
Rev. bras. anestesiol ; 63(3): 249-253, maio-jun. 2013. ilus, tab
Article in Portuguese | LILACS | ID: lil-675840


JUSTIFICATIVA E OBJETIVOS: Os efeitos farmacodinâmicos dos bloqueadores neuromusculares (BNM) podem ser influenciados por diferentes drogas, entre elas os hipnóticos. O objetivo deste estudo foi avaliar a influência do propofol e do etomidato sobre o bloqueio neuromuscular produzido pelo cisatracúrio. MÉTODO: Foram incluídos 60 pacientes, ASA I e II, submetidos a cirurgias eletivas sob anestesia geral, distribuídos aleatoriamente em dois grupos de acordo com o hipnótico empregado: GI (propofol) e GII (etomidato). As pacientes receberam midazolam (0,1 por via muscular como medicação pré-anestésica, a indução foi com propofol (2,5 ou etomidato (0,3 precedido de fentanil (250 µg) e seguido de cisatracúrio (0,1 Os pacientes foram ventilados com oxigênio a 100% até a obtenção de redução de 95% ou mais na amplitude da resposta do adutor do polegar, quando foi feita a laringoscopia e a intubação traqueal. A função neuromuscular foi monitorizada com aceleromiografia. Avaliaram-se o início de ação do cisatracúrio, as condições de intubação traqueal e as repercussões hemodinâmicas. RESULTADOS: Os tempos médios e os desvios padrão para o início de ação do cisatracúrio foram: GI (86,6 ± 14,3") e GII (116,9 ± 11,6"), com diferença significativa (p < 0,0001). As condições de intubação traqueal foram aceitáveis em 100% dos pacientes do GI e em 53,3% no GII (p < 0,0001). CONCLUSÕES: A instalação do bloqueio neuromuscular com o cisatracúrio foi mais rápida e as condições de intubação traqueal foram melhores nos pacientes que receberam propofol em relação ao grupo que recebeu etomidato, sem repercussões hemodinâmicas.

BACKGROUND AND OBJECTIVE: Different drugs, including hypnotics, may influence the pharmacodynamic effects of neuromuscular blockers (NMB). The aim of this study was to evaluate the influence of propofol and etomidate on cisatracurium-induced neuromuscular blockade. METHOD: We included 60 patients, ASA I and II, undergoing elective surgery under general anesthesia in the study and randomly allocated them into two groups, according to their hypnotic drug: GI (propofol) and GII (etomidate). Patients received intramuscular (IM) midazolam (0.1 as premedication and we performed induction with propofol (2.5 or etomidate (0.3, preceded by fentanyl (250 mg) and followed by cisatracurium (0.1 The patients were ventilated with 100% oxygen until obtaining a reduction of 95% or more in the adductor pollicis response amplitude, with subsequent laryngoscopy and tracheal intubation. Neuromuscular function was monitored by acceleromyograhpy. We evaluated the onset of action of cisatracurium, tracheal intubation conditions, and hemodynamic repercussions. RESULTS: The mean time and standard deviations of cisatracurium onset were: GI (86.6 ± 14.3 s) and GII (116.9 ± 11.6 s), with a significant difference (p < 0, 0001). Intubation conditions were acceptable in 100% of GI and 53.3% of GII patients (p < 0.0001). CONCLUSION: Induction of neuromuscular blockade with cisatracurium was faster, with better intubation conditions in patients receiving propofol compared to those receiving etomidate, without hemodynamic repercussions.

JUSTIFICATIVA Y OBJETIVOS: Los efectos farmacodinámicos de los bloqueantes neuromusculares (BNM) pueden estar influenciados por diferentes fármacos, entre ellos los hipnóticos. El objetivo de este estudio, fue evaluar la influencia del propofol y del etomidato sobre el bloqueo neuromuscular producido por el cisatracurio. MÉTODO: Se incluyeron en el estudio 60 pacientes, con ASA I y II, sometidos a cirugías electivas bajo anestesia general, distribuidos aleatoriamente en dos grupos de acuerdo con el hipnótico usado: GI (propofol) y GII (etomidato). Las pacientes recibieron midazolam (0,1 por vía muscular como medicación preanestésica, la inducción fue con propofol (2,5 o etomidato (0,3 precedido de fentanilo (250 µg) y seguido de cisatracurio (0,1 Los pacientes fueron ventilados con oxígeno al 100% hasta la obtención de la reducción de un 95% o más en la amplitud de la respuesta del aductor del pulgar cuando se hizo la laringoscopia y la intubación traqueal. La función neuromuscular fue monitorizada con aceleromiografía. Se evaluaron el inicio de acción del cisatracurio, las condiciones de intubación traqueal y las repercusiones hemodinámicas. RESULTADOS: Los tiempos promedios y las desviaciones estándar para el inicio de acción del cisatracurio fueron: GI (86,6 ± 14,3") y GII (116,9 ± 11,6"), con una diferencia significativa (p < 0,0001). Las condiciones de intubación traqueal fueron aceptables en un 100% de los pacientes del GI y en 53,3% en el GII (p < 0,0001). CONCLUSIONES: La instalación del bloqueo neuromuscular con el cisatracurio fue más rápida y las condiciones de intubación traqueal fueron mejores en los pacientes que recibieron propofol con relación al grupo que recibió etomidato, sin repercusiones hemodinámicas.

Adult , Female , Humans , Atracurium/analogs & derivatives , Etomidate/pharmacology , Hypnotics and Sedatives/pharmacology , Neuromuscular Blockade , Neuromuscular Blocking Agents/pharmacology , Propofol/pharmacology , Atracurium/pharmacology , Drug Interactions , Myography/methods
Braz. j. med. biol. res ; 46(3): 263-269, 15/mar. 2013. graf
Article in English | LILACS | ID: lil-670895


The N-acylhydrazone (NAH) analogues N-methyl 2-thienylidene 3,4-benzoylhydrazine (LASSBio-785) and N-benzyl 2-thienylidene 3,4-benzoylhydrazine (LASSBio-786) were prepared from 2-thienylidene 3,4-methylenedioxybenzoylhydrazine (LASSBio-294). The ability of LASSBio-785 and LASSBio-786 to decrease central nervous system activity was investigated in male Swiss mice. LASSBio-785 or LASSBio-786 (30 mg/kg, ip) reduced locomotor activity from 209 ± 26 (control) to 140 ± 18 (P < 0.05) or 146 ± 15 crossings/min (P < 0.05), respectively. LASSBio-785 (15 or 30 mg/kg, iv) also reduced locomotor activity from 200 ± 15 to 116 ± 29 (P < 0.05) or 60 ± 16 crossings/min (P < 0.01), respectively. Likewise, LASSBio-786 (15 or 30 mg/kg, iv) reduced locomotor activity from 200 ± 15 to 127 ± 10 (P < 0.01) or 96 ± 14 crossings/min (P < 0.01), respectively. Pretreatment with flumazenil (20 mg/kg, ip) prevented the locomotor impairment induced by NAH analogues (15 mg/kg, iv), providing evidence that the benzodiazepine (BDZ) receptor is involved. This finding was supported by the structural similarity of NAH analogues to midazolam. However, LASSBio-785 showed weak binding to the BDZ receptor. LASSBio-785 or LASSBio-786 (30 mg/kg, ip, n = 10) increased pentobarbital-induced sleeping time from 42 ± 5 (DMSO) to 66 ± 6 (P < 0.05) or 75 ± 4 min (P < 0.05), respectively. The dose required to achieve 50% hypnosis (HD50) following iv injection of LASSBio-785 or LASSBio-786 was 15.8 or 9.5 mg/kg, respectively. These data suggest that both NAH analogues might be useful for the development of new neuroactive drugs for the treatment of insomnia or for use in conjunction with general anesthesia.

Animals , Male , Mice , Hydrazines/pharmacology , Hydrazones/pharmacology , Hypnotics and Sedatives/pharmacology , Motor Activity/drug effects , Receptors, GABA/drug effects , Thiophenes/pharmacology , Hydrazines/chemistry , Hydrazones/chemistry , Receptors, GABA/physiology , Thiophenes/chemistry