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[PMID]:24796695
[Au] Autor:Zhang H; Xu X; Chen Y; Qiu Y; Liu X; Liu BF; Zhang G
[Ad] Endereço:Systems Biology Theme, Huazhong University of Science and Technology, Wuhan, China.
[Ti] Título:Synthesis and evaluation of fluorine-substituted phenyl acetate derivatives as ultra-short recovery sedative/hypnotic agents.
[So] Source:PLoS One;9(5):e96518, 2014.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Soft drugs are molecules that are purposefully designed to be rapidly metabolized (metabolically labile). In anesthesia, the soft drug is useful because it enables precise titration to effect and rapid recovery, which might allow swift and clear-headed recovery of consciousness and early home readiness. Propofol may cause delayed awakening after prolonged infusion. Propanidid and AZD3043 have a different metabolic pathway compared to propofol, resulting in a short-acting clinical profile. Fluorine imparts a variety of properties to certain medicines, including an enhanced absorption rate and improved drug transport across the blood-brain barrier. We hypothesized that the introduction of fluorine to the frame structure of propanidid and AZD3043 would further accelerate the swift and clear-headed recovery of consciousness. To test this hypothesis, we developed a series of fluorine-containing phenyl acetate derivatives. METHODOLOGY/PRINCIPAL FINDINGS: Fluorine-containing phenyl acetate derivatives were synthesized, and their hypnotic potencies and durations of LORR following bolus or infusion administration were determined in mice, rats and rabbits. The metabolic half-lives in the blood of various species were determined chromatographically. In vitro radioligand binding and γ-aminobutyric acidA (GABAA) receptor electrophysiology studies were performed. Among the 12 synthesized fluorine-containing phenyl acetate derivatives, compound 5j induced comparable duration of LORR with AZD3043, but more rapid recovery than AZD3043, propanidid and propofol. The time of compound 5j to return to walk and behavioral recovery are approximately reduced by more than 50% compared to AZD3043 in mice and rats and rabbits. The HD50 of compound 5j decreased with increasing animal size. CONCLUSIONS/SIGNIFICANCE: The rapid recovery might make compound 5j suitable for precise titration and allow swift and clear-headed recovery of consciousness and early home readiness.
[Mh] Termos MeSH primário: Acetatos/química
Período de Recuperação da Anestesia
Flúor/química
Hipnóticos e Sedativos/farmacocinética
Fenóis/química
Propanidida/análogos & derivados
[Mh] Termos MeSH secundário: Acetatos/farmacocinética
Animais
Barreira Hematoencefálica
Flúor/farmacocinética
Meia-Vida
Hipnóticos e Sedativos/química
Masculino
Camundongos
Fenóis/farmacocinética
Propanidida/química
Propanidida/farmacocinética
Coelhos
Ratos
Ratos Sprague-Dawley
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acetates); 0 (Hypnotics and Sedatives); 0 (Phenols); 284SYP0193 (Fluorine); 355G9R500Y (phenyl acetate); AO82L471NS (Propanidid)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140507
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0096518


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[PMID]:12075631
[Au] Autor:Ball C; Westhorpe R
[Ad] Endereço:Geoffrey Kaye Museum of Anaesthetic History.
[Ti] Título:Intravenous Induction Agents--propanidid.
[So] Source:Anaesth Intensive Care;30(3):261, 2002 Jun.
[Is] ISSN:0310-057X
[Cp] País de publicação:Australia
[La] Idioma:eng
[Mh] Termos MeSH primário: Anestésicos Intravenosos/administração & dosagem
Propanidida/administração & dosagem
[Mh] Termos MeSH secundário: Anestesia Geral/métodos
Anestésicos Intravenosos/farmacologia
Seres Humanos
Propanidida/farmacologia
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anesthetics, Intravenous); AO82L471NS (Propanidid)
[Em] Mês de entrada:0212
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:020622
[St] Status:MEDLINE


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[PMID]:10197760
[Au] Autor:Raeva S; Vainberg N; Dubinin V
[Ad] Endereço:Laboratory of Human Cell Neurophysiology, Institute of Chemical Physics, Russian Academy of Sciences, Moscow.
[Ti] Título:Analysis of spontaneous activity patterns of human thalamic ventrolateral neurons and their modifications due to functional brain changes.
[So] Source:Neuroscience;88(2):365-76, 1999 Jan.
[Is] ISSN:0306-4522
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In the human thalamic ventralis lateralis nucleus the spontaneous activity of 235 single units during 38 stereotactic operations in locally anaesthetized parkinsonian patients was analysed. Two basic cell types (A and B) were shown to exist in this nucleus: (i) with unitary irregular (2-40/s) discharges characterized by a tendency to spike grouping in the range of 4-6 Hz and 10-30 Hz (A-type, 74%), (ii) with bursting discharges firing in short trains (5-30 ms) characterized by an unstable rhythmic 3-6 Hz pattern similar to a low-threshold Ca2+ intrinsic burst structure of discharges (B-type, 26%). The functional brain changes after a motor tests performance were accompanied by the appearance of two different transient modifications of activity of A-cells pattern into rhythmic burst discharges: (i) in the range of 3-6 Hz, similar to the bursts found for B-cells and recorded mainly in the anterior ventrolateral region in rigid patients, (ii) in the range of 5 +/- 1 Hz, characterized by other interspike interval and recorded in the posterior ventrolateral region in patients with tremor. Modifications during short-term anaesthesia resulted in 10-15 Hz burst discharges that were associated with gradual disappearance of A-cells activity. In contrast to what happens for A-cells, the activity of bursting B-units was characterized by an invariant intrinsic structure of discharges irrespective of the functional brain changes or the forms of parkinsonian pathology. The nature of A- and B-units as well as the mechanisms of transient modifications of their spontaneous activity patterns due to the functional brain changes are discussed.
[Mh] Termos MeSH primário: Neurônios Motores/fisiologia
Doença de Parkinson/fisiopatologia
Núcleos Talâmicos/citologia
Núcleos Talâmicos/fisiologia
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Potenciais de Ação/fisiologia
Anestésicos Intravenosos/administração & dosagem
Eletromiografia
Potenciais Evocados/efeitos dos fármacos
Potenciais Evocados/fisiologia
Seres Humanos
Doença de Parkinson/complicações
Propanidida/administração & dosagem
Desempenho Psicomotor
Sono/fisiologia
Tremor/etiologia
Tremor/fisiopatologia
Vigília/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anesthetics, Intravenous); AO82L471NS (Propanidid)
[Em] Mês de entrada:9906
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:990410
[St] Status:MEDLINE


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[PMID]:9173826
[Au] Autor:Buravtsev VA; Medvinskii ID
[Ti] Título:[Readaptation after total intravenous anesthesia in one-day surgery].
[Ti] Título:Readaptatsiia posle total'noi vnutrivennoi anestezii v khirurgii odnogo dnia..
[So] Source:Anesteziol Reanimatol;(1):67-9, 1997 Jan-Feb.
[Is] ISSN:0201-7563
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:The authors analyze the stages of readaptation and recovery of clear consciousness in the immediate postoperative period in 200 patients administered one of the four variants of intravenous anesthesia in a one-day surgical hospital. The purpose of this work was to optimize the anesthetic care and the readaptation period. The stages of readaptation were assessed by psychophysiological testing. This process coursed most smoothly after propofol-phentanyl and hypnomidate-phentanyl anesthesia. Readaptation after sombrevin-phentanyl coursed reliably slower. The longest recovery was observed after calipsol-diazepam anesthesia, despite drug stimulation. This type of narcosis is irrational for one-day surgery, for it requires prolonged postoperative monitoring and thus makes the hospital stay longer.
[Mh] Termos MeSH primário: Procedimentos Cirúrgicos Ambulatórios
Anestesia Intravenosa
[Mh] Termos MeSH secundário: Adaptação Fisiológica
Adulto
Anestésicos Dissociativos/farmacologia
Anestésicos Intravenosos/farmacologia
Etomidato/farmacologia
Fentanila/farmacologia
Seres Humanos
Ketamina/farmacologia
Propanidida/farmacologia
Propofol/farmacologia
Testes Psicológicos
[Pt] Tipo de publicação:COMPARATIVE STUDY; ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anesthetics, Dissociative); 0 (Anesthetics, Intravenous); 690G0D6V8H (Ketamine); AO82L471NS (Propanidid); UF599785JZ (Fentanyl); YI7VU623SF (Propofol); Z22628B598 (Etomidate)
[Em] Mês de entrada:9706
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:970101
[St] Status:MEDLINE


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[PMID]:7573906
[Au] Autor:Klockgether-Radke A; Kersten J; Schröder T; Stafforst D; Kettler D; Hellige G
[Ad] Endereço:Zentrum Anaesthesiologie, Rettungs- und Intensivmedizin, Georg-August-Universität Göttingen.
[Ti] Título:[Anesthesia with propanidid in a liposomal preparation. An experimental study in swine].
[Ti] Título:Anästhesie mit Propanidid in liposomaler Zubereitung. Eine experimentelle Studie am Schwein..
[So] Source:Anaesthesist;44(8):573-80, 1995 Aug.
[Is] ISSN:0003-2417
[Cp] País de publicação:Germany
[La] Idioma:ger
[Ab] Resumo:BACKGROUND: Propanidid was widely used as a short-acting i.v. anaesthetic until it was withdrawn due to severe haemodynamic side effects. It was presumed that anaphylactoid reactions with massive histamine release were caused by the solvent cremophor rather than by propanidid itself. A new liposomal preparation of propanidid was examined in this animal study and compared with propanidid in cremophor solution and with propofol. METHODS: Eighteen pigs were randomly assigned to one of the following groups: Group 1 (n = 6): Propanidid in liposomal preparation (PropaLip; Braun Melsungen, Germany). Anaesthesia was induced with 60 mg/kg, followed by continuous infusion of 400 mg/kg.h. Group 2 (n = 6): Propanidid in cremophor solution (PropaCrem; Sombrevin, Gedeon Richter, Budapest) 15 mg/kg, 100 mg/kg.h. Group 3 (n = 6): Propofol (Disoprivan, Zeneca, Plankstadt, Germany) 5 mg/kg, 20 mg/kg.h. After induction and tracheal intubation, the animals were ventilated with 50% oxygen in air. Basic monitoring included noninvasive blood pressure measurements, electrocardiographic monitoring, and capnography. In a short surgical procedure, arterial and pulmonary artery catheters were placed via the right carotid artery and right internal jugular vein, respectively. As soon as the animals responded to a pain stimulus a second anaesthetic induction was performed, followed by a 60-min continuous infusion of the agent studied with invasive haemodynamic monitoring including arterial and pulmonary arterial pressures and cardiac output. Blood samples were taken for the measurement of serum levels of adrenaline, noradrenaline, cortisol, aldosterone, adrenocorticotropic hormone, and histamine. RESULTS: Intubation conditions and quality of anaesthesia were best in propofol animals, followed by PropaCrem animals. In spite of the large dose of 410 mg/kg.h, resulting in a volume load of as much as 16.4 ml/kg.h, the PropaLip animals showed evidence of poor anaesthetic quality. In group 1 we recorded the highest increases in heart rate (91 vs. 115/min), cardiac output (5.4 vs. 7.7 l/min), plasma catecholamine levels, and histamine concentrations (124-268 ng/ml). CONCLUSIONS: In our animal study, propanidid in liposomal preparation failed to show promise as a new anaesthetic agent. Our results are discussed in view of a drug targeting the cells of the reticuloendothelial system, especially the liver, where liposomes are eliminated from the blood. This may result in the transport of propanidid to one of its major places of inactivation.
[Mh] Termos MeSH primário: Anestesia Intravenosa
Anestésicos Intravenosos
Portadores de Fármacos
Propanidida
[Mh] Termos MeSH secundário: Anestésicos Intravenosos/administração & dosagem
Anestésicos Intravenosos/efeitos adversos
Animais
Catecolaminas/sangue
Portadores de Fármacos/efeitos adversos
Feminino
Hemodinâmica/efeitos dos fármacos
Histamina/sangue
Lipossomos/efeitos adversos
Masculino
Medição da Dor/efeitos dos fármacos
Veículos Farmacêuticos/efeitos adversos
Polietilenoglicóis/efeitos adversos
Medicação Pré-Anestésica
Propanidida/administração & dosagem
Propanidida/efeitos adversos
Suínos
[Pt] Tipo de publicação:COMPARATIVE STUDY; ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anesthetics, Intravenous); 0 (Catecholamines); 0 (Drug Carriers); 0 (Liposomes); 0 (Pharmaceutical Vehicles); 30IQX730WE (Polyethylene Glycols); 39279-69-1 (cremophor); 820484N8I3 (Histamine); AO82L471NS (Propanidid)
[Em] Mês de entrada:9510
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:950801
[St] Status:MEDLINE


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[PMID]:8122725
[Au] Autor:Sütterlin R
[Ti] Título:[Comments on the paper by H. Habazettl et al. The anesthetic usefulness of propanidid as a liposome dispersion].
[Ti] Título:Anästhesiologische Wirksamkeit von Propanidid als Liposomendispersion..
[So] Source:Anaesthesist;43(1):50-2, 1994 Jan.
[Is] ISSN:0003-2417
[Cp] País de publicação:Germany
[La] Idioma:ger
[Mh] Termos MeSH primário: Propanidida/administração & dosagem
[Mh] Termos MeSH secundário: Portadores de Fármacos
Seres Humanos
Lipossomos
[Pt] Tipo de publicação:COMMENT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Carriers); 0 (Liposomes); AO82L471NS (Propanidid)
[Em] Mês de entrada:9404
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:940101
[St] Status:MEDLINE


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[PMID]:16092193
[Au] Autor:Zawisza P; Przyborowski L
[Ad] Endereço:Akademia Medyczna, ul. Okopowa 1, 20-022 Lublin.
[Ti] Título:[Propanidid and etomidate identification from the blood by thin-layer chromatography].
[Ti] Título:Identyfikacja propanidydu i etomidatu we krwi za pomoca chromatografii cienkowarstwowej..
[So] Source:Acta Pol Pharm;49(5-6):15-7, 1992.
[Is] ISSN:0001-6837
[Cp] País de publicação:Poland
[La] Idioma:pol
[Ab] Resumo:Propanidid and etomidate were extracted from blood with diethyl ether at pH ca. 8 (phosphate buffer), then separated and identified by thin-layer chromatography on silica gel, using diethyl ether-acetone (3:1, v/v) for propanidid or dioxane-acetic acid (47:3, v/v) for etomidate as the mobile phase. Both compounds can be revealed on dried chromatograms using sodium carbonate solution up to the amount 1 microg/cm3 of plasma, and it is sufficient sensivity for propanidid adhibited in therapeutic doses, whereas this limits the detection of etomidate for overdosed patients only.
[Mh] Termos MeSH primário: Cromatografia em Camada Delgada
Etomidato/sangue
Propanidida/sangue
[Mh] Termos MeSH secundário: Anestésicos Intravenosos/sangue
Seres Humanos
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anesthetics, Intravenous); AO82L471NS (Propanidid); Z22628B598 (Etomidate)
[Em] Mês de entrada:0510
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:920101
[St] Status:MEDLINE


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[PMID]:16092192
[Au] Autor:Zawisza P; Przyborowski L
[Ad] Endereço:Akademia Medyczna, ul. Okopowa 1, 20-022 Lublin.
[Ti] Título:[High-performance liquid chromatographic determination of propanidid and etomidate].
[Ti] Título:Oznaczenie propanidydu i etomidatu we krwi metoda wysokosprawnej chromatografii cieczowej..
[So] Source:Acta Pol Pharm;49(5-6):11-3, 1992.
[Is] ISSN:0001-6837
[Cp] País de publicação:Poland
[La] Idioma:pol
[Ab] Resumo:High-performance reversed-phase liquid chromatographic determination of propanidid and etomidate was performed on ODS silica, after precipitation of the proteins in plasma with methanol, extraction of the drugs with diethyl ether, evaporation and dissolving in a mobile phase: acetonitrile-phosphate buffer pH 4.44 (7:3, v/v); UV detection at 254 nm. Dionine hydrochloride was used as an internal standard. Propanidid was determined in a range 5-25 microg/cm3 of plasma and etomidate in 0.1-0.5 microg/cm3 of plasma, thus enables the analysis of therapeutic levels of the drugs.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão
Etomidato/sangue
Propanidida/sangue
[Mh] Termos MeSH secundário: Anestésicos Intravenosos/sangue
Seres Humanos
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anesthetics, Intravenous); AO82L471NS (Propanidid); Z22628B598 (Etomidate)
[Em] Mês de entrada:0510
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:920101
[St] Status:MEDLINE


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[PMID]:1608193
[Au] Autor:Antonchenko IV; Popov SV; Chekhov AM; Borisova EV; Gutsol LIa; Gimrikh EO
[Ti] Título:[A case of managing ventricular tachycardia with sombrevin].
[Ti] Título:Sluchai kupirovaniia zheludochkovoi takhikardii sombrevinom..
[So] Source:Klin Med (Mosk);70(1):109-11, 1992 Jan.
[Is] ISSN:0023-2149
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Mh] Termos MeSH primário: Propanidida/uso terapêutico
Taquicardia/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Doença Crônica
Eletrocardiografia/efeitos dos fármacos
Seres Humanos
Masculino
Taquicardia/diagnóstico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
AO82L471NS (Propanidid)
[Em] Mês de entrada:9207
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:920101
[St] Status:MEDLINE


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[PMID]:1524155
[Au] Autor:Habazettl H; Vollmar B; Röhrich F; Conzen P; Doenicke A; Baethmann A
[Ad] Endereço:Institut für Chirurgische Forschung, Ludwig-Maximilians-Universität, München.
[Ti] Título:[Anesthesiologic efficacy of propanidid as a liposome dispersion. An experimental study with rats].
[Ti] Título:Anästhesiologische Wirksamkeit von Propanidid als Liposomendispersion. Eine experimentelle studie mit ratten..
[So] Source:Anaesthesist;41(8):448-56, 1992 Aug.
[Is] ISSN:0003-2417
[Cp] País de publicação:Germany
[La] Idioma:ger
[Ab] Resumo:BACKGROUND: Propanidid, an ultra-short-acting i.v. anaesthetic agent, was widely used in the 1960s. Reports of anaphylactoid reactions in patients associated with release of histamine following administration of the drug, however, led to withdrawal of this useful anaesthetic. Since the adverse side effects of the former solution could be attributed to the solvent cremophor, attempts have recently been made to produce a propanidid solution without addition of the solvent. We report on comparative investigations employing a new liposomal solution (B. Braun, Melsungen, FRG) and the conventional cremophor preparation with regard to anaesthetic properties, haemodynamic side effects, and electroencephalographic effects (EEG). METHODS: Sprague-Dawley rats (n = 46) were implanted with venous and arterial lines and epidural EEG electrodes during chloral-hydrate anaesthesia. The following day, arterial blood pressure (ABP), heart rate (HR), and EEG were monitored in awake animals and then after induction of anaesthesia by a bolus of the respective propanidid preparation, followed by an infusion period of 15 min in six different experimental groups. Animals of groups L-60, L-90, L-120, or C-60, C-90, or C-120 groups received 60, 90, or 120 mg.100 g-1.h-1 of the liposomal (L) or cremophor (C) preparation. During anaesthesia, the corneal reflex and nociception to tail-clamping were also tested. At termination of the infusion, blood samples were drawn for determination of plasma propanidid concentrations. RESULTS: Both preparations were similarly effective in induction and maintenance of anaesthesia in a dose-dependent manner; both similarly lowered ABP and HR. The corneal reflex and nociceptive responses to tail clamping were also comparably suppressed. However, whereas the liposomal preparation was well tolerated at higher dose levels, the cremophor preparation caused considerable dose-dependent mortality of 11%, 86%, and 86% in animals in groups C-60, C-90, and C-120, respectively. Both preparations were found to induce a burst-suppression pattern in the EEG associated with clonic seizures, with a lower incidence with the liposomal preparation (22% and 50% in groups L-90 and L-120) as compared to the cremophor preparation (100% and 89% in groups C-90 and C-120). A remarkable variability in propanidid plasma concentrations was found at the end of the infusion period, although no differences were observed between both preparations. Discontinuation of infusion of propanidid resulted in rapid awakening (less than 5 min), irrespective of whether the liposomal or conventional preparation was employed. CONCLUSION: The present findings demonstrate largely identical anaesthetic potencies of a new liposomal solution as compared to the conventional cremophor preparation of propanidid. The liposomal preparation, however, was superior as far as tolerance and incidence of clonic seizures was concerned. The present findings should prompt further studies on the suitability of liposomal propanidid as a short-acting anaesthetic agent in patients.
[Mh] Termos MeSH primário: Anestesia Intravenosa
Propanidida
[Mh] Termos MeSH secundário: Animais
Eletroencefalografia
Hemodinâmica/efeitos dos fármacos
Hemodinâmica/fisiologia
Lipossomos
Masculino
Polietilenoglicóis/efeitos adversos
Ratos
Ratos Endogâmicos
Solventes/efeitos adversos
[Pt] Tipo de publicação:COMPARATIVE STUDY; ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Liposomes); 0 (Solvents); 30IQX730WE (Polyethylene Glycols); 39279-69-1 (cremophor); AO82L471NS (Propanidid)
[Em] Mês de entrada:9210
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:920801
[St] Status:MEDLINE



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