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[PMID]:29320603
[Au] Autor:McTague A; Martland T; Appleton R
[Ad] Endereço:Molecular Neurosciences, Developmental Neurosciences Programme, UCL Great Ormond Street Institute of Child Health, London, UK.
[Ti] Título:Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children.
[So] Source:Cochrane Database Syst Rev;1:CD001905, 2018 01 10.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Tonic-clonic convulsions and convulsive status epilepticus (currently defined as a tonic-clonic convulsion lasting at least 30 minutes) are medical emergencies and require urgent and appropriate anticonvulsant treatment. International consensus is that an anticonvulsant drug should be administered for any tonic-clonic convulsion that has been continuing for at least five minutes. Benzodiazepines (diazepam, lorazepam, midazolam) are traditionally regarded as first-line drugs and phenobarbital, phenytoin and paraldehyde as second-line drugs. This is an update of a Cochrane Review first published in 2002 and updated in 2008. OBJECTIVES: To evaluate the effectiveness and safety of anticonvulsant drugs used to treat any acute tonic-clonic convulsion of any duration, including established convulsive (tonic-clonic) status epilepticus in children who present to a hospital or emergency medical department. SEARCH METHODS: For the latest update we searched the Cochrane Epilepsy Group's Specialised Register (23 May 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 23 May 2017), MEDLINE (Ovid, 1946 to 23 May 2017), ClinicalTrials.gov (23 May 2017), and the WHO International Clinical Trials Registry Platform (ICTRP, 23 May 2017). SELECTION CRITERIA: Randomised and quasi-randomised trials comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and extracted data. We contacted study authors for additional information. MAIN RESULTS: The review includes 18 randomised trials involving 2199 participants, and a range of drug treatment options, doses and routes of administration (rectal, buccal, nasal, intramuscular and intravenous). The studies vary by design, setting and population, both in terms of their ages and also in their clinical situation. We have made many comparisons of drugs and of routes of administration of drugs in this review; our key findings are as follows:(1) This review provides only low- to very low-quality evidence comparing buccal midazolam with rectal diazepam for the treatment of acute tonic-clonic convulsions (risk ratio (RR) for seizure cessation 1.25, 95% confidence interval (CI) 1.13 to 1.38; 4 trials; 690 children). However, there is uncertainty about the effect and therefore insufficient evidence to support its use. There were no included studies which compare intranasal and buccal midazolam.(2) Buccal and intranasal anticonvulsants were shown to lead to similar rates of seizure cessation as intravenous anticonvulsants, e.g. intranasal lorazepam appears to be as effective as intravenous lorazepam (RR 0.96, 95% CI 0.82 to 1.13; 1 trial; 141 children; high-quality evidence) and intranasal midazolam was equivalent to intravenous diazepam (RR 0.98, 95% CI 0.91 to 1.06; 2 trials; 122 children; moderate-quality evidence).(3) Intramuscular midazolam also showed a similar rate of seizure cessation to intravenous diazepam (RR 0.97, 95% CI 0.87 to 1.09; 2 trials; 105 children; low-quality evidence).(4) For intravenous routes of administration, lorazepam appears to be as effective as diazepam in stopping acute tonic clonic convulsions: RR 1.04, 95% CI 0.94 to 1.16; 3 trials; 414 children; low-quality evidence. Furthermore, we found no statistically significant or clinically important differences between intravenous midazolam and diazepam (RR for seizure cessation 1.08, 95% CI 0.97 to 1.21; 1 trial; 80 children; moderate-quality evidence) or intravenous midazolam and lorazepam (RR for seizure cessation 0.98, 95% CI 0.91 to 1.04; 1 trial; 80 children; moderate-quality evidence). In general, intravenously-administered anticonvulsants led to more rapid seizure cessation but this was usually compromised by the time taken to establish intravenous access.(5) There is limited evidence from a single trial to suggest that intranasal lorazepam may be more effective than intramuscular paraldehyde in stopping acute tonic-clonic convulsions (RR 1.22, 95% CI 0.99 to 1.52; 160 children; moderate-quality evidence).(6) Adverse side effects were observed and reported very infrequently in the included studies. Respiratory depression was the most common and most clinically relevant side effect and, where reported, the frequency of this adverse event was observed in 0% to up to 18% of children. None of the studies individually demonstrated any difference in the rates of respiratory depression between the different anticonvulsants or their different routes of administration; but when pooled, three studies (439 children) provided moderate-quality evidence that lorazepam was significantly associated with fewer occurrences of respiratory depression than diazepam (RR 0.72, 95% CI 0.55 to 0.93).Much of the evidence provided in this review is of mostly moderate to high quality. However, the quality of the evidence provided for some important outcomes is low to very low, particularly for comparisons of non-intravenous routes of drug administration. Low- to very low-quality evidence was provided where limited data and imprecise results were available for analysis, methodological inadequacies were present in some studies which may have introduced bias into the results, study settings were not applicable to wider clinical practice, and where inconsistency was present in some pooled analyses. AUTHORS' CONCLUSIONS: We have not identified any new high-quality evidence on the efficacy or safety of an anticonvulsant in stopping an acute tonic-clonic convulsion that would inform clinical practice. There appears to be a very low risk of adverse events, specifically respiratory depression. Intravenous lorazepam and diazepam appear to be associated with similar rates of seizure cessation and respiratory depression. Although intravenous lorazepam and intravenous diazepam lead to more rapid seizure cessation, the time taken to obtain intravenous access may undermine this effect. In the absence of intravenous access, buccal midazolam or rectal diazepam are therefore acceptable first-line anticonvulsants for the treatment of an acute tonic-clonic convulsion that has lasted at least five minutes. There is no evidence provided by this review to support the use of intranasal midazolam or lorazepam as alternatives to buccal midazolam or rectal diazepam.
[Mh] Termos MeSH primário: Anticonvulsivantes/uso terapêutico
Epilepsia Tônico-Clônica/tratamento farmacológico
Estado Epiléptico/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração por Inalação
Administração Oral
Administração Retal
Anticonvulsivantes/administração & dosagem
Criança
Diazepam/administração & dosagem
Seres Humanos
Injeções Intramusculares
Injeções Intravenosas
Lorazepam/administração & dosagem
Midazolam/administração & dosagem
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Anticonvulsants); O26FZP769L (Lorazepam); Q3JTX2Q7TU (Diazepam); R60L0SM5BC (Midazolam)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD001905.pub3


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[PMID]:29411034
[Au] Autor:Blay E; Barnard C; Bilimoria KY
[Ad] Endereço:Northwestern Memorial Hospital, Chicago, Illinois.
[Ti] Título:Oversedation of a Patient With Obstructive Sleep Apnea Prior to Imaging.
[So] Source:JAMA;319(5):495-496, 2018 Feb 06.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Parada Cardíaca/induzido quimicamente
Hipnóticos e Sedativos/efeitos adversos
Lorazepam/efeitos adversos
Apneia Obstrutiva do Sono
[Mh] Termos MeSH secundário: Idoso
Registros Eletrônicos de Saúde
Parada Cardíaca/terapia
Seres Humanos
Hipnóticos e Sedativos/administração & dosagem
Doença Iatrogênica
Lorazepam/administração & dosagem
Imagem por Ressonância Magnética
Análise de Causa Fundamental
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hypnotics and Sedatives); O26FZP769L (Lorazepam)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180208
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.22004


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[PMID]:28975307
[Au] Autor:Hui D; Frisbee-Hume S; Wilson A; Dibaj SS; Nguyen T; De La Cruz M; Walker P; Zhukovsky DS; Delgado-Guay M; Vidal M; Epner D; Reddy A; Tanco K; Williams J; Hall S; Liu D; Hess K; Amin S; Breitbart W; Bruera E
[Ad] Endereço:Department of Palliative Care, Rehabilitation and Integrative Medicine, MD Anderson Cancer Center, Houston, Texas.
[Ti] Título:Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial.
[So] Source:JAMA;318(11):1047-1056, 2017 09 19.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: The use of benzodiazepines to control agitation in delirium in the last days of life is controversial. Objective: To compare the effect of lorazepam vs placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium in the setting of advanced cancer. Design, Setting, and Participants: Single-center, double-blind, parallel-group, randomized clinical trial conducted at an acute palliative care unit at MD Anderson Cancer Center, Texas, enrolling 93 patients with advanced cancer and agitated delirium despite scheduled haloperidol from February 11, 2014, to June 30, 2016, with data collection completed in October 2016. Interventions: Lorazepam (3 mg) intravenously (n = 47) or placebo (n = 43) in addition to haloperidol (2 mg) intravenously upon the onset of an agitation episode. Main Outcomes and Measures: The primary outcome was change in Richmond Agitation-Sedation Scale (RASS) score (range, -5 [unarousable] to 4 [very agitated or combative]) from baseline to 8 hours after treatment administration. Secondary end points were rescue neuroleptic use, delirium recall, comfort (perceived by caregivers and nurses), communication capacity, delirium severity, adverse effects, discharge outcomes, and overall survival. Results: Among 90 randomized patients (mean age, 62 years; women, 42 [47%]), 58 (64%) received the study medication and 52 (90%) completed the trial. Lorazepam + haloperidol resulted in a significantly greater reduction of RASS score at 8 hours (-4.1 points) than placebo + haloperidol (-2.3 points) (mean difference, -1.9 points [95% CI, -2.8 to -0.9]; P < .001). The lorazepam + haloperidol group required less median rescue neuroleptics (2.0 mg) than the placebo + haloperidol group (4.0 mg) (median difference, -1.0 mg [95% CI, -2.0 to 0]; P = .009) and was perceived to be more comfortable by both blinded caregivers and nurses (caregivers: 84% for the lorazepam + haloperidol group vs 37% for the placebo + haloperidol group; mean difference, 47% [95% CI, 14% to 73%], P = .007; nurses: 77% for the lorazepam + haloperidol group vs 30% for the placebo + haloperidol group; mean difference, 47% [95% CI, 17% to 71%], P = .005). No significant between-group differences were found in delirium-related distress and survival. The most common adverse effect was hypokinesia (3 patients in the lorazepam + haloperidol group [19%] and 4 patients in the placebo + haloperidol group [27%]). Conclusions and Relevance: In this preliminary trial of hospitalized patients with agitated delirium in the setting of advanced cancer, the addition of lorazepam to haloperidol compared with haloperidol alone resulted in a significantly greater reduction in agitation at 8 hours. Further research is needed to assess generalizability and adverse effects. Trial Registration: clinicaltrials.gov Identifier: NCT01949662.
[Mh] Termos MeSH primário: Ansiolíticos/administração & dosagem
Antipsicóticos/administração & dosagem
Delírio/tratamento farmacológico
Haloperidol/administração & dosagem
Lorazepam/administração & dosagem
Neoplasias/complicações
Cuidados Paliativos
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Ansiolíticos/efeitos adversos
Antipsicóticos/efeitos adversos
Delírio/etiologia
Método Duplo-Cego
Quimioterapia Combinada
Feminino
Haloperidol/efeitos adversos
Hospitalização
Seres Humanos
Lorazepam/efeitos adversos
Masculino
Meia-Idade
Neoplasias/psicologia
Neoplasias/terapia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (Antipsychotic Agents); J6292F8L3D (Haloperidol); O26FZP769L (Lorazepam)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171005
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.11468


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[PMID]:28438026
[Au] Autor:Johnson PN; Nguyen A; Neely SB; Johnson M
[Ad] Endereço:1 University of Oklahoma College of Pharmacy, Oklahoma City, OK, USA.
[Ti] Título:Intramuscular Lorazepam for Status Epilepticus in Children With Complex Medical and Physical Disabilities.
[So] Source:Ann Pharmacother;51(8):656-662, 2017 Aug.
[Is] ISSN:1542-6270
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: A protocol was developed to achieve status epilepticus (SE) resolution: step 1, intramuscular (IM) lorazepam; step 2, repeat IM lorazepam; step 3, rectal diazepam. OBJECTIVE: The primary objective was to identify the number of patients with SE resolution after step 1. Secondary objectives included categorization of mean number of IM doses per episode and patient factors associated with SE resolution. METHODS: This was a retrospective study of patients <21 years old with complex medical and physical disabilities admitted over 5 years. For analysis, IM dosing was categorized as high dose (>0.05 mg/kg/dose) and low dose (≤0.05 mg/kg/dose). A generalized linear mixed-model regression was used to assess the relationship with SE resolution at step 1 and patient characteristics. RESULTS: A total of 44 patients were included (n = 162 episodes). SE resolution was noted in 68.5% of episodes after step 1. Models were stratified by gender to present odds of SE resolution at step 1 versus step 2/3. For women, no covariate was significant. For men, the odds of SE resolution at step 1 were 14.9 times higher in those receiving 2 versus 4 maintenance antiepileptics, adjusting for covariates. Additionally, odds of resolution at step 1 was 3.1 times higher for high-dose versus low-dose lorazepam in males, adjusting for covariates, but was not statistically significant. CONCLUSIONS: SE resolution was noted in 68.5% after step 1. Unadjusted, females had a higher odds of SE resolution at step 1 than males. In males, high-dose lorazepam had higher odds of SE resolution at step 1 than low-dose lorazepam, though not significantly different.
[Mh] Termos MeSH primário: Anticonvulsivantes/administração & dosagem
Anticonvulsivantes/uso terapêutico
Lorazepam/administração & dosagem
Lorazepam/uso terapêutico
Estado Epiléptico/complicações
Estado Epiléptico/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração Retal
Adolescente
Adulto
Criança
Pré-Escolar
Diazepam/administração & dosagem
Diazepam/uso terapêutico
Relação Dose-Resposta a Droga
Esquema de Medicação
Feminino
Hospitalização
Seres Humanos
Injeções Intramusculares
Modelos Lineares
Masculino
Razão de Chances
Estudos Retrospectivos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticonvulsants); O26FZP769L (Lorazepam); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170426
[St] Status:MEDLINE
[do] DOI:10.1177/1060028017706522


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[PMID]:28415411
[Au] Autor:Shah V; Sharma M; Pandya R; Parikh RK; Bharatiya B; Shukla A; Tsai HC
[Ad] Endereço:Department of Pharmaceutics and Pharmaceutical Technology, L. M. College of Pharmacy, Ahmedabad 380009, Gujarat, India.
[Ti] Título:Quality by Design approach for an in situ gelling microemulsion of Lorazepam via intranasal route.
[So] Source:Mater Sci Eng C Mater Biol Appl;75:1231-1241, 2017 Jun 01.
[Is] ISSN:1873-0191
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The present study illustrates the application of the concept of Quality by Design for development, optimization and evaluation of Lorazepam loaded microemulsion containing ion responsive In situ gelator gellan gum and carbopol 934. A novel approach involving interactions between surfactant and polymer was employed to achieve controlled drug release and reduced mucociliary clearance. Microemulsion formulated using preliminary solubility study and pseudo ternary phase diagrams showed significantly improved solubilization capacity of Lorazepam with 54.31±6.07nm droplets size. The effect of oil to surfactant/cosurfactant ratio and concentration of gelling agent on the drug release and viscosity of microemulsion gel (MEG) was evaluated using a 3 full factorial design. The gel of optimized formulation (MEG ) showed a drug release up to 6h of 97.32±1.35% of total drug loaded. The change in shear-dependent viscosity for different formulations on interaction with Simulated Nasal Fluid depicts the crucial role of surfactant-polymer interactions on the gelation properties along with calcium ions binding on the polymer chains. It is proposed that the surfactant-polymer interactions in the form of a stoichiometric hydrogen bonding between oxyethylene and carboxylic groups of the polymers used, provides exceptional ME stability and adhesion properties. Compared with the marketed formulation, optimized MEG showed improved pharmacodynamic activity. Ex vivo diffusion studies revealed significantly higher release for MEG compared to microemulsion and drug solution. MEG showed higher flux and permeation across goat nasal mucosa. According to the study, it could be concluded that formulation would successfully provide the rapid onset of action, and decrease the mucociliary clearance due to formation of in situ gelling mucoadhesive system.
[Mh] Termos MeSH primário: Sistemas de Liberação de Medicamentos/métodos
Lorazepam/química
[Mh] Termos MeSH secundário: Administração Intranasal
Emulsões
Seres Humanos
Lorazepam/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Emulsions); O26FZP769L (Lorazepam)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170724
[Lr] Data última revisão:
170724
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE


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[PMID]:28160051
[Au] Autor:El Balkhi S; Chaslot M; Picard N; Dulaurent S; Delage M; Mathieu O; Saint-Marcoux F
[Ad] Endereço:Department of Pharmacology, Service de pharmacologie, toxicologie et pharmacovigilance, CHU de Limoges, Limoges University Hospital, 2 Ave Martin Luther King, 87042, Limoges Cedex, France. souleiman.elbalkhi@chu-limoges.fr.
[Ti] Título:Characterization and identification of eight designer benzodiazepine metabolites by incubation with human liver microsomes and analysis by a triple quadrupole mass spectrometer.
[So] Source:Int J Legal Med;131(4):979-988, 2017 Jul.
[Is] ISSN:1437-1596
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Designer benzodiazepines (DBZDs) have become of particular importance in the past few years. The metabolite monitoring of DBZD in biological fluids could be of great interest in clinical and forensic toxicology. However, DBZD metabolites are not known or not commercially available. The identification of some DBZD metabolites has been mostly explored by self-administration studies or by in vitro studies followed by high-resolution mass spectrometry. The question arose whether a unit resolution instrument could be efficient enough to allow the identification of DBZD metabolites. In this study, we used an in vitro experiment where eight DBZDs (diclazepam, flubromazepam, etizolam, deschloroetizolam, flubromazolam, nifoxipam, meclonazepam and clonazolam) were incubated with human liver microsomes (HLMs) and metabolite identification was carried out by using a UHPLC coupled to a QTRAP triple quadrupole linear iontrap tandem mass spectrometer system. Post-mortem samples obtained from a real poisoning case, involving deschloroetizolam and diclazepam, were also analysed and discussed. Our study using HLM allowed the identification of 26 metabolites of the 8 DBZDs. These were denitro-, mono- or di-hydroxylated and desmethyl metabolites. In the forensic case, diclazepam was not detected whereas its metabolites (lormetazepam and lorazepam) were present at high concentrations in urine. We also identified hydroxy-deschloroetizolam in urine, while the parent compound was not detected in this matrix. This supports the approach that LC coupled to a simple QTRAP could be used by laboratories to identify other not-known/not-commercialized new psychoactive substance (NPS) metabolites.
[Mh] Termos MeSH primário: Benzodiazepinas/química
Drogas Desenhadas/química
Microssomos Hepáticos/química
[Mh] Termos MeSH secundário: Adulto
Benzodiazepinas/análise
Cromatografia Líquida
Drogas Desenhadas/análise
Seres Humanos
Lorazepam/análogos & derivados
Lorazepam/urina
Masculino
Oxazepam/urina
Transtornos Relacionados ao Uso de Substâncias/urina
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Designer Drugs); 12794-10-4 (Benzodiazepines); 6GOW6DWN2A (Oxazepam); GU56C842ZA (lormetazepam); O26FZP769L (Lorazepam)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170205
[St] Status:MEDLINE
[do] DOI:10.1007/s00414-017-1541-6


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[PMID]:28157273
[Au] Autor:Kienzler-Norwood F; Costard L; Sadangi C; Müller P; Neubert V; Bauer S; Rosenow F; Norwood BA
[Ad] Endereço:Department of Neurology, Epilepsy Center-Marburg, Philipps University, Marburg, Germany.
[Ti] Título:A novel animal model of acquired human temporal lobe epilepsy based on the simultaneous administration of kainic acid and lorazepam.
[So] Source:Epilepsia;58(2):222-230, 2017 Feb.
[Is] ISSN:1528-1167
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Kainic acid (KA) is a potent glutamate analog that is used to induce neurodegeneration and model temporal lobe epilepsy (TLE) in rodents. KA reliably induces severe, prolonged seizures, that is, convulsive status epilepticus (cSE), which is typically fatal without pharmacologic intervention. Although the use of KA to model human epilepsy has proven unquestionably valuable for >30 years, significant variability and mortality continue to confound results. These issues are probably the consequence of cSE, an all-or-nothing response that is inherently capricious and uncontrollable. The relevance of cSE to the human condition is dubious, however, as most patients with epilepsy never experienced it. We sought to develop a simple, KA-based animal model of TLE that avoids cSE and its confounds. METHODS: Adult, male Sprague-Dawley rats received coincident subcutaneous injections of KA (5 mg) and lorazepam (0.25 mg), approximately 15.0 and 0.75 mg/kg, respectively. Continuous video-electroencephalography (EEG) was used to monitor acute seizure activity and detect spontaneous seizures. Immunocytochemistry, Fluoro-Jade B staining, and Timm staining were used to characterize both acute and chronic neuropathology. RESULTS: Acutely, focal hippocampal seizures were induced, which began after about 30 min and were self-terminating after a few hours. Widespread hippocampal neurodegeneration was detected after 4 days. Spontaneous, focal hippocampal seizures began after an average of 12 days in all animals. Classic hippocampal sclerosis and mossy fiber sprouting characterized the long-term neuropathology. Morbidity and mortality rates were both 0%. SIGNIFICANCE: We show here that the effects of systemic KA can be limited to the hippocampus simply with coadministration of a benzodiazepine at a low dose. This means that lorazepam can block convulsive seizures without truly stopping seizure activity. This novel, cSE-free animal model reliably mimics the defining characteristics of acquired mesial TLE: hippocampal sclerosis and spontaneous hippocampal-onset seizures after a prolonged seizure-free period, without significant morbidity, mortality, or nonresponders.
[Mh] Termos MeSH primário: Anticonvulsivantes/uso terapêutico
Epilepsia do Lobo Temporal/induzido quimicamente
Epilepsia do Lobo Temporal/tratamento farmacológico
Agonistas de Aminoácidos Excitatórios/toxicidade
Ácido Caínico/toxicidade
Lorazepam/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Eletroencefalografia
Hipocampo/efeitos dos fármacos
Hipocampo/patologia
Seres Humanos
Ácido Caínico/administração & dosagem
Masculino
Fibras Musgosas Hipocampais/patologia
Doenças Neurodegenerativas/etiologia
Ratos
Ratos Sprague-Dawley
Esclerose/etiologia
Gravação em Vídeo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Excitatory Amino Acid Agonists); O26FZP769L (Lorazepam); SIV03811UC (Kainic Acid)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170627
[Lr] Data última revisão:
170627
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170204
[St] Status:MEDLINE
[do] DOI:10.1111/epi.13579


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[PMID]:28131321
[Au] Autor:Carter BS; Brunkhorst J
[Ad] Endereço:Department of Pediatrics, Division of Neonatology, University of Missouri at Kansas City School of Medicine, 2401 Gillham Rd, Kansas City, MO 64108; Children׳s Mercy Bioethics Center, Kansas City, MO. Electronic address: bscarter@cmh.edu.
[Ti] Título:Neonatal pain management.
[So] Source:Semin Perinatol;41(2):111-116, 2017 Mar.
[Is] ISSN:1558-075X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pain management in the neonatal ICU remains challenging for many clinicians and in many complex care circumstances. The authors review general pain management principles and address the use of pain scales, non-pharmacologic management, and various agents that may be useful in general neonatal practice, procedurally, or at the end of life. Chronic pain and neonatal abstinence are also noted.
[Mh] Termos MeSH primário: Analgésicos Opioides/uso terapêutico
Hipnóticos e Sedativos/uso terapêutico
Método Canguru/métodos
Manejo da Dor
Cuidados Paliativos
[Mh] Termos MeSH secundário: Aminas/uso terapêutico
Ansiolíticos/uso terapêutico
Barbitúricos/uso terapêutico
Dor Crônica/terapia
Ácidos Cicloexanocarboxílicos/uso terapêutico
Dexmedetomidina/uso terapêutico
Seres Humanos
Recém-Nascido
Unidades de Terapia Intensiva Neonatal
Ketamina/uso terapêutico
Lorazepam/uso terapêutico
Midazolam/uso terapêutico
Síndrome de Abstinência Neonatal/terapia
Medição da Dor
Propofol/uso terapêutico
Comportamento de Sucção
Sacarose/uso terapêutico
Assistência Terminal
Ácido gama-Aminobutírico/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Amines); 0 (Analgesics, Opioid); 0 (Anti-Anxiety Agents); 0 (Barbiturates); 0 (Cyclohexanecarboxylic Acids); 0 (Hypnotics and Sedatives); 56-12-2 (gamma-Aminobutyric Acid); 57-50-1 (Sucrose); 67VB76HONO (Dexmedetomidine); 690G0D6V8H (Ketamine); 6CW7F3G59X (gabapentin); O26FZP769L (Lorazepam); R60L0SM5BC (Midazolam); YI7VU623SF (Propofol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170130
[St] Status:MEDLINE


  9 / 2735 MEDLINE  
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[PMID]:28126558
[Au] Autor:van der Vossen AC; van der Velde I; Smeets OS; Postma DJ; Eckhardt M; Vermes A; Koch BC; Vulto AG; Hanff LM
[Ad] Endereço:Department of Hospital Pharmacy, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: a.vandervossen@erasmusmc.nl.
[Ti] Título:Formulating a poorly water soluble drug into an oral solution suitable for paediatric patients; lorazepam as a model drug.
[So] Source:Eur J Pharm Sci;100:205-210, 2017 Mar 30.
[Is] ISSN:1879-0720
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Many drugs are unavailable in suitable oral paediatric dosage forms, and pharmacists often have to compound drugs to provide paediatric patients with an acceptable formulation in the right dose. Liquid formulations offer the advantage of dosing flexibility and ease of administration to young patients, but drug substances often show poor aqueous solubility. The objective of this work was to study different solvents and matrices to design a liquid formulation for poorly water soluble drugs, using lorazepam as model drug. METHODS: Three different formulation strategies were explored to improve the solubility. Firstly, water-soluble organic solvents were used to improve the aqueous solubility directly, secondly, ionic surfactants were used to solubilise the model drug, and thirdly, complexation of lorazepam with cyclodextrin was studied. Specific attention was paid to excipients, adequate taste correction and palatability. For the final formulation, physical and chemical stability and microbiological quality were assessed for 12months. RESULTS: An organic solvent based formulation, containing a mixture of polyethylene glycol and glycerol 85%, with a minimum amount of propylene glycol, proved to be physically and chemically stable. Development of the non-ionic surfactants formulation was discontinued due to taste problems. The cyclodextrin formulations were physically stable, but lorazepam content declined to 90% within five months. The final formulation contained in volume concentration (%v/v) 87% glycerol, 10% polyethylene glycol 400 and 3% propylene glycol. Orange essence was the preferred taste corrector. The formulation remained stable for 12months at 4°C, with lorazepam content remaining >95%. Related substances increased during the study period but remained below 2%. In-use stability was proven up to 4weeks. CONCLUSION: An organic solvent based oral formulation was shown to be superior to a non-ionic surfactant based formulation or a cyclodextrin formulation. These results may help to formulate paediatric formulations of other poorly water soluble drugs, to aid pharmacy compounding.
[Mh] Termos MeSH primário: Lorazepam/química
[Mh] Termos MeSH secundário: Administração Oral
Adulto
Estabilidade de Medicamentos
Aromatizantes/química
Glicerol/química
Seres Humanos
Pediatria
Polietilenoglicóis/química
Propilenoglicol/química
Solubilidade
Soluções
Água/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Flavoring Agents); 0 (Solutions); 059QF0KO0R (Water); 30IQX730WE (Polyethylene Glycols); 6DC9Q167V3 (Propylene Glycol); O26FZP769L (Lorazepam); PDC6A3C0OX (Glycerol)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170703
[Lr] Data última revisão:
170703
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170128
[St] Status:MEDLINE


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[PMID]:28114315
[Au] Autor:Lin CC; Hung YY; Tsai MC; Huang TL
[Ad] Endereço:Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
[Ti] Título:The Lorazepam and Diazepam Protocol for Catatonia Due to General Medical Condition and Substance in Liaison Psychiatry.
[So] Source:PLoS One;12(1):e0170452, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The lorazepam-diazepam protocol had been proved to rapidly and effectively relieve catatonia in patients with schizophrenia or mood disorder. This study aims to investigate the efficacy of lorazepam-diazepam protocol in catatonia due to general medical conditions (GMC) and substance. METHOD: Patients with catatonia that required psychiatric intervention in various settings of a medical center were included. The lorazepam-diazepam protocol had been used to treat the catatonia due to GMC or substance according to DSM-IV criteria. The treatment response had been assessed by two psychiatrists. RESULTS: Eighteen (85.7%) of 21 catatonic patients due to GMC or substance became free of catatonia after the lorazepam-diazepam protocol. Five (23.8%) of the 21 patients had passed away with various causes of death and wide range of time periods after catatonia. CONCLUSION: Our results showed that the lorazepam-diazepam protocol could rapidly and effectively relieve catatonia due to GMC and substance.
[Mh] Termos MeSH primário: Catatonia/tratamento farmacológico
Diazepam/administração & dosagem
Lorazepam/administração & dosagem
[Mh] Termos MeSH secundário: Adulto
Manual Diagnóstico e Estatístico de Transtornos Mentais
Feminino
Seguimentos
Seres Humanos
Masculino
Meia-Idade
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
O26FZP769L (Lorazepam); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170124
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0170452



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