Base de dados : MEDLINE
Pesquisa : D02.033.100.291.805 [Categoria DeCS]
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  1 / 1992 MEDLINE  
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[PMID]:28800628
[Au] Autor:Salem JE; Germain M; Hulot JS; Voiriot P; Lebourgeois B; Waldura J; Tregouet DA; Charbit B; Funck-Brentano C
[Ad] Endereço:Sorbonne-Universités, UPMC Univ Paris 06, INSERM, UMRS-1166, Institute of Cardio metabolism and Nutrition (ICAN), Paris, France.
[Ti] Título:GENomE wide analysis of sotalol-induced IKr inhibition during ventricular REPOLarization, "GENEREPOL study": Lack of common variants with large effect sizes.
[So] Source:PLoS One;12(8):e0181875, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Many drugs used for non-cardiovascular and cardiovascular purposes, such as sotalol, have the side effect of prolonging cardiac repolarization, which can trigger life-threatening cardiac arrhythmias by inhibiting the potassium-channel IKr (KCNH2). On the electrocardiogram (ECG), IKr inhibition induces an increase in QTc and Tpeak-Tend (TpTe) interval and a decrease of T wave maximal amplitude (TAmp). These changes vary markedly between subjects, suggesting the existence of predisposing genetic factors. 990 healthy individuals, prospectively challenged with an oral 80mg sotalol dose, were monitored for changes in ventricular repolarization on ECG between baseline and 3 hours post dosing. QTc and TpTe increased by 5.5±3.5% and 15±19.6%, respectively, and TAmp decreased by 13.2±15.5%. A principal-component analysis derived from the latter ECG changes was performed. A random subsample of 489 individuals were subjected to a genome-wide-association analysis where 8,306,856 imputed single nucleotide polymorphisms (SNPs) were tested for association with QTc, TpTe and TAmp modulations, as well their derived principal-components, to search for common genetic variants associated with sotalol-induced IKr inhibition. None of the studied SNPs reached the statistical threshold for genome-wide significance. This study supports the lack of common variants with larger effect sizes than one would expect based on previous ECG genome-wide-association studies. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00773201.
[Mh] Termos MeSH primário: Potenciais de Ação/efeitos dos fármacos
Estudo de Associação Genômica Ampla
Ventrículos do Coração/efeitos dos fármacos
Polimorfismo de Nucleotídeo Único/genética
Canais de Potássio/metabolismo
Sotalol/farmacologia
[Mh] Termos MeSH secundário: Adulto
Estudos de Coortes
Demografia
Eletrocardiografia
Feminino
Seres Humanos
Masculino
Fenótipo
Análise de Componente Principal
Reprodutibilidade dos Testes
Sotalol/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Potassium Channels); A6D97U294I (Sotalol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170812
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181875


  2 / 1992 MEDLINE  
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[PMID]:28341360
[Au] Autor:Pokorney SD; Mi X; Hammill BG; Allen LaPointe NM; Curtis LH; Al-Khatib SM
[Ad] Endereço:Electrophysiology Section, Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina. Electronic address: sean.pokorney@duke.edu.
[Ti] Título:Use of Antiarrhythmic Medications in Medicare Part D Patients With an Implantable Cardioverter-Defibrillator and Ventricular Tachycardia.
[So] Source:Am J Cardiol;119(9):1401-1406, 2017 May 01.
[Is] ISSN:1879-1913
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ventricular tachycardia (VT) is common in cardiomyopathy patients with an implantable cardioverter-defibrillator. This analysis evaluated antiarrhythmic medication use and change in use over time in patients with VT and structural heart disease. Query of Medicare claims identified patients with an implantable cardioverter-defibrillator and VT. Patients with atrial fibrillation or supraventricular tachycardia were excluded. Two cohorts were created of patients enrolled in Medicare Part D for the 12 months before 2007 and 2012. Patients were identified through a search for antiarrhythmic medication fills with a supply covering January 1 of the cohort year. Adjusted logistic regression modeling evaluated the association between patient characteristics and antiarrhythmic medication use. The 2007 (n = 2,334) and 2012 (n = 3,892) Medicare Part D cohorts had similar demographics: median age 76 years, 64%-67% male, and 87%-89% white. Of the 2007 cohort, 1,380 (59%) patients were on a beta blocker, and 484 (20.7%) were on an antiarrhythmic medication (70% amiodarone and 20% sotalol). Between 2007 and 2012, there was a statistically significant higher use of any antiarrhythmic medication (p = 0.014), beta blockers (p <0.0001), mexiletine (p = 0.005), and ranolazine (p <0.0001), while amiodarone use remained unchanged (p = 0.53). After multivariable adjustment, male gender and renal disease were associated with higher antiarrhythmic medication use. In conclusion, although antiarrhythmic medication and beta blocker use in patients with VT increased over time, <1 in 4 patients were on an antiarrhythmic medication and only 65% of the patients were on a beta blocker.
[Mh] Termos MeSH primário: Antiarrítmicos/uso terapêutico
Morte Súbita Cardíaca/prevenção & controle
Taquicardia Ventricular/terapia
[Mh] Termos MeSH secundário: Antagonistas Adrenérgicos beta/uso terapêutico
Idoso
Idoso de 80 Anos ou mais
Amiodarona/uso terapêutico
Bases de Dados Factuais
Desfibriladores Implantáveis
Cardioversão Elétrica
Feminino
Seres Humanos
Modelos Logísticos
Masculino
Medicare Part D
Mexiletina/uso terapêutico
Ranolazina/uso terapêutico
Bloqueadores dos Canais de Sódio/uso terapêutico
Sotalol/uso terapêutico
Estados Unidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenergic beta-Antagonists); 0 (Anti-Arrhythmia Agents); 0 (Sodium Channel Blockers); 1U511HHV4Z (Mexiletine); A6D97U294I (Sotalol); A6IEZ5M406 (Ranolazine); N3RQ532IUT (Amiodarone)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170425
[Lr] Data última revisão:
170425
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170326
[St] Status:MEDLINE


  3 / 1992 MEDLINE  
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[PMID]:28283175
[Au] Autor:Li X; Zhang Y; Liu H; Jiang H; Ge H; Zhang Y
[Ad] Endereço:Department of Pediatric Cardiology, Heart Center, The First Hospital of Tsinghua University, Medical Center, Tsinghua University, Beijing, People's Republic of China. Electronic address: li-xiaomei@mail.tsinghua.edu.cn.
[Ti] Título:Efficacy of Intravenous Sotalol for Treatment of Incessant Tachyarrhythmias in Children.
[So] Source:Am J Cardiol;119(9):1366-1370, 2017 May 01.
[Is] ISSN:1879-1913
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Our objective was to evaluate the efficacy and safety of intravenous (IV) sotalol in the treatment of incessant tachyarrhythmias in children with normal cardiac function. Eighty-three children admitted to hospital from October 2011 to December 2014 were treated with IV sotalol or IV sotalol plus IV propafenone. The time to conversion to sinus rhythm and maintaining sinus rhythm were evaluated. Blood pressure, heart rate, QTc, PR intervals, and rhythm were monitored; 50 patients (60%) were converted to sinus rhythm with IV sotalol; time to conversion was 12.0 ± 18.0 hours; 12 additional patients (15%) were converted with IV sotalol combined with IV propafenone; time to conversion was 13.1 ± 17.6 hours. A total of 62 patients (75%) were converted. Success rates of IV sotalol for different tachycardias were similar, whereas the time to conversion differed. The time to conversion for atrioventricular reentrant tachycardia was shorter than atrial tachycardia or atrial flutter (p <0.05). QTc prolongation (from 253 to 486 ms and from 398 ms to 500 ms) was seen in 2 patients (2%) within 48 hours after conversion. The QTc reverted to normal range at 48 and 144 hours, respectively, after withdrawal of IV sotalol. A 1 month old with atrial flutter developed bradycardia (7:1 atrioventricular conduction) 5 minutes after IV sotalol, and heart rate increased gradually after drug withdrawal. No other adverse effects were observed. In conclusion, IV sotalol can be safely and effectively used to terminate pediatric tachycardias in patients with normal cardiac function. No proarrhythmic or significant toxicities were detected. Close monitoring of QTc and heart rate is required after IV sotalol. Adding IV propafenone to IV sotalol in resistant cases enhance conversion.
[Mh] Termos MeSH primário: Antiarrítmicos/uso terapêutico
Propafenona/uso terapêutico
Sotalol/uso terapêutico
Taquicardia/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Fibrilação Atrial/tratamento farmacológico
Flutter Atrial/tratamento farmacológico
Criança
Pré-Escolar
Quimioterapia Combinada
Feminino
Seres Humanos
Lactente
Recém-Nascido
Infusões Intravenosas
Masculino
Taquicardia por Reentrada no Nó Atrioventricular/tratamento farmacológico
Taquicardia Atrial Ectópica/tratamento farmacológico
Taquicardia Ventricular/tratamento farmacológico
Fatores de Tempo
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 68IQX3T69U (Propafenone); A6D97U294I (Sotalol)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170425
[Lr] Data última revisão:
170425
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170312
[St] Status:MEDLINE


  4 / 1992 MEDLINE  
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[PMID]:28189026
[Au] Autor:Stadlmair LF; Letzel T; Drewes JE; Graßmann J
[Ad] Endereço:Chair of Urban Water Systems Engineering, Department of Civil, Geo and Environmental Engineering, Technical University of Munich, Am Coloumbwall 3, 85748 Garching, Germany. Electronic address: lara.stadlmair@tum.de.
[Ti] Título:Mass spectrometry based in vitro assay investigations on the transformation of pharmaceutical compounds by oxidative enzymes.
[So] Source:Chemosphere;174:466-477, 2017 May.
[Is] ISSN:1879-1298
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The ubiquitous presence of trace organic chemicals in wastewater and surface water leads to a growing demand for novel removal technologies. The use of isolated enzymes has been shown to possess the capability for a targeted application but requires a clearer mechanistic understanding. In this study, the potential of peroxidase from horseradish (HRP) and laccase from Pleurotus ostreatus (LccPO) to transform selected trace organic chemicals was studied using mass spectrometry (MS)-based in vitro enzyme assays. Conversion by HRP appeared to be more efficient compared to LccPO. Diclofenac (DCF) and sotalol (STL) were completely transformed by HRP after 4 h and immediate conversion was observed for acetaminophen (APAP). During treatment with LccPO, 60% of DCF was still detectable after 24 h and no conversion was found for STL. APAP was completely transformed after 20 min. Sulfamethoxazole (SMX), carbamazepine (CBZ), ibuprofen (IBP) and naproxen (NAP) were insusceptible to enzymatic conversion. In pharmaceutical mixtures, HRP exhibited a preference for DCF and APAP and the generally less efficient conversion of STL was enhanced in presence of APAP. Transformation product pattern after treatment with HRP revealed polymerization products for DCF while STL showed cleavage reactions. DCF product formation shifted towards a proposed dimeric iminoquinone product in presence of APAP whereas a generally less pronounced product formation in mixtures was observed for STL. In conclusion, the enzymatic treatment approach worked selectively and efficiently for a few pharmaceuticals. However, for application the investigation and possibly immobilization of multiplex enzymes being able to transform diverse chemical structures is recommended.
[Mh] Termos MeSH primário: Peroxidase do Rábano Silvestre/química
Lacase/química
Poluentes Químicos da Água/química
[Mh] Termos MeSH secundário: Acetaminofen/química
Carbamazepina/química
Diclofenaco/química
Ibuprofeno/química
Espectrometria de Massas
Naproxeno/química
Oxirredução
Sotalol/química
Sulfametoxazol/química
Purificação da Água/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Water Pollutants, Chemical); 144O8QL0L1 (Diclofenac); 33CM23913M (Carbamazepine); 362O9ITL9D (Acetaminophen); 57Y76R9ATQ (Naproxen); A6D97U294I (Sotalol); EC 1.10.3.2 (Laccase); EC 1.11.1.- (Horseradish Peroxidase); JE42381TNV (Sulfamethoxazole); WK2XYI10QM (Ibuprofen)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170512
[Lr] Data última revisão:
170512
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170212
[St] Status:MEDLINE


  5 / 1992 MEDLINE  
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[PMID]:28070113
[Au] Autor:Yokoyama H; Nakamura Y; Saito H; Nagayama Y; Hoshiai K; Wada T; Izumi-Nakaseko H; Ando K; Akie Y; Sugiyama A
[Ad] Endereço:Department of Pharmacology, Faculty of Medicine, Toho University.
[Ti] Título:Pharmacological characterization of microminipig as a model to assess the drug-induced cardiovascular responses for non-clinical toxicity and/or safety pharmacology studies.
[So] Source:J Toxicol Sci;42(1):93-101, 2017.
[Is] ISSN:1880-3989
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:We tried to establish the halothane-anesthetized microminipigs as an alternative animal model for non-clinical toxicity and/or safety pharmacology studies. In order to characterize the halothane-anesthetized microminipigs, we firstly clarified the effects of halothane anesthesia on their cardiovascular system (n = 5). Then, we examined the cardiovascular effects of dl-sotalol in doses of 0.1, 0.3 and 1 mg/kg, i.v. on the halothane-anesthetized microminipigs (n = 6). Induction of the halothane anesthesia by itself prolonged the QT interval as well as QTcF, suggesting that the halothane anesthesia can reduce the cardiac repolarization reserve in microminipigs like in dogs. dl-Sotalol showed more potent negative chronotropic, dromotropic and hypotensive effects together with repolarization delay in microminipigs than in dogs, although each cardiovascular response to dl-sotalol was directionally similar between them, suggesting greater basal sympathetic tone and/or smaller volume of distribution of the drug in microminipigs than in dogs. Analyses of proarrhythmic surrogate markers indicate that T -T and short-term variability of QT interval may be more sensitive to detect the dl-sotalol-induced direct electrophysiological changes in microminipigs than in dogs, but its reverse will be true for J-T c. Thus, these results may help better understand the drug-induced cardiovascular responses in microminipigs.
[Mh] Termos MeSH primário: Antagonistas Adrenérgicos beta/farmacologia
Anestésicos Inalatórios/farmacologia
Eletrocardiografia/efeitos dos fármacos
Halotano/farmacologia
Modelos Animais
Sotalol/farmacologia
Porco Miniatura
[Mh] Termos MeSH secundário: Anestesia
Animais
Síndrome do QT Longo/induzido quimicamente
Masculino
Suínos
Testes de Toxicidade/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenergic beta-Antagonists); 0 (Anesthetics, Inhalation); A6D97U294I (Sotalol); UQT9G45D1P (Halothane)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170523
[Lr] Data última revisão:
170523
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170111
[St] Status:MEDLINE
[do] DOI:10.2131/jts.42.93


  6 / 1992 MEDLINE  
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[PMID]:28001104
[Au] Autor:Newhard D; Jung S
[Ti] Título:What Is Your Diagnosis?
[So] Source:J Am Vet Med Assoc;250(1):47-50, 2017 Jan 01.
[Is] ISSN:1943-569X
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Aneurisma Dissecante/veterinária
Doenças do Gato/diagnóstico por imagem
Insuficiência Cardíaca/veterinária
[Mh] Termos MeSH secundário: Aneurisma Dissecante/diagnóstico por imagem
Aneurisma Dissecante/tratamento farmacológico
Animais
Gatos
Ecocardiografia/veterinária
Enalapril/administração & dosagem
Enalapril/uso terapêutico
Furosemida/administração & dosagem
Furosemida/uso terapêutico
Insuficiência Cardíaca/diagnóstico por imagem
Insuficiência Cardíaca/tratamento farmacológico
Masculino
Radiografia Torácica/veterinária
Sotalol/administração & dosagem
Sotalol/uso terapêutico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
69PN84IO1A (Enalapril); 7LXU5N7ZO5 (Furosemide); A6D97U294I (Sotalol)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161222
[St] Status:MEDLINE
[do] DOI:10.2460/javma.250.1.47


  7 / 1992 MEDLINE  
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[PMID]:27956191
[Au] Autor:Rahman Z; Zidan AS; Korang-Yeboah M; Yang Y; Siddiqui A; Shakleya D; Khan MA; Cruz C; Ashraf M
[Ad] Endereço:Division of Product Quality and Research, Center for Drug Evaluation and Research, Food and Drug Administration, MD, United States; Irma Lerma Rangel College of Pharmacy, Texas A&M University, United States. Electronic address: rahman.ziyaur@gmail.com.
[Ti] Título:Effects of excipients and curing process on the abuse deterrent properties of directly compressed tablets.
[So] Source:Int J Pharm;517(1-2):303-311, 2017 Jan 30.
[Is] ISSN:1873-3476
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The objective of the present investigation was to understand the effects of excipients and curing process on the abuse deterrent properties (ADP) of Polyox™ based directly compressible abuse deterrent tablet formulations (ADFs). The excipients investigated were lactose (monohydrate or anhydrous), microcrystalline cellulose and hydroxypropyl methylcellulose. The ADPs studied were tablet crush resistance or hardness, particle size distribution following mechanical manipulation, drug extraction in water and alcohol, syringeability and injectability. Other non-ADPs such as surface morphology and tablet dissolution were also studied. It was found that presence of 50% or more of water soluble or swellable excipient in the ADF tablets significantly affected the tablet hardness, particle size distribution following mechanical manipulation and drug extraction while small amount (5%) of excipients had either minimal or no effect on ADPs of these tablets. Addition of high molecular weight HPMC (K 100M) affected syringeability and injectability of ADF. Curing process was found to affect ADPs (hardness, particle size distribution, drug extraction and syringeability and injectability) when compared with uncured tablet. In conclusion, addition of large amount of excipients, especially water soluble ones in Polyox™ based ADF tablets increase the risk of abuse by various routes of administration.
[Mh] Termos MeSH primário: Composição de Medicamentos/métodos
Excipientes/química
Lactose/química
Comprimidos/química
[Mh] Termos MeSH secundário: Celulose/química
Liberação Controlada de Fármacos
Dureza
Derivados da Hipromelose/química
Injeções
Tamanho da Partícula
Polietilenoglicóis/química
Solubilidade
Sotalol/química
Sotalol/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Excipients); 0 (Polyox WSR-301); 0 (Tablets); 30IQX730WE (Polyethylene Glycols); 3NXW29V3WO (Hypromellose Derivatives); 9004-34-6 (Cellulose); A6D97U294I (Sotalol); J2B2A4N98G (Lactose); OP1R32D61U (microcrystalline cellulose)
[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:161214
[St] Status:MEDLINE


  8 / 1992 MEDLINE  
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[PMID]:27882422
[Au] Autor:Ge H; Li X; Liu H; Jiang H
[Ad] Endereço:Department of Pediatric Cardiology, Heart Center, The First Hospital of Tsinghua University, Medical Center, Tsinghua University, Beijing, China.
[Ti] Título:Predictors of Pharmacological Therapy of Ectopic Atrial Tachycardia in Children.
[So] Source:Pediatr Cardiol;38(2):289-295, 2017 Feb.
[Is] ISSN:1432-1971
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ectopic atrial tachycardia (EAT) is a relatively common type of supraventricular tachycardia in the pediatric population, and it can be resistant to antiarrhythmic drugs and lead to tachycardia-induced cardiomyopathy (TIC) if not properly managed. The purpose of this study was to determine the predictors of the response to pharmacological therapy in children with EAT. From January 2009 to April 2014, 115 children were admitted to our hospital with a diagnosis of EAT and placed on antiarrhythmic drugs. We examined the clinical history, response to therapy, and follow-up of the children. The incidence of TIC secondary to EAT was 22.6% (n = 26) in children. Incessant EAT accounted for 44.3% of all patients. Control of EAT with antiarrhythmic therapy was achieved in 73.9% (n = 85) of the children. The combination of sotalol and propafenone performed well in controlling EAT in children [complete control in 35 (49.3%) of 71]. The mean time of conversion to sinus rhythm was 24 days, and the mean duration of therapy was 11 months in children with resolution. Multivariate predictors of the control of EAT were age at presentation (OR 0.289, P = 0.038) and tachycardia type (OR 0.276, P = 0.006). TIC occurs in 22.6% of children with EAT. Incessant EAT is more frequently complicated by TIC. Independent factors associated with a good response to pharmacological therapy include a younger age at presentation and non-incessant tachycardia in children with EAT.
[Mh] Termos MeSH primário: Antiarrítmicos/uso terapêutico
Cardiomiopatias/epidemiologia
Propafenona/uso terapêutico
Sotalol/uso terapêutico
Taquicardia Atrial Ectópica/complicações
Taquicardia Atrial Ectópica/tratamento farmacológico
[Mh] Termos MeSH secundário: Amiodarona/uso terapêutico
Criança
Pré-Escolar
China
Quimioterapia Combinada
Feminino
Seguimentos
Seres Humanos
Lactente
Modelos Logísticos
Masculino
Metoprolol/uso terapêutico
Análise Multivariada
Estudos Retrospectivos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 68IQX3T69U (Propafenone); A6D97U294I (Sotalol); GEB06NHM23 (Metoprolol); N3RQ532IUT (Amiodarone)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161125
[St] Status:MEDLINE
[do] DOI:10.1007/s00246-016-1511-7


  9 / 1992 MEDLINE  
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[PMID]:27756610
[Au] Autor:Ishizaka T; Yoshimatsu Y; Maeda Y; Takasaki W; Chiba K; Mori K
[Ad] Endereço:Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 134-8630, Japan. Electronic address: ishizaka.tomomichi.du@daiichisankyo.co.jp.
[Ti] Título:Promising approach for the preclinical assessment of cardiac risks using left ventricular pressure-volume loop analyses in anesthetized monkeys.
[So] Source:J Pharmacol Toxicol Methods;84:1-10, 2017 Mar - Apr.
[Is] ISSN:1873-488X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Load-independent cardiac parameters obtained from the ventricular pressure-volume relationship are recognized as gold standard indexes for evaluating cardiac inotropy. In this study, for better analyses of cardiac risks, load-independent pressure-volume loop parameters were assessed in addition to load-dependent inotropic, hemodynamic and electrocardiographic changes in isoflurane-anesthetized monkeys. METHODS: The animals were given milrinone (a PDE 3 inhibitor), metoprolol (a ß-blocker), or dl-sotalol (a ß+I blocker) intravenously over 10min at two dose levels including clinically relevant doses (n=5/drug). RESULTS: Milrinone and metoprolol produced positive and negative inotropy, respectively. These effects were detected as changes in the slope of the preload-recruitable stroke work, which is a load-independent inotropic parameter. However, dl-sotalol did not alter the slope of the preload-recruitable stroke work. That means dl-sotalol produced no inotropy, although it decreased load-dependent inotropic parameters, including maximal upstroke velocity of left ventricular pressure, attributable to decreased heart rate and blood pressure. Other typical pharmacological effects of the compounds tested were also detected. Both ß-blockers produced PR prolongation, decreased left ventricular end-systolic pressure, increased left ventricular end-diastolic pressure, and increased maximal descending velocity of left ventricular pressure and time constant for isovolumic relaxation. dl-Sotalol also prolonged heart-rate-corrected QT interval. Milrinone induced reflex tachycardia, PR shortening, and decreased left ventricular end-diastolic pressure. DISCUSSION: The overall assessment by not only load-dependent inotropic parameters but also load-independent parameters obtained from the ventricular pressure-volume loop analysis using monkeys can provide further appropriate information for the assessment of drug-induced cardiac risks.
[Mh] Termos MeSH primário: Antagonistas Adrenérgicos beta/efeitos adversos
Anestesia
Cardiopatias/induzido quimicamente
Inibidores da Fosfodiesterase 3/efeitos adversos
Pressão Ventricular/efeitos dos fármacos
[Mh] Termos MeSH secundário: Antagonistas Adrenérgicos beta/farmacologia
Anestesia/métodos
Animais
Débito Cardíaco/efeitos dos fármacos
Débito Cardíaco/fisiologia
Cardiotônicos/efeitos adversos
Cardiotônicos/farmacologia
Avaliação Pré-Clínica de Medicamentos/métodos
Feminino
Cardiopatias/fisiopatologia
Frequência Cardíaca/efeitos dos fármacos
Frequência Cardíaca/fisiologia
Hemodinâmica/efeitos dos fármacos
Hemodinâmica/fisiologia
Macaca fascicularis
Masculino
Metoprolol/efeitos adversos
Metoprolol/farmacologia
Milrinona/efeitos adversos
Milrinona/farmacologia
Contração Miocárdica/efeitos dos fármacos
Contração Miocárdica/fisiologia
Inibidores da Fosfodiesterase 3/farmacologia
Fatores de Risco
Sotalol/efeitos adversos
Sotalol/farmacologia
Pressão Ventricular/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenergic beta-Antagonists); 0 (Cardiotonic Agents); 0 (Phosphodiesterase 3 Inhibitors); A6D97U294I (Sotalol); GEB06NHM23 (Metoprolol); JU9YAX04C7 (Milrinone)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170707
[Lr] Data última revisão:
170707
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161107
[St] Status:MEDLINE


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[PMID]:27903390
[Au] Autor:He R; Du X; Liu SW; Sun LJ; Li Y; Zeng H; Li YY; Sun C; Zhang Y; Ma CS; Gao W
[Ad] Endereço:*Department of Cardiology, Peking University Third Hospital, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of Health, Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Beijing 100191, China.
[Ti] Título:[Current status of antiarrhythmic drug use and safety assessment in Chinese patients with atrial fibrillation].
[So] Source:Zhonghua Xin Xue Guan Bing Za Zhi;44(11):935-939, 2016 Nov 24.
[Is] ISSN:0253-3758
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To investigate the current status of antiarrhythmic drugs (AADs) use in Chinese patients with atrial fibrillation(AF) and assess the safety of AADs in this patient cohort. From January 2011 to December 2013, a total of 4 008 AF patients treated with AADs was enrolled in this study and patients were followed up for 24 months. Detailed information of prescribed drug, the causes of drug discontinuation and side effects were recorded. Amiodarone was prescribed to 64.3%(2 579 cases) and propafenone to 31.1%(1 247 cases) of the enrolled patients, only 148 patients(3.7%) were treated with sotalol and 34 patients (0.8%) were treated with moracizine. The prevalence of heart failure (4.0%(102/2 579) vs. 1.4%(17/1 247, <0.001), coronary heart disease (13.5% (348/2 579) vs. 7.4%(93/1 247), <0.001) and non-ischemic cardiomyopathy (3.1%(78/2 579) vs. 0.7%(9/1 247), <0.001) was significantly higher in patients treated with amiodarone than in the patients treated with propafenone. During the follow-up period, the discontinuation rate of amiodarone, propafenone, sotalol and moracizine was 28.8%(743/2 579), 25.1%(313/1 247), 14.2%(21/148) and 32.4%(11/34) respectively. The reasons of discontinuing amiodarone were: follow physicians' decision (75.7%, 563 cases), no effect (3.0%, 22 cases), side effects (4.3%, 32 cases) and patients' own decision (17.0%, 126 cases). The side effects of amiodarone included thyroid dysfunction (56.3%, 18 cases), bradycardia (12.5%, 4 cases), interstitial pneumonitis/pulmonary interstitial fibrosis (6.2%, 2 cases) and others (gastrointestinal symptom, rash, hepatic dysfunction, etc.). Amiodarone and propafenone are the most common AADs used in Chinese patients with atrial fibrillation. The prescription of AADs is essentially in accordance to the guideline of AF treatment. However, the discontinuation rates of AADs are high in Chinese AF patients. Lacking of better AADs is still a major problem in AF pharmacotherapy. Clinical Trial Registry Chinese Clinical Trial Registry, ChiCTR-OCH-13003729.
[Mh] Termos MeSH primário: Fibrilação Atrial
[Mh] Termos MeSH secundário: Amiodarona
Antiarrítmicos
Seres Humanos
Propafenona
Sistema de Registros
Segurança
Sotalol
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 68IQX3T69U (Propafenone); A6D97U294I (Sotalol); N3RQ532IUT (Amiodarone)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170816
[Lr] Data última revisão:
170816
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161202
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0253-3758.2016.11.007



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