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[PMID]:27723808
[Au] Autor:Sasaoka S; Matsui T; Hane Y; Abe J; Ueda N; Motooka Y; Hatahira H; Fukuda A; Naganuma M; Hasegawa S; Kinosada Y; Nakamura M
[Ad] Endereço:Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan.
[Ti] Título:Time-to-Onset Analysis of Drug-Induced Long QT Syndrome Based on a Spontaneous Reporting System for Adverse Drug Events.
[So] Source:PLoS One;11(10):e0164309, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Long QT syndrome (LQTS) is a disorder of the heart's electrical activity that infrequently causes severe ventricular arrhythmias such as a type of ventricular tachycardia called torsade de pointes (TdP) and ventricular fibrillation, which can be fatal. There have been no previous reports on the time-to-onset for LQTS based on data from spontaneous reporting systems. The aim of this study was to assess the time-to-onset of LQTS according to drug treatment. We analyzed the association between 113 drugs in 37 therapeutic categories and LQTS including TdP using data obtained from the Japanese Adverse Drug Event Report database. For signal detection, we used the reporting odds ratio (ROR). Furthermore, we analyzed the time-to-onset data and assessed the hazard type using the Weibull shape parameter. The RORs (95% confidence interval) for bepridil, amiodarone, pilsicainide, nilotinib, disopyramide, arsenic trioxide, clarithromycin, cibenzoline, donepezil, famotidine, sulpiride, and nifekalant were 174.4 (148.6-204.6), 17.3 (14.7-20.4), 52.0 (43.4-62.4), 13.9 (11.5-16.7), 69.3 (55.3-86.8), 54.2 (43.2-68.0), 4.7 (3.8-5.8), 19.9 (15.9-25.0), 8.1 (6.5-10.1), 3.2 (2.5-4.1), 7.1 (5.5-9.2), and 254.8 (168.5-385.4), respectively. The medians and quartiles of time-to-onset for aprindine (oral) and bepridil were 20.0 (11.0-35.8) and 18.0 (6.0-43.0) days, respectively. The lower 95% confidence interval of the shape parameter ß of bepridil was over 1 and the hazard was considered to increase over time.Our study indicated that the pattern of LQTS onset might differ among drugs. Based on these results, careful long-term observation is recommended, especially for specific drugs such as bepridil and aprindine. This information may be useful for the prevention of sudden death following LQTS and for efficient therapeutic planning.
[Mh] Termos MeSH primário: Aprindina/efeitos adversos
Bepridil/efeitos adversos
Bases de Dados Factuais
Síndrome do QT Longo
[Mh] Termos MeSH secundário: Administração Oral
Aprindina/administração & dosagem
Bepridil/administração & dosagem
Feminino
Seres Humanos
Síndrome do QT Longo/induzido quimicamente
Síndrome do QT Longo/epidemiologia
Síndrome do QT Longo/fisiopatologia
Masculino
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
5Y48085P9Q (Aprindine); 755BO701MA (Bepridil)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170428
[Lr] Data última revisão:
170428
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161011
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0164309


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[PMID]:26162947
[Au] Autor:Nakatani Y; Sakamoto T; Nishida K; Kataoka N; Yamaguchi Y; Sakabe M; Fujiki A; Mizumaki K; Inoue H
[Ad] Endereço:Second Department of Internal Medicine, University of Toyama, Toyama, Japan.
[Ti] Título:Bepridil enhances aprindine-induced prolongation of atrial effective refractory period in a canine atrial rapid pacing model.
[So] Source:J Cardiol;66(5):445-50, 2015 Nov.
[Is] ISSN:1876-4738
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Bepridil in combination with aprindine could restore sinus rhythm in patients with persistent atrial fibrillation (AF). The present study aimed to investigate the electrophysiological mechanisms of the combined effects of bepridil and aprindine. METHODS: Subjects consisted of 6 dogs without and 6 dogs with atrial rapid pacing (ARP) carried out at 400 bpm for 2 weeks. Bepridil was administered for 1 week in both groups (ARP dogs were administered bepridil in the second week). The electrophysiological effects of the intravenous administration of aprindine (1mg/kg) were evaluated before and after the administration of bepridil. RESULTS: In non-paced dogs, the atrial effective refractory period (AERP) became longer after the administration of bepridil (from 151±10 ms to 170±7 ms, p<0.05); however, no additional AERP prolongation was observed after the acute administration of aprindine. In ARP dogs, the AERP shortened with ARP for a week, and tended to lengthen after the administration of bepridil (from 93±5 ms to 118±9 ms, p=0.08). In these dogs, the acute aprindine administration did not prolong the AERP before the administration of bepridil, although it did after the administration of bepridil (from 118±9 ms to 142±8 ms, p<0.01). AF duration did not change after the administration of bepridil, although it shortened significantly after the additional administration of aprindine (from 2.2±0.3s to 1.4±0.8s, p<0.05). CONCLUSIONS: Bepridil enhances the effect of aprindine for the prevention of AF by reversing atrial electrical remodeling.
[Mh] Termos MeSH primário: Antiarrítmicos/administração & dosagem
Aprindina/administração & dosagem
Fibrilação Atrial/tratamento farmacológico
Função Atrial/efeitos dos fármacos
Bepridil/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Fibrilação Atrial/veterinária
Remodelamento Atrial/efeitos dos fármacos
Cães
Quimioterapia Combinada/métodos
Átrios do Coração/efeitos dos fármacos
Átrios do Coração/fisiopatologia
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 5Y48085P9Q (Aprindine); 755BO701MA (Bepridil)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:151013
[Lr] Data última revisão:
151013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150712
[St] Status:MEDLINE


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[PMID]:19336897
[Au] Autor:Tsuchishita Y; Fukumoto K; Kusumoto M; Ueno K
[Ad] Endereço:Department of Pharmacy, Maizuru Kyosai Hospital, Federation of National Public Services and Affiliated Mutual Associations, Japan.
[Ti] Título:Relationship between serum aprindine concentration and neurologic side effects in Japanese.
[So] Source:Biol Pharm Bull;32(4):637-9, 2009 Apr.
[Is] ISSN:0918-6158
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to evaluate the relationship between the neurologic side effects associated with serum aprindine concentrations and the safety range of aprindine for the prevention of neurologic side effects in 142 Japanese inpatients. Serum aprindine concentrations were determined by high-performance liquid chromatography. A poor positive correlation was observed between dose and serum aprindine concentration (r(2)=0.0419, p=0.0114), and between age and ratio of serum aprindine concentration to the dose per body weight of aprindine (r(2)=0.0159, p=0.121). When aprindine concentration was <1 microg/ml, almost no patients showed neurologic side effects associated with aprindine. On the other hand, about 50% of the patients showed neurologic side effects when aprindine concentrations were >1 microg/ml. Here, the side effects associated with aprindine such as dizziness or intention tremors were observed in 15 patients, which later disappeared after discontinuance of aprindine therapy or a decrease in the dose. In conclusion, serum aprindine concentration should be maintained under approximately 1 microg/ml in Japanese patients to prevent neurologic side effects.
[Mh] Termos MeSH primário: Antiarrítmicos/efeitos adversos
Antiarrítmicos/sangue
Aprindina/efeitos adversos
Aprindina/sangue
Síndromes Neurotóxicas/sangue
[Mh] Termos MeSH secundário: Adulto
Fatores Etários
Idoso
Idoso de 80 Anos ou mais
Relação Dose-Resposta a Droga
Feminino
Seres Humanos
Japão/epidemiologia
Masculino
Meia-Idade
Síndromes Neurotóxicas/epidemiologia
Síndromes Neurotóxicas/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 5Y48085P9Q (Aprindine)
[Em] Mês de entrada:0905
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:090402
[St] Status:MEDLINE


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[PMID]:17878753
[Au] Autor:Fujiki A; Sakamoto T; Nishida K; Mizumaki K; Inoue H
[Ad] Endereço:Second Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan. fujiki@med.u-toyoma.ac.jp
[Ti] Título:Relation of interleukin-6 and C-reactive protein levels to sinus maintenance after pharmacological cardioversion in persistent atrial fibrillation.
[So] Source:J Cardiovasc Pharmacol;50(3):264-6, 2007 Sep.
[Is] ISSN:0160-2446
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECT: The aim of this study was to investigate whether interleukin-6 (IL-6) and C-reactive protein (CRP) have significant relation to sinus maintenance after pharmacological conversion of long-lasting atrial fibrillation (AF) with respect to use of renin-angiotensin-aldosterone system (RAS) inhibitors. METHODS: We studied 35 consecutive patients with AF lasting > or =1 month who had successful pharmacological cardioversion with bepridil alone or in combination with aprindine. The IL-6 and CRP levels in plasma were measured after pharmacological restoration of sinus rhythm. RESULTS: During the 1-year follow-up period, sinus rhythm was maintained in 20 patients (Group I), and the other 15 patients had recurrence of AF (Group II). Both plasma levels of IL-6 and CRP were significantly lower in Group I than in Group II (IL-6: 1.19 +/- 0.51 versus 1.84 +/- 0.66 ng/L, P < 0.005; CRP: 0.59 +/- 0.40 versus 1.24 +/- 0.79 mg/L, P < 0.005). The use of RAS inhibitors and left atrial dimension and the left ventricular ejection fraction showed no differences between the 2 groups. There was significant positive correlation between levels of IL-6 and CRP. CONCLUSION: In long-lasting persistent AF, lower levels of IL-6 and CRP appear to be associated with maintenance of sinus rhythm after pharmacological cardioversion irrespective of the use of RAS inhibitors. Further studies are needed to clarify the role of RAS inhibitors.
[Mh] Termos MeSH primário: Antiarrítmicos/farmacologia
Fibrilação Atrial/tratamento farmacológico
Proteína C-Reativa/metabolismo
Interleucina-6/metabolismo
[Mh] Termos MeSH secundário: Idoso
Antiarrítmicos/uso terapêutico
Aprindina/farmacologia
Aprindina/uso terapêutico
Fibrilação Atrial/fisiopatologia
Bepridil/farmacologia
Bepridil/uso terapêutico
Quimioterapia Combinada
Ecocardiografia
Feminino
Seguimentos
Seres Humanos
Interleucina-6/sangue
Masculino
Meia-Idade
Recidiva
Sistema Renina-Angiotensina/efeitos dos fármacos
Fatores de Tempo
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 0 (Interleukin-6); 5Y48085P9Q (Aprindine); 755BO701MA (Bepridil); 9007-41-4 (C-Reactive Protein)
[Em] Mês de entrada:0711
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:070920
[St] Status:MEDLINE


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[PMID]:16936425
[Au] Autor:Fujiki A; Sakamoto T; Iwamoto J; Nishida K; Nagasawa H; Mizumaki K; Inoue H
[Ad] Endereço:The Second Department of Internal Medicine, Faculty of Medicine, University of Toyama, Japan. fujiki@med.u-toyama.ac.jp
[Ti] Título:Pharmacological cardioversion of persistent atrial fibrillation with and without a history of drug-resistant paroxysmal atrial fibrillation.
[So] Source:Circ J;70(9):1138-41, 2006 Sep.
[Is] ISSN:1346-9843
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Suppression by antiarrhythmic drugs of the maintenance mechanisms could convert persistent atrial fibrillation (AF) to sinus rhythm (SR). Whether a history of drug-resistant paroxysmal AF (PAF) would affect the outcome of pharmacological conversion of persistent AF by bepridil or in combination with aprindine was evaluated in the present study. METHODS AND RESULTS: The study group comprised 51 consecutive patients (24 men, 61+/-8 years) undergoing pharmacological conversion of persistent AF lasting >1 month. Drug-resistant PAF was defined as AF and at least 2 ineffective antiarrhythmic drugs for suppression of AF recurrence. Fast Fourier transform analysis of fibrillation waves was used to measure fibrillation cycle length (FCL) from the peak frequency. Fifteen patients had a history of drug-resistant PAF (Group I), and the remaining 36 did not (Group II) before diagnosis of persistent AF. Ten patients (67%) in Group I and 26 patients (72%) in Group II were restored to SR by bepridil alone or in combination with aprindine after 29+/-15 days of drug administration. Before conversion to SR, bepridil increased the FCL more in Group II than in Group I. During a 12-month follow-up period, 4 of 10 patients in Group I and 2 of 26 patients in Group II (p<0.01) had recurrence of persistent AF with bepridil alone or in combination with aprindine. CONCLUSIONS: A history of drug-resistant PAF does not affect the efficacy of pharmacological conversion by bepridil or in combination with aprindine. However, recurrence of AF was significantly higher in patients with such a history.
[Mh] Termos MeSH primário: Antiarrítmicos/administração & dosagem
Aprindina/administração & dosagem
Fibrilação Atrial/terapia
Bepridil/administração & dosagem
Resistência a Medicamentos/efeitos dos fármacos
Cardioversão Elétrica
[Mh] Termos MeSH secundário: Combinação de Medicamentos
Eletrocardiografia/métodos
Feminino
Seguimentos
Seres Humanos
Masculino
Meia-Idade
[Pt] Tipo de publicação:CLINICAL TRIAL; COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 0 (Drug Combinations); 5Y48085P9Q (Aprindine); 755BO701MA (Bepridil)
[Em] Mês de entrada:0609
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:060829
[St] Status:MEDLINE


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[PMID]:16613191
[Au] Autor:Sugi K
[Ad] Endereço:Division of Cardiovascular Medicine, Toho University Ohashi Medical Center.
[Ti] Título:[Strategy for cardiac arrhythmias in acute coronary syndrome].
[So] Source:Nihon Rinsho;64(4):729-33, 2006 Apr.
[Is] ISSN:0047-1852
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:Acute coronary syndrome causes several types of arrhythmia because of its electrical instability and ischemia. The most important arrhythmia is ventricular tachycardia which degenerates to ventricular fibrillation. Prompt direct current cardioversion will be needed and prevention of ventricular tachyarrhythmia by potassium channel blocker became more popular in Japan. Nifekalant or amiodarone should be selected. Atrial fibrillation also occurred in the patients with acute coronary syndrome, and it may deteriorate hemodynamics condition. Therefore, termination and prevention of atrial fibrillation is another important issue in acute coronary syndrome. Aprindine, amiodarone, or bepridil will be the choice to prevent recurrent atrial fibrillation after direct current cardioversion.
[Mh] Termos MeSH primário: Angina Instável/complicações
Antiasmáticos/uso terapêutico
Cardioversão Elétrica/métodos
Infarto do Miocárdio/complicações
Taquicardia Ventricular/etiologia
Taquicardia Ventricular/terapia
[Mh] Termos MeSH secundário: Amiodarona/uso terapêutico
Aprindina/uso terapêutico
Fibrilação Atrial/prevenção & controle
Fibrilação Atrial/terapia
Bepridil/uso terapêutico
Seres Humanos
Bloqueadores dos Canais de Potássio/uso terapêutico
Pirimidinonas/uso terapêutico
Recidiva
Síndrome
Taquicardia Ventricular/prevenção & controle
Fibrilação Ventricular/etiologia
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Asthmatic Agents); 0 (Potassium Channel Blockers); 0 (Pyrimidinones); 5VZ7GZM43E (nifekalant); 5Y48085P9Q (Aprindine); 755BO701MA (Bepridil); N3RQ532IUT (Amiodarone)
[Em] Mês de entrada:0605
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:060415
[St] Status:MEDLINE


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[PMID]:16508157
[Au] Autor:Taguchi M; Fujiki A; Iwamoto J; Inoue H; Tahara K; Saigusa K; Horiuchi I; Oshima Y; Hashimoto Y
[Ad] Endereço:Graduate School of Pharmaceutical Sciences, University of Toyama, Sugitani, Japan.
[Ti] Título:Nonlinear mixed effects model analysis of the pharmacokinetics of routinely administered bepridil in Japanese patients with arrhythmias.
[So] Source:Biol Pharm Bull;29(3):517-21, 2006 Mar.
[Is] ISSN:0918-6158
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:This study was performed to evaluate variability in the pharmacokinetics of bepridil in 38 Japanese patients with arrhythmias, and to investigate the effects of aprindine as well as CYP2D6 and CYP3A5 polymorphisms on the oral clearance of bepridil. We determined the polymorphic alleles of CYP2D6 and CYP3A5 in each subject. The plasma concentration of bepridil at steady-state following repetitive oral administration was measured with an HPLC-based method, and the oral clearance was estimated using the nonlinear mixed effects model (NONMEM) program. Mean oral clearance was significantly greater in the patients with the CYP2D6*10 allele than in those without it. On the other hand, no significant effect of the CYP3A5 polymorphism was observed on the pharmacokinetics of bepridil. In addition, aprindine seemed to reduce the oral clearance of bepridil in the patients with the CYP2D6*10 allele.
[Mh] Termos MeSH primário: Antiarrítmicos/farmacocinética
Antiarrítmicos/uso terapêutico
Arritmias Cardíacas/tratamento farmacológico
Arritmias Cardíacas/metabolismo
Bepridil/farmacocinética
Bepridil/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Idoso
Algoritmos
Aprindina/farmacocinética
Aprindina/uso terapêutico
Citocromo P-450 CYP2D6/genética
Citocromo P-450 CYP2D6/metabolismo
Citocromo P-450 CYP3A
Sistema Enzimático do Citocromo P-450/genética
Sistema Enzimático do Citocromo P-450/metabolismo
Interpretação Estatística de Dados
Quimioterapia Combinada
Feminino
Genótipo
Seres Humanos
Masculino
Meia-Idade
Dinâmica não Linear
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 5Y48085P9Q (Aprindine); 755BO701MA (Bepridil); 9035-51-2 (Cytochrome P-450 Enzyme System); EC 1.14.14.1 (CYP3A5 protein, human); EC 1.14.14.1 (Cytochrome P-450 CYP2D6); EC 1.14.14.1 (Cytochrome P-450 CYP3A)
[Em] Mês de entrada:0605
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:060302
[St] Status:MEDLINE


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[PMID]:16275488
[Au] Autor:Nogami Y; Takase B; Matsui T; Hattori H; Hamabe A; Fujita M; Ohsuzu F; Ishihara M; Maekara T
[Ad] Endereço:Surgery-2, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
[Ti] Título:Effect of antiarrhythmic agents on heart rate variability indices after myocardial infarction: comparative experimental study of aprindine and procainamide.
[So] Source:Biomed Pharmacother;59 Suppl 1:S169-73, 2005 Oct.
[Is] ISSN:0753-3322
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:The cardiac arrhythmic suppression trial (CAST) reported that antiarrhythmic treatments in post-myocardial infarction (MI) patients resulted in poor outcome and decreased in heart rate variability indices (HRV). The goal of the present study was to determine whether aprindine and procainamide, antiarrhythmic agents that increase HRV, result in beneficial effects in post-MI rabbits. Four weeks before experiment, MI was induced in four rabbits by ligating the major branch of left coronary artery. A total of eight rabbits (four post-MI and four normal rabbits) were randomly assigned to treatment with either intravenous aprindine (1 mg/kg) or intravenous procainamide (15 mg/kg). Frequency domain HRV (low frequency spectra, LF, 0.04-0.15 Hz; high frequency spectra, HF, 0.15-0.40 Hz) were assessed by MemCalc software. Aprindine significantly increased HF and LF in both MI and normal rabbits, whereas procainamide tended to decrease HF and LF in MI and normal rabbits (in total rabbits; aprindine, LF, from 6.3 +/- 7.9 to 16.5 +/- 15.0 ms(2)/Hz, P < 0.05; HF, from 8.0 +/- 11.7 to 17.5 +/- 15.0 ms(2)/Hz, P < 0.05; procainamide, LF, from 4.9 +/- 7.4 to 4.8 +/- 8.5 ms(2)/Hz, NS; HF, from 11.1 +/- 23.0 to 5.1 +/- 10.6 ms(2)/Hz, NS). Under pharmacological denervation with propranolol (0.1 mg/kg) and atropine (0.04 mg/kg), aprindine increased LF and HF (LF, from 0.2 +/- 0.2 to 0.8 +/- 0.7 ms(2)/Hz, P < 0.05; HF, from 0.1 +/- 0.0 to 0.2 +/- 0.0 ms(2)/Hz, P < 0.05). These data suggest that aprindine can increase HRV in post-MI rabbits. Further experiments in human subjects would be of benefit.
[Mh] Termos MeSH primário: Antiarrítmicos/farmacologia
Aprindina/farmacologia
Arritmias Cardíacas/tratamento farmacológico
Frequência Cardíaca/efeitos dos fármacos
Infarto do Miocárdio/fisiopatologia
Procainamida/farmacologia
[Mh] Termos MeSH secundário: Antagonistas Adrenérgicos beta/farmacologia
Animais
Arritmias Cardíacas/etiologia
Arritmias Cardíacas/fisiopatologia
Atropina/farmacologia
Pressão Sanguínea/efeitos dos fármacos
Denervação
Masculino
Infarto do Miocárdio/complicações
Propranolol/farmacologia
Coelhos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenergic beta-Antagonists); 0 (Anti-Arrhythmia Agents); 5Y48085P9Q (Aprindine); 7C0697DR9I (Atropine); 9Y8NXQ24VQ (Propranolol); L39WTC366D (Procainamide)
[Em] Mês de entrada:0512
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:051109
[St] Status:MEDLINE


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[PMID]:15882977
[Au] Autor:Tanaka H; Miake J; Notsu T; Sonyama K; Sasaki N; Iitsuka K; Kato M; Taniguchi S; Igawa O; Yoshida A; Shigemasa C; Hoshikawa Y; Kurata Y; Kuniyasu A; Nakayama H; Inagaki N; Nanba E; Shiota G; Morisaki T; Ninomiya H; Kitakaze M; Hisatome I
[Ad] Endereço:Division of Cardiovascular Medicine, The First Department of Internal Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
[Ti] Título:Proteasomal degradation of Kir6.2 channel protein and its inhibition by a Na+ channel blocker aprindine.
[So] Source:Biochem Biophys Res Commun;331(4):1001-6, 2005 Jun 17.
[Is] ISSN:0006-291X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:ATP-sensitive K+ channels (K(ATP):SUR2A+Kir6.2) play a pivotal role in cardiac protection against ischemia and reperfusion injury. When expressed in COS cells, Kir6.2 was short-lived with a half-life time of 1.9 h. The half-life time of Kir6.2 was prolonged by proteasome inhibitors MG132, ALLN, proteasome inhibitor 1, and lactacystine, but not at all by a lysosomal inhibitor chloroquine. MG132 also increased the level of ubiquitinated Kir6.2 without affecting its localization in the endoplasmic reticulum and Golgi apparatus. In electrophysiological recordings, MG132 augmented nicorandil-activated K(ATP) currents in COS cells expressing SUR2A and Kir6.2 as well as the same currents in neonatal rat cardiomyocytes. Like MG132, a Na+ channel blocker aprindine prolonged the half-life time of Kir6.2 and augmented K(ATP). Finally, both aprindine and MG132 inhibited the 20S proteasome activity in vitro. These results suggest a novel activity of aprindine to enhance K(ATP) currents by inhibiting proteasomal degradation of Kir 6.2 channels, which may be beneficial in the setting of cardiac ischemia.
[Mh] Termos MeSH primário: Aprindina/farmacologia
Canais de Potássio Corretores do Fluxo de Internalização/metabolismo
Complexo de Endopeptidases do Proteassoma/metabolismo
Bloqueadores dos Canais de Sódio/farmacologia
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Retículo Endoplasmático/metabolismo
Complexo de Golgi/metabolismo
Hidrólise
Canais de Potássio Corretores do Fluxo de Internalização/antagonistas & inibidores
Ratos
Ubiquitina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Kir6.2 channel); 0 (Potassium Channels, Inwardly Rectifying); 0 (Sodium Channel Blockers); 0 (Ubiquitin); 5Y48085P9Q (Aprindine); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[Em] Mês de entrada:0507
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:050511
[St] Status:MEDLINE


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[PMID]:15564697
[Au] Autor:Fujiki A; Sakabe M; Nishida K; Sugao M; Tsuneda T; Iwamoto J; Mizumaki K; Inoue H
[Ad] Endereço:The Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan.
[Ti] Título:Drug-induced changes in fibrillation cycle length and organization index can predict chemical cardioversion of long-lasting atrial fibrillation with bepridil alone or in combination with aprindine.
[So] Source:Circ J;68(12):1139-45, 2004 Dec.
[Is] ISSN:1346-9843
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The aim of this study was to investigate whether drug-induced changes in fibrillation wave characteristics can predict pharmacological conversion of long lasting persistent atrial fibrillation (AF). METHODS AND RESULTS: The study group comprised 23 consecutive patients with AF lasting > or =1 month. Patients first received bepridil (200 mg/day) for 2-4 weeks. When sinus rhythm was not restored with bepridil, oral aprindine (40 or 60 mg/day) was added to bepridil. Fast Fourier transform analysis of fibrillation waves using lead V1 was performed to calculate the fibrillation cycle length (FCL). The spectral areas were measured and the maximum area divided by the total area was termed the fibrillation organization index (FOI). Sinus rhythm was restored in 16 of 23 patients (70%); 8 of these 16 patients received only bepridil (Group I) and the other 8 responders received bepridil and aprindine (Group II). In Group I bepridil increased both FCL (p<0.001) and FOI (p<0.01) and terminated AF after 20+/-12 days. In Group II bepridil increased FCL (p<0.001), but did not change FOI. The addition of aprindine terminated AF in association with an increase in both FCL (p<0.005) and FOI (p<0.005) within 19+/-8 days. In the remaining 7 patients who did not have restoration of sinus rhythm, bepridil increased both FCL and FOI significantly, but less than in Group I, and the addition of aprindine did not further increase either of them. Chemical cardioversion of AF occurred in all patients with FCL > or =190 ms and FOI > or =45% after drug administration. CONCLUSION: Bepridil alone or in combination with aprindine converted long lasting persistent AF in association with an increase in both FCL and FOI. The combination of FCL and FOI after drug administration is helpful in predicting chemical cardioversion of persistent AF.
[Mh] Termos MeSH primário: Antiarrítmicos/uso terapêutico
Aprindina/uso terapêutico
Fibrilação Atrial/tratamento farmacológico
Fibrilação Atrial/fisiopatologia
Bepridil/uso terapêutico
Coração/fisiopatologia
[Mh] Termos MeSH secundário: Idoso
Quimioterapia Combinada
Eletrocardiografia
Feminino
Coração/efeitos dos fármacos
Frequência Cardíaca/efeitos dos fármacos
Seres Humanos
Masculino
Meia-Idade
Valor Preditivo dos Testes
Fatores de Tempo
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 5Y48085P9Q (Aprindine); 755BO701MA (Bepridil)
[Em] Mês de entrada:0503
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:041127
[St] Status:MEDLINE



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