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[PMID]: 28446489 [Au] Autor: Alsaad AA; Ortiz Gonzalez Y; Austin CO; Kusumoto F [Ad] Endereço: Internal Medicine, Mayo Clinic Florida, Jacksonville, Florida, USA. [Ti] Título: Revisiting propafenone toxicity. [So] Source: BMJ Case Rep;2017, 2017 Apr 26. [Is] ISSN: 1757-790X [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Propafenone is a Vaughan Williams class 1c antiarrhythmic medication widely used for treatment of arrhythmias. Although the long-term safety of propafenone use has not been established, it is commonly used for treatment of atrial fibrillation in patients with no structural heart disease. Propafenone is well known as treatment for its effect in terminating paroxysmal episodes of atrial fibrillation. Herein, we discuss an unusual adverse reaction to propafenone in a patient who presented with symptomatic bradycardia and hypotension. The aim of this article is to increase physician awareness for propafenone toxicity and its management, with a focused literature review on propafenone pharmacotherapy. [Mh] Termos MeSH primário: Antiarrítmicos/efeitos adversos Bradicardia/diagnóstico Hipotensão/diagnóstico Propafenona/efeitos adversos [Mh] Termos MeSH secundário: Idoso Bradicardia/induzido quimicamente Seres Humanos Hipotensão/induzido quimicamente Masculino [Pt] Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Arrhythmia Agents); 68IQX3T69U (Propafenone) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170613 [Lr] Data última revisão: 170613 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170428 [St] Status: MEDLINE

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[PMID]: 28390833 [Au] Autor: Chen X; Yang Z [Ad] Endereço: Department of Emergency Room, Taizhou First People's Hospital, Huangyan Hospital of Wenzhou Medical University, Zhejiang, China. [Ti] Título: Successful treatment of propafenone-induced cardiac arrest by calcium gluconate. [So] Source: Am J Emerg Med;35(8):1209.e1-1209.e2, 2017 Aug. [Is] ISSN: 1532-8171 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Propafenone is prescribed for the control of cardiac ventricular arrhythmias. Poisoning from propafenone intoxication is rare, but the survival rate of patients is low. We present a case of a 37-year-old man who developed cardiac arrest due to propafenone intoxication. Cardiopulmonary resuscitation, plasmapheresis, and other medical treatments had no effect on cardiac arrest. After repeated administrations of calcium gluconate, the patient achieved a full recovery. To the best of our knowledge, this is the first case report in which a full recovery from cardiac arrest was achieved by administration of calcium gluconate. We recommend that for patients poisoned by propafenone, close monitoring for decreased blood calcium is important. [Mh] Termos MeSH primário: Antiarrítmicos/envenenamento Gluconato de Cálcio/uso terapêutico Reanimação Cardiopulmonar/métodos Overdose de Drogas/terapia Parada Cardíaca/induzido quimicamente Propafenona/envenenamento [Mh] Termos MeSH secundário: Adulto Overdose de Drogas/fisiopatologia Parada Cardíaca/fisiopatologia Parada Cardíaca/terapia Seres Humanos Masculino Plasmaferese/métodos Tentativa de Suicídio Resultado do Tratamento [Pt] Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Arrhythmia Agents); 68IQX3T69U (Propafenone); SQE6VB453K (Calcium Gluconate) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171004 [Lr] Data última revisão: 171004 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170410 [St] Status: 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

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[PMID]: 28261841 [Au] Autor: Patel H; Ghoghari A; Bhatt C; Shah S; Jha A; Desai N; Srinivas NR [Ad] Endereço: Zydus Research Centre, Bioanalytical Laboratory, Ahmedabad, India. [Ti] Título: A sensitive quantitative assay for the determination of propafenone and two metabolites, 5-hydroxypropafenone and N-depropylpropafenone, in human K2EDTA plasma using LC-MS/MS with ESI operated in positive mode. [So] Source: Biomed Chromatogr;31(10), 2017 Oct. [Is] ISSN: 1099-0801 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Propafenone is a potent antiarrhythmic agent; clinically propafenone has been used for a number of cardiac arrhythmias because it possesses multiple modes of action, via beta adrenergic receptor blockade and calcium antagonistic activity. Propafenone (PPF) exhibits extensive saturable presystemic biotransformation (first-pass effect) resulting in two active metabolites: 5-hydroxypropafenone (5-OH PPF) formed by CYP2D6 and N-depropylpropafenone (NDP) formed by both CYP3A4 and CYP1A2 enzymes. A specific and sensitive LC-MS/MS method was developed and validated for quantitation of PPF, 5-OH PPF and NDP using turboion spray in a positive ion mode. A solid-phase extraction was employed for the extraction from human plasma. Chromatographic separation of analytes was achieved using an ACE-5 C (50 × 4.6 mm) column with a gradient mobile phase comprising ammonium acetate containing 0.01% TFA in purified water and acetonitrile. The retention times achieved were 1.36, 1.23, 1.24 min and 1.34 min for PPF, 5-OH PPF, NDP and IS (carbamazepine), respectively. Quantitation was performed by monitoring multiple reaction monitoring transition pairs of m/z 342.30 to m/z 116.20, m/z 358.30 to m/z 116.20, m/z 300.30 to m/z 74.20 and m/z 237.20 to m/z 194.10, respectively. The developed method was validated for various parameters. The calibration curves of PPF and 5-OH PPF showed linearity from 1 to 500 ng/mL, with a lower limit of quantitation of 1.0 ng/mL and for NDP linearity from 0.1 to 25 ng/mL with a lower limit of quantitation of 0.1 ng/mL. The bias and precision for intra- and-inter batch assays were <10 and 5%, respectively. The developed assay was used to evaluate pharmacokinetic properties of propafenone and its major metabolites in healthy human subjects. [Mh] Termos MeSH primário: Cromatografia Líquida/métodos Propafenona/análogos & derivados Propafenona/sangue Espectrometria de Massas em Tandem/métodos [Mh] Termos MeSH secundário: Administração Oral Estabilidade de Medicamentos Ácido Edético Seres Humanos Limite de Detecção Modelos Lineares Propafenona/administração & dosagem Propafenona/química Propafenona/farmacocinética Reprodutibilidade dos Testes [Pt] Tipo de publicação: CLINICAL TRIAL; JOURNAL ARTICLE [Nm] Nome de substância: 68IQX3T69U (Propafenone); 7AC8BF38NP (5-hydroxypropafenone); 9G34HU7RV0 (Edetic Acid); KN087PHW5T (N-depropylpropafenone) [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: 170307 [St] Status: MEDLINE [do] DOI: 10.1002/bmc.3967

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[PMID]: 28087064 [Au] Autor: Rouini MR; Afshar M [Ad] Endereço: Biopharmaceutics and pharmacokinetics division, department of pharmaceutics, faculty of pharmacy, Tehran university of medical sciences, P.O. Box 14155-6451, Tehran, Iran. [Ti] Título: Effect of CYP2D6 polymorphisms on the pharmacokinetics of propafenone and its two main metabolites. [So] Source: Therapie;72(3):373-382, 2017 Jun. [Is] ISSN: 0040-5957 [Cp] País de publicação: France [La] Idioma: eng [Ab] Resumo: AIM OF THE STUDY: Propafenone (PPF) is an antiarrhythmic drug, metabolized mainly by CYP2D6 to 5-hydroxypropafenone (5OH-PPF) and by CYP3A4 to norpropafenone (NOR-PPF). CYP2D6 shows a high degree of genetic polymorphism which is associated with diminished antiarrhythmic efficacy or cardiac seizures/cardiotoxicity. This study aimed to investigate the effect of the CYP2D6 polymorphism on the pharmacokinetics of PPF and its two main metabolites. The usefulness of PPF/5OH-PPF ratio for CYP2D6 phenotyping in healthy adults was also evaluated. METHODS: Twelve healthy volunteers, 3 poor metabolizers (PM), 2 intermediate metabolizers (IM) and seven extensive metabolizers (EM) received an oral dose of PPF. Concentrations of PPF and its metabolites were analyzed in serum samples over 27h. RESULTS: The PPF/5OH-PPF ratio distinguished EMs from PMs, but not from IMs. In PMs, the mean transit time (MTT) values were almost the same for PPF and NOR-PPF and much higher than those of EMs and IMs. 5OH-PPF was not detected in EMs. Mean MTT values of 5OH-PPF and NOR-PPF in IMs were 5.27- and 1.52-fold higher than those of EMs. CONCLUSION: A single time point serum PPF-MR approach is a useful tool to identify PMs. CYP2D6 polymorphism significantly affects the pharmacokinetics of PPF and its two metabolites. [Mh] Termos MeSH primário: Antiarrítmicos/farmacocinética Citocromo P-450 CYP2D6/genética Polimorfismo Genético Propafenona/farmacocinética [Mh] Termos MeSH secundário: Adulto Antiarrítmicos/sangue Feminino Seres Humanos Masculino Meia-Idade Propafenona/análogos & derivados Propafenona/sangue Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Arrhythmia Agents); 68IQX3T69U (Propafenone); 7AC8BF38NP (5-hydroxypropafenone); EC 1.14.14.1 (Cytochrome P-450 CYP2D6) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170926 [Lr] Data última revisão: 170926 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170115 [St] Status: 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

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[PMID]: 27585695 [Au] Autor: Shafi T; Jabeen I [Ti] Título: Grid-independent Descriptors (GRIND) Analysis and SAR Guided Molecular Docking Studies to Probe Selectivity Profiles of Inhibitors of Multidrug Resistance Transporters ABCB1 and ABCG2. [So] Source: Curr Cancer Drug Targets;17(2):177-190, 2017. [Is] ISSN: 1873-5576 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: BACKGROUND: ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP/ABCG2) are major determinants of pharmacokinetic, safety and efficacy profiles of drugs thereby effluxing a broad range of endogenous substances across the plasma membrane. Overexpression of these transporters in various tumors is also implicated in the development of multidrug resistance (MDR) and thus, hampers the success of cancer chemotherapy. Modulators of these efflux transporters in combination with chemotherapeutics could be a promising concept to increase the effective intracellular concentration of anticancer drugs. However, broad and overlapped specificity for substrates and modulators of ABCB1 and ABCG2, merely induce toxicity and unwanted drug-drug interactions and thus, lead to late-stage failure of drugs. OBJECTIVE: In present investigation, we aim to identify specific 3D structural requirements for selective inhibition of ABCB1 and ABCG2 transport function. METHOD: GRID Independent Molecular Descriptor (GRIND) models of selective inhibitors of both transporters have been developed, using their most probable binding conformations obtained from molecular docking protocol. RESULTS: Our results demonstrated a dominant role of molecular shape and different H-bonding patterns in drug-ABCB1/ABCG2 selective interactions. Moreover, distinct distances of different pharmacophoric features from steric hot spots of the molecules provided a strong basis of selectivity for both transporters. Additionally, our results suggested the presence of two H-bond donors at a distance of 8.4-8.8 Å in selective modulators of ABCG2. CONCLUSION: Our findings concluded that molecular shape along with three dimensional pattern of Hbonding in MDR modulators play a critical role in determining the selectivity between the two targets. [Mh] Termos MeSH primário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores Antineoplásicos/farmacologia Proteínas de Neoplasias/antagonistas & inibidores Relação Estrutura-Atividade [Mh] Termos MeSH secundário: Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores Subfamília B de Transportador de Cassetes de Ligação de ATP/química Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/química Antineoplásicos/química Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos Seres Humanos Ligações de Hidrogênio Simulação de Acoplamento Molecular Proteínas de Neoplasias/química Propafenona/química Propafenona/farmacologia Quinolinas/química Quinolinas/farmacologia Reprodutibilidade dos Testes Homologia Estrutural de Proteína [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (ABCB1 protein, human); 0 (ABCG2 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family B); 0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (Antineoplastic Agents); 0 (Neoplasm Proteins); 0 (Quinolines); 68IQX3T69U (Propafenone); J58862DTVD (tariquidar) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160903 [St] Status: MEDLINE [do] DOI: 10.2174/1568009616666160901094140

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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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[PMID]: 27362390 [Au] Autor: Farkowski MM; Maciag A; Zurawska M; Pytkowski M; Kowalik I; Wozniak J; Sterlinski M; Szwed H [Ti] Título: Comparative effectiveness and safety of antazoline­based and propafenone­based strategies for pharmacological cardioversion of short­duration atrial fibrillation in the emergency department. [So] Source: Pol Arch Med Wewn;126(6):381-7, 2016 Jun 24. [Is] ISSN: 1897-9483 [Cp] País de publicação: Poland [La] Idioma: eng [Ab] Resumo: INTRODUCTION    Numerous studies described the effectiveness and safety of antazoline in pharmacological cardioversion of short­duration atrial fibrillation (AF). However, there are no data on the comparison of antazoline and antiarrhythmic drugs listed in clinical guidelines. OBJECTIVES    The aim of the study was to assess the comparative effectiveness and safety of antazoline­based and propafenone­based strategies in pharmacological cardioversion of short­duration AF performed in our emergency department. PATIENTS AND METHODS    We conducted a retrospective case­control study based on the analysis of medical records of patients undergoing pharmacological cardioversion of short­duration AF with intravenous antazoline or propafenone at our department in the years 2008-2012. The primary endpoint was the successful cardioversion of AF. The primary safety endpoint was hospitalization due to the adverse effects of the treatment. RESULTS    We analyzed 432 cases of cardioversion. The mean age of patients was 68.9 ±9.8 years; 65% of the patients were male; 90% of the patients had a history of AF. Antazoline was administered 334 times and propafenone-98 times. The mean dose of antazoline was 172 ±65 mg, while all patients in the propafenone group received the drug at a fixed dose of 70 mg (1 vial). Cardioversion with antazoline was successful in 239 cases (71.6%) and with propafenone-in 54 patients (55.1%) (relative risk [RR], 1.30; 95% confidence interval [CI], 1.07-1.57). The rate of hospitalization due to the adverse effects of the treatment were low and similar between the study groups: 10 (3.0%) for antazoline and 4 (4.1%) for propafenone (RR, 0.73; 95% CI, 0.23-2.27). CONCLUSIONS    The antazoline­based strategy was more effective and safer in comparison with propafenone­based strategy in the pharmacological cardioversion of short­duration AF in our emergency department. [Mh] Termos MeSH primário: Antazolina/uso terapêutico Antiarrítmicos/uso terapêutico Fibrilação Atrial/tratamento farmacológico Propafenona/uso terapêutico [Mh] Termos MeSH secundário: Idoso Idoso de 80 Anos ou mais Antazolina/efeitos adversos Antiarrítmicos/efeitos adversos Serviço Hospitalar de Emergência Feminino Seres Humanos Masculino Meia-Idade Segurança do Paciente Propafenona/efeitos adversos Estudos Retrospectivos Resultado do Tratamento [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Arrhythmia Agents); 68IQX3T69U (Propafenone); DHA8014SS1 (Antazoline) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 170817 [Lr] Data última revisão: 170817 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160701 [St] Status: MEDLINE [do] DOI: 10.20452/pamw.3452

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[PMID]: 27304669 [Au] Autor: Ngo ST; Fang ST; Huang SH; Chou CL; Huy PD; Li MS; Chen YC [Ad] Endereço: Institute for Computational Science and Technology , Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City, Vietnam. [Ti] Título: Anti-arrhythmic Medication Propafenone a Potential Drug for Alzheimer's Disease Inhibiting Aggregation of Aß: In Silico and in Vitro Studies. [So] Source: J Chem Inf Model;56(7):1344-56, 2016 Jul 25. [Is] ISSN: 1549-960X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Alzheimer's disease (AD) is the most common form of dementia caused by the formation of Aß aggregates. So far, no effective medicine for the treatment of AD is available. Many efforts have been made to find effective medicine to cope with AD. Curcumin is a drug candidate for AD, being a potent anti-amyloidogenic compound, but the results of clinical trials for it were either negative or inclusive. In the present study, we took advantages from accumulated knowledge about curcumin and have screened out four compounds that have chemical and structural similarity with curcumin more than 80% from all FDA-approved oral drugs. Using all-atom molecular dynamics simulation and the free energy perturbation method we showed that among predicted compounds anti-arrhythmic medication propafenone shows the best anti-amyloidogenic activity. The in vitro experiment further revealed that it can inhibit Aß aggregation and protect cells against Aß induced cytotoxicity to almost the same extent as curcumin. Our results suggest that propafenone may be a potent drug for the treatment of Alzheimer's disease. [Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico Peptídeos beta-Amiloides/química Antiarrítmicos/farmacologia Simulação por Computador Fragmentos de Peptídeos/química Propafenona/farmacologia Agregados Proteicos/efeitos dos fármacos [Mh] Termos MeSH secundário: Administração Oral Doença de Alzheimer/metabolismo Peptídeos beta-Amiloides/metabolismo Antiarrítmicos/metabolismo Antiarrítmicos/farmacocinética Antiarrítmicos/uso terapêutico Sítios de Ligação Disponibilidade Biológica Sobrevivência Celular/efeitos dos fármacos Curcumina/farmacologia Relação Dose-Resposta a Droga Interações Medicamentosas Radicais Livres/metabolismo Ligações de Hidrogênio Simulação de Acoplamento Molecular Simulação de Dinâmica Molecular Fragmentos de Peptídeos/metabolismo Propafenona/metabolismo Propafenona/farmacocinética Propafenona/uso terapêutico Estrutura Secundária de Proteína Eletricidade Estática Termodinâmica [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Amyloid beta-Peptides); 0 (Anti-Arrhythmia Agents); 0 (Free Radicals); 0 (Peptide Fragments); 0 (Protein Aggregates); 0 (amyloid beta-protein (1-40)); 68IQX3T69U (Propafenone); IT942ZTH98 (Curcumin) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 170731 [Lr] Data última revisão: 170731 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160616 [St] Status: MEDLINE [do] DOI: 10.1021/acs.jcim.6b00029

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