Class of 2015 Abstract / Objectives: To determine the quality of evidence in the literature reporting the potential effect of QT prolongation and cardiovascular interactions of amiodarone with fluoroquinolones and macrolides. Methods: A thorough database search was conducted utilizing PubMed, Embase, Micromedex, and Facts and Comparison. Studies were eligible if they involved human subjects, original submission in English, and focusing on any drugs within the macrolide class along with amiodarone or any drugs within the fluoroquinolone class along with amiodarone was included. Drug-drug interactions (DDI) within the literature were evaluated using one of two tools: (1) van Roon to assess the quality of randomized controlled studies, and (2) the Drug Interaction Probability Scale (DIPS) to assess case reports. Results: Five case reports were included for evaluation. None of the patients within the case reports were less than 65 years old. Four of the five case reports included ciprofloxacin as part of the proposed drug interaction with amiodarone. The range of DIPS scores were 4-7 with a median score of 6. Conclusions: The evidence purporting this drug-drug interaction is of poor quality and low quantity. Additional studies of high quality must be conducted on the subject of this DDI to provide clinicians the ability to make more informed clinical decisions.

Background: Two of the excipients in intravenous formulations of amiodarone, polysorbate 80 and benzyl alcohol, have been shown to cause hypotension. A newer formulation of amiodarone, which contains cyclodextrin, is devoid of these excipients. Objective: To evaluate the change in mean arterial pressure when utilizing 2 intravenous amiodarone formulations. Methods: This was a retrospective cohort analysis conducted at an academic medical center. Patients received intravenous amiodarone containing either polysorbate 80/benzyl alcohol (control) or cyclodextrin (cyclodextrin). Patients received these formulations based on a standard institutional protocol of 1 mg/min for 6 hours, followed by 0.5 mg/min for at least 18 hours or until discontinued by the provider. All data were collected from the medical record and included changes in blood pressures, time to lowest systolic blood pressure, concurrent antihypertensive use, and number of patients requiring treatment for hypotension. Results: A total of 160 patients (120 control, 40 cyclodextrin) were included. There was a statistically significant difference in mean arterial pressure between the groups receiving the control formulation of amiodarone compared with the cyclodextrin formulation across the 24-hour maintenance phase infusion (P < 0.001). There was a significant difference between formulations with regard to the change in mean arterial pressure during the 0- to 6-hour and 12- to 18-hour time blocks. There was a statistically significant difference in the number of patients receiving fluid boluses for treatment of hypotension (P = 0.001). Conclusions: The excipients in the formulation of intravenous amiodarone may have a significant role in the hypotensive effects seen throughout the duration the maintenance phase infusion.

O objeto de estudo são os eventos cardíacos resultantes da infusão contínua de cloridrato de amiodarona em pacientes que evoluíram com fibrilação atrial em pós-operatório de cirurgia cardíaca. Os objetivos foram descrever as características dos pacientes que receberam infusão contínua de cloridrato de amidoarona, apresentar a prevalência de bradicardia e hipotensão encontrada nos pacientes que receberam infusão contínua de cloridrato de amiodarona e discutir as implicações dos achados para a prática dos enfermeiros a partir da prevalência encontrada de bradicardia e hipotensão decorrente da infusão contínua desta substância. Trata-se de um estudo transversal, retrospectivo, documental, por meio de análise de prontuários e avaliação quantitativa dos mesmos. Desenvolvida em uma unidade de pós-operatório de cirurgia cardíaca em um hospital universitário pertencente à rede sentinela no município do Rio de Janeiro. Foi considerado hipotensão em presença de PAS menor que 90 mmHg e bradicardia em presença de frequência cardíaca menor que 60 bpm. As variáveis que caracterizavam a população do estudo e as aferições de pressão arterial e frequência cardíaca foram transcritas para um instrumento de coleta de dados dos anos de 2010 e 2011, gerando 1782 horas de infusão contínua de cloridrato de amiodarona em 27 pacientes cirúrgicos (10,50%). Tratou-se de uma população predominantemente feminina, com idade a cima de 60 anos, período de internação superior a uma semana, apresentava hipertensão arterial prévia (59,26%), era portadora de fibrilação atrial (55,56%) e o diagnóstico cirúrgico de revascularização do miocárdio com circulação extracorpórea foi predominante (70,37%). Os dados mostram que 85,19% dos pacientes eram portadores de pelo menos um fator de risco, 70,37% apresentavam dois fatores de risco e 55,55% apresentavam três fatores de risco para desenvolver fibrilação atrial no pós-operatório de cirurgia cardíaca. Foi encontrada uma prevalência de 85,19% pacientes que apresentaram bradicardia, 66,67% apresentaram hipotensão e 59,26% apresentaram tanto bradicardia como hipotensão. Foram 160 episódios de bradicardia com 6,40 episódios por paciente e 77 episódios de hipotensão com 4,2 por paciente. A bradicardia ocorreu principalmente entre 48 e 72 horas do inicio da infusão. Já a hipotensão aumentou progressivamente nas primeiras 48 horas de infusão. Na presença de bradicardia a intervenção mais frequente foi redução da vazão de amiodarona já na presença de hipotensão, a manutenção de infusão de noradrenalina foi a conduta mais regular. Como estratégia de melhoria para segurança do paciente, foram elaboradas condutas como método de barreira para prevenção de eventos adversos como a bradicardia e hipotensão. Os principais cuidados de enfermagem a serem implementados pelo enfermeiro foram o levantamento de fatores de risco para a fibrilação atrial, a detecção da fibrilação atrial, a manutenção de monitorização cardíaca contínua, aferição horária do ritmo cardíaco e o controle da frequência cardíaca e pressão arterial, objetivando intervir precocemente em presença de hipotensão ou bradicardia. / The subject-matter of the following study is the cardiac events that are consequences from the continuous infusion of amiodarone hydrochloride into patients that developed atrial fibrillation in a postoperative care from a cardiac surgery. The aims of the study are: to describe the characteristics of the patients that received continuous infusion of amiodarone hydrochloride; to present the prevalence of bradycardia and hypotension in the patients that received continuous infusion of amiodarone hydrochloride; and to discuss the implications of the findings for the practice of nurses from the prevalence of bradycardia and hypotension that stemmed from the continuous infusion of amiodarone hydrochloride. This is a cross-sectional, retrospective, documentary study through the analysis and quantitative evaluation of medical records. It was developed in a cardiac surgery postoperative unit in a university hospital that belongs to the Rede Sentinela in the City of Rio de Janeiro. Hypotension was defined as the presence of a systemic arterial blood pressure (ABP) lower than 90 mmHg and bradycardia as the presence of a heart rate below 60 bpm. The variables that characterized the population of the study and the measuring of arterial blood pressure and heart rate were transcribed into a data collection instrument through the years 2010 and 2011, creating 1782 hours of continuous infusion of amiodarone hydrochloride into 27 surgical patients (10,50%). The population of the study was mainly composed of women over 60 years old, with an admission over a week period, they showed pre-existing arterial hypertension (58,26%) and have atrial fibrillation (55,56%) and the surgical diagnosis of myocardium revascularization with extracorporeal circulation was predominant (70,37%). The data showed that 85,19% of the patients were carriers of at least one risk factor, 70,37% showed two risk factors and 55,55% showed three risk factors to develop atrial fibrillation in the postoperative of a cardiac surgery. It was found a predominance of 85,19% patients that showed bradycardia, 66,67% showed hypotension and 59,29% showed bradycardia as well as hypotension. There were 160 bradycardia episodes in a rate of 6,40 episodes per patients and 77 hypotension in a rate of 4,2 episodes per patients. The bradycardia happened mainly between the 48 and 72 hours after the infusion. Now, the hypotension increased progressively in the first 48 hours after the infusion. In the presence of bradycardia the medical intervention most frequent was the reduction of the amiodarone flow rate, while in the presence of hypotension the continuity of the norepinephrine infusion was the most common conduct. As strategy to improve the patient safety, conducts were devised as barrier method to prevent adverse events such as the bradycardia and hypotension. The main nursing care implemented by the nurse were the survey of risk factors to the atrial fibrillation, the detection of atrial fibrillation, the continuity of the continuous cardiac monitoring, hourly measuring of the heart rate and the control of the heart rate and arterial blood pressure, in order for a earlier medical intervention in the presence of hypotension or bradycardia.

O objeto de estudo são os eventos cardíacos resultantes da infusão contínua de cloridrato de amiodarona em pacientes que evoluíram com fibrilação atrial em pós-operatório de cirurgia cardíaca. Os objetivos foram descrever as características dos pacientes que receberam infusão contínua de cloridrato de amidoarona, apresentar a prevalência de bradicardia e hipotensão encontrada nos pacientes que receberam infusão contínua de cloridrato de amiodarona e discutir as implicações dos achados para a prática dos enfermeiros a partir da prevalência encontrada de bradicardia e hipotensão decorrente da infusão contínua desta substância. Trata-se de um estudo transversal, retrospectivo, documental, por meio de análise de prontuários e avaliação quantitativa dos mesmos. Desenvolvida em uma unidade de pós-operatório de cirurgia cardíaca em um hospital universitário pertencente à rede sentinela no município do Rio de Janeiro. Foi considerado hipotensão em presença de PAS menor que 90 mmHg e bradicardia em presença de frequência cardíaca menor que 60 bpm. As variáveis que caracterizavam a população do estudo e as aferições de pressão arterial e frequência cardíaca foram transcritas para um instrumento de coleta de dados dos anos de 2010 e 2011, gerando 1782 horas de infusão contínua de cloridrato de amiodarona em 27 pacientes cirúrgicos (10,50%). Tratou-se de uma população predominantemente feminina, com idade a cima de 60 anos, período de internação superior a uma semana, apresentava hipertensão arterial prévia (59,26%), era portadora de fibrilação atrial (55,56%) e o diagnóstico cirúrgico de revascularização do miocárdio com circulação extracorpórea foi predominante (70,37%). Os dados mostram que 85,19% dos pacientes eram portadores de pelo menos um fator de risco, 70,37% apresentavam dois fatores de risco e 55,55% apresentavam três fatores de risco para desenvolver fibrilação atrial no pós-operatório de cirurgia cardíaca. Foi encontrada uma prevalência de 85,19% pacientes que apresentaram bradicardia, 66,67% apresentaram hipotensão e 59,26% apresentaram tanto bradicardia como hipotensão. Foram 160 episódios de bradicardia com 6,40 episódios por paciente e 77 episódios de hipotensão com 4,2 por paciente. A bradicardia ocorreu principalmente entre 48 e 72 horas do inicio da infusão. Já a hipotensão aumentou progressivamente nas primeiras 48 horas de infusão. Na presença de bradicardia a intervenção mais frequente foi redução da vazão de amiodarona já na presença de hipotensão, a manutenção de infusão de noradrenalina foi a conduta mais regular. Como estratégia de melhoria para segurança do paciente, foram elaboradas condutas como método de barreira para prevenção de eventos adversos como a bradicardia e hipotensão. Os principais cuidados de enfermagem a serem implementados pelo enfermeiro foram o levantamento de fatores de risco para a fibrilação atrial, a detecção da fibrilação atrial, a manutenção de monitorização cardíaca contínua, aferição horária do ritmo cardíaco e o controle da frequência cardíaca e pressão arterial, objetivando intervir precocemente em presença de hipotensão ou bradicardia. / The subject-matter of the following study is the cardiac events that are consequences from the continuous infusion of amiodarone hydrochloride into patients that developed atrial fibrillation in a postoperative care from a cardiac surgery. The aims of the study are: to describe the characteristics of the patients that received continuous infusion of amiodarone hydrochloride; to present the prevalence of bradycardia and hypotension in the patients that received continuous infusion of amiodarone hydrochloride; and to discuss the implications of the findings for the practice of nurses from the prevalence of bradycardia and hypotension that stemmed from the continuous infusion of amiodarone hydrochloride. This is a cross-sectional, retrospective, documentary study through the analysis and quantitative evaluation of medical records. It was developed in a cardiac surgery postoperative unit in a university hospital that belongs to the Rede Sentinela in the City of Rio de Janeiro. Hypotension was defined as the presence of a systemic arterial blood pressure (ABP) lower than 90 mmHg and bradycardia as the presence of a heart rate below 60 bpm. The variables that characterized the population of the study and the measuring of arterial blood pressure and heart rate were transcribed into a data collection instrument through the years 2010 and 2011, creating 1782 hours of continuous infusion of amiodarone hydrochloride into 27 surgical patients (10,50%). The population of the study was mainly composed of women over 60 years old, with an admission over a week period, they showed pre-existing arterial hypertension (58,26%) and have atrial fibrillation (55,56%) and the surgical diagnosis of myocardium revascularization with extracorporeal circulation was predominant (70,37%). The data showed that 85,19% of the patients were carriers of at least one risk factor, 70,37% showed two risk factors and 55,55% showed three risk factors to develop atrial fibrillation in the postoperative of a cardiac surgery. It was found a predominance of 85,19% patients that showed bradycardia, 66,67% showed hypotension and 59,29% showed bradycardia as well as hypotension. There were 160 bradycardia episodes in a rate of 6,40 episodes per patients and 77 hypotension in a rate of 4,2 episodes per patients. The bradycardia happened mainly between the 48 and 72 hours after the infusion. Now, the hypotension increased progressively in the first 48 hours after the infusion. In the presence of bradycardia the medical intervention most frequent was the reduction of the amiodarone flow rate, while in the presence of hypotension the continuity of the norepinephrine infusion was the most common conduct. As strategy to improve the patient safety, conducts were devised as barrier method to prevent adverse events such as the bradycardia and hypotension. The main nursing care implemented by the nurse were the survey of risk factors to the atrial fibrillation, the detection of atrial fibrillation, the continuity of the continuous cardiac monitoring, hourly measuring of the heart rate and the control of the heart rate and arterial blood pressure, in order for a earlier medical intervention in the presence of hypotension or bradycardia.

No description available.

Adverse reactions to the antiarrhythmic medication amiodarone are severe, potentially life-threatening, and not rare. One in three patients on long-term therapy experience elevated liver enzymes, and clinically apparent liver toxicity occurs in 1% of patients treated. We report the case of a 76-year-old patient with amiodarone-induced intrahepatic cholestasis and prolonged hyperbilirubinemia despite the discontinuation of the offending agent. Current research hypothesizes that amiodarone leads to hepatic injury both by direct hepatotoxicity and by increasing the likelihood of hepatocytes to create abnormal, toxic metabolites. Increased awareness of such an adverse effect can guide clinicians toward the possible underlying etiologies of prolonged jaundice.

京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第22752号 / 薬科博第126号 / 新制||薬科||14(附属図書館) / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 金子 周司, 教授 土居 雅夫, 教授 竹島 浩 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

Adverse effects of amiodarone are rarely seen in pediatric patients, but may occur if amiodarone is applied for long-term treatment. Two rather rare phenomena are blue-gray skin pigmentation and pulmonary mass. They represent important differential diagnoses from more common clinical complications like pneumonia and drug-induced toxic skin lesions.

O emprego da catálise de transferência de fase substituindo uma ou mais etapas da síntese de um fármaco, pode ser um recurso vantajoso sob o ponto de vista tecnológico. Empregado na síntese de importantes fármacos que são a dicicloverina, caramifeno eamiodarona, a catálise de transferência de fase revelou-se muito vantajosa na síntese dos dois primeiros. A dicicloverina e o caramifeno tiveram as suas rotas de obtenção verticalizadas, com bons resultados e custos bem mais baixos quando comparados com os atualmente adquiridos no exterior. Ficou evidente que a catálise de transferência de fase pode ser aplicada com sucesso na produção destes e outros fármacos em associação com técnicas já conhecidas com ótimos resultados. / The phase transfer catalysis application replacing one or more steps in the drug synthesis, can be of advantage in the technologycal approach. Applied to the synthesis of important drugs such as diciclomine, caramiphen,and amiodarone, the phase transfer catalysis resulted in a very advantageous method in the first two drugs. The diciclomine and the caramiphen, gets their obtention routes from raw materiaIs wi th good resul ts and low coasts, when compared wi th the drugs presently purchassed in foreign countries. It is clear that the phase transfer catalysis, can be applied succesfully in the manufacturing of these and other drugs, in conjuction with known techniques with good results.

O emprego da catálise de transferência de fase substituindo uma ou mais etapas da síntese de um fármaco, pode ser um recurso vantajoso sob o ponto de vista tecnológico. Empregado na síntese de importantes fármacos que são a dicicloverina, caramifeno eamiodarona, a catálise de transferência de fase revelou-se muito vantajosa na síntese dos dois primeiros. A dicicloverina e o caramifeno tiveram as suas rotas de obtenção verticalizadas, com bons resultados e custos bem mais baixos quando comparados com os atualmente adquiridos no exterior. Ficou evidente que a catálise de transferência de fase pode ser aplicada com sucesso na produção destes e outros fármacos em associação com técnicas já conhecidas com ótimos resultados. / The phase transfer catalysis application replacing one or more steps in the drug synthesis, can be of advantage in the technologycal approach. Applied to the synthesis of important drugs such as diciclomine, caramiphen,and amiodarone, the phase transfer catalysis resulted in a very advantageous method in the first two drugs. The diciclomine and the caramiphen, gets their obtention routes from raw materiaIs wi th good resul ts and low coasts, when compared wi th the drugs presently purchassed in foreign countries. It is clear that the phase transfer catalysis, can be applied succesfully in the manufacturing of these and other drugs, in conjuction with known techniques with good results.