Assuntos
Aprovação de Equipamentos , Equipamentos e Provisões/economia , Centers for Medicare and Medicaid Services, U.S. , Ensaios Clínicos como Assunto/economia , Controle de Custos , Indústria Farmacêutica , Humanos , Mecanismo de Reembolso , Apoio à Pesquisa como Assunto , Tecnologia de Alto Custo , Estados Unidos , United States Food and Drug AdministrationRESUMO
Myocardial size and contractility were measured by gated radionuclide ventriculography in 70 patients before and a mean of 66 days after beginning amiodarone therapy. The mean dose of amiodarone at the time of the second study was 481 mg. The mean left ventricular (LV) ejection fraction (EF) increased slightly, from 40% to 43% (p = 0.001). The mean right ventricular EF remained unchanged (38% to 39%, difference not significant [NS]). The LV end-diastolic volume (count-based method) increased by 9% (p = 0.01), but no change could be demonstrated for end-systolic volume (4%, NS). The LV stroke volume increased 19% (p = 0.001), but cardiac output remained unchanged (5%, NS) because the heart rate decreased by 9 beats/min (p = 0.001). The right ventricular end-diastolic volume increased by 12% (p = 0.01) and end-systolic volume increased by 11% (p = 0.03). Stroke volume increased by 18% (p = 0.005). There was no significant correlation between the change in LVEF and the pre-amiodarone LVEF, the time interval between studies, or with indexes of amiodarone effect (change in heart rate, QRS, QTc, TSH, amiodarone dosage). In 5 patients (7%), LVEF decreased significantly, requiring discontinuation of amiodarone therapy in 1 patient. At the time of the second study congestive heart failure was manifest in 19%, and there was a trend suggesting that congestive heart failure was more likely if the initial LVEF was less than or equal to 35% (p = 0.10). Thus, amiodarone may rarely adversely affect contractility, although myocardial contractility is typically unchanged. There is an associated small increase in the size of both ventricles.
Assuntos
Amiodarona/farmacologia , Benzofuranos/farmacologia , Coração/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Idoso , Amiodarona/efeitos adversos , Arritmias Cardíacas/complicações , Arritmias Cardíacas/tratamento farmacológico , Débito Cardíaco/efeitos dos fármacos , Feminino , Coração/diagnóstico por imagem , Cardiopatias/complicações , Insuficiência Cardíaca/induzido quimicamente , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Cintilografia , Volume Sistólico/efeitos dos fármacosRESUMO
Reports of pulmonary infiltrates in patients taking amiodarone, initiated the study of 69 patients for pulmonary toxicity using serial chest roentgenograms (CXRs), pulmonary function tests (PFTs), and symptoms before and during therapy. Mean PFTs did not significantly change from their baseline normal values, but 10 percent of patients had a greater than or equal to 15 percent fall in total lung capacity, and 28 percent a greater than or equal to 15 percent fall in diffusion capacity (DCO) following treatment. Initial abnormalities in pulmonary function or CXR were predictive of risk of developing pulmonary toxicity. Degree of exposure to amiodarone (dose plus duration) correlated only weakly with development of pulmonary toxicity, which could occur in patients taking relatively small doses of the drug. Pulmonary complications of amiodarone are common, in most cases reversible, and often confused with congestive heart failure or pneumonia. Patients should be evaluated before treatment by assessing symptoms, CXRs, and DCO. Patients with initial abnormalities in these parameters, particularly both CXR and DCO abnormalities, should be considered for alternative therapy.
Assuntos
Amiodarona/efeitos adversos , Benzofuranos/efeitos adversos , Pulmão/efeitos dos fármacos , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Infecções/diagnóstico , Pulmão/diagnóstico por imagem , Pneumopatias/induzido quimicamente , Pneumopatias/diagnóstico , Pneumopatias/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Capacidade de Difusão Pulmonar , Ventilação Pulmonar , Radiografia , Testes de Função Respiratória , Risco , Capacidade Pulmonar TotalRESUMO
Serum levels of quinidine or procainamide were measured in patients who had amiodarone added to their antiarrhythmic regimen. Dosages of quinidine or procainamide were held constant. Eleven of 11 patients had an increase in the serum quinidine level, and 11 of 12 other patients had an increase in the serum procainamide level. The dose requirement to maintain a stable plasma level of quinidine or procainamide decreased by 37% and 20%, respectively. Clinical toxicity occasionally occurred with the increase in serum levels of quinidine and procainamide, and the dose of these drugs should be decreased when amiodarone is administered concurrently.
Assuntos
Amiodarona/farmacologia , Benzofuranos/farmacologia , Procainamida/sangue , Quinidina/sangue , Adulto , Idoso , Arritmias Cardíacas/tratamento farmacológico , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procainamida/intoxicação , Estudos Prospectivos , Quinidina/intoxicaçãoRESUMO
Amiodarone was used to treat cardiac arrhythmias that had been refractory to conventional medical therapy. The first 70 consecutive patients treated with amiodarone in this study had at least 6 months of follow-up (range 6 to 24, mean 11) and form the basis for this report. Sixty-six patients were treated for ventricular arrhythmias and four for supraventricular tachycardias. Amiodarone therapy consisted of a loading dose of 600 mg orally twice a day for 7 days, and 600 mg daily thereafter. Doses were reduced only if side effects occurred. Because of frequent side effects, the dose was reduced from 572 +/- 283 mg per day (mean +/- standard deviation) at 45 days to 372 +/- 174 mg per day at 6 months. With a mean follow-up of 11 months in the 54 patients who continued to take amiodarone, only 4 patients had ventricular fibrillation. Three additional patients experienced recurrent sustained ventricular tachycardia in long-term follow-up. All 70 patients had extensive clinical and laboratory evaluation in follow-up. Side effects were common, occurring in 93% of patients. Thirteen patients (19%) had to discontinue the medication because of severe side effects. Fifty-six patients had gastrointestinal side effects, most commonly constipation. All patients but 1 eventually developed corneal microdeposits, and 43 patients were symptomatic. Cardiovascular side effects were uncommon. Symptomatic pulmonary side effects occurred in seven patients, with unequivocal pulmonary toxicity occurring in five. Neurologic side effects, most commonly tremor and ataxia, occurred in 52 patients. Thyroid dysfunction occurred in 3 patients, and 32 patients had cutaneous abnormalities. Miscellaneous other side effects occurred in 32 patients. Amiodarone appears to be useful in the management of refractory arrhythmias. Because virtually all patients develop side effects when given a maintenance daily dose of 600 mg, lower maintenance doses should be used. It is unknown if the more severe side effects are dose-related. Amiodarone is difficult to administer because of its narrow toxic-therapeutic range and prolonged loading phase. More importantly, the first sign of antiarrhythmic failure may be manifest as sudden cardiac death.
Assuntos
Amiodarona/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Benzofuranos/uso terapêutico , Amiodarona/efeitos adversos , Amiodarona/toxicidade , Doenças da Córnea/induzido quimicamente , Glicosídeos Digitálicos/uso terapêutico , Interações Medicamentosas , Dispneia/induzido quimicamente , Epididimite/induzido quimicamente , Seguimentos , Insuficiência Cardíaca/induzido quimicamente , Humanos , Hipotensão Ortostática/induzido quimicamente , Testes de Função Hepática , Masculino , Fibrose Pulmonar/induzido quimicamente , Volume Sistólico/efeitos dos fármacos , Tireotropina/sangueRESUMO
The electrophysiologic effects of clofilium phosphate, a new quaternary ammonium antiarrhythmic agent, were evaluated in 15 patients with a variety of cardiac dysrhythmias. Ten patients had ventricular dysrhythmias and five patients had supraventricular dysrhythmias. Clofilium was administered as a single bolus intravenously in doses ranging from 60 to 300 micrograms/kg during electrophysiologic testing. Blood pressure and heart rate were unchanged, and there were no significant side effects. Conduction time was unchanged in atrial tissue, ventricular tissue, atrioventricular node, and in the His-Purkinje system. QT intervals lengthened, atrial effective refractory period increased, and ventricular effective refractory period increased. The effective refractory period of the AV node was unchanged. Refractoriness of the bundle branches or His-Purkinje system was increased in eight patients. Inducible supraventricular arrhythmias were improved in four of four patients, and inducible ventricular arrhythmias were improved in at least five of nine patients. Clofilium is a model for an antiarrhythmic drug which should be useful in interrupting or suppressing reentrant arrhythmias because it increases refractoriness without major changes in conduction time.
Assuntos
Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Sistema de Condução Cardíaco/efeitos dos fármacos , Compostos de Amônio Quaternário/uso terapêutico , Adulto , Idoso , Antiarrítmicos/efeitos adversos , Nó Atrioventricular/efeitos dos fármacos , Fascículo Atrioventricular/efeitos dos fármacos , Avaliação de Medicamentos , Eletrocardiografia , Feminino , Átrios do Coração/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Ramos Subendocárdicos/efeitos dos fármacos , Compostos de Amônio Quaternário/efeitos adversosRESUMO
Five patients with recurrent, life-threatening ventricular arrhythmias were given bretylium tosylate intravenously for a minimum of 4 days. Arrhythmias were not related to acute ischemia in any patient. Four patients had inducible ventricular tachycardia, and one patient had inducible ventricular fibrillation requiring cardioversion while taking no medications. Programmed electrical stimulation was then repeated to assess the ability of bretylium to suppress inducible ventricular tachycardia. Bretylium tosylate, at a mean dose of 2.3 mg intravenously per minute, did not suppress inducible ventricular arrhythmias in any patient. Rapid ventricular tachycardia was induced in all patients, and ventricular fibrillation was induced in one patient. Two patients required external cardioversion to terminate their arrhythmias. Bretylium tosylate, given in relatively large doses chronically, did not suppress inducible ventricular arrhythmias in these five otherwise drug-refractory patients with chronic recurrent ventricular tachycardia. This failure to suppress inducible ventricular arrhythmias cannot be attributed to the initial catecholamine release which occurs in the first hour or two after the drug is administered.