RESUMO
Paroxysmal atrial fibrillation is a grossly irregular tachycardia. Forty-nine patients with paroxysmal atrial fibrillation who were taking a variety of antiarrhythmic medications including the class IC agents propafenone and flecainide were followed up for a median of 371 days with use of transtelephonic electrocardiogram (ECG) monitoring to document symptomatic rhythms. Eighteen patients had 96 episodes of regular tachycardia; the cumulative incidence rate was 25% at 6 months, 33% at 1 year and 41% at 18 months. Eighty of the 96 episodes occurred with a heart rate less than or equal to 180 beats/min and could have been explained by atrial flutter with 2:1 block. However, nine patients had a total of 16 episodes with a rate greater than 180 beats/min that were probably not due to atrial flutter with block; the cumulative incidence rate of these fast regular tachycardias was 14% at 6 months, 17% at 1 year and 25% at 18 months. QRS duration during the first episode of regular tachycardia was significantly longer in patients taking a class IC drug (median 105 vs 90 ms, p less than 0.001 Wilcoxon rank sum test). In contrast to drug therapy with amiodarone or the combination of digoxin and verapamil, the QRS duration of regular tachycardias during class IC therapy was directly related to the tachycardia heart rate (Spearman's rank, p less than 0.01). All episodes of fast, regular tachycardias with a QRS duration greater than 120 ms occurred in patients taking a class IC drug. Clinicians treating patients with paroxysmal atrial fibrillation should expect a substantial incidence of regular tachycardia in addition to atrial fibrillation.
Assuntos
Fibrilação Atrial/fisiopatologia , Frequência Cardíaca , Adulto , Idoso , Fibrilação Atrial/complicações , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Estudos Retrospectivos , Taquicardia/etiologia , TelefoneRESUMO
The dose-response relations for efficacy and tolerance of the antiarrhythmic drug flecainide acetate were studied in 28 patients with paroxysmal supraventricular tachycardia (Group 1) and 45 patients with paroxysmal atrial fibrillation or flutter (Group 2). Recurrent symptomatic tachycardia was documented with use of transtelephonic electrocardiographic recording. Patients received flecainide in doses of 25, 50, 100 and 150 mg twice daily and placebo for 1 month treatment periods. Among 14 patients in Group 1 who qualified for efficacy analysis, 4 (29%) had no tachycardia while taking placebo. The number with no tachycardia increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 12 (86%) of 14 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Among 28 patients in Group 2, 2 (7%) had no tachycardia while taking placebo. The number with no tachycardia also increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 17 (61%) of 28 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Noncardiac adverse experiences were the leading cause of premature study discontinuation during flecainide treatment periods (five patients in Group 1 and six patients in Group 2).
Assuntos
Fibrilação Atrial/tratamento farmacológico , Flutter Atrial/tratamento farmacológico , Flecainida/administração & dosagem , Taquicardia Paroxística/tratamento farmacológico , Taquicardia Supraventricular/tratamento farmacológico , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Flecainida/efeitos adversos , Flecainida/uso terapêutico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: The purpose of this study was to assess the effectiveness of azimilide, a class III antiarrhythmic drug, in reducing the frequency of symptomatic arrhythmia recurrences in patients with atrial fibrillation, atrial flutter or both. BACKGROUND: Atrial fibrillation is an increasingly common disorder of the heart rhythm, and most patients with this problem are identified because they have symptoms associated with their arrhythmia. New antiarrhythmic therapies are needed to treat patients with this problem. METHODS: A total of 384 patients with a history of atrial fibrillation, atrial flutter or both were randomly assigned to receive once daily doses of placebo or azimilide; recurrent symptomatic arrhythmias were documented using transtelephonic electrocardiogram (ECG) recording. Azimilide 50 mg, 100 mg or 125 mg was tested; the primary efficacy analysis compared the time to first symptomatic recurrence in the combined azimilide 100 mg and 125 mg dose groups with that in the placebo group using the log-rank test. RESULTS: In the primary efficacy analysis, the time to first symptomatic arrhythmia recurrence was significantly prolonged in the combined azimilide 100 mg and 125 mg daily dose group compared with the placebo group (chi-square 7.96, p = 0.005); the hazard ratio (placebo: azimilide) for this comparison was 1.58 (95% confidence interval [CI] = 1.15, 2.16). In comparisons between individual doses and placebo, the hazard ratio for the 50 mg daily dose was 1.17 (95% CI = 0.83, 1.66; p = 0.37); for the 100 mg group, dose was 1.38 (95% CI = 0.96, 1.98; p = 0.08), and for the 125 mg group, dose was 1.83 (95% CI = 1.24, 2.70; p = 0.002). CONCLUSIONS: Azimilide significantly lengthened the symptomatic arrhythmia-free interval in patients with a history of atrial fibrillation, atrial flutter or both.
Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Imidazóis/uso terapêutico , Imidazolidinas , Piperazinas/uso terapêutico , Idoso , Antiarrítmicos/administração & dosagem , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/fisiopatologia , Flutter Atrial/tratamento farmacológico , Flutter Atrial/fisiopatologia , Relação Dose-Resposta a Droga , Eletrocardiografia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hidantoínas , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVES: This study was performed to determine the incidence of symptomatic, sustained atrial fibrillation in a group of patients with paroxysmal supraventricular tachycardia. The effects of the mechanism of paroxysmal supraventricular tachycardia (atrioventricular [AV] node reentry vs. AV reentry through an accessory pathway) and heart rate during the tachycardia on the occurrence of atrial fibrillation were also assessed. BACKGROUND: There is a substantial incidence of atrial fibrillation in patients with paroxysmal supraventricular tachycardia, but the precise incidence and the factors that determine it are unknown. METHODS: One hundred sixty-nine patients with paroxysmal supraventricular tachycardia were followed up by regular clinic visits and transtelephonic electrocardiographic monitoring during symptomatic episodes of arrhythmia. The Kaplan-Meier product-limit method was used to estimate the proportion of patients remaining free of atrial fibrillation during the observation period. The Cox proportional hazards model was used to assess the effect of mechanism and heart rate during paroxysmal supraventricular tachycardia on the atrial fibrillation-free period. RESULTS: Thirty-two (19%) of the 169 patients had an episode of atrial fibrillation during a mean follow-up period of 31 months. The cumulative percent of patients experiencing an episode of atrial fibrillation was 6% within 1 month, 9% within 4 months and 12% within 1 year. The mechanism of paroxysmal supraventricular tachycardia was not associated with the time to occurrence of atrial fibrillation; the hazard ratio corresponding to classification in the AV node reentry group was 0.8 (p > 0.6). The heart rate during paroxysmal supraventricular tachycardia was not associated with the time to occurrence of atrial fibrillation; the hazard ratio associated with an increase in heart rate of 50 beats/min during the tachycardia was 1.15 (p > 0.5). CONCLUSIONS: This study suggests that atrial fibrillation will develop in approximately 12% of patients with paroxysmal supraventricular tachycardia during a 1-year follow-up period. The occurrence of atrial fibrillation is not related to the mechanism or heart rate of the paroxysmal supraventricular tachycardia.
Assuntos
Fibrilação Atrial/epidemiologia , Taquicardia Paroxística/complicações , Taquicardia Supraventricular/complicações , Fibrilação Atrial/complicações , Fibrilação Atrial/fisiopatologia , Eletrocardiografia/métodos , Feminino , Seguimentos , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca/fisiologia , Humanos , Incidência , Masculino , Monitorização Fisiológica/métodos , Modelos de Riscos Proporcionais , Taquicardia por Reentrada no Nó Atrioventricular/fisiopatologia , Taquicardia Paroxística/fisiopatologia , Taquicardia Supraventricular/fisiopatologia , Telefone , Fatores de TempoRESUMO
BACKGROUND: Our goal was to determine whether patient age affects a physician's reported likelihood of using anticoagulant therapy or the intensity of anticoagulant therapy for patients with nonvalvular atrial fibrillation. METHODS: We surveyed a nationwide sample of 1189 randomly selected office-based practitioners in three strata: primary care (geriatrics, internal medicine, family practice, and general practice), cardiology, and neurology. A vignette-based questionnaire was used to measure attitudes and beliefs regarding anticoagulation risks and effectiveness, barriers to anticoagulation in clinical practice, and likelihood of using anticoagulation and target intensity of anticoagulation at three patient ages (55, 65, and 75 years) for four clinical scenarios (chronic non-valvular atrial fibrillation with mild left atrial enlargement, intermittent or paroxysmal atrial fibrillation, recent-onset atrial fibrillation, and atrial fibrillation with recent [3 months] embolic stroke). RESULTS: The overall response rate was 38%. The mean likelihoods of using anticoagulation for the three ages were unequal (P < .0001) for each scenario. Most physicians were "very" or "somewhat" likely to use anticoagulant therapy for a 65-year-old with left atrial enlargement (71%), intermittent or paryoxysmal atrial fibrillation (68%), recent-onset atrial fibrillation (86%), or embolic stroke (96%). Fewer physicians were likely to use anticoagulant therapy for a 75-year-old with left atrial enlargement (63%), intermittent or paroxysmal atrial fibrillation (56%), recent-onset atrial fibrillation (80%), or embolic stroke (93%). Among physicians equally likely to use anticoagulation for 65- and 75-year-old patients, intensity of anticoagulant therapy (target international normalized ratio or prothrombin time ratio) was lower (P < .04) for the 75-year-old. CONCLUSION: Anticoagulant therapy may be less often and less intensively used for elderly patients with nonvalvular atrial fibrillation.
Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/etiologia , Padrões de Prática Médica/estatística & dados numéricos , Idoso , Atitude do Pessoal de Saúde , Cardiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pessoa de Meia-Idade , Neurologia , Atenção Primária à Saúde , Inquéritos e Questionários , Estados UnidosRESUMO
The purpose of this article is to investigate the occurrence of symptomatic paroxysmal supraventricular tachycardia (PSVT) in untreated patients and to assess factors that influenced its occurrence. We studied 34 patients with this arrhythmia during an observation period in which they received no antiarrhythmic drug therapy for up to 90 days. Recurrence of PSVT was documented by telephone transmission of the electrocardiogram. Each patient was allowed to have exactly one episode of tachycardia before being removed from the study. We measured how long patients remained free of their tachycardia (the tachycardia-free period) and heart rate during tachycardia. Twenty-nine of the 34 patients had an attack of symptomatic tachycardia within the 90-day observation period. The proportion of patients who had not had any symptomatic PSVT by each day of follow-up was calculated using the Kaplan-Meier method as follows: 75% by day 3, 50% by day 19, 25% by day 36, and 17% by day 90. Patients with any other heart or lung disease had significantly shorter tachycardia-free periods. The mean heart rate during spontaneous tachycardia was 203.5 +/- 34.9 beats per minute (range, 142 to 288 beats per minute). Patients with longer tachycardia-free periods had significantly faster heart rates during tachycardia.
Assuntos
Taquicardia Supraventricular/fisiopatologia , Adulto , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de TempoRESUMO
Esmolol is a new ultra-short-acting beta-adrenergic receptor blocking agent that may be useful in the treatment of patients with heart disease. We gave esmolol as an intravenous bolus injection (over 30 seconds) to 12 healthy men in a dose-ranging study; each subject received two doses. Our dosing schedule began with 30 mg in the first subject and ended with 100 mg and 150 mg in the final four subjects. We measured blood esmolol concentration, PR interval, QRS duration, QTc interval, cardiac cycle, systolic blood pressure, and diastolic blood pressure. Esmolol doses of 150 mg produced blood esmolol concentrations of 0.868 to 1.47 micrograms/ml. The peak PR interval recorded after esmolol was significantly longer than the control PR interval in four subjects who received 100 and 150 mg doses (192 +/- 7.9 msec vs. 177 +/- 10.6 msec; P = 0.00002). Peak prolongation of the PR interval was recorded 6 to 10 minutes after the bolus, at which time blood esmolol concentrations were negligible. Esmolol did not consistently affect any other pharmacodynamic variable. Giving esmolol as an intravenous bolus injection may be a simple alternative to loading and maintenance infusion in some clinical settings.
Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Propanolaminas/administração & dosagem , Antagonistas Adrenérgicos beta/metabolismo , Adulto , Pressão Sanguínea/efeitos dos fármacos , Eletrocardiografia , Coração/efeitos dos fármacos , Humanos , Cinética , Masculino , Propanolaminas/metabolismoRESUMO
To compare the effects of intravenous and oral verapamil we examined the prolongation of the PR interval in 11 patients after (1) a single 10 mg IV bolus given over 2 min, (2) a single oral dose of 120 mg, and (3) a sustained concentration-maintaining infusion. Maximal PR interval prolongation was delayed relative to peak plasma verapamil concentration in all patients after the bolus and in seven of 11 patients after oral dosing. In all 11 patients oral verapamil was less potent than a single intravenous bolus of verapamil; the plasma verapamil concentration corresponding to a 10% prolongation of the PR was 39.5 +/- 21.7 ng/ml after the bolus and 146.3 +/- 75.1 ng/ml after the oral dose (P = 0.001). However, there was no such difference between oral verapamil and an infusion in six patients. The plasma verapamil concentration corresponding to a 10% PR prolongation was 35.7 +/- 24 ng/ml after the bolus, 132.5 +/- 80.8 ng/ml after the oral dose, and 85.2 +/- 29.9 ng/ml after the infusion. Maximum PR prolongation (drug efficacy) was comparable for the three methods of administration. There was no evidence of tachyphalaxis during prolonged infusions. We conclude that both oral doses and infusions of verapamil are less potent then bolus doses, but that drug efficacy at the concentrations reached is equivalent for the three. Plasma verapamil concentrations determined after bolus doses appear to underestimate effective plasma concentration when the drug is given by the oral or infusion methods.
Assuntos
Verapamil/administração & dosagem , Administração Oral , Adulto , Eletrocardiografia , Feminino , Humanos , Infusões Parenterais , Masculino , Fatores de TempoRESUMO
Plasma concentrations of verapamil and its metabolite, norverapamil, were measured in six patients with supraventricular tachycardia after the first and seventh dose of a regimen consisting of 120 mg every 8 hr by month. Steady state was reached by the seventh dose and the area under the concentration-time curve (AUC) at steady state (1999 +/- 435[SD] ng/ml . hr) was greater than that after the first dose (788 +/- 224, P less than 0.001). This unexpected cumulation was associated with prolongation of verapamil half-life (t1/2) from 2.75 +/- 1.14 to 4.52 +/- 1.10 hr. Norverapamil AUC also rose from 1225 +/- 405 to 2312 +/- 963 ng/ml/hr during the attainment of steady state. We conclude that verapamil cumulates to a greater extent than predicted from its t1/2, due to reduction in hepatic clearance.
Assuntos
Verapamil/metabolismo , Administração Oral , Adulto , Idoso , Feminino , Meia-Vida , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Verapamil/administração & dosagem , Verapamil/análogos & derivadosRESUMO
Esmolol is an investigational ultra-short-acting beta-adrenergic blocker that has potential application in many clinical cardiology settings. The purpose of this study was to investigate the effect of a bolus dose of esmolol on heart rate, blood pressure, and PR interval in healthy, exercising male subjects. We gave a single esmolol bolus over 30 seconds to 13 men who exercised to a predetermined target heart rate. Each subject performed the exercise protocol twice, receiving a different dose between 10 and 300 mg each time. An additional eight subjects received two esmolol boluses 5 minutes apart while performing the same exercise protocol. Esmolol doses of 180 mg or greater caused a 13% to 18% decrease in heart rate, an 11% to 18% decrease in blood pressure, and a 13% to 22% prolongation of the PR interval. The median time to peak esmolol effect was 1 minute for heart rate, 2 minutes for blood pressure, and 4 minutes for PR interval. The median time required to recover 50%, 75%, and 90% of the decrement in heart rate was 8, 10, and 13 minutes, respectively. The rapid onset and disappearance of esmolol effects may make it an appealing drug in acute care settings.
Assuntos
Esforço Físico , Propanolaminas/farmacologia , Adulto , Pressão Sanguínea/efeitos dos fármacos , Eletrocardiografia , Frequência Cardíaca/efeitos dos fármacos , Humanos , MasculinoRESUMO
The kinetics and dynamics of single doses of verapamil (10 mg iv and 120 mg by mouth) were followed in eight subjects on oral cimetidine (300 mg every 6 hr) and placebo. Cimetidine had no effect on intravenous verapamil kinetics but induced a significant rise in oral verapamil bioavailability. Other kinetic parameters of verapamil were not altered by cimetidine. Verapamil induced a significant slowing of atrioventricular conduction (39.8 msec intravenous; 24.5 msec oral). Although there was a significant increase in oral verapamil bioavailability, after cimetidine, there was no change in PR interval prolongation with either oral or intravenous verapamil. Our data demonstrate the importance of correlating measurable drug effects with kinetic studies when drug interactions are studied and their clinical significance is assessed.
Assuntos
Cimetidina/farmacologia , Verapamil/metabolismo , Administração Oral , Adulto , Disponibilidade Biológica , Pressão Sanguínea/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Método Duplo-Cego , Interações Medicamentosas , Eletrocardiografia , Humanos , Injeções Intravenosas , Cinética , Masculino , Distribuição Aleatória , Fatores de Tempo , Verapamil/sangueRESUMO
Stimulation of complex dosage regimens for drugs with multicompartmental kinetics is described using the method of separate exponentials. This approach requires that alpha- and beta-phases are treated separately throughout and summed only at the end of the stimulation. The method was used to devise a loading regimen for pirmenol, comprising a priming injection, and a rapid loading infusion, followed by a maintenance infusion. The regimen was tested in a patient with excellent agreement. The method of separate exponentials is mathematically simple and of informational value in that it demonstrates when the early distribution phase is important. Its use can avoid the potentially dangerous assumption of one-compartmental kinetics in the design of intravenous loading regimens.
Assuntos
Preparações Farmacêuticas/administração & dosagem , Antiarrítmicos/metabolismo , Humanos , Infusões Parenterais , Injeções Intravenosas , Cinética , Matemática , Modelos Biológicos , Piperidinas/administração & dosagem , Piperidinas/metabolismoRESUMO
The relationship between alpha 1-acid glycoprotein (AAG) plasma concentration and plasma verapamil binding was examined in samples obtained 15 minutes after 10 mg IV verapamil to 15 subjects. There was a good correlation (r = 0.83) between the binding ratio and AAG concentration, suggesting that AAG could bind verapamil. This was confirmed in vitro by the addition of AAG to an albumin solution, which resulted in a strong correlation between binding ratio (r = 0.99) and AAG concentration. The relationship between both free and total plasma concentrations and the effects of verapamil on the PR interval was also examined several times after 10 mg IV verapamil in seven of the subjects. While there was a correlation between log of both concentrations and the percent prolongation in PR interval (P less than 0.001), the correlation was stronger with free drug concentration (r2 = 0.58) than with total plasma concentration (r2 = 0.36). The range of free concentrations associated with a given effect (220%) was also narrower than that for total concentration (300%). While these data indicate that AAG is responsible for most of the variability in plasma verapamil binding, which in turn contributes somewhat to variation in effectiveness of a given total plasma concentration, neither of these causes of individual variations is likely to have a major clinical impact in patients who, apart from arrhythmia, are otherwise healthy.
Assuntos
Orosomucoide/metabolismo , Verapamil/metabolismo , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Lidocaína/metabolismo , Masculino , Propranolol/metabolismo , Ligação Proteica , Verapamil/sangueRESUMO
Symptomatic paroxysmal supraventricular tachycardia is a troubling arrhythmia for many patients. To test the efficacy of oral diltiazem to reduce symptomatic recurrences of paroxysmal supraventricular tachycardia, we enrolled 17 patients in a double-blind, placebo-controlled crossover study. Sixteen of 17 patients completed a dose-ranging phase and were entered into the randomized phase. Although the time to first recurrence of tachycardia was slightly longer when patients took diltiazem, the difference was not significant (p = 0.15). The hazard ratio of the time to first recurrence on placebo compared with oral diltiazem was 2.7 (95% confidence interval, 0.8 to 9.1). Of the patients who had a recurrence of tachycardia in both treatment periods, the median reduction in heart rate in patients receiving diltiazem was 20 beats/min. (p less than 0.01; 95% confidence interval, 6 to 42).
Assuntos
Diltiazem/uso terapêutico , Taquicardia Supraventricular/tratamento farmacológico , Administração Oral , Diltiazem/administração & dosagem , Método Duplo-Cego , Frequência Cardíaca/efeitos dos fármacos , Humanos , Taquicardia Supraventricular/fisiopatologiaRESUMO
The oral form of pirmenol has not been administered to man. Pirmenol was given by mouth to eight patients with chronic, stable premature ventricular beats (PVBs) to determine effective dose and kinetics. The patients were evaluated with a dose-ranging protocol following by a double-blind, crossover, placebo-controlled study of doses that were effective during dose ranging. Oral doses of 150 to 250 mg induced at least 90% suppression of PVBs 18 of the 19 times they were administered during both protocols. During the double blind experiment, a single oral dose of pirmenol suppressed 95 +/- 8% PVBs/hr (mean +/- SD) for 3 consecutive hr, while placebo suppressed 4 +/- 42% PVBs/hr (P less than 0.01). a 90% or greater reduction in PVBs persisted for a median of 6 hr (range 1 to 8 hr). The range of plasma pirmenol concentrations associated with an at last 90% reduction in PVBs was 0.7 to 2.0 micrograms/ml. Median half-life (t1/2) was 9.3 hr (range 6.0 to 12.4) with 86.6 +/- 2.4% protein binding and 82.6 +/- 23.6% bioavailability. At peak drug level there was lengthening of the QTc interval (0.036 sec, P less than 0.05), but no change in heart rate, blood pressure, PR interval or QRS duration, or symptoms. In this single-dose study, pirmenol effectively reduced PVBs, has a relatively long t1/2, and was minimally toxic.
Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Piperidinas/farmacologia , Administração Oral , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Frequência Cardíaca/efeitos dos fármacos , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Piperidinas/metabolismo , Piperidinas/uso terapêutico , Fatores de TempoRESUMO
We examined the hemodynamic effects of pirmenol, a new antiarrhythmic drug, for the first time in man. Right and left heart pressures, Fick cardiac output, and radionuclide ejection fraction were measured before and during infusion of pirmenol in 10 patients with coronary artery disease who were undergoing routine diagnostic cardiac catheterization. Pirmenol was given as a 50-mg IV injection over 2 min followed by a constant infusion of 2.5 mg/min for up to 36 min. Plasma pirmenol levels were within or near the previously determined therapeutic range in all patients. There were no significant changes in systolic blood pressure or cardiac output. Diastolic blood pressure rose from a mean (+/- SD) 78 +/- 7 during the control period to 82 +/- 6 during the infusion, heart rate rose from 66 +/- 6 during the control period to 75 +/- 7 during infusion and ejection fraction fell from 60 +/- 8 during control to 55 +/- 12 during infusion. Although the left ventricular end-diastolic pressure rose from 6 +/- 2 during control to 8 +/- 3 during the infusion, the left ventricular stroke work index fell and the left ventricular work index per minute did not change. The fall in ejection fraction did not correlate with the control ejection fraction, plasma pirmenol levels, or the change in heart rate. The decline in ejection fraction and the failure of the left ventricular work index per minute to rise despite a small rise in left ventricular end-diastolic pressure may indicate a potential myocardial depressant effect of pirmenol.
Assuntos
Antiarrítmicos/farmacologia , Hemodinâmica/efeitos dos fármacos , Piperidinas/farmacologia , Avaliação de Medicamentos , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-IdadeRESUMO
The efficacy, pharmacokinetics, and pharmacodynamics of pirmenol, a class Ia antiarrhythmic agent, were studied in patients with frequent symptomatic premature ventricular complexes (PVCs). Pirmenol was given every 12 hours to eight patients in a dose-ranging protocol, and median PVC suppression of 94% (range 72% to 100%) was achieved. The median effective pirmenol dose was 300 mg/day (range 200 to 500 mg/day), and mean (+/- SD) trough plasma pirmenol concentration at the effective dose was 0.98 +/- 0.29 micrograms/ml. The mean half-life of elimination was 10.5 +/- 2 hours. There was considerable overlap among patients with respect to plasma pirmenol concentration and times at which PVC frequency returned to 25%, 50%, and 75% of baseline during drug washout trials. Altering pirmenol's dose interval (while maintaining a constant daily dose) from 12 to 6 hours did not improve drug efficacy. Pirmenol was given to seven patients for long-term therapy (24 to 44 months). Median PVC suppression at 24 months was 70%. Pirmenol is safe and well tolerated, and it can be administered twice daily for PVC suppression.
Assuntos
Antiarrítmicos/administração & dosagem , Piperidinas/administração & dosagem , Administração Oral , Adulto , Antiarrítmicos/farmacocinética , Antiarrítmicos/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Eletrocardiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Piperidinas/farmacocinética , Piperidinas/farmacologia , Fatores de TempoRESUMO
Forty-nine healthy male volunteers received the test article for bidisomide (SC-40230) in a double-blind, placebo-controlled, dose-ranging study. Intravenous doses ranged from 0.03 to 2.5 mg/kg. There was a close relationship between the dose and the peak plasma concentration. The PR, QRS, QT, RR, and QTc intervals each demonstrated a statistically significant response to the dose administered. The PR and QRS intervals lengthened and the other intervals shortened (although to a lesser degree). The compound was well tolerated, with mild symptoms only at higher doses. Bioavailability was studied in 12 male volunteers, with each receiving 2.0 mg/kg of bidisomide, both orally and intravenously, in an open-label crossover trial. After a 10-minute zero-order intravenous infusion, bidisomide plasma levels could best be described in terms of a three-compartment pharmacokinetic model with the mean half-life values of alpha, beta, and gamma phases of 0.12, 1.77, and 12.3 hours, respectively. The mean absolute oral bioavailability was 43%.
Assuntos
Antiarrítmicos/farmacocinética , Piperidinas/farmacocinética , Administração Oral , Adulto , Antiarrítmicos/administração & dosagem , Antiarrítmicos/sangue , Disponibilidade Biológica , Relação Dose-Resposta a Droga , Método Duplo-Cego , Eletrocardiografia/efeitos dos fármacos , Humanos , Injeções Intravenosas , Masculino , Piperidinas/administração & dosagem , Piperidinas/sangue , Distribuição AleatóriaRESUMO
In a recent clinical trial, the class Ic antiarrhythmic drugs encainide and flecainide were found to be associated with an increased mortality risk in patients with new myocardial infarction and ventricular arrhythmias. The purpose of this study was to assess whether an increased mortality risk also accompanied the use of these drugs to treat patients with supraventricular arrhythmias. Data were obtained from the respective pharmaceutical sponsors on the mortality observed with each drug in United States and foreign protocols enrolling patients with supraventricular arrhythmias. Mortality in the encainide population (343 patients) and the flecainide population (236 patients) was compared with that in a research arrhythmia clinic, the Duke population (154 patients). Nine deaths occurred in the combined encainide-flecainide population and 10 deaths occurred in the Duke population; the follow-up periods averaged 488 days and 1,285 days, respectively. The 6-year survival functions of these 2 populations, estimated by the Kaplan-Meier technique, did not differ significantly (p = 0.62). The hazard ratio for the combined encainide-flecainide population relative to the Duke population was estimated to be 0.6 with a 95% confidence interval of 0.2, 1.7. These descriptive comparisons did not demonstrate any excess mortality when flecainide and encainide were used in patients with supraventricular arrhythmias.
Assuntos
Anilidas/efeitos adversos , Antiarrítmicos/efeitos adversos , Arritmias Cardíacas/mortalidade , Flecainida/efeitos adversos , Taquicardia Supraventricular/mortalidade , Adulto , Idoso , Arritmias Cardíacas/tratamento farmacológico , Encainida , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , North Carolina , Taxa de Sobrevida , Taquicardia Supraventricular/tratamento farmacológico , Estados UnidosRESUMO
Paroxysmal atrial tachycardia is a familiar arrhythmia that has been studied extensively for the past decade using intracardiac recording and programmed electrical stimulation. These studies have thoroughly documented the mechanisms of this arrhythmia and its associated atrioventricular conduction abnormalities, but little is known about the spontaneous clinical behavior of this arrhythmia. A group of 34 patients with paroxysmal atrial tachycardia were studied using telephone transmission of the electrocardiogram to document recurrent tachycardia. When antiarrhythmic therapy was withdrawn, median time to the first recurrence of tachycardia was 19 days, mean heart rate during spontaneous tachycardia was 203.5 +/- 34.9 beats/min, and the median duration of an attack was 20 minutes. In a group of patients who were followed while many consecutive attacks were documented, the time intervals between attacks were found to be uncorrelated and to fit an exponential probability distribution (i.e., the occurrence of paroxysmal atrial tachycardia behaved like a Poisson process). Paroxysmal atrial tachycardia does not occur in a chaotic and unpredictable fashion; it is an event that occurs according to common probability models.