Propafenone versus Disopyramide for Treatment of Chronic Symptomatic Ventricular Arrhythmias

ABSTRACT The efficacy and safety of propafenone, 150 mg four times daily, were compared with those of disopyramide, 100 mg four times daily, in a randomized single-blind, cross-over study in 38 patients with symptomatic premature ventricular complexes (PVCs). The 24-hour ambulatory ECG, employed for assessing antiarrhythmic efficacy, was analyzed blindly. The median reduction in the number of PVCs was higher with propafenone than with disopyramide (91.4% vs. 63.5%, respectively, p<0.01). A reduction of at least 80% was achieved by propafenone in 22 (59%) and by disopyramide in 16 patients (43%) (NS). Ventricular tachycardias (VTs) were abolished by propafenone in eight out of 11, and by disopyramide in five out of nine patients with VTs (NS) A possible proarrhythmic effect was seen in three patients during disopyramide and in one patient during propafenone treatment. Micturition disturbances (p<0.001) and a dry mouth (p<0.01) were more commonly associated with disopyramide than with propafenone. In conclusion, in the given dosages, propafenone was superior to disopyramide in suppressing PVCs and had fewer side-effects.     

Regular Ventricular Rhythms Before Conversion of Recent Onset Atrial Fibrillation to Sinus Rhythm

The incidence of fast atrial tachycardias with regular ventricular rhythm was assessed in a population of 243 patients with recent onset (< 72 hours) atrial fibrillation (AF), without heart failure, randomly treated with single loading oral dose of propafenone (600 mg), flecainide (300 mg), digoxin (1 mg), or placebo for acute conversion to sinus rhythm (SR). Fast atrial arrhythmias developed in 14 (6%) patients: 6/92 treated with propafenone, 3/34 treated with flecainide, 1/25 treated with digoxin, and 4/ 92 who received placebo (P = NS). Heart rate > 175 beats/min with 1:1 AV conduction ensued in 4 cases: 2 treated with flecainide and 2 treated with placebo; in the other cases 2:1 AV conduction was observed. Widening of QRS during regular tachycardia was observed in 4 patients; 3 who received propafenone and 1 who received flecainide. Conversion to SR within 4 hours was achieved in 55/92 (60%) patients treated with propafenone, 20/34 (59%) patients treated with flecainide, 7/25 (28%) patients treated with digoxin, and 19/92 (20%) treated with placebo (P < 0.001 propafenone vs placebo and flecainide vs placebo; P < 0.05 propafenone vs digoxin and flecainide vs digoxin). Periods of regular tachycardia are expected in recent onset AF and may not necessarily represent a proarrhythmic effect of Class 1C drugs, rather than mark the transition from AF to SR. Class 1C agents are probably responsible for widening of the QRS complex seen during these tachycardias. Propafenone and flecainide appear equally effective in converting recent onset AF.     

Comparative Investigation of the Antiarrhythmic Effect of Propafenone (Rytmonorm) and Lidocaine in Patients with Ventricular Arrhythmias during Acute Myocardial Infarction

ABSTRACT Propafenone, a new class I antiarrhythmic drug, given as a bolus injection followed by oral medication, or lidocaine were given to 20 consecutive patients admitted with chest pain suggesting acute myocardial infarction and showing high grades, i.e. multiform, pairs or R-on-T premature ventricular complexes or short runs of ventricular tachycardia. Before institution of therapy the mean number (±1 SD) of premature ventricular contractions (PVCs) per hour was 169±123 in the lidocaine group and 324±440 in the propafenone group. During the next 24 hours lidocaine reduced the numbers of PVCs by 73% and propafenone by 75%. The mean number (±1 SD) of 5-minute periods with high grade PVCs was 4.3±2.9 in the lidocaine group and 5.8±4.5 in the propafenone group. During therapy this number was equally reduced in both groups to 2.4. One patient in the lidocaine group developed ventricular fibrillation and three patients in the propafenone group were excluded because of increasing numbers of PVCs. One patient in the propafenone group showed a torsade-de-pointes ventricular tachycardia.     

凉血清热法联合盐酸普罗帕酮治疗气阴两虚型阵发性房颤临床研究

目的:研究凉血清热法联合盐酸普罗帕酮治疗气阴两虚型阵发性房颤的疗效。方法:90例气阴两虚型阵发性房颤患者随机分为观察组和对照组各45例。观察组给予凉血清热汤剂联合盐酸普罗帕酮治疗,对照组给予单纯盐酸普罗帕酮治疗。比较两组整体疗效和治疗前后房颤发作情况,记录最大P波时限(Pmax)、最小P波时限(Pmin)、P波离散度(Pdis)及平均心率等心电图指标的变化。结果:观察组治疗总有效率高于对照组,差异有统计学意义(P0.05)。两组治疗后房颤发作次数和持续时间较治疗前均减少,差异有统计学意义(P0.05);治疗后,观察组房颤发作次数和持续时间均少于对照组,差异有统计学意义(P0.05)。两组治疗后Pmax、Pdis及平均心率较治疗前均显著降低,差异有统计学意义(P0.05);治疗后,观察组Pmax、Pdis及平均心率均显著低于对照组,差异有统计学意义(P0.05)。结论:凉血清热法联合盐酸普罗帕酮治疗气阴两虚型阵发性房颤疗效显著,有助于改善患者的临床症状和心电图表现。     

盐酸普罗帕酮片溶出度质量分析

采用紫外分光光度法对若干市售盐酸普罗帕酮片的溶出性能进行考察。结果表明不同帮家的盐酸普罗帕酮片体外溶出性能具有一定的差异。     

静脉注射心律平与顿服心律平转复房颤疗效及安全性比较

关键词 房颤 心律平 顿服 文摘 目的 观察监测临床广泛应用的静脉输注心律平转复房颤的患者,是否能安全院外处方顿服心律平转复房颤。方法 临床入选>阵发房颤患者,随机分为两组静脉负荷量心律平组和口服负荷量心律平组,对成功转复的患者院外处方顿服心律平治疗,比较两组转复率、副作用发生率、急诊就诊率 结果两组首次顿服心律平发生副作用（8.9%vs5.7%,p>0.05）,无统计学差异.而院外顿服负荷量心律平治疗副作用发生率（8.9%vs1.25%,p<0.05）,急诊就诊率（19.0%vs5%,p<0.001）,据统计学差异。结论患者首次转负房颤,宜院内口服负荷量,发生副作用可及时处理,保证患者安全,即使能耐受静脉冲击量心律平转复房颤,也不能预测顿服心律平不良反应的发生。     

普罗帕酮在健康受试者中的药动—药效学结合模型研究

目的:采用药动-药效结合模型观察普罗帕酮血浆浓度与心电图指标PR间期延长百分率的数量关系,并求算药效学参数。方法:选择健康汉族受试者10名,其中CYP2D6表型的快代谢型(EM)和中速代谢型(IM)各5名。受试者口服普罗帕酮片剂400mg,于给药后15h内抽取静脉血,并同步测定受试者PR间期。普罗帕酮浓度采用高效液相色谱分析法测定。采用CAPP软件对普罗帕酮血药浓度及PR间期延长百分率进行药动-药效结合模型计算。结果:10例健康志愿者的普罗帕酮血浆浓度与效应之间存在着滞后现象。经采用CAPP软件拟合数据,发现效应与浓度之间符合Sigmoid E_(max)模型。IM组的AUC(μg·h·L~(-1))明显高于EM组(5126±1030 vs2948±1230,P<0.05);相对应药效参数Ce_(50)IM组也比EM组大(P<0.05)。另外,效应曲线S线程度的参数γEM组大于IM组(P<0.05)。结论:CYP2D6遗传多态性不但对普罗帕酮的药动学有影响,而且对其药效学参数可能也有明显的影响。     

普罗帕酮对钾通道亚型Kv4.2和Kv4.3电流的影响

目的　研究普罗帕酮对钾通道亚型Kv4 2和Kv4 3电流的影响。方法　采用全细胞膜片钳技术记录稳定表达Kv4 2和Kv4 3电流的人胚胎肾细胞株 (HEK2 93细胞 )电流的变化。结果　①普罗帕酮明显抑制Kv4 2和Kv4 3电流 ,呈浓度依赖性 ,IC50 分别为 1 0 3 μmol·L- 1 和 71 μmol·L- 1 ;②普罗帕酮明显加速Kv4 2和Kv4 3电流失活 ,1 0μmol·L- 1 的普罗帕酮可使Kv4 2电流衰减时间常数τ由(38 9± 2 1 )ms变为 (9 9± 1 8)ms ,半数最大失活膜电位V1 /2 由 (- 66 6± 0 8)mV左移至 (- 70 9± 1 1 )mV ;1 0 0μmol·L- 1 的普罗帕酮可使Kv4 3电流衰减时间常数τ(1 4 4 8± 2 0 8)ms变为 (1 8 5± 2 8)ms,半数最大失活膜电位V1 /2 由 (- 4 5 6± 1 9)mV左移至 (- 52 3± 2 1 )mV ;③普罗帕酮明显左移Kv4 2和Kv4 3电流的激活曲线 ,1 0μmol·L- 1 的普罗帕酮可使Kv4 2电流半数最大激活膜电位V1 /2 由 (- 4 1± 0 5)mV左移至 (- 1 6 1± 2 4)mV ;1 0 0μmol·L- 1 的普罗帕酮可使Kv4 3半数最大激活膜电位V1 /2由 (- 6 0± 1 1 )mV左移至 (- 1 6 5± 3 0 )mV。结论　普罗帕酮明显抑制Kv4 2 ,Kv4 3电流 ,该作用可能是其治疗心律失常的机制之一。