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1.
L Santoro F Barbieri R Nucciotti F Battaglia F Crispi M Ragno P Greco G Caruso 《Muscle & nerve》1992,15(7):788-795
Amiodarone was injected endoneurially at increasing doses into the exposed tibial nerve of rats to study its electrophysiologic and pathologic effects on peripheral nerve fibers. Forty-five male Wistar rats were used, and each of the following concentrations was injected into 15 nerves: 25 micrograms/mL, 50 micrograms/mL, and 100 micrograms/mL. Microinjection of a 25 micrograms/mL concentration of amiodarone resulted in a subacute, incomplete conduction block evident at day 3 postinjection. This conduction block remained stable until day 10 and recovery was complete at day 35. Microinjection of a 50 micrograms/mL concentration of amiodarone produced a faster evolving conduction block, and significant axon degeneration (approximately 40% of fibers). Injection of a 100 micrograms/mL concentration resulted in severe acute motor axon degeneration followed by complete but delayed regeneration. Results of morphological studies closely correlated with electrophysiological findings. Amiodarone thus seems to have a direct toxic effect on axons at high concentrations in the peripheral nerve, and we suggest that different pathological changes described in human amiodarone neuropathy could be related to different concentrations of the drug in the nerve, perhaps due to variability of blood-nerve barrier efficacy. 相似文献
2.
Single intravenous bolus doses of amiodarone hydrochloride of 30, 60, 90 and 120 mg/kg were administered to male Sprague-Dawley rats to determine the effects of dose on amiodarone pharmacokinetics. Serial blood samples and total urine were collected over 48 hr and assayed for amiodarone and desethylamiodarone by HPLC. The blood amiodarone concentration-time curves for the four doses were best described by a triexponential equation with terminal half-lives (t
1/2
) ranging from 17 to 20 hr. Over the dose range studied, no changes in , t
1/2
, or central compartment volume (Vc=1.2–1.4 L/kg) were observed. On the other hand, reductions in amiodarone clearance (CL and steady-state volume of distribution (V
ss
of 44% (17.7 to 10.0 ml/min per kg) and 50% (16.4 to 8.2 L/kg), respectively, were noted as the dose of amiodarone increased. The conversion of amiodarone to desethylamiodarone (fm was dose-independent and amounted to approximately 10% of each amiodarone dose. No amiodarone or desethylamiodarone was detected in the urine of any of the treated animals. The blood-to-plasma concentration ratio of amiodarone was concentration-independent and therefore did not account for the dose-dependent changes in Vss
and CL observed. The data suggested that the dose-dependent changes noted were due to an alteration in the volume (s) of the peripheral tissue compartment(s).Supported by a Grant-in-Aid from the American Heart Association, Nebraska Affiliate. 相似文献
3.
目的观察正常及模拟“缺血”时胺碘酮对绵羊心室浦肯野纤维起搏离子流(If)的影响。方法双微电极电压钳制术,使膜电位过度极化以激活If。结果胺碘酮1×10-5mol/L在正常台氏液中显著降低浦肯野纤维If幅值;模拟“缺血”也使If幅值降低,在此基础上,胺碘酮使If幅值进一步减小,加剧了“缺血”对If离子流的抑制作用。结论提示胺碘酮能抑制心肌缺血时心室正常自律性活动。 相似文献
4.
目的 评价文献中运用心律平与胺碘酮治疗心律失常的疗效.方法 运用计算机检索Pubmed、EMbase、Cochrane图书馆、中国生物医学文献数据库中关于心律平和胺碘酮在治疗心律失常疗效的随机对照试验,将检索时限定为2000年1月~2014年7月.对检索到的论文进行客观质量评价,应用Cochrane协作网提供的Rev Man 5.3软件进行Meta分析.结果 通过药物静脉注射给药,2组心律失常总有效率差异有统计学意义(OR=1.68,95% CI:1.25 ~2.26,P<0.0001);药物口服给药,2组心律失常总有效率差异有统计学意义(OR=1.49,95% CI:1.09 ~ 2.03,P=0.010);2组不良反应发生率比较差异无统计学意义(OR=0.85,95% CI:0.62 ~ 1.16,P>0.05).结论 胺碘酮组治疗心率失常的疗效优于心律平,但对于药物的不良反应率并不增加. 相似文献
5.
1例77岁男性陈旧性下壁心肌梗死患者入院行经皮冠状动脉介入(PCI)治疗,术后第2天突发胸闷,心电图示频发室性早搏,给予改善心肌血供、维持电解质平衡及抗心律失常治疗后病情逐渐稳定。考虑频发室性早搏与PCI术、血钾偏低、不规范使用胺碘酮及患者睡眠差、情绪紧张相关。 相似文献
6.
Prescription sequence symmetry analysis: assessing risk,temporality, and consistency for adverse drug reactions across datasets in five countries 下载免费PDF全文
7.
8.
Rainer Meierhenrich Marcelo E Helguera Gregory A Kidwell U Tebbe 《International journal of cardiology》1997,60(3):19-294
Increased QT dispersion, defined as the difference between the maximum and minimum QT interval on the standard 12-lead electrocardiogram, is assumed to reflect regional inhomogeneity of ventricular repolarization and has been shown to be associated with an increased risk of arrhythmic events. The purpose of the present study is to examine the influence of amiodarone on QT dispersion in patients with life-threatening ventricular arrhythmias and to evaluate the predictive value of QT dispersion after amiodarone therapy for further arrhythmic events. ECG's were obtained in 47 patients 1–2 days before and 6–8 weeks after amiodarone was started. All patients had coronary artery disease with a mean EF of 34±14%. The QT interval was measured in each lead of a digitized ECG displayed on a high resolution monitor (250 mm s−1). Amiodarone therapy resulted in a significant increase in the maximal QTc interval (476±44 to 505±44 ms, p<0.001). However, measurement of QT dispersion (70±34 vs 73±29 ms) and Qtc dispersion (78±37 vs 77±31 ms) revealed no significant difference before and after amiodarone. During a one year follow-up period 26 patients were free of arrhythmic events and 7 patients developed further arrhythmic events. The remaining 14 patients were excluded from the one year follow-up analysis because of drug discontinuation (n=8), death due to heart failure (n=1), medical intervention (n=3) and incomplete follow-up (n=2). No measure of QT dispersion was predictive of recurrent arrhythmic events during treatment with amiodarone.
Conclusion: Treatment with amiodarone results in significant QT prolongation without altering QT dispersion. Measurements of QT dispersion were not predictive of amiodarone efficacy in this patient population. 相似文献
9.
胺碘酮的肺毒性及其防治 总被引:5,自引:0,他引:5
胺碘酮属Ⅲ类抗心律失常药,用于室性心律失常、心房颤动等的预防治疗。长期用药发生不良反应的风险增加,其中以肺毒性最为常见,发生率为1%-17%,多在连续用药3~12月后出现间质性肺炎或过敏性肺炎。胺碘酮致肺毒性的机制尚不明确,可能为药物直接细胞毒性作用,过敏反应、炎性反应或免疫反应的结果;患者原有肺部疾病、药物剂量较大或使用时间过长与肺毒性相关。临床主要表现为干咳、呼吸困难、乏力、体重下降、发热等。胸片以肺实质和间质同时受累最为常见。应用胺碘酮后,出现新发症状或原症状加重,新出现的胸片异常或胸部病变加重,肺功能检查示CO或肺总量下降〉15%,应考虑为肺毒性反应。建议使用胺碘酮前进行利益/风险评价,长期用药应使用最小有效剂量,定期检测肺功能,以减少和及时发现肺毒性。一旦临床诊断为肺毒性,应及时减量和停药,多数患者停药后可缓解,严重者可短期使用皮质激素治疗。 相似文献
10.
JEAN‐YVES LE HEUZEY M.D. GAETANO M. DE FERRARI M.D. DAVID RADZIK M.D. MASSIMO SANTINI M.D. JUNREN ZHU M.D. JEAN‐MARC DAVY M.D. 《Journal of cardiovascular electrophysiology》2010,21(6):597-605
Dronedarone versus Amiodarone in Patients with AF. Introduction: We compared the efficacy and safety of amiodarone and dronedarone in patients with persistent atrial fibrillation (AF). Methods: Five hundred and four amiodarone‐naïve patients were randomized to receive dronedarone 400 mg bid (n = 249) or amiodarone 600 mg qd for 28 days then 200 mg qd (n = 255) for at least 6 months. Primary composite endpoint was recurrence of AF (including unsuccessful electrical cardioversion, no spontaneous conversion and no electrical cardioversion) or premature study discontinuation. Main safety endpoint (MSE) was occurrence of thyroid‐, hepatic‐, pulmonary‐, neurologic‐, skin‐, eye‐, or gastrointestinal‐specific events, or premature study drug discontinuation following an adverse event. Results: Median treatment duration was 7 months. The primary composite endpoint was 75.1 and 58.8% with dronedarone and amiodarone, respectively, at 12 months (hazard ratio [HR] 1.59; 95% confidence interval [CI] 1.28–1.98; P < 0.0001), mainly driven by AF recurrence with dronedarone compared with amiodarone (63.5 vs 42.0%). AF recurrence after successful cardioversion was 36.5 and 24.3% with dronedarone and amiodarone, respectively. Premature drug discontinuation tended to be less frequent with dronedarone (10.4 vs 13.3%). MSE was 39.3 and 44.5% with dronedarone and amiodarone, respectively, at 12 months (HR = 0.80; 95% CI 0.60–1.07; P = 0.129), and mainly driven by fewer thyroid, neurologic, skin, and ocular events in the dronedarone group. Conclusion: In this short‐term study, dronedarone was less effective than amiodarone in decreasing AF recurrence, but had a better safety profile, specifically with regard to thyroid and neurologic events and a lack of interaction with oral anticoagulants. (J Cardiovasc Electrophysiol, Vol. 21, pp. 597‐605, June 2010) 相似文献