稳心颗粒联合胺碘酮治疗室性期前收缩的疗效观察

目的 观察稳心颗粒联用胺碘酮治疗室性期前收缩的疗效及安全性。方法选择室性期前收缩患者84例，随机分为二组：稳心颗粒加胺碘酮组（A组）43例，胺碘酮组（B组）41例。A组给予步长稳心颗粒9g，3次／d，胺碘酮0．2g，1次／d，疗程4周。B组给予胺碘酮0．2g，3次／d，疗程4周。治疗前及疗程结束后行24h动态心电图及血常规、肝、肾功能检查。结果两组均可显著减少室性期前收缩的发生。A组总有效率88．37％，B组总有效率70．73％。稳心颗粒＋胺碘酮组疗效优于单用胺碘酮组（P〈0．05）。结论稳心颗粒联用胺碘酮可显著减少室性期前收缩的发生，疗效优于单用胺碘酮，同时可以减少胺碘酮等抗心律失常药物的剂量。     

两药联用治疗老年缺血性心脏病心力衰竭室性心律失常疗效观察

总结近2年来用步长稳心颗粒与胺碘酮联用治疗39例老年缺血性心脏病心力衰竭合并室性心律失常的临床疗效，并与31例单用胺碘酮治疗的患者进行比较。报告如下：     

小剂量倍他乐克联用胺碘酮在室性心律失常中治疗的安全性分析

目的探讨小剂量倍他乐克联用胺碘酮在室性心律失常治疗中的临床效果。方法选择我科收治的60例室性心律失常患者,分为对照组和治疗组,每组各30例。两组患者在常规治疗的基础上,对照组采取单用倍他乐克治疗,疗程半年。治疗组给予口服小剂量倍他乐克联用胺碘酮进行治疗。结果对照组的总有效率为70.0%,治疗组的总有效率为93.3%,治疗组的治疗效果明显优于对照组,差异有统计学意义（P〈0.05）。结论小剂量倍他乐克联用胺碘酮对室性心律失常的治疗中效果满意,值得临床推广。     

胺碘酮治疗急性心肌梗死室性心律失常150例临床报告

目的评价胺碘酮治疗急性心肌梗死（acute myocardial infarction,AMI）室性心律失常的疗效和安全性。方法观察150例AMI患者采用胺碘酮治疗室性心律失常的疗效和安全性,随访1年。结果反复发作的持续性室速、室颤患者,首剂3～5mg／kg胺碘酮10min内静脉注射;再以1—1．5mg／min维持,室速均被有效终止。以200mg／d胺碘酮作为长期维持量能有效控制室性期前收缩。结论采用胺碘酮治疗AMI患者室性心律失常效果满意,安全可靠。     

1例胺碘酮合用莫西沙星致QTc间期延长并发尖端扭转型室速的病例分析

目的:探讨QTc延长并发尖端扭转型室速的原因,为临床用药的安全性提供参考。方法:临床药师参与1例胺碘酮合用莫西沙星致QTc间期延长并发尖端扭转型室速的治疗,分析不良反应发生的原因及处理方法。结果:此次不良反应可能与胺碘酮和莫西沙星有关,该患者危险因素较多,临床用药时应加强用药安全的监督。结论:临床使用胺碘酮联用莫西沙星时,临床药师应掌握药物相互作用,加强药学监护,提高用药安全性。     

胺碘酮治疗冠心病急性心肌梗死伴高危快速型心律失常的有效性和安全性研究

目的探讨胺碘酮治疗冠心病急性心肌梗死伴高危快速型心律失常的有效性和安全性。方法收集我院近3年120例冠心病急性心肌梗死伴高危快速型心律失常的患者作为研究对象。根据心律失常类型分为:快速性室上性和快速性室性,快速性室上性患者按随机数字表法分为30例普鲁卡因胺组和30例胺碘酮A组,分别给予普鲁卡因胺和胺碘酮。快速性室性患者按随机数字表法分为30例利多卡因组和30例胺碘酮B组,分别给予利多卡因和胺碘酮。以接受治疗24 h为动态观察期。评价各组间服药24 h后治疗有效率及用药安全性。结果 1发生快速性室上性时,普鲁卡因胺组与胺碘酮A组治疗有效率及不良反应差异有统计学意义(P<0.05);2发生快速性室性时,利多卡因组与胺碘酮B组治疗有效率及不良反应差异有统计学意义(P<0.05)。结论本次研究认为胺碘酮能有效控制冠心病急性心肌梗死伴高危快速型心律失常,安全性好。     

胺碘酮治疗扩张型心肌病心力衰竭并发室性心动过速的疗效和安全性

目的观察胺碘酮治疗扩张型心肌病心力衰竭并发非持续性和持续性室性心动过速的疗效及安全性。方法对56例扩张型心肌病心力衰竭并发室性心动过速的患者首剂给予胺碘酮3～5mg/kg的负荷量,30min无效再重复负荷量。维持量为胺碘酮0.5～1mg/min持续静脉滴注24～72h,同时在静脉使用胺碘酮的同时给予口服胺碘酮0.2～0.4g,每天3次。结果胺碘酮静脉使用量每天1050～1500mg,使用时间24～72h,非持续性室速消失38例、持续性室速转复为窦性心律12例,2例演变为室颤死亡,总有效率89.3%。结论胺碘酮治疗充血性心力衰竭并发室性心动过速安全有效。     

厄贝沙坦联用胺碘酮治疗慢性心力衰竭合并室性心律失常的疗效分析

目的探讨厄贝沙坦联用胺碘酮治疗慢性心力衰竭(CHF)合并室性心律失常(VA)临床疗效。方法选择常宁市中医院CHF合并VA患者91例,随机分为观察组和对照组。两组患者均给予常规治疗,对照组同时给予胺碘酮。观察组给予胺碘酮和厄贝沙坦。结果观察组心功能疗效总有效率与对照组比较,差异有统计学意义(P<0.05);观察组VA疗效总有效率与对照组比较,差异有统计学意义(P<0.05)。结论厄贝沙坦联用胺碘酮能显著CHF合并VA患者临床症状,改善心功能,控制心律失常,临床效果显著。     

利多卡因与胺碘酮在颅脑损伤并发急性室性心律失常治疗中的对比应用

目的观察利多卡因与胺碘酮在发作急性室性心律失常的颅脑损伤患者中的疗效对比。方法 118例急性室性心律失常患者随机分成两组,分别给予利多卡因和胺碘酮行抗心律失常治疗,观察疗效。结果胺碘酮组在抗急性室性心律失常的治疗总有效率高于利多卡因组,有统计学意义(P<0.05)。结论在颅脑损伤合并急性室性心律失常的治疗中,胺碘酮治疗效果优于利多卡因,可作为首选。     

胺碘酮治疗风心二尖瓣置换术后室性心律失常57例分析

目的：评估胺碘酮在治疗二尖瓣置换术后室性心律失常的有效性与安全性。方法：2007-06/2009-05我们对57例二尖瓣置换术后发生室性心律失常的患者应用静脉胺碘酮进行治疗,并应用心电监护与心电图评价治疗效果。结果：57例患者应用胺碘酮后有45例有效控制了室性心律失常,有效率79%,2例出现心动过缓,减量胺碘酮用量后心动过缓消失,2例因术后恶性心律失常及低心排死亡,2例出现脑部并发症,其中1例死亡,1例偏瘫。结论：静脉应用胺碘酮可以有效治疗二尖瓣术后室性心律失常。     

Monotherapy versus combination therapy with class III antiarrhythmic agents to attenuate transmural dispersion of repolarization: a potential risk factor for torsade de pointes

Class III antiarrhythmic agents are used for conversion to and maintenance of sinus rhythm from arrhythmias of atrial or ventricular origin. Monotherapy can be limited by adverse events or recurrent arrhythmias. Sotalol, dofetilide, and ibutilide may induce torsade de pointes in 2-8% of patients, whereas amiodarone induces torsade de pointes in less than 1%. We reviewed the literature regarding the possible combination of class III antiarrhythmics and risk for inducing torsade de pointes. Animal studies using amiodarone plus sotalol or d-sotalol suggest that these drug combinations prolong the QTc interval but do not induce torsade de pointes. Similar data extracted from human studies of ibutilide in patients also receiving amiodarone or sotalol showed greater efficacy with combination therapy than with monotherapy, without increased torsade de pointes induction. Reduced transmural dispersion of repolarization with amiodarone and sotalol combination therapy may serve as a mechanism for reducing the risk of torsade de pointes compared with sotalol monotherapy.     

Pharmacokinetic drug interactions with amiodarone

Amiodarone alters the pharmacokinetics, and in some cases the pharmacodynamics, of several clinically important drugs. The major mechanisms of its drug interactions is inhibition of hepatic metabolism, but it can also affect the bioavailability, protein binding and renal excretion of coadministered drugs. It significantly increases the plasma concentrations of digoxin, warfarin, many Class I antiarrhythmic drugs (quinidine, procainamide, aprindine and flecainide) and phenytoin, in some instances resulting in overt signs of clinical toxicity, including adverse cardiovascular, cardiac and central nervous system effects. In most cases 20 to 50% reductions in doses of the affected drugs are necessary to offset the pharmacokinetic alterations and increased plasma drug concentrations caused by amiodarone. Interactions between amiodarone and beta-blockers (e.g. propranolol) and calcium channel blockers (e.g. diltiazem) are associated more with electrophysiological (sinus bradycardia and sinus arrest) and/or haemodynamic toxicity, due to additive pharmacological effects, than to changes in pharmacokinetics. In patients undergoing surgical procedures amiodarone interacts with general and local anaesthetic agents, resulting in an increased risk of cardiac system complications including hypotension and bradycardia. There is still a need for prospective controlled clinical studies to be conducted on many likely combinations of other drugs with amiodarone to increase understanding of the magnitude, time-course, mechanism and relevance of pharmacokinetic changes caused by this drug.     

Cytotoxicity evaluation after coexposure to perchloroethylene and selected peroxidant drugs in rat hepatocytes.

There is evidence of hepatotoxic effects caused by Perchloroethylene (PCE), presumably due to reactive metabolic intermediates; lipid peroxidation is under study as a potential mechanism of toxicity. We aimed to verify if PCE levels comparable to those reached in the blood of exposed subjects can cause cell damage and lipid peroxidation. The association of PCE with lipid peroxidation inducing drugs (cyclosporine A, valproic acid and amiodarone) was also tested on rat isolated hepatocytes. AST and LDH release, MTT test and lipid peroxidation assay showed that PCE determines dose-dependent effects on rat isolated hepatocytes. The toxic potential resulting from our data would be valproic acid < cyclosporine A < amiodarone. While valproic acid and cyclosporine caused a mild toxicity, the effects of amiodarone were more severe; in particular, the association of PCE with amiodarone showed a clear additive effect. The role of lipid peroxidation in the liver toxicity exerted by the tested compounds was confirmed by our data, and resulted relevant after treatment of cells with amiodarone and PCE. Extrapolating these results to human, we can suggest that a subject professionally exposed to PCE, who chronically assumes a lipid peroxidation inducing drug like amiodarone, may be potentially exposed to a higher risk of liver toxicity.     

Effects of amiodarone with and without polysorbate 80 on myocardial oxygen consumption and coronary blood flow during treadmill exercise in the dog.

Since amiodarone has been reported to possess antianginal activity, this study examined the effects of amiodarone on coronary blood flow and myocardial oxygen consumption during exercise. Studies were performed in 14 chronically instrumented dogs trained to run on a motor-driven treadmill. Left circumflex coronary artery blood flow was measured with an electromagnetic flowmeter while aortic and coronary sinus catheters allowed measurement of myocardial oxygen extraction. During control conditions, graded exercise resulted in progressive increases in heart rate, aortic pressure, and coronary blood flow. Two preparations of amiodarone, 5 mg/kg, one dissolved in sterile water and the other in 10% polysorbate 80, were given intravenously to separate groups of dogs. Amiodarone in sterile water caused no hemodynamic changes at rest. However, the increase in heart rate during exercise was blunted after amiodarone, so that heart rate during the heaviest level of exercise was significantly less than during control exercise. Coronary blood flow and myocardial oxygen consumption were unchanged. Amiodarone with polysorbate 80 also blunted the increase in heart rate during exercise, but in addition caused a significant decrease in aortic pressure both at rest and during exercise. Myocardial oxygen consumption and coronary blood flow were significantly decreased after administration of amiodarone with polysorbate 80 at rest and during all exercise levels. Amiodarone with or without polysorbate 80 did not change myocardial oxygen extraction. These data demonstrate that amiodarone exerts a negative chronotropic effect during exercise. However, the decreased arterial pressure and myocardial oxygen consumption were not due to amiodarone, but was seen only with the combination of amiodarone dissolved in polysorbate 80.     

The effect of levosimendan during long-term amiodarone treatment in dogs

The haemodynamic and electrophysiological effects of levosimendan were studied in conscious dogs receiving long-term oral amiodarone treatment. Instrumented dogs were administered increasing doses of levosimendan (up to 0.9 microg/kg/min. intravenously) in three successive 30 min. infusions. This schedule was repeated on the 21st day of treatment with oral amiodarone 100 mg/kg/day. The extent of increase in left ventricular systolic pressure (LVSP) and the decrease in left ventricular end-diastolic pressure (LVEDP) seen with levosimendan were similar before and after long-term treatment with amiodarone. The levosimendan-induced increases in isovolumic contraction (+dP/dt) and in left ventricular contractility (dP/dt/P) seen prior to amiodarone administration were augmented during amiodarone treatment, an effect that was statistically significant (P<0.05) at the highest doses of levosimendan. A tendency towards a shortening of the QT interval and a rise in heart rate was observed for levosimendan alone but they did not exceed the physiological range when the drug was given in combination with amiodarone. QTc value was unaffected by levosimendan either alone or with amiodarone. These effects were apparent in animals with therapeutically meaningful plasma levels of levosimendan, amiodarone and desethylamiodarone levels. The results of this study show that the improvement in ventricular contractile performance usually associated with administration of levosimendan was somewhat enhanced by chronic oral treatment with amiodarone. It seems reasonable to infer that the inotropic potency and electrophysiological safety of parenteral levosimendan will be maintained in patients with heart failure during long-term treatment with oral amiodarone.     

Fluconazole- and levofloxacin-induced torsades de pointes in an intensive care unit patient.

Patients initiated on fluconazole and levofloxacin should be closely monitored for QTc-interval prolongation. While there have been published reports of fluconazole and levofloxacin causing QTc-interval prolongation when given alone, coadministration of these two agents may further increase this risk. This case describes an episode of TdP in which levofloxacin and fluconazole were likely significant factors. QT prolongation was present at baseline prior to drug initiation (QTc = 454-505 ms) and levofloxacin resulted in further prolongation (QTc = 480-536 ms). After two days of therapy with fluconazole, overlapping with levofloxacin, the patient had an episode of PMVT with syncope, and progressive QT prolongation was evident (QTc = 554 ms). Only mild hypokalemia (potassium concentration = 3.6 meq/L) was present, and not additional etiologies for TdP were identified. Levofloxacin and fluconazole were discontinued and no further PMVT was observed, but the QT interval did not return to normal until after an additional 11 days (QTc = 436 ms). As in many cases of TdP, multiple factors were involved. Renal failure, drug dosing, mild hypokalemia, and a baseline abnormal QT interval potentiated the role of levofloxacin and fluconazole in the development of TdP. We recommend that neither drug be used alone or in combination when there is baseline QT prolongation. We also recommend that concomitant use of these agents be avoided when possible. If combination therapy is required, caution is warranted, particularly in patients with risk factors for QT prolongation. Specific attention should be given to drug dosing, interactions, electrolytes, and ECG monitoring.     

Hypotensive action of commercial intravenous amiodarone and polysorbate 80 in dogs

Commercial intravenous amiodarone has been reported to have antiarrhythmic actions and to cause only mild hypotension in humans. In the dog, however, amiodarone was observed to cause severe hypotension. Since commercial intravenous amiodarone is amiodarone compound (50 mg/ml) dissolved in water with polysorbate 80 (Tween 80) (100 mg/kg), the effects of amiodarone in ethanol (5 mg/kg) and polysorbate 80 (10 mg/kg) were studied individually, and in combination in anesthetized dogs. Commercial intravenous amiodarone and polysorbate 80 caused at least a 60% drop in mean blood pressure and left ventricular maximum dP/dt for at least 30 min, whereas amiodarone in ethanol did not. The drop in blood pressure was not principally due to peripheral vasodilation. Therefore, in dogs the diluent polysorbate 80 is the major cause of severe hypotension resulting from commercial intravenous amiodarone. These studies show that commercial intravenous amiodarone produces results different in dogs than has been previously reported in humans. Therefore: (a) canine models for studying the antiarrhythmic actions of commercial intravenous amiodarone would produce results complicated by severe hypotension; and (b) polysorbate 80 is not an inert substance, but is a potent cardiac depressant.     

Effects of amiodarone administration during pregnancy in Fischer 344 rats

Amiodarone is a class III anti-arrhythmic compound that is iodinated, cationic and amphiphilic in nature. The clinical use of amiodarone may be associated with various side-effects, including pulmonary and hepatic toxicity. Use of this compound during pregnancy may therefore place the fetus at risk through in utero exposure. This study was designed to observe any gross developmental effects that may be caused by the administration of amiodarone to Fischer 344 rats during pregnancy, investigate the placental transfer of amiodarone and its principal metabolite, desethylamiodarone and determine the levels of amiodarone and desethylamiodarone in the maternal and newborn lung, liver and plasma. To conduct this study, 35 mg/kg of amiodarone was administered daily to pregnant rats for either the last 7 days of pregnancy, the last 14 days of pregnancy, or for the full 22 days of pregnancy. Drug treatment had no effect on the length of gestation or litter size. Maternal weight gain was decreased only when amiodarone was administered during the last 7 days of gestation. The birthweights of the offspring were decreased, however, crown to rump length was unaffected. Both amiodarone and desethylamiodarone accumulated in the offspring through placental transfer. The levels of both compounds were greater in maternal and newborn lung when compared to maternal and newborn liver, respectively. The maternal lung and liver concentrations of both compounds were significantly higher than the respective newborn concentrations. The newborn plasma concentrations of amiodarone and desethylamiodarone were significantly lower than maternal levels indicating that the placenta may not be totally permeable to the two drugs.     

胺碘酮联合美托洛尔治疗心力衰竭的效果观察

目的：探讨胺碘酮联合美托洛尔治疗心力衰竭的临床疗效。方法选取2012年10月-2013年10月本院收治的心力衰竭患者160例,将其随机分为观察组和对照组各80例,对照组给予胺碘酮治疗,观察组在对照组治疗的基础上加用美托洛尔,观察两组患者的心功能改善情况,并进行疗效评定。结果观察组总有效率为98.75%,显著高于对照组的85.00%,差异有统计学意义（P〈0.05）。两组治疗后SBP、DBP、HR、LVEDD、LVESD及LVEF均较治疗前改善,且治疗后观察组上述指标均优于对照组（P〈0.05）。结论胺碘酮联合美托洛尔治疗心力衰竭疗效显著,心功能改善明显,值得临床推广应用。     

Amiodarone in the prevention and treatment of arrhythmia

There is good evidence that amiodarone is effective against a variety of arrhythmias and that it may be superior to other drugs in some settings. Because of its proven efficacy and safety, amiodarone is currently the leading antiarrhythmic drug. The electrophysiological actions of amiodarone are complex and not completely understood. It is generally classified as a Vaughan-Williams class III agent, prolonging repolarization by inhibition of outward potassium channels. Amiodarone is particularly useful because its safety has been clearly demonstrated by a large body of evidence, including several randomized trials. Compared with many other antiarrhythmic drugs, amiodarone causes few cardiovascular adverse effects; however, its overall tolerance is limited by considerable non-cardiac toxicity. Although amiodarone will continue to give way to the implantable cardioverter defibrillator (ICD) as primary therapy for many patients presenting with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF), it is likely that the use of amiodarone in ICD patients will continue to prevent ICD discharges. Evaluation of combined use of amiodarone and ICD may provide the first opportunity to conduct a placebo-controlled trial of amiodarone efficacy against VT recurrence. Pharmacological therapy remains the major approach to management of atrial fibrillation (AF), and the use of amiodarone is likely to increase in future years. This review will analyze the evidence that amiodarone is a safe and effective antiarrhythmic drug.