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胺碘酮——有起有伏,而后再度起伏。

Amiodarone -- waxed and waned and waxed again.

作者信息

Doggrell S A

机构信息

Department of Physiology and Pharmacology, University of Queensland, Brisbane, 4072 Australia.

出版信息

Expert Opin Pharmacother. 2001 Nov;2(11):1877-90. doi: 10.1517/14656566.2.11.1877.

Abstract

Amiodarone has been used as an anti-arrhythmic drug since the 1970s and has an established role in the treatment of ventricular tachyarrhythmias. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile. Amiodarone is a structural analogue of thyroid hormone and some of its anti-arrhythmic properties and toxicity may be attributable to interactions with nuclear thyroid hormone receptors. The lipid solubility of amiodarone gives it an exceptionally long half-life. Oral amiodarone takes days to work in ventricular tachyarrhythmias, but iv. amiodarone has immediate effect and can be used in life threatening ventricular arrhythmias. Intravenous amiodarone administered after out-of-hospital cardiac arrest due to ventricular fibrillation improves survival to hospital admission. Many survivors of myocardial infarction (MI) die during the subsequent year, probably due to ventricular arrhythmia. Amiodarone reduces sudden death after MI and this benefit is predominantly observed in patients with preserved cardiac function. Sudden cardiac death, predominantly due to ventricular arrhythmias, is also commonly seen in patients with heart failure. The Grupo de Estudio de la Sobrevida en lsuficiencia Cardiaca en Argentina (GESICA) and Estudio Piloto Argentino de Muerte Subita y Amiodarona (EPAMSA) trials showed survival benefit of amiodarone in heart failure, whereas Congestive Heart Failure-Survival Trial of Anti-arrhythmic Therapy (CHF-STAT) did not. Subsequent meta-analysis established a survival benefit of amiodarone in heart failure. Implanted Cardioverter Def ibrillators (ICDs) also give survival benefit to patients at risk of sudden death. In patients with a history of ventricular fibrillation or haemodynamically-compromising ventricular tachycardia, ICDs have been shown to be superior to anti-arrhythmic drugs, principally amiodarone. Further analysis has been undertaken to ascertain which patients are most likely to benefit from ICDs, as these are more expensive than treatment with amiodarone. Patients with severely depressed ejection fractions should be the first to be considered for ICDs. A new indication for amiodarone is atrial fibrillation or flutter. Amiodarone is effective in chronic and recent onset atrial fibrillation and orally or iv. for atrial fibrillation after heart surgery. In atrial fibrillation amiodarone is more than or equi-effective with flecainide, quinidine, racemic sotalol, propafenone and diltiazem and therefore should be considered for first line therapy. Amiodarone is also safe and effective in controlling refractory tachyarrhythmias in infants and is safe after cardiac surgery.

摘要

自20世纪70年代以来,胺碘酮一直被用作抗心律失常药物,在治疗室性快速心律失常方面具有既定作用。尽管胺碘酮被认为是III类抗心律失常药物,但它也具有I类、II类和IV类作用,这使其具有独特的药理和抗心律失常特性。胺碘酮是甲状腺激素的结构类似物,其一些抗心律失常特性和毒性可能归因于与核甲状腺激素受体的相互作用。胺碘酮的脂溶性使其半衰期极长。口服胺碘酮在室性快速心律失常中起效需数天,但静脉注射胺碘酮具有即刻效应,可用于危及生命的室性心律失常。因室颤导致院外心脏骤停后静脉注射胺碘酮可提高入院生存率。许多心肌梗死(MI)幸存者在随后的一年中死亡,可能是由于室性心律失常。胺碘酮可降低心肌梗死后的猝死率,这种益处主要在心脏功能保留的患者中观察到。主要由于室性心律失常导致的心脏性猝死在心力衰竭患者中也很常见。阿根廷心力衰竭生存研究组(GESICA)和阿根廷胺碘酮与猝死初步研究(EPAMSA)试验显示胺碘酮对心力衰竭患者有生存益处,而充血性心力衰竭抗心律失常治疗生存试验(CHF - STAT)则未显示。随后的荟萃分析证实胺碘酮对心力衰竭患者有生存益处。植入式心脏复律除颤器(ICD)也能使有猝死风险的患者受益。对于有室颤或血流动力学不稳定的室性心动过速病史的患者,ICD已被证明优于抗心律失常药物,主要是胺碘酮。已进行进一步分析以确定哪些患者最可能从ICD中获益,因为ICD比胺碘酮治疗更昂贵。射血分数严重降低的患者应首先考虑使用ICD。胺碘酮的一个新适应证是心房颤动或心房扑动。胺碘酮对慢性和近期发作的心房颤动有效,可口服或静脉注射用于心脏手术后的心房颤动。在心房颤动中,胺碘酮与氟卡尼、奎尼丁、消旋索他洛尔、普罗帕酮和地尔硫卓相比效果相当或更优,因此应考虑作为一线治疗药物。胺碘酮在控制婴儿难治性快速心律失常方面也安全有效,且在心脏手术后也很安全。

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