Singh B N
Am Heart J. 1983 Oct;106(4 Pt 2):788-97. doi: 10.1016/0002-8703(83)90002-9.
Although synthesized as a coronary dilator for use as an antianginal agent over 20 years ago, amiodarone hydrochloride has recently drawn much attention as a potent antiarrhythmic compound for the control of a variety of cardiac dysrhythmias. The rapidly expanding clinical and experimental data continue to emphasize the unusual electrophysiologic, pharmacologic, and especially pharmacokinetic properties of this benzofuran derivative. The compound is a potent coronary dilator and has minimal negative inotropic propensity of a direct nature while exhibiting a mild degree of noncompetitive sympathetic antagonism. Pharmacokinetically, it has a long elimination half-life with a correspondingly long and variable latency of onset of therapeutic effect. Electrophysiologically, the drug has the propensity to lengthen the action potential duration and hence the voltage-dependent effective refractory period in all cardiac tissues after long-term, rather than short-term, administration. It has little effect on depolarization, conduction velocity, or the slow response. The precise ionic mechanisms mediating its effects on repolarization are not known. Clinically, the electrophysiologic effects of the drug differ significantly when it is given by mouth over a longer period and when it is given intravenously, a difference that remains to be explained in terms of mechanism. These differences, however, account for the varying spectrum of the drug's action after single intravenous doses (when its antiarrhythmic effects are essentially explained by the drug's action on the atrioventricular node and possibly its antiadrenergic actions) in comparison to long-term oral administration, which predictably suppresses ectopic activity and lengthens the effective refractory period in all cardiac tissues. These features may account for the drug's remarkable efficacy in the control of supraventricular and ventricular tachyarrhythmias. The safe and rational therapeutic uses of amiodarone as an antiarrhythmic agent presuppose detailed understanding of its manifold pharmacodynamic and pharmacokinetic properties.
虽然盐酸胺碘酮早在20多年前就被合成作为一种冠状动脉扩张剂用作抗心绞痛药物，但最近它作为一种有效的抗心律失常化合物，用于控制各种心律失常，备受关注。迅速增加的临床和实验数据不断强调这种苯并呋喃衍生物不同寻常的电生理、药理尤其是药代动力学特性。该化合物是一种强效冠状动脉扩张剂，直接性质的负性肌力倾向极小，同时表现出轻度的非竞争性交感神经拮抗作用。在药代动力学方面，它的消除半衰期很长，相应地，治疗效果起效的潜伏期也很长且多变。在电生理方面，长期而非短期给药后，该药物倾向于延长所有心脏组织的动作电位持续时间，从而延长电压依赖性有效不应期。它对去极化、传导速度或慢反应几乎没有影响。介导其对复极化作用的精确离子机制尚不清楚。临床上，口服较长时间给药与静脉给药时，该药物的电生理效应有显著差异，这一差异在机制方面仍有待解释。然而，这些差异解释了单次静脉给药后药物作用谱的变化（此时其抗心律失常作用主要由药物对房室结的作用及其抗肾上腺素能作用来解释），与长期口服给药相比，长期口服给药可预期地抑制异位活动并延长所有心脏组织的有效不应期。这些特性可能解释了该药物在控制室上性和室性快速心律失常方面的显著疗效。作为抗心律失常药物，胺碘酮安全合理的治疗应用前提是详细了解其多种药效学和药代动力学特性。
