Toal Corey B, Meredith Peter A, Elliott Henry L
Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.
Blood Press. 2012 Jul;21 Suppl 1(Suppl 1):3-10. doi: 10.3109/08037051.2012.690615. Epub 2012 Jul 5.
Calcium-channel blockers (CCBs) constitute a diverse group of compounds but are often referred to as a single homogeneous class of drug and the clinical responses indiscriminately summarized. Even within the dihydropyridine subgroup, there are significant differences in formulations, pharmacokinetics, durations of action and their effects on blood pressure, heart rate, end organs and the sympathetic nervous system. Amlodipine and nifedipine in the gastrointestinal therapeutic system (GITS) formulation are the most studied of the once-daily CCBs. Amlodipine has an inherently long pharmacokinetic half-life, whereas, in contrast, nifedipine has an inherently short half-life but in the GITS formulation the sophisticated delivery system allows for once-daily dosing. This article is derived from a systematic review of the published literature in hypertensive patients. The following search terms in three main databases (MEDLINE, Embase, Science Citation Index) from 1990 to 2011 were utilized: amlodipine, nifedipine, sympathetic nervous system, sympathetic response, sympathetic nerve activity, noradrenaline, norepinephrine and heart rate. More than 1500 articles were then screened to derive the relevant analysis. As markers of sympathetic nervous system activation, studies of plasma norepinephrine concentrations, power spectral analysis, muscle sympathetic nerve activity and norepinephrine spillover were reviewed. Overall, each drug lowered blood pressure in hypertensive patients in association with only small changes in heart rate (i.e. <1 beat/min). Plasma norepinephrine concentrations, as the most widely reported marker of sympathetic nervous system activity, showed greater increases in patients treated with amlodipine than with nifedipine GITS. The evidence indicates that both these once-daily dihydropyridine CCBs lower blood pressure effectively with minimal effects on heart rate. There are small differences between the drugs in the extent to which each activates the sympathetic nervous system with an overall non-significant trend in favour of nifedipine GITS.
钙通道阻滞剂（CCB）是一类多样的化合物，但常被视为单一的同类药物，其临床反应也被不加区分地总结。即使在二氢吡啶亚组中，不同制剂在剂型、药代动力学、作用持续时间以及对血压、心率、终末器官和交感神经系统的影响方面也存在显著差异。氨氯地平和胃肠道治疗系统（GITS）剂型的硝苯地平是每日一次服用的CCB中研究最多的。氨氯地平本身具有较长的药代动力学半衰期，而相比之下，硝苯地平本身半衰期较短，但在GITS剂型中，复杂的给药系统使其能够每日一次给药。本文源自对高血压患者已发表文献的系统综述。利用1990年至2011年期间在三个主要数据库（MEDLINE、Embase、科学引文索引）中使用了以下检索词：氨氯地平、硝苯地平、交感神经系统、交感反应、交感神经活动、去甲肾上腺素、去甲肾上腺素和心率。然后筛选了1500多篇文章以进行相关分析。作为交感神经系统激活的标志物，对血浆去甲肾上腺素浓度、功率谱分析、肌肉交感神经活动和去甲肾上腺素溢出的研究进行了综述。总体而言，每种药物在降低高血压患者血压的同时，心率仅有微小变化（即<1次/分钟）。作为交感神经系统活动报道最广泛的标志物，血浆去甲肾上腺素浓度在接受氨氯地平治疗的患者中升高幅度大于接受硝苯地平GITS治疗的患者。证据表明，这两种每日一次服用的二氢吡啶类CCB均能有效降低血压，对心率影响最小。两种药物在激活交感神经系统的程度上存在细微差异，总体上有不显著的趋势表明硝苯地平GITS更具优势。
