Lenz M L, Pool J L, Laddu A R, Varghese A, Johnston W, Taylor A A
Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Am J Hypertens. 1995 Feb;8(2):133-45. doi: 10.1016/0895-7061(94)00162-5.
alpha-Blockers and calcium antagonists are commonly used in the treatment of hypertension, but few data are available concerning first dose or steady state (SS) hemodynamic and pharmacokinetic effects of these drugs when they are used in combination therapy. To examine these interactions, we measured supine and standing blood pressure (BP), heart rate (HR), and cardiac index (CI) for 6 h in 24 hypertensive patients after 2 weeks of placebo, again after the first dose or 3 weeks of therapy (SS) with either 120 mg verapamil (V) twice a day, or 1 mg terazosin (T) titrated weekly to 5 mg daily, and finally when T was added to V (group VT) or V added to T (group TV), acutely and at SS. Changes in supine hemodynamics when T was added to V or when V was added to T were similar and included a further reduction in BP, a transient increase in HR, and little or no change in CI. Both groups experienced significant decreases in standing blood pressure, especially 0.5 to 2 h following initiation of combination therapy despite significant increases in standing HR and CI. Standing BP tended to be lower in group TV after the first dose, but minimum standing systolic BP was not significantly different between groups (group TV 97 mm Hg at 1 h; group VT 109 mm Hg at 1.5 h, P > .05). Four patients in group TV and two in group VT experienced symptomatic orthostatic hypotension with the first dose of double-agent treatment. Pharmacokinetic interactions, including an increase in the bioavailability of T when V was added, did not correlate with the degree of orthostasis. After 3 weeks of combined therapy, the orthostatic change in BP had attenuated and symptoms had improved in all patients. We conclude that T and V represent an effective combination for the treatment of essential hypertension, but that orthostasis may result when initiating combination therapy. The orthostasis seen in some patients appears to be due to the combined vasodilatory effects rather than negative ionotropic or chronotropic effects.
α受体阻滞剂和钙拮抗剂常用于治疗高血压，但关于这些药物联合治疗时首剂或稳态（SS）血流动力学及药代动力学效应的数据较少。为研究这些相互作用，我们在24例高血压患者中，于服用安慰剂2周后、服用120mg维拉帕米（V）每日2次首剂或治疗3周（SS）后、以及最终将特拉唑嗪（T）加至V（VT组）或V加至T（TV组）急性给药及稳态时，测量了仰卧位和站立位血压（BP）、心率（HR）及心脏指数（CI）6小时。当T加至V或V加至T时，仰卧位血流动力学变化相似，包括BP进一步降低、HR短暂升高、CI几乎无变化或无变化。两组站立位血压均显著降低，尤其是联合治疗开始后0.5至2小时，尽管站立位HR和CI显著升高。首剂后TV组站立位BP倾向于更低，但两组最低站立位收缩压无显著差异（TV组1小时时为97mmHg；VT组1.5小时时为109mmHg，P>.05）。TV组4例患者和VT组2例患者在双药治疗首剂时出现症状性体位性低血压。药代动力学相互作用，包括加用V时T的生物利用度增加，与体位性低血压程度无关。联合治疗3周后，所有患者BP的体位性变化减弱且症状改善。我们得出结论，T和V是治疗原发性高血压的有效组合，但开始联合治疗时可能会导致体位性低血压。部分患者出现的体位性低血压似乎是由于联合血管舒张作用而非负性变力或变时作用所致。
