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健康受试者单次皮下注射特布他林心血管效应的逐搏测量

Beat-to-Beat Measurement of Cardiovascular Effects of a Single Subcutaneous Dose of Terbutaline in Healthy Subjects.

作者信息

Mulder W M C, de Klerk S, Settels J J, van Boxtel C J

机构信息

Department of Clinical Pharmacology and Pharmacotherapy, Academic Medical Centre, PO Box 22660, Amsterdam, 1100 DD, The Netherlands.

TNO Biomedical Instrumentation, Academic Medical Centre, Amsterdam, The Netherlands.

出版信息

Clin Drug Investig. 2002 Sep;22(9):593-600. doi: 10.2165/00044011-200222090-00004.

Abstract

OBJECTIVE

To evaluate the cardiovascular effects over time of a single subcutaneous (SC) dose of terbutaline 0.75mg in young healthy volunteers using continuous, beat-to-beat monitoring of cardiovascular effects.

DESIGN AND METHODS

Nine healthy young volunteers were administered a SC dose of terbutaline sulphate 0.75mg. Cardiovascular effects were continuously monitored over 2 hours using Finapres and Modelflow technology. Blood was drawn at several timepoints for determination of the plasma terbutaline concentration.

RESULTS

The peak plasma concentration of terbutaline was 17.3 ± 4.5 (µg/L at 28.9 ± 12.5 minutes after SC administration. Changes in cardiovascular parameters were observed very quickly, with increases in stroke volume (16.7 ±8.9%), cardiac output (46.0 ± 22.6%), systolic blood pressure (15.1 ± 11.6%) and heart rate (48.1 ± 15.7%) at 9.3 ± 3.8, 16.9 ± 4.8, 21.3 ± 8.9 and 49.7 ± 16.4 minutes, respectively. In five of eight subjects a very rapid (at 9.6 ± 3.7 minutes) drop in diastolic blood pressure (9.8 ± 5.1 %) was observed, while total peripheral resistance decreased maximally by 33.5 ± 7.9% at 18.9 ± 7.1 minutes.

CONCLUSIONS

The magnitude of the cardiovascular effects again stresses the need for cautious use of SC terbutaline in patients with a history of cardiovascular disease. The time-course of some of the cardiovascular effects of a SC dose of terbutaline in relation to terbutaline plasma concentrations was unexpected and suggests direct β2-adrenoreceptor-mediated effects on the heart. Further investigations using both selective and nonselective β-receptor antagonists are needed to unravel the complex interactions of β2-receptor-mediated terbutaline-induced effects and cardiovascular reflex mechanisms.

摘要

目的

通过对心血管效应进行连续逐搏监测,评估单次皮下注射0.75mg特布他林对年轻健康志愿者心血管系统的长期影响。

设计与方法

对9名健康年轻志愿者皮下注射0.75mg硫酸特布他林。使用Finapres和Modelflow技术在2小时内持续监测心血管效应。在多个时间点采集血液以测定血浆特布他林浓度。

结果

皮下注射后28.9±12.5分钟时,特布他林的血浆峰值浓度为17.3±4.5(μg/L)。心血管参数变化出现得非常迅速,心搏量在9.3±3.8分钟时增加(16.7±8.9%),心输出量在16.9±4.8分钟时增加(46.0±22.6%),收缩压在21.3±8.9分钟时增加(15.1±11.6%),心率在49.7±16.4分钟时增加(48.1±15.7%)。在8名受试者中的5名中,观察到舒张压在9.6±3.7分钟时迅速下降(9.8±5.1%),而总外周阻力在18.9±7.1分钟时最大下降33.5±7.9%。

结论

心血管效应的程度再次强调了有心血管疾病史的患者谨慎使用皮下注射特布他林的必要性。皮下注射特布他林的某些心血管效应与特布他林血浆浓度的时间进程出乎意料,提示对心脏有直接的β2 - 肾上腺素能受体介导的作用。需要使用选择性和非选择性β受体拮抗剂进行进一步研究,以阐明β2受体介导的特布他林诱导效应与心血管反射机制之间的复杂相互作用。

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