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[持续静脉输注硝酸甘油耐受性的产生]

[Development of tolerance in continuous nitroglycerin infusion].

作者信息

Niestegge H, Cordes G, Blümchen G

机构信息

Klinik Roderbirken der LVA Rheinprovinz, Leichlingen, und Schwarz Pharma, Monheim.

出版信息

Herz. 1989 Feb;14(1):66-70.

PMID:2493413
Abstract

For treatment of unstable angina pectoris or recent myocardial infarction, intravenous NTG is frequently employed, beginning with doses of 3 mg/h or more; thereafter, dependent on the clinical course, in particular, if the blood pressure is lowered notably, the dose may be reduced to 1 or 2 mg/h. Reports published in recent years have documented to the development of tolerance to nitrates when given orally in higher doses three times daily or administered by the transdermal mode. Accordingly, we suspected that tolerance development would be the inevitable outcome during a continuous intravenous infusion of NTG. Consequently, this placebo-controlled study was undertaken to determine whether tolerance develops during a continuous 28-hour infusion of NTG and whether tolerance is reversible on interruption of the treatment with a twelve-hour infusion-free interval. The studies were performed in ten male patients ranging in age from 49 to 65 years, mean age 53 years. All patients had recovered from myocardial infarction (mean interval since infarction 42 days) and had reproducible, asymptomatic ST-segment depression of at least 0.2 mV during exercise testing after discontinuation of all antiischemic drugs with a washout period of three days. Exercise testing was performed at four hours after beginning the infusion of 1.5 mg/h NTG or placebo (2 p.m.), at 28 hours after beginning the infusion (2 p.m. on the second day) and, after having discontinued the infusion for a twelve-hour period (from 10 p.m. to 10 a.m.), at four hours after having re-started the infusion (2 p.m. on the third day).(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

对于不稳定型心绞痛或近期心肌梗死的治疗,常采用静脉滴注硝酸甘油(NTG),起始剂量为3毫克/小时或更高;此后,根据临床病程,特别是如果血压显著降低,剂量可减至1或2毫克/小时。近年来发表的报告记录了每日三次口服高剂量或经皮给药时硝酸盐耐受性的产生。因此,我们怀疑在持续静脉输注NTG过程中耐受性的产生将是不可避免的结果。因此,进行了这项安慰剂对照研究,以确定在持续28小时输注NTG期间是否会产生耐受性,以及在中断治疗12小时无输注间隔后耐受性是否可逆。研究在10名年龄在49至65岁之间的男性患者中进行,平均年龄53岁。所有患者均已从心肌梗死中恢复(自梗死以来的平均间隔时间为42天),并且在停用所有抗缺血药物并经过三天洗脱期后,运动试验期间有可重复的、无症状的ST段压低至少0.2毫伏。在开始输注1.5毫克/小时NTG或安慰剂后4小时(下午2点)、开始输注后28小时(第二天下午2点)以及在中断输注12小时(晚上10点至上午10点)后重新开始输注后4小时(第三天下午2点)进行运动试验。(摘要截断于250字)

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