The nitrefazole-ethanol interaction in man: cardiovascular responses and the accumulation of acetaldehyde and catecholamines.
The nitrefazole-ethanol interaction in man: cardiovascular responses and the accumulation of acetaldehyde and catecholamines.
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硝硝唑-乙醇在人体中的相互作用：心血管反应以及乙醛和儿茶酚胺的积累。
DOI：
10.1111/j.1530-0277.1985.tb05739.x
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
K. Lindros
中科院分区：
文献类型：
--
作者：
A. Suokas;M. Kupari;J. Pettersson;K. Lindros
研究了用新型抗酒精药物硝利唑（2-甲基-4-硝基-1-(4-硝基-苯基)咪唑，Altimol）预处理后摄入乙醇对心血管的影响。通过超声心动图和收缩时间间隔检查六名健康芬兰男性志愿者的左心室功能，这些志愿者在口服 800 或 1600 mg 硝硝唑剂量后 24 小时摄入 0.15-0.25 g 乙醇/kg。摄入乙醇后，血液中乙醛蓄积（25-150μM），血浆去甲肾上腺素增加1.5-2倍，血浆肾上腺素增加3-10倍，皮肤温度升高0.5-2.0℃。心率增加 70%，心输出量增加 107%。舒张压降低30%，外周血管阻力降低54%。喷射分数和最大周向纤维缩短速度分别提高了 26% 和 71%；射血前期/射血时间比减少了 46%。两名接受硝利唑治疗的受试者在摄入乙醇后观察到明显的血管迷走神经衰竭，第三名受试者在实验后不久出现昏厥。因此，在用硝硝唑预处理的受试者中，摄入相当少量的乙醇导致乙醛显着积累，这显然是由于乙醛脱氢酶抑制所致。这会导致血浆儿茶酚胺升高和心脏功能强烈增强。显着的心血管变化证明了硝利唑的功效，这表明，特别是对于患有隐匿性心肌疾病的酗酒者，硝利唑与乙醇的相互作用可能比其他抗酒精药物产生的相互作用更危险。
The cardiovascular effects of ethanol ingestion after pretreatment with a new antialcohol drug, nitrefazole (2-methyl-4-nitro-1-(4-nitro-phenyl)imidazole, Altimol) were studied. Left ventricular function was examined by echocardiography and systolic time intervals in six healthy Finnish male volunteers who ingested 0.15-0.25 g of ethanol/kg, 24 hr after an 800 or 1600-mg peroral dose of nitrefazole. After ethanol ingestion, accumulation of acetaldehyde in blood (25-150 microM) was accompanied by a 1.5-2-fold increase in plasma noradrenaline, a 3-10-fold increase in plasma adrenaline, and a 0.5-2.0 degrees C rise in skin temperature. Heart rate increased by 70% and cardiac output by 107%. Diastolic blood pressure decreased by 30% and peripheral vascular resistance by 54%. Ejection fraction and maximum circumferential fiber-shortening velocity increased by 26 and 71%, respectively; the pre-ejection period/ejection time ratio decreased by 46%. An apparent vasovagal collapse was noticed in two nitrefazole-treated subjects after ethanol ingestion, and a third subject experienced a fainting attack shortly after the experiment. Thus, in subjects pretreated with nitrefazole, ingestion of rather small amounts of ethanol results in marked accumulation of acetaldehyde apparently due to aldehyde dehydrogenase inhibition. This causes elevation of plasma catecholamines and intense enhancement of cardiac performance. The marked cardiovascular changes demonstrate the potency of nitrefazole, suggesting that, particularly with alcoholics with occult myocardial diseases, its interaction with ethanol may be even more hazardous than that produced by other antialcohol drugs.