RESPIRATORY CONSEQUENCES OF OPIATES

阿片类药物的呼吸系统后果

• 批准号: 3337227
• 负责人: TEODORO V SANTIAGO
• 金额: $ 14.9万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-01-01 至 1987-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3337227
• 关键词: carbon dioxide tension; cerebral ischemia /hypoxia; drug adverse effect; drug interactions; emphysema; exercise; human subject; hypercapnia; hypoxia; methadone; morphine; naloxone; neural information processing; neurochemistry; opiate alkaloid; pulmonary respiration; radiotracer; respiratory airflow disorder; respiratory pharmacology; sleep

Over the last several years, it has been recognized that the body generates substances with opioid activity under specific physiologic and pathologic situations. This has elicited considerable interest regarding breathing in view of the potent respiratory depressant effects of opiate drugs. The proposed studies will continue to examine the role of these endogenously generated opiates (i.e., endorphins) on respiration and gas exchange. Utilizing both direct assays of beta-endorphin activity and reversal by the opiate antagonist naloxone of the postulated endorphin effects on breathing, three general areas selected on the basis that endorphins are known to be released or effects reminiscent of morphine are manifested will be studied. In normal human volunteers, the effects of non-stress-induced (Metyrapone) endorphin elaboration on ventilation and the control of breathing during wakefulness and sleep will be evaluated. The hypothesis that these endorphins will modify and depress breathing and generate sleep-related irregularities of breathing will be tested. In patients with Chronic Obstructive Pulmonary Disease (COPD), the hypothesis that endorphin elaboration is the mechanism for the relief of dyspnea by exercise rehabilitation will be examined. Finally, in animal models of airway obstruction and lung injury, endorphin release and their effects on respiration and gas exchange will be investigated; the hypothesis that endogenously generated opiates contribute to the generation of fatigue, minimize the magnitude of the shunt-like hypoxia of acute lung injury and help generate the ventilatory adaptations (i.e., impaired load compensation) to chronic airway obstruction should be elucidated. The proposed studies directly bear on the understanding of several clinical problems including emphysema, sleep apnea and the Adult Respiratory Distress Syndrome. Identifying endorphin influences in these conditions should improve our ability to predict the ventilatory responses of these patients.

在过去的几年中，人们已经认识到身体会产生 在特定生理和病理学下具有阿片类药物活性的物质 情况。 这引起了人们对呼吸的极大兴趣 阿片类药物的有效呼吸抑制作用的视图。 这 拟议的研究将继续检查这些内源性的作用 产生的阿片类药物（即内啡肽）在呼吸和气体交换方面。 利用β-内啡肽活性的直接测定和逆转 鸦片内啡肽对纳洛酮对纳洛酮的影响 呼吸，以内啡肽为基础选择的三个一般区域 已知会释放或让人联想吗啡的影响表现出来 被研究。 在正常的人类志愿者中，无压力诱导的影响 （Metyrapone）对通风的内啡肽阐述和控制 将评估清醒和睡眠期间的呼吸。 假设 这些内啡肽会修改，抑制呼吸并产生 将测试与睡眠有关的呼吸不规则。 在患者中 慢性阻塞性肺疾病（COPD），这是内啡肽的假设 阐述是通过运动缓解呼吸困难的机制 将检查康复。 最后，在气道动物模型中 阻塞和肺损伤，内啡肽释放及其对 将研究呼吸和气体交换；假设是 内源性产生的阿片类药物有助于产生疲劳， 最大程度地减少急性肺损伤的分流状缺氧的大小和 帮助产生通风适应（即负载受损 赔偿）应阐明慢性气道阻塞。 这 拟议的研究直接了解了几个临床的理解 包括肺气肿，睡眠呼吸暂停和成人呼吸的问题 遇险综合征。 在这些条件下识别内啡肽的影响 应该提高我们预测这些通气反应的能力 患者。