Horner Richard L
Departments of Physiology and Medicine, University of Toronto, Toronto, ON, Canada.
Expert Opin Ther Targets. 2023 Jul-Dec;27(7):609-626. doi: 10.1080/14728222.2023.2240018. Epub 2023 Jul 26.
Obstructive sleep apnea (OSA) is a common and serious breathing disorder. Several pathophysiological factors predispose individuals to OSA. These factors are quantifiable, and modifiable pharmacologically.
Four key pharmacotherapeutic targets are identified and mapped to the major determinants of OSA pathophysiology. PubMed and Clinicaltrials.gov were searched through April 2023.
Target #1: Pharyngeal Motor Effectors. Increasing pharyngeal muscle activity and responsivity with noradrenergic-antimuscarinic combination is central to recent breakthrough OSA pharmacotherapy. Assumptions, knowledge gaps, future directions, and other targets are identified. #2: Upper Airway Sensory Afferents. There is translational potential of sensitizing and amplifying reflex pharyngeal dilator muscle responses to negative airway pressure via intranasal delivery of new potassium channel blockers. Rationales, advantages, findings, and potential strategies to enhance effectiveness are identified. #3: Chemosensory Afferents and Ventilatory Control. Strategies to manipulate ventilatory control system sensitivity by carbonic anhydrase inhibitors are supported in theory and initial studies. Intranasal delivery of agents to stimulate central respiratory activity are also introduced. #4: Sleep-Wake Mechanisms. Arousability is the fourth therapeutic target rationalized. Evolving automated tools to measure key pathophysiological factors predisposing to OSA will accelerate pharmacotherapy. Although not currently ready for general clinical settings, the identified targets are of future promise.
阻塞性睡眠呼吸暂停（OSA）是一种常见且严重的呼吸障碍。多种病理生理因素使个体易患OSA。这些因素是可量化的，并且可以通过药物进行调节。
确定了四个关键的药物治疗靶点，并将其映射到OSA病理生理学的主要决定因素上。检索了截至2023年4月的PubMed和Clinicaltrials.gov。
靶点1：咽部运动效应器。通过去甲肾上腺素能-抗毒蕈碱联合用药增加咽部肌肉活动和反应性是近期OSA药物治疗突破的核心。确定了假设、知识空白、未来方向和其他靶点。靶点2：上呼吸道感觉传入神经。通过鼻内递送新型钾通道阻滞剂来敏化和放大咽部扩张肌对气道负压的反射反应具有转化潜力。确定了原理、优势、研究结果以及提高有效性的潜在策略。靶点3：化学感觉传入神经与通气控制。碳酸酐酶抑制剂操纵通气控制系统敏感性的策略在理论和初步研究中得到支持。还介绍了鼻内递送刺激中枢呼吸活动的药物。靶点4：睡眠-觉醒机制。觉醒能力是第四个合理化的治疗靶点。不断发展的测量易患OSA的关键病理生理因素的自动化工具将加速药物治疗。尽管目前还未准备好应用于一般临床环境，但所确定的靶点具有未来应用前景。
