Smith Ian E, Quinnell Timothy G
Respiratory Support and Sleep Cerntre, Papworth Hospital, Papworth Everard, Cambridge CB3 8RE, UK.
Drugs. 2004;64(13):1385-99. doi: 10.2165/00003495-200464130-00001.
Obstructive sleep apnoea (OSA) is common, causes considerable morbidity and probably contributes to mortality particularly through associated cardiovascular disease. The physical therapy of continuous positive airway pressure (CPAP) is extremely effective in the majority of patients but most patients would prefer an alternative. Intuitively, OSA should be amenable to pharmacotherapy. The upper airway of affected individuals can be narrowed but is patent during wakefulness. Collapse of the airway during sleep occurs when negative intra-luminal pressure generated by inspiratory effort exceeds the tone of the upper airway dilators. This mismatch may be in part due to respiratory drive instability but the state-dependent fall in drive to the airway dilator muscles is the biggest factor in most patients. Various drugs have been investigated as treatment for OSA. Acetazolamide, theophylline, nicotine, opioid antagonists and medroxyprogesterone have been used to increase respiratory drive. Clonidine has been tested with the aim of reducing rapid eye movement sleep when OSA is often most severe. Various antidepressants have been used to suppress rapid eye movement sleep and to preferentially activate the upper airway dilators. The drug trials have often been of poor design and none has included more than a few patients. Most of the drugs have been found to be ineffective and those that have worked for some patients (acetazolamide and protriptyline) have produced intolerable adverse effects. There have been recent advances in the understanding of the neurotransmitters involved in the control of sleep and the upper airway motor neurones, offering the possibility of novel approaches to the drug treatment of OSA for those patients who cannot tolerate or do not benefit from CPAP. It seems likely that a better understanding of the mechanisms of OSA in individual patients and tailoring of drug therapy will be the way forward.
阻塞性睡眠呼吸暂停（OSA）很常见，会导致相当高的发病率，并且可能尤其通过相关的心血管疾病导致死亡。持续气道正压通气（CPAP）物理疗法对大多数患者极为有效，但大多数患者更希望有其他选择。直观地说，OSA应该适合药物治疗。受影响个体的上呼吸道可能会变窄，但在清醒时是通畅的。睡眠期间气道塌陷发生在吸气努力产生的管腔内负压超过上呼吸道扩张肌的张力时。这种不匹配可能部分归因于呼吸驱动不稳定，但在大多数患者中，驱动气道扩张肌的驱动力随状态下降是最大的因素。已经对各种药物进行了研究，以作为OSA的治疗方法。乙酰唑胺、茶碱、尼古丁、阿片类拮抗剂和甲羟孕酮已被用于增加呼吸驱动力。可乐定已被测试，目的是在OSA通常最严重时减少快速眼动睡眠。各种抗抑郁药已被用于抑制快速眼动睡眠并优先激活上呼吸道扩张肌。药物试验的设计往往很差，而且没有一项试验纳入的患者超过少数几个。大多数药物已被发现无效，而那些对一些患者有效的药物（乙酰唑胺和普罗替林）产生了无法忍受的不良反应。最近在对参与睡眠控制和上呼吸道运动神经元的神经递质的理解方面取得了进展，为那些不能耐受CPAP或从CPAP中无获益的患者提供了药物治疗OSA的新方法的可能性。对于个体患者，似乎更好地理解OSA的机制并量身定制药物治疗将是前进的方向。
