Pharmacotherapy of obstructive sleep apnea. Is salvation just around a corner.pdf

Obstructive sleep apnea (OSA) is recurrent upper airway obstruction caused by a loss of upper airway muscle tone during sleep, which leads to intermittent hypoxia and sleep fragmentation1 . OSA is a common disorder affecting 25-30% of adult population and more than 50% of obese individuals 2 . Continuous positive airway pressure (CPAP) relieves OSA, but poor adherence severely limits its use 3 . Mandibular advancement devices have better compliance, but not as effective as CPAP 4 . There is no effective pharmacotherapy. Successful drug development is possible only when the pathogenesis of the disease is fully understood. Four key pathophysiological mechanisms of OSA have been identified: (1) anatomically compromised or collapsible upper airway; (2) inadequate compensatory responses of the upper airway dilator muscles during sleep; (3) a low arousal threshold, (4) an overly sensitive ventilatory control drive 5 . Anatomic predisposition plays a primary role in OSA pathogenesis 6 , whereas faulty neuromuscular mechanisms during sleep fail to compensate adequately for compromised pharyngeal patency 7