Pharmacotherapy for obstructive sleep apnea: targeting specific pathophysiological traits

ABSTRACT

Introduction

The pathophysiology of obstructive sleep apnea (OSA) is multi-factorial and complex. Varying OSA’s pathophysiological traits have been identified, including pharyngeal collapsibility, upper airway muscle reactivity, arousal threshold, and regulation of the ventilatory drive. Being CPAP of difficult tolerance and other interventions reserved to specific subpopulations new pharmacological treatments for OSA might be resolutive.

Areas covered

Several existing and newly developed pharmacological drugs can impact one or more endotypes and could therefore be proposed as treatment options for sleep disordered breathing. With this review we will explore different pathophysiological traits as new targets for OSA therapy. This review will summarize the most promising pharmacological treatment for OSA accordingly with their mechanisms of action on upper airway collapsibility, muscle responsiveness, arousal threshold, and loop gain.

Expert opinion

Only understanding the pathophysiological traits causing OSA in each patient and placing the disease in the framework of patient comorbidities, we will be able to evolve interventions toward OSA. The development of new drug’s combinations will permit different approaches and different choices beside conventional treatments. In the next future, we hope that sleep specialists will select the treatment for a specific patient on the base of its pathophysiology, defining a precision medicine for OSA.

KEYWORDS:

• OSA endotypes
• OSA pharmacotherapy
• OSA phenotypes
• Precision medicine
• CPAP
• sleep disordered breathing
• atomoxetine

Article highlights

• Diuretics and drugs for weight loss modify upper airway anatomy and may play a role in OSA alleviation in certain patients.

• Promising results have been obtained with drugs that increase upper airway muscle reaction during sleep.

• Reducing loop gain seems to be also a way to act on OSA severity.

• The lack of positive results on medications acting on the arousal threshold makes this strategy less encouraging.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.