Sedative Hypnotics

Benzodiazepines are commonly prescribed orally to treat anxiety disorders, mood disorders, and insomnia. In addition, they are used parenterally as premedications before procedures such as endoscopy or minor surgery. The most prescribed agents include alprazolam (Xanax®, Niravam®), clonazepam (Klonopin®), diazepam (Valium®), lorazepam (Ativan®), midazolam (Versed®), and temazepam (Restoril®) (29). Benzodiazepines exert respiratory-depressant effects centrally in addition to decreasing upper airway tone. The respiratory-depressant effects of benzodiaze-pines range from mild to the most severe outcome, death (14).

Individuals with sleep apnea or COPD are most at risk for benzodiazepine-associated respiratory distress; however, parenteral midazolam use induced OSA and a severe reduction in SpO2 in five of 21 patients with no history of OSA. Nasal CPAP reversed the respiratory deterioration in these patients (25). In another study of elderly patients with mild sleep apnea, seven subjects received temazepam 15 mg/night to 30 mg/night and eight subjects received placebo. There was no difference in respiratory distress between the two groups (30). In addition to the respiratory-depressant effects during sleep, benzodiazepines have the potential to cause next-day hangover and contribute to excessive daytime sleepiness and cognitive impairment already experienced by individuals with OSA (31). Because benzodiazepine-associated respiratory function worsening in OSA is difficult to predict, sleep experts recommend avoiding benzodiazepines in untreated patients with severe OSA, especially in those with daytime hypoventilation (14).

Zaleplon (Sonata®), Zolpidem (Ambien®, Ambien® CR), and eszopiclone (Lunesta®) are nonbenzodiazepine hypnotics that act on the benzodiazepine receptor complex. They are selective for the alpha-1 benzodiazepine receptor and demonstrate hypnotic efficacy without significant anxiolytic, anticonvulsant, or muscle relaxant effects (31). All of these "Z-hypnotics" are FDA-approved for insomnia although eszopiclone and zolpidem controlled-release are the only agents approved for long-term treatment (32,33). Compared to n onselective benzodiazepines, Z-hypnotics are less likely to affect sleep architecture at recommended hypnotic doses (31-34).

Zolpidem is the most prescribed and most well-studied agent. Ten patients with stable COPD were given zolpidem 10 mg over eight consecutive nights in order to assess zolpidem's impact on respiratory function. Zolpidem did not impair sleep architecture or diurnal pulmonary function tests or central control of breathing (35). Other data indicate that zolpidem 20 mg induces a significant reduction of respiratory flow in healthy individuals and decreases oxygen saturation in patients with sleep apnea syndrome (34). Zaleplon and eszopiclone's impact on respiratory function has not been assessed in patients with COPD or OSA; however, since they possess the same pharmacologic activity, there is a dose-related potential for compromising respiratory function in patients treated with these agents as well.

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