Orexin receptor antagonists should be avoided in which condition?

• A. Normal liver function
• B. Narcolepsy with cataplexy
• C. Severe liver impairment
• D. Healthy adults

Answer: (C)

Orexin receptor antagonists are cleared by the liver, so how well the liver works directly affects how much of the drug stays in the body. In severe liver impairment, the drug isn’t metabolized efficiently, leading to higher levels in the blood. That can cause stronger or longer-lasting sedation, next-day impairment, and the potential for liver-related toxicity. Because of that, these drugs are not recommended for people with severe hepatic impairment.

In contrast, someone with normal liver function or a healthy adult without liver disease has normal drug clearance, so the medication can be used as intended. Narcolepsy with cataplexy would make a sleep-promoting drug counterproductive, since it can worsen daytime wakefulness control, but the primary safety concern here is the impaired liver function that would cause dangerous drug buildup.