Which drug class is most associated with respiratory depression risk when overdosed?

• A. Benzodiazepines
• B. Opioids (e.g., morphine, fentanyl)
• C. Antihistamines
• D. NSAIDs

Answer: (B)

Opioids cause respiratory depression in overdose because they activate mu-opioid receptors in the brainstem, which dampens the ventilatory drive to CO2 and reduces both the rate and depth of breathing. This can lead to dangerous hypoventilation or apnea, especially with potent agents like fentanyl or when taken with other depressants. While other drug classes can cause sedation, they do not exert as direct and profound an effect on breathing as opioids do. Antihistamines and NSAIDs may cause dizziness or sedation in some cases, but they are not associated with the same high risk of life-threatening respiratory depression in overdose. In practice, naloxone is used to rapidly reverse opioid-induced respiratory depression.