Which of the following is a mechanism of action of methylxanthines used in the treatment of apnea of prematurity?

• A. Decreases CO2 sensitivity
• B. Decreases diaphragmatic activity
• C. Increases minute ventilation
• D. Increases tidal volume

Answer: (C)

Methylxanthines work in apnea of prematurity by stimulating the central respiratory drive, which increases minute ventilation. They block adenosine receptors in the brainstem, removing inhibitory input to the respiratory centers and enhancing the ventilatory response. This central stimulation helps the infant breathe more consistently, reducing apnea episodes. The drugs can also inhibit phosphodiesterase, raising cAMP and potentially improving diaphragmatic contractility, but the clinically relevant effect for treating apnea is the rise in minute ventilation. They do not decrease CO2 sensitivity or diaphragmatic activity; in fact, they tend to enhance respiratory drive and effort. While they may modestly influence tidal volume, the primary therapeutic mechanism is the overall increase in minute ventilation.