Theophylline has a narrow therapeutic index and multiple adverse effects. At therapeutic plasma concentrations (10–20 mcg/mL), its primary mechanism of bronchodilation is:

• A Non-selective competitive inhibition of phosphodiesterase (PDE3 and PDE4) increasing intracellular cAMP and cGMP ✓
• B Adenosine receptor antagonism causing direct airway smooth muscle relaxation
• C Beta-2 adrenoceptor sensitization increasing response to endogenous catecholamines
• D Activation of histone deacetylase-2 (HDAC2) restoring steroid sensitivity in airway inflammation

Explanation

At therapeutic concentrations, theophylline primarily acts as a non-selective phosphodiesterase inhibitor, preventing breakdown of cAMP and cGMP in bronchial smooth muscle and inflammatory cells. Increased cAMP leads to bronchial smooth muscle relaxation via PKA-mediated phosphorylation of myosin light chain kinase. At sub-therapeutic concentrations, adenosine receptor antagonism becomes relatively more important and may account for some anti-inflammatory and bronchodilatory effects, but is NOT the primary mechanism at therapeutic levels.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.