In asthma, which drug inhibits phosphodiesterase, has a narrow therapeutic index, and is used as a bronchodilator?

• A. Albuterol
• B. Ipratropium
• C. Theophylline
• D. Montelukast

Answer: (C)

The drug that fits here is theophylline. It works by inhibiting phosphodiesterase, which prevents the breakdown of cyclic AMP in bronchial smooth muscle. Higher cAMP levels lead to activation of protein kinase A, which causes relaxation of the airway muscles and thus bronchodilation. Theophylline also has some adenosine receptor–blocking effects that can contribute to its bronchodilatory action, but the key therapeutic mechanism is PDE inhibition.

A major reason this drug is notable is its narrow therapeutic index: the effective blood concentration is close to the level at which toxicity can occur. Therapeutic levels are typically in a relatively narrow range, and increases beyond this can cause serious adverse effects such as tachyarrhythmias and seizures. Because of this, careful dosing and monitoring of blood levels are required, and many patients experience interactions with other drugs or variability in metabolism (it is processed by liver enzymes and can be affected by other medications or even caffeine).

The other options act through different pathways. A beta-2 agonist stimulates receptors that increase cAMP via a different route, producing bronchodilation; an antimuscarinic agent blocks acetylcholine effects to reduce bronchoconstriction; a leukotriene receptor antagonist blocks inflammatory mediators. None of these inhibit phosphodiesterase, so they don’t fit the description.