Drug-Induced Bronchospasm in a Patient with CAD

This patient with coronary artery disease has been stable on sublingual nitroglycerin, metoprolol, aspirin, and enalapril for a year, and now develops new-onset breathlessness and wheeze. The task is to identify which drug in this regimen is most likely responsible for these new respiratory symptoms.

Why Metoprolol Is the Correct Answer

Metoprolol is a β1-selective (cardioselective) beta-blocker, but this selectivity is relative and dose-dependent, not absolute. At the dose used here (50 mg twice daily), or in patients with underlying airway hyperreactivity, metoprolol can lose its β1-selectivity and block bronchial β2-receptors. Since β2-receptor stimulation normally maintains bronchodilation, blocking these receptors unmasks or precipitates bronchoconstriction, presenting clinically as new-onset breathlessness and wheeze. Beta-blocker-induced bronchospasm is a well-recognised adverse effect and is the classic explanation for respiratory symptoms appearing after initiation or up-titration of a beta-blocker such as metoprolol.

Analysis of the Other Options

• Enalapril: This ACE inhibitor is well known to cause a persistent dry, non-productive cough due to accumulation of bradykinin, and rarely angioedema, but it does not typically cause wheeze or bronchospasm. The symptom profile here (breathlessness with wheeze) does not fit an ACE-inhibitor effect.
• Nitroglycerin: As a vasodilator, its main adverse effects are headache, flushing, and hypotension-related symptoms (dizziness, occasionally reflex tachycardia). It has no recognised mechanism for causing bronchoconstriction or wheeze, making it an unlikely cause here.
• Aspirin: Aspirin can precipitate bronchospasm in patients with Aspirin-Exacerbated Respiratory Disease (AERD), but this typically occurs in patients with a pre-existing history of asthma and nasal polyps, and usually manifests soon after aspirin exposure rather than after a year of stable use. It is a less likely explanation in this patient without such a history.

Conclusion

Given that metoprolol is a beta-blocker capable of causing bronchospasm through partial loss of β1-selectivity and blockade of bronchial β2-receptors, it is the drug most likely implicated in this patient's new breathlessness and wheeze.