Calcium channel blocker-associated pulmonary toxicity: epidemiology, mechanisms, and clinical management

Calcium channel blockers are first-line medications for the treatment of hypertension, angina pectoris, and arrhythmias, and are generally well-tolerated. However, in recent years, there have been reports indicating that CCBs may cause severe pulmonary toxicity, such as non-cardiogenic pulmonary edema and acute respiratory distress syndrome. This article employs a comprehensive review methodology to systematically summarize the clinical types, incidence, risk factors, mechanisms of injury, and management strategies for CCB-related pulmonary toxicity. Current evidence indicates that pulmonary toxicity is extremely rare at standard therapeutic doses; however, the incidence increases significantly in cases of acute overdose and among specific populations (pregnant women, patients with underlying cardiopulmonary diseases). Pharmacovigilance studies have identified significant signals suggesting an association between nifedipine, diltiazem, and verapamil to pulmonary edema, with amlodipine having the highest number of related clinical reports. Major risk factors include drug overdose, pregnancy, underlying cardiopulmonary disease, and differences among CCB subclasses. Toxicity associated with dihydropyridine CCBs is primarily characterized by vasodilatory shock, whereas non-dihydropyridine CCBs exhibit a combination of cardiac depressant and vasodilatory effects. Mechanisms involve hemodynamic changes, increased capillary permeability, inflammatory activation, and alveolar epithelial dysfunction. Early recognition, drug discontinuation, selection of vasoactive agents based on the type of shock, and life support are key to improving prognosis.