Therapeutic application of calcium-channel antagonists for pulmonary hypertension.
Calcium-channel antagonists may provide an effective approach to the treatment of pulmonary hypertensive disorders. Biochemical evidence suggests that pulmonary vasoconstriction results from the transmembrane flux of calcium into vascular smooth muscle; accordingly, the pulmonary pressor responses in experimental hypoxic pulmonary hypertension can be attenuated by verapamil and nifedipine. In patients with chronic obstructive lung disease, nifedipine decreases pulmonary artery pressures and pulmonary vascular resistance in proportion to the severity of hypoxemia before treatment. However, little pulmonary vasodilator effect is seen when hypoxemia is corrected by inhalation of oxygen, and systemic arterial oxygen desaturation can occur after nifedipine in patients breathing room air; most importantly, long-term studies in patients with chronic lung disease are lacking. In selected patients with primary pulmonary hypertension and other obliterative diseases of the pulmonary vasculature, nifedipine produces short- and long-term hemodynamic improvement at rest and during exercise, and these benefits are frequently paralleled by amelioration of dyspnea and fatigue. However, in patients in whom right ventricular function has been severely compromised by chronic pressure overload, both verapamil and nifedipine may exert notable depressant effects on right ventricular performance, despite the decrease in right ventricular afterload that would be expected to accompany a decrease in pulmonary vascular resistance. These negative inotropic actions may result in serious deleterious clinical reactions. Although calcium-channel antagonists represent a promising approach to the management of patients with pulmonary hypertension, the long-term efficacy and safety of these drugs in this disorder remain to be established.
D000818:Animals; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002417:Cattle; D004110:Diltiazem / Q000494:pharmacology / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D008168:Lung / Q000098:blood supply; D008173:Lung Diseases, Obstructive / Q000188:drug therapy / Q000503:physiopathology; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine