Hemodynamic consequences of combined beta-adrenergic and slow calcium channel blockade in man.
The administration of verapamil to patients receiving beta-adrenergic blocking drugs is reported to produce adverse circulatory reactions, but a systematic investigation of this potential drug interaction has not been performed in man. We administered 40-, 80- and 120-mg doses of verapamil orally to 15 patients with angina pectoris who were receiving high doses of propranolol or metoprolol. Verapamil produced dose-dependent decreases in cardiac performance: with 120 mg, cardiac index decreased by 0.38 l/min/m2, stroke volume index decreased by 2.8 ml/beat/m2 and heart rate decreased by 6 beats/min, associated with increases in pulmonary capillary wedge (2.2 mm Hg) and mean right atrial pressures (1.7 mm Hg) (all p less than 0.01); two patients had marked, but asymptomatic, hypotensive reactions. In contrast, repeat administration of 120-mg doses of verapamil 24--30 hours after withdrawal of beta blockade produced no significant cardiodepressant effects despite significantly higher plasma levels of verapamil than during propranolol therapy (383.1 vs 205.1 ng/ml, p less than 0.01). In conclusion, verapamil produces significant negative inotropic and chronotropic effects in patients treated with beta-adrenergic antagonists; combination therapy should therefore be used with caution in patients with angina pectoris.
D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy*; D003327:Coronary Disease / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000097:blood / Q000627:therapeutic use*; D008875:Middle Aged; D011412:Propanolamines / Q000627:therapeutic use*; D011433:Propranolol / Q000097:blood / Q000627:therapeutic use*; D014700:Verapamil / Q000097:blood / Q000627:therapeutic use*
D011412:Propanolamines; D011433:Propranolol; D014700:Verapamil; D008790:Metoprolol