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Synergistic adverse hemodynamic interaction between oral verapamil and propranolol
Author(s) -
Carruthers S George,
Freeman David J,
Bailey David G
Publication year - 1989
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1989.167
Subject(s) - propranolol , verapamil , chronotropic , heart rate , cmax , pharmacology , medicine , hemodynamics , pharmacokinetics , crossover study , oral administration , adverse effect , drug interaction , blood pressure , anesthesia , alternative medicine , pathology , calcium , placebo
The interaction between oral verapamil and propranolol may involve negative chronotropic, inotropic or dromotropic effects. The immediate effects of orally administered verapamil (120 mg) and propranolol (80 mg), alone and combined, on submaximal exercise hemodynamics and on pharmacokinetics were studied in eight healthy male volunteers in a randomized, double‐blind, crossover manner. Maximum effects on heart rate, systolic blood pressure, PR interval and rate‐adjusted PR prolongation were greatest with the combined administration of verapamil and propranolol. The combination caused a high frequency of adverse drug events, predominantly exercise fatigue. Verapamil increased the AUC and C max and shortened the t max of propranolol. Propranolol decreased the AUC and C max of verapamil. The greater reduction of heart rate with the combination of verapamil and propranolol was only partially explained by higher plasma concentrations of propranolol. The combination of propranolol and verapamil produced clinically important synergistic adverse effects during exercise. Negative dromotropic effects occurred primarily by direct AV node inhibition and were more important than previously recognized. Clinical Pharmacology and Therapeutics (1989) 46, 469–477; doi: 10.1038/clpt.1989.167