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Dose‐response effects of cardioselective beta blockade in coronary artery disease
Author(s) -
Silke Bernard,
Nelson Gregory,
Hussain Mussharaf,
Verma Satya Prakesh,
Taylor Stanley H
Publication year - 1984
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.1984.136
Subject(s) - blockade , coronary artery disease , medicine , beta (programming language) , cardiology , anesthesia , computer science , receptor , programming language
The hemodynamic dose‐response effects of intravenous acebutolol, a cardioselective β‐adrenoceptor antagonist with intrinsic sympathomimetic activity, were evaluated in 12 male subjects with angiographically confirmed coronary artery disease. At rest after a saline solution control period, four doubling intravenous boluses of acebutolol (logarithmic cumulative dosage of 20, 40, 80, and 160 mg) were injected at 4‐min intervals; hemodynamic variables were recorded 2 to 4 min after each injection. Hemodynamic effects of the drug during steady‐state exercise were evaluated by comparison of a control exercise period with observations made at the same workload (25W to 50W) after the maximum cumulative dose (160 mg). After the four intravenous boluses, plasma acebutolol concentrations rose in log‐linear fashion and levels achieved (0.6 to 3.5 µ/ml) were within the range at which substantial pharmacodynamic activity is usually present (i.e., 0.02 to 0.2 µ/ml). Compared with control measurements at rest after saline solution injection, these plasma concentrations of acebutolol resulted in a quadratic reduction in heart rate (maximum ΔHR, −4 bpm) and a linear increase in pulmonary artery occluded pressure (maximum ΔPAOP, +3 mm Hg) without change in systemic arterial pressure. There was a small reduction in cardiac output (Δ cardiac index [CI], −0.2 l/min/m 2 ). During steady‐state supine bicycle exercise, there were significant reductions in systolic blood pressure (ΔSBP, −15 mm Hg, or 9%) HR (−9 bpm or −9%), cardiac output (ΔCI, −1.0 l/min/m 2 , or −18%), and increase in PAOP (+8 mm Hg, or +38%). The relatively small changes induced in resting hemodynamic variables over a wide intravenous dose range of acebutolol demonstrated its relative hemodynamic safety in severe coronary artery disease. Relief of exercise‐induced angina was achieved at the cost of a relatively modest depression of left ventricular function. Clinical Pharmacology and Therapeutics (1984) 36, 40–46; doi: 10.1038/clpt.1984.136