Article date: November 1983
By: B Silke, SP Verma, M Hussain, GI Nelson, RC Okoli, SH Taylor, in Volume 16, Issue 5, pages 529-535
The haemodynamic dose‐response effects of intravenous penbutolol, a newer beta‐adrenoceptor antagonist with intrinsic sympathomimetic activity but without cardioselectivity, were evaluated in 10 patients with angiographically documented coronary artery disease. Following four logarithmetically cumulative i.v. boluses (0.5‐4 mg dosage range) there was a log linear increase in plasma penbutolol concentration; the levels achieved (51 +/‐ 8 to 219 +/‐ 19 ng/ml) were in the therapeutic range (12 to 250 ng/ml). Penbutolol resulted in a linear decrease in heart rate (maximum delta HR ‐ 4 beats/min; P less than 0.01); there was a small increase in pulmonary artery occluded pressure which reached its maximum at the lower doses (maximum delta PAOP + 1 mm Hg; P less than 0.01). The resting cardiac output, blood pressure and calculated systemic vascular resistance were unchanged. During 4 min steady‐state supine bicycle exercise there was attenuation of exercise cardiac output (delta C.I. ‐ 0.6 1 min‐1 m‐2; P less than 0.01) and systolic pressor response (delta SBP ‐ 13 mm Hg; P less than 0.01) compared with control observations without change in other measured or derived variables. The haemodynamic profile of penbutolol compared favourably with other beta‐adrenoceptor antagonists previously evaluated under similar conditions in patients with ischaemic heart disease. Over the i.v. dose‐range evaluated penbutolol attenuated exercise‐induced angina with a relatively modest depression of cardiac performance; the small change induced in resting haemodynamic variables may, in part, have been contributed to by the intrinsic sympathomimetic activity of penbutolol.
DOI: 10.1111/j.1365-2125.1983.tb02211.x
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