title: Haemodynamic dose-response effects of i.v. penbutolol in angina pectoris.
abstract: 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.
mesh_terms: D000328:Adult; D000787:Angina Pectoris / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010394:Penbutolol / Q000097:blood / Q000494:pharmacology*; D005082:Physical Exertion; D011412:Propanolamines / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects
chemical_list: D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D010394:Penbutolol