Propranolol in the treatment of angina pectoris. Comparison of duration of action in acute and sustained oral therapy.
Authors: U Thadani, J O Parker
Journal: Circulation (1979)

The duration of action of single oral doses of 80 and 160 mg of propranolol during acute and sustained therapy was studied in nine patients with stable, exercise-induced angina pectoris.Plasma propranolol levels peaked 2 hours after both doses during acute and sustained therapy, but there were wide variations between individuals in plasma concentration with both dosage schedules.Plasma half-lives after 80 and 160 mg were 3.99 and 4.65 hours during acute therapy and 3.46 and 6.35 hours during sustained therapy.Despite a twofold increase in plasma levels during sustained therapy, the increase in walking time to angina was similar to that seen with acute therapy.After acute administration of 80 and 160 mg propranolol, walking time to angina increased significantly compared with the values after placebo.This improvement in exercise tolerance, however, was similar after the two doses of propranolol; it appeared within 1 hour and persisted for 12 hours after both doses.Improvement in exercise tolerance was maintained over 12 hours during sustained twice-daily therapy with 80 mg propranolol.However, when the dose of propranolol was increased to 160 mg twice daily, we observed no further improvement in exercise tolerance.During both modes of therapy, the im- provement in exercise tolerance was associated with significant reduction in electrocardiographic ST-segment depression.At both rest and exercise, the heart rate, systolic blood pressure and rate-pressure product decreased at 1 hour and the effects persisted for 12 hours during acute therapy and for 24 hours during sustained therapy.The circulatory effects were, however, more marked during sustained therapy.These studies show that twice-daily therapy with 80 mg propranolol should be adequate for treating patients with angina pec- toris due to coronary artery disease.The improvement in exercise tolerance to be expected during sustained therapy can be assessed from the exercise studies carried out within 1-2 hours after the oral administration of single dose of 80 or 160 mg propranolol.PROPRANOLOL IS EFFECTIVE in the manage- ment of patients with angina pectoris,1 6 and is usually prescribed in doses four times daily.Recent studies from this laboratory in patients with stable exercise in- duced angina pectoris have shown that after single oral doses of 80 and 160 mg propranolol, the increase in exercise tolerance and reduction in heart rate (HR) and systolic blood pressure (SBP) at rest and during exercise persist for 12 hours.7These observations suggest that propranolol administered in these doses twice daily would be effective.However, it is not known how the duration of action after single oral doses compares with those seen during sustained, twice-daily therapy.The present investigation was designed to compare the duration of action of propranolol after acute and sustained twice-daily oral therapy in patients with angina pectoris. MethodsNine male patients aged 45-64 years (average 53 years) with uncomplicated stable, exercise-induced angina pectoris were studied.All had significant cor- onary artery disease as defined by obstructive disease of > 75% luminal narrowing of one or more coronary