Propranolol in the Treatment of Angina Pectoris: Comparison of Duration of Action in Acute and Sustained Oral Therapy

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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. Plasmac 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 olerance, 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 improvement in exercise tolerance was associated with significant reduction in electrocardiographic ST-segment epression. 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 pectoris 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.

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