Prevention of propranolol withdrawal mechanism by prolonged small dose propranolol schedule

Abrupt withdrawal of propranolol may be followed by a "propranolol withdrawal syndrome "due, at least in part, to enhanced beta adrenergic sensitivity. Tapering propranolol dosage is frequently used in the hope of preventing adverse withdrawal events but the success of such a maneuver has not been shown. The rationale for the dose tapering schedule in this study was based on earlier observations after abrupt withdrawal of propranolol. Nine hypertensive patients were gradually withdrawn from long-term propranolol therapy, either by serial dose reduction for 6 to 9 days (n = 3) or by reduction to a prolonged small dose (30 mg daily) for 2 weeks before complete withdrawal (n = 6). During dose reduction of propranolol and for 2 additional weeks of placebo therapy, serial measurements were made of cardiac sensitivity to isoproterenol, heart rate at rest, blood pressure, plasma catecholamines, serum thyroxine (T4) and triiodothyronine (T3) and symptoms. Serial dose reduction decreased but did not prevent cardiac hypersensitivity in two of three patients. The prolonged small dose therapy largely prevented cardiac hypersensitivity and overshoot in heart rate, blood pressure and plasma catecholamines and symptoms. Serum T4 decreased significantly and T3 tended to increase during and after prolonged small dose treatment. These results indicate that prolonged administration of small dose propranolol before complete withdrawal in hypertensive patients prevents enhanced cardiac beta adrenergic sensitivity and other adverse events.