Mechanism of propranolol withdrawal phenomena

Nine patients on chronic treatment with propranolol for essential hypertension for 3 months or longer were studied after abrupt discontinuation of the drug. Each patient demonstrated transient supersensitivity to the chronotropic effects of isoproterenol, beginning 2--6 days (median 4 days) after propranolol withdrawal, lasting for 3--13 days (median 6 days), with the maximum sensitivity on day 6. A significantly lower dose of isoproterenol was necessary to increase heart rate 25 beats/min on day 6 (median dose 1.2 microgram, range 0.3--3.4 microgram) compared with after day 14, when sensitivity had stabilized (median dose 2.3 microgram, range 1.4--7.6 microgram). Six patients had transient symptoms (headache, chest pain, palpitations and sweating) after abrupt propranolol withdrawal, coinciding with supersensitivity to isoproterenol in five. Transient increases in plasma catecholamines and blood pressures and sustained increases in heart rate occurred during the period of isoproterenol supersensitivity in most patients, and may have contributed to symptoms noted. The delayed onset and potentially long duration of beta-adrenergic supersensitivity after abrupt propranolol withdrawal have important clinical implications.