Withdrawal of beta-blocking drugs

Our early observations indicated that when treatment was changed from propranolol to placebo, anginal patients experienced a higher incidence of chest pain during the first week of placebo treatment compared to the second week. Since then, there have been several reports of myocardial infarction and sudden death occurring when propranolol therapy has been stopped. However, more formal hospital studies have indicated that ischemia from propranolol withdrawal is relatively infrequent. Studies in normal subjects and hypertensive patients have shown an increase in beta-receptor sensitivity as suggested by increased responsiveness to isoprenaline after propranolol withdrawal. Some investigators have found an increase in free triiodothyronine levels. Catecholamine levels do not appear to be raised. Other relevant factors in ischemic patients might be a reversal of the favorable rightward shift of the oxyhemoglobin dissociation curve or a reversal of reduced platelet aggregation produced by propranolol. Last, propranolol withdrawal in patients who have received the drug for a considerable period might unmask a withdrawal in patients who have received the drug for a considerable period might unmask a progression of the disease process, so that in the absence of beta blockade oxygen supply is inadequate to meet the requirements of relatively ischemic areas even at rest. Whether all beta blockers are similar to propranolol in this regard is unknown. We are examining, in normal volunteers, the sensitivity of the beta receptor after the withdrawal of atenolol, pindolol, or propranolol, administered for at least 2 weeks after final dose adjustment to levels sufficient to produce maximum inhibition of exercise tachycardia. The sensitivity of the beta receptor is being assessed by the response of bolus injections of isoprenaline and the response to exercise tachycardia.