The beta-adrenergic blockade withdrawal phenomenon

Early trials of beta-blocking drugs in angina indicated an increase in symptoms above pretreatment levels when placebo was substituted for active drug. This was followed by some reports of sudden death after beta-blockade withdrawal. There is evidence of increased beta-receptor sensitivity as suggested by increased responsiveness to isoprenaline after propranolol withdrawal. This may be due to an increased beta-receptor population. Other factors may be a reversal of the reduced free triiodothyroxine, of the rightward shift of the oxyhaemaglobin dissociation curve, and of reduced platelet aggregation, when the beta-blocking drug is stopped. Finally, progression of the disease process may take place during treatment, which is unmasked when treatment is withdrawn. beta-Blocking agents may differ; we have observed that in normal volunteers, withdrawal of pindolol, which has partial agonist properties, was not associated with postblockade increase in response to isoprenaline. The beta-blocker withdrawal syndrome is a real phenomenon, although overall the incidence is low. Besides stopping the beta-blocker, exertion may be a frequent prerequisite for the development of significant clinical sequelae, so exertion should be restricted when stopping a beta-blocking drug. Also the dose should be reduced gradually, particularly the final decrements.