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. In addition there were reports of sudden death after beta-blockade withdrawal. There is evidence of increased beta-receptor sensitivity as demonstrated by increased responsiveness to isoprenaline after propranolol withdrawal. This may be due to increased beta-receptor population. Other factors may be a reversal of the reduced free triiodothyronine levels or of the favourable rightward shift of oxyhaemoglobin dissociation curve, or increased platelet aggregation when the beta-blocking drug is stopped. Also, progression of the disease process may have taken place during treatment which is unmasked on withdrawal. Studying different beta-blocking agents we have observed that in normal volunteers withdrawal of pindolol, which has partial agonist properties, was not associated with post blockade increase in response to isoprenaline. The beta-blocker withdrawal syndrome is a real phenomenon, although overall the incidence is probably not high. Exertion may be a prerequisite for the development of significant clinical sequelae, therefore exercise should be restricted on withdrawal of beta-blocking drugs. The dosage should be reduced gradually, particularly the final decrement.