Opioid facilitation of ß-adrenergic blockade: A new pharmacological condition?

Abstract

Recently, propranolol was suggested to prevent hyperlactatemia in a child with hypovolemic shock through ß-adrenergic blockade. Though it is a known inhibitor of glycolysis, propranolol, outside this observation, has never been reported to fully protect against lactate overproduction. On the other hand, literature evidence exists for a cross-talk between ß-adrenergic receptors (protein targets of propranolol) and δ-opioid receptor. In this literature context, it is hypothesized here that anti-diarrheic racecadotril (a pro-drug of thiorphan, an inhibitor of enkephalinases), which, in the cited observation, was co-administered with propranolol, might have facilitated the ß-blocker-driven inhibition of glycolysis and resulting lactate production. The opioid-facilitated ß-adrenergic blockade would be essentially additivity or even synergism putatively existing between antagonism of δ-adrenergic receptors and agonism of d-opioid receptor in lowering cellular cAMP and dependent functions.