The Management of Acute Poisoning Due to β-Adrenoceptor Antagonists

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Abstract
Although many cases of β-adrenoceptor antagonist (β-blocker) poisoning are uneventful, a proportion develop serious and sometimes fatal cardiovascular system depression with severe hypotension. As β-adrenergic tone is not essential for cardiovascular function in health, there is no physiological reason why total β-adrenoceptor blockade should have serious consequences in the resting individual. The toxic actions of β-blockers appear to be related to properties such as membrane depressant activity and possibly due to actions on β-adrenoceptors distinct from those in the cardiovascular system. Most reports of serious adverse effects following overdosage concern β-blockers with significant membrane depressant activity, and in particular propranolol and oxprenolol, with which progressive heart block and bradycardia are features. Sotalol toxicity, with its unique electrophysio-logical action, is a special case. Animal experiments confirm that β-blockers with membrane depressant activity are more toxic than the newer more selective ones, such as atenolol and nadolol. However, experimental models also reveal that artificial ventilation markedly reduces the toxicity of all β-blockers tested, suggesting a respiratory depressant action with very high doses. Treatment of serious overdosage in man should include maintenance of adequate ventilation. High dose intravenous glucagon is recommended, because its inotropic action depends on direct stimulation of adenylate cyclase. β-Agonists such as isoprenaline (isoproterenol) or prenalterol may be effective, but the nature of agonist-competitive antagonist interactions may necessitate the use of unrealistically large doses to overcome very high tissue β-blocker concentrations.