Beta-2 mimetics and magnesium: true or false friends?

Abstract

Physiological beta stimulation may be involved in the regulation of magnesium status namely by homeostatic increase of magnesemia during magnesium deficiency. But conversely excessive beta stimulation namely by use of pharmacological high doses of beta mimetics may induce a decrease of magnesemia. Two different types of magnesium therapy ought to be distinguished. Nutritional magnesium therapy which may physiologically palliate a magnesium deficiency due to an insufficient magnesium intake. It is devoid of any toxicity. Pharmacological magnesium therapy, whatever the magnesium status, causes a iatrogenic magnesium load. It may induce magnesium toxicity. Tocolysis is the one common obstetrical indication for beta mimetics and magnesium. Beta-2 mimetics are the reference tocolytic drugs in most countries. But high doses of beta-2 mimetics for suppression of premature labor are associated to a high incidence of maternal, fetal and neonatal side effects. Tocolysis must then be discontinued or limited to shorter treatments with the lowest possible doses. Nutritional magnesium therapy which palliates gestational magnesium deficiency is efficient and atoxic. Conversely, high doses of intravenous MgSO4 for tocolysis are less efficient and unsafe. Because of its maternal and above all pediatric side effects, this maternal pharmacological magnesium therapy should be abandoned for tocolysis. Investigation of the therapeutic ratio of various magnesium salts before their clinical use could help to determine if other anions different from sulfate could decrease the toxicity. Beta-2 agonists are first line asthma therapy, but their safety is debated. Asthma and Chronic Obstructive Pulmonary Disease (COPD) per se may induce magnesium depletion related to a dysregulation of the control mechanisms of magnesium status. It requires a correction of its causal regulation, but nutritional magnesium supplementation is ineffective. When chronic primary magnesium deficiency coexists with obstructive bronchial disorders, it constitutes a decompensatory factor. Atoxic nutritional magnesium therapy may palliate this coexistent magnesium deficiency. Pharmacological magnesium treatment for obstructive pulmonary diseases is not very efficient with low safety. Combination of palliating nutritional magnesium therapy and of beta-2 mimetics for tocolysis or pulmonary obstructive indications may be beneficial and remain atoxic. Conversely combination of intravenous tocolytic high doses of magnesium and of beta-2 mimetics is contra-indicated because of its dubious efficiency and its possible toxicity. The possible role of SO4- as regards toxicity must be discussed. Contra-indications of lower intravenous or inhaled Mg doses for pulmonary bronchial obstruction are less imperative than for tocolysis. The selection of a particular magnesium salt among others should take into account reliable plasmacological and toxicological data. It seems necessary to determine the therapeutic ratio (LD50/ED50) of the various available magnesium salts before pharmacological use.