Although magnesium is a divalent cation like other metals, we will refer to it as magnesium in this text. It is an essential cofactor in more than 350 enzyme reactions in cardiac, neurologic, neuromuscular, and endocrine processes, as well as in basic energy, structural, nucleic acid, and signal transduction pathways.107,136 Hypomagnesemia results in nausea, vomiting, weakness, muscle spasms, neurologic and muscular excitation (tremor, hyperreflexia, and tetany), and cardiac dysrhythmias. Hypermagnesemia produces cardiovascular effects, including conduction disturbances, hypotension, and cardiac arrest; respiratory depression; gastrointestinal (GI) complaints of nausea, vomiting, and thirst; and neuromuscular sequelae, including weakness, paralysis, and central nervous system (CNS) depression.4,77,131 Magnesium as chloride, citrate, hydroxide, oxide or sulfate is used to repair xenobiotic-associated hypomagnesemia and as an adjunctive treatment for cardiovascular toxins, fluoride toxicity, pesticide poisoning, and alcohol use disorders.
In 1679, Nehemiah Grew described the process of obtaining the eponymous salts in the springs of Epsom through evaporation, which he later published in 1695 to be magnesium sulfate (MgSO4).105 Later as an antidote, MgSO4 was used as a therapy for tetanus in 1906.63 In 1923, MgSO4 was introduced to treat the convulsions of nephritis in children, which was later extended to the advanced chronic nephritis in adults.131 On the basis of reports in 1925 and 1926, MgSO4 came into common practice for the prevention and control of seizures in severe toxemia of pregnancy; its use for this indication was “grandfathered” by the US Food and Drug Administration (FDA).20 The cardiac utility of MgSO4 was demonstrated in 1935 and 1943 as therapy to suppress “paroxysmal tachycardia.”13,139 Magnesium sulfate also continues in use as a uterine tocolytic, a bronchodilator a migraine therapy and as a nutritional adjunct to prevent hypomagnesemia in hyperalimentation.
Chemistry and Preparation
Magnesium has the atomic number 12, with a molecular weight of 24.3 Da. Despite having a smaller atomic radius than calcium, magnesium binds water tighter, with two hydration shells, leading to a radius 400 times larger than its dehydrated form.64 This property underlies its calcium antagonism, despite similar chemical reactivity and charge.64 For clinical use, magnesium is prepared as a salt, typically in combination with chloride, citrate, hydroxide oxide, or sulfate. Magnesium as MgSO4 is typically formulated in its heptahydrate form MgSO4•7H2O, with a molecular weight of 120.38 Da alone and 246.47 when accounting for water. It occurs as colorless crystals or white powder, which is freely soluble in water.
The use of magnesium as an oral saline cathartic (eg, magnesium citrate, magnesium hydroxide, and MgSO4) is discussed in Antidotes in Depth: A2.