CHAPTER 2-96: MAGNESIUM

INTRODUCTION

Magnesium (Mg) is a divalent cation that is required for a variety of intracellular processes and is an essential ion for proper neuromuscular functioning. Oral magnesium salts are widely available in over-the-counter antacids (eg, Maalox and Mylanta) and cathartics (milk of magnesia and magnesium citrate and sulfate). IV magnesium sulfate is used to treat toxemia of pregnancy, polymorphous ventricular tachycardia, refractory ventricular arrhythmias, and severe bronchospasm.

MECHANISM OF TOXICITY

1. The toxic effects of magnesium involve mainly the cardiovascular, skeletal muscle, and central nervous systems.

   1. Cardiovascular effects include altered automaticity and conduction due to effects on both potassium and calcium ion channels; decreased myocardial contractility by alteration of intracellular calcium mobility; vascular smooth muscle relaxation by reduction in available intracellular calcium; and impaired catecholamine release by inhibition of calcium-mediated exocytosis.

   2. Skeletal muscle effects are probably mediated by antagonizing calcium permeable channels, calcium binding proteins, and calcium-mediated release of acetylcholine.

   3. Toxic effects in the central nervous system are less well defined but probably involve stimulation of NDMA and GABA_-A receptors, increased calcitonin gene-related peptide, and possibly inhibited production of nitrous oxide and substance P.

2. Pharmacokinetics. The average adult body content of magnesium is approximately 24 g. Because magnesium is found primarily in bone, muscle, and intracellular fluids, serum levels may not accurately represent body stores. Magnesium transport channels are located in the ileum and colon and account for most dietary absorption. The oral bioavailability ranges from 20% to 40% depending on the salt form. Although best modeled with two-compartment pharmacokinetics, the average volume of distribution is about 0.5 L/Kg, and the elimination half-life averages 4–5 hours in healthy adults. Magnesium is primarily excreted by the kidney, and impaired elimination can occur when the creatinine clearance is less than 30 mL/min.

TOXIC DOSE

The adult recommended daily allowance for magnesium is 320–420 mg per day. Although most acute or chronic overexposures do not result in hypermagnesemia, poisoning has been reported after IV overdose, enemas, or massive oral overdose. Toxicity after standard doses has been observed in patients with renal insufficiency and in patients with impaired neuromuscular functioning (myasthenia gravis or treatment with neuromuscular blocking drugs).

1. Commonly available antacids (Maalox, Mylanta, and others) contain 12.5–37.5 mEq of magnesium per 15 mL (1 tablespoon), milk of magnesia contains about 40 mEq/15 mL, and magnesium sulfate (in Epsom salts and IV preparations) contains 8 mEq/g.

2. Ingestion of 200 g of magnesium sulfate caused coma in a young woman with normal renal function. Pediatric deaths have been reported after the use of Epsom salt enemas.

CLINICAL PRESENTATION

Orally administered magnesium causes diarrhea, usually within 3 hours. Repeated or excessive doses of magnesium-containing cathartics can cause serious fluid and electrolyte abnormalities. Moderate toxicity may cause nausea, vomiting, muscle weakness, and cutaneous flushing. Higher levels can cause cardiac conduction abnormalities (bradycardia, QT ...