Magnesium and its therapeutic uses: A review

doi:10.1016/0002-9343(94)90117-1

The American Journal of Medicine

Volume 96, Issue 1, January 1994, Pages 63-76

https://doi.org/10.1016/0002-9343(94)90117-1 Get rights and content

Abstract

Magnesium has been reported as an effective medical therapy in an expanding array of conditions. Evidence investigating magnesium's use is presented, with a number of studies suggesting it should be seriously considered in such conditions as ischemic heart disease, cardiac arrhythmias, and asthma.

Magnesium balance and metabolism are briefly reviewed, and then various hypotheses are presented that may explain magnesium's physiologic mechanisms of action, most likely involving calcium and potassium flux across cellular membranes in smooth muscle. In a number of the conditions to be discussed, it has been uncertain whether magnesium administration serves the purpose of merely correcting an underlying deficiency state or of utilizing a specific pharmacologic effect of magnesium. Magnesium deficiency is a relatively common condition, and predisposing factors as well as recent methods for assessing total body stores of magnesium are discussed. Physicians should be familiar with the numerous conditions and therapeutics that are risk factors for an underlying magnesium deficiency and in which, empiric magnesium replacement should be considered.

Guidelines for administration of parenteral magnesium are presented with specific focus on the low risk of adverse effects, as suggested by the large and rapid dosing regimens used in many of the clinical studies discussed here.

References (130)

ES Barker et al.
Studies of the renal excretion of magnesium in man
J Clin Invest
(1959)
CH Barton et al.
Renal magnesium wasting associated with amphotericin B therapy
Am J Med
(1984)
S Kupfer et al.
Effects of cardiac glycosides on renal tubular transport of calcium, magnesium, inorganic phosphate, and glucose in the dog
J Clin Invest
(1965)
R Patel et al.
Symptomatic hypomagnesemia associated with gentamicin therapy
Nephron
(1979)
JM Kalbfleisch et al.
Effects of ethanol administration on urinary excretion of magnesium and other electrolytes in alcoholic and normal subjects
J Clin Invest
(1963)
JH Dirks
The kidney and magnesium regulation
Kidney Int
(1983)
J McManus et al.
A decreased response to parathyroid hormone in magnesium deficiency
J Endocrinol
(1971)
RK Rude et al.
Parathyroid hormone secretion in magnesium deficiency
J Clin Endocrinol Metab
(1978)
R Whang et al.
Magnesium depletion as a cause of refractory potassium repletion
Arch Intern Med
(1985)
E Ryzen et al.
Magnesium deficiency in a medical ICU population
Crit Care Med
(1985)

JR Oster et al.

Management of magnesium depletion

Am J Nephrol

(1988)

KN Watson et al.

Magnesium sulfate: rationale for its use in preeclampsia

EB Flink et al.

Alterations of long-chain free fatty acid and magnesium in acute myocardial infarction

Arch Intern Med

(1981)

SM Horner

Efficacy of intravenous magnesium in acute myocardial infarction in reducing arrhythmias and mortality

Circulation

(1992)

KL Woods et al.

Intravenous magnesium sulphate in suspected acute myocardial infarction: results of the Second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2)

Lancet

(1992)

C Vigorito et al.

Hemodynamic effects of magnesium sulfate on the normal human heart

Am J Cardiol

(1991)

H Miyagi et al.

Effect of magnesium on anginal attack induced by hyperventilation in patients with variant angina

Circulation

(1989)

TW Anderson et al.

Sudden death and ischemic heart disease

N Engl J Med

(1969)

K Goto et al.

Magnesium deficiency detected by intravenous loading test in variant angina pectoris

Am J Cardiol

(1990)

LA DiCarlo et al.

Effects of magnesium sulfate on cardiac conduction and refractoriness in humans

J Am Coll Cardiol

(1986)

RH Seller et al.

Digitalis toxicity and hypomagnesemia

Am Heart J

(1970)

MF Ghani et al.

The effectiveness of magnesium chloride in the treatment of ventricular tachyarrhythmias due to digitalis intoxication

Am Heart J

(1974)

MS Neff et al.

Magnesium sulfate in digitalis toxicity

Am J Cardiol

(1972)

MJ Specter et al.

Studies on magnesium's mechanism of action in digitalis-induced arrhythmias

Circulation

(1975)

GA Beller et al.

Correlation of serum magnesium levels and cardiac digitalis intoxication

Am J Cardiol

(1974)

SM Green et al.

Antiarrhythmic efficacy of magnesium in the setting of life-threatening digoxin toxicity

Am J Emerg Med

(1989)

L Cohen et al.

Magnesium sulfate and digitalis-toxic arrhythmias

JAMA

(1983)

T Dyckner et al.

Ventricular extrasystoles and intracellular electrolytes before and after potassium and magnesium infusions in patients on diuretic treatment

Am Heart J

(1979)

D Siegel et al.

Diuretics, serum and intracellular electrolyte levels, and ventricular arrhythmias in hypertensive men

JAMA

(1992)

EJ Topol et al.

Hypomagnesemic torsades de pointes

Am J Cardiol

(1983)

D Tzivoni et al.

Magnesium therapy for torsades de pointes

Am J Cardiol

(1984)

GN Kay et al.

Torsade de pointes: the long-short initiating sequence and other clinical features: observations in 32 patients

J Am Coll Cardiol

(1983)

JM Wharton et al.

Torsade de pointes during administration of pentamidine isethionate

Am J Med

(1987)

P Mitchell et al.

Torsades de pointes during intravenous pentamidine isethionate therapy

Can Med Assoc J

(1989)

WEC Wacker et al.

Magnesium metabolism

N Engl J Med

(1968)

WEC Wacker et al.

Magnesium metabolism

N Engl J Med

(1968)

WEC Wacker et al.

Magnesium metabolism

N Engl J Med

(1968)

RA Reinhart

Magnesium metabolism

Arch Intern Med

(1988)

RJ Elin

Assessment of magnesium status

Clin Chem

(1987)

LA Graham et al.

Gastrointestinal absorption and excretion of magnesium 28 in man

Metab Clin Exp

(1960)

PG Brannan et al.

Magnesium absorption in the human small intestine

J Clin Invest

(1976)

AC Schmulen et al.

Effect of 1,25-(OH)2D3 on jejunal absorption of magnesium in patients with chronic renal disease

Am J Physiol

(1980)

SR Levine et al.

Hypomagnesemia and ventricular tachycardia

Chest

(1982)

JL Caddell et al.

Studies in protein-calorie malnutrition

N Engl J Med

(1967)

GA Quamme et al.

The physiology of renal magnesium handling

Renal Physiol

(1986)

SG Massry et al.

Effect of NaCl infusion on urinary Ca and Mg during reduction in their filtered loads

Am J Physiol

(1967)

RK Rude et al.

Magnesium deficiency and excess

Annu Rev Med

(1981)

IM Shafik et al.

Early adaptation of renal magnesium reabsorption in response to magnesium restriction

Am J Physiol

(1989)

S Hanna et al.

The influence of aldosterone on magnesium metabolism

Lancet

(1960)

J Lemann et al.

Studies of the acute effects of aldosterone and cortisol on the interrelationship between renal sodium, calcium and magnesium excretion in normal man

Nephron

(1970)

RL Schilsky et al.

Hypomagnesemia and renal magnesium wasting in patients receiving cisplatin

Ann Intern Med

(1979)

GM Shah et al.

Symptomatic hypocalcemia and hypomagnesemia with renal magnesium wasting associated with pentamidine therapy in a patient with AIDS

Am J Med

(1990)

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ReviewMagnesium and its therapeutic uses: A review

Abstract

J Clin Invest

Am J Med

J Clin Invest

Nephron

J Clin Invest

Kidney Int

J Endocrinol

J Clin Endocrinol Metab

Arch Intern Med

Crit Care Med

Am J Nephrol

Arch Intern Med

Circulation

Lancet

Am J Cardiol

Circulation

N Engl J Med

Am J Cardiol

J Am Coll Cardiol

Am Heart J

Am Heart J

Am J Cardiol

Circulation

Am J Cardiol

Am J Emerg Med

JAMA

Am Heart J

JAMA

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

Am J Med

Can Med Assoc J

Magnesium metabolism

N Engl J Med

Magnesium metabolism

N Engl J Med

Magnesium metabolism

N Engl J Med

Magnesium metabolism

Arch Intern Med

Assessment of magnesium status

Clin Chem

Gastrointestinal absorption and excretion of magnesium 28 in man

Metab Clin Exp

Magnesium absorption in the human small intestine

J Clin Invest

Effect of 1,25-(OH)2D3 on jejunal absorption of magnesium in patients with chronic renal disease

Am J Physiol

Hypomagnesemia and ventricular tachycardia

Chest

Studies in protein-calorie malnutrition

N Engl J Med

The physiology of renal magnesium handling

Renal Physiol

Effect of NaCl infusion on urinary Ca and Mg during reduction in their filtered loads

Am J Physiol

Magnesium deficiency and excess

Annu Rev Med

Early adaptation of renal magnesium reabsorption in response to magnesium restriction

Am J Physiol

The influence of aldosterone on magnesium metabolism

Lancet

Studies of the acute effects of aldosterone and cortisol on the interrelationship between renal sodium, calcium and magnesium excretion in normal man

Nephron

Hypomagnesemia and renal magnesium wasting in patients receiving cisplatin

Ann Intern Med

Symptomatic hypocalcemia and hypomagnesemia with renal magnesium wasting associated with pentamidine therapy in a patient with AIDS

Am J Med

Review
Magnesium and its therapeutic uses: A review