Introduction
Magnesium is an essential mineral and electrolyte that serves as a critical cofactor in over 300 enzymatic reactions throughout the body. As a medication, magnesium is available in various salt formulations (sulfate, oxide, citrate, chloride) for oral and parenteral administration. It plays vital roles in neuromuscular function, cardiac excitability, nucleic acid synthesis, and energy metabolism.
Mechanism of Action
Magnesium acts as a natural calcium channel blocker, competing with calcium for binding sites. It regulates various cellular functions including:
- Neuromuscular transmission by modulating acetylcholine release
- Myocardial contractility through calcium antagonism
- Enzyme systems involved in ATP metabolism
- DNA and protein synthesis
As a pharmaceutical agent, magnesium produces anticonvulsant effects (by depressing CNS and neuromuscular transmission), antiarrhythmic effects (by prolonging conduction time), and tocolytic effects (by relaxing uterine smooth muscle).
Indications
FDA-approved indications:- Treatment and prevention of hypomagnesemia
- Prevention and treatment of seizures in pre-eclampsia and eclampsia (magnesium sulfate)
- Short-term treatment of constipation (as magnesium citrate or hydroxide)
- As a laxative for bowel preparation (magnesium citrate)
- As an antacid for relief of acid indigestion (magnesium hydroxide)
- Torsades de pointes and digitalis-induced arrhythmias
- Acute asthma exacerbations
- Migraine prophylaxis
- Neuroprotection in preterm infants
Dosage and Administration
Oral supplementation:- Adults: 200-400 mg elemental magnesium daily in divided doses
- Children: 3-6 mg/kg/day elemental magnesium in divided doses
- Hypomagnesemia: 1-2 g (8-16 mEq) IV over 5-60 minutes, then 0.5-1 g/hr infusion
- Eclampsia: 4-6 g IV loading dose over 20-30 minutes, then 1-2 g/hr maintenance infusion
- Torsades de pointes: 1-2 g IV over 5-60 minutes
- Renal impairment: Reduce dose or avoid; monitor serum levels closely
- Elderly: Consider reduced doses due to decreased renal function
- Pregnancy: Category A (oral); Category B (parenteral for pre-eclampsia/eclampsia)
Pharmacokinetics
Absorption: Oral bioavailability varies by salt formulation (5-30%); citrate and chloride have higher bioavailability than oxide. Absorption occurs primarily in small intestine via active transport and passive diffusion. Distribution: Distributed primarily in bone (60%), muscle (20%), and soft tissues (19%); serum contains approximately 1%. Crosses placenta and enters breast milk. Metabolism: Not metabolized; functions as an electrolyte. Elimination: Primarily renal excretion (90-95%); glomerular filtration with tubular reabsorption. Renal clearance correlates with creatinine clearance.Contraindications
- Hypermagnesemia
- Severe renal impairment (CrCl < 20 mL/min)
- Heart block
- Myasthenia gravis
- Hypersensitivity to magnesium salts
- Acute abdominal conditions (for laxative use)
Warnings and Precautions
- Toxicity risk: Monitor for signs of hypermagnesemia (hypotension, hyporeflexia, respiratory depression)
- Renal impairment: Increased risk of accumulation; requires dose adjustment and close monitoring
- Concurrent calcium channel blockers: May potentiate hypotensive and cardiac effects
- Neuromuscular diseases: May exacerbate weakness
- Prolonged IV administration: Requires continuous cardiac monitoring
Drug Interactions
- Neuromuscular blocking agents: Potentiates effects, may cause prolonged paralysis
- Cardiac glycosides: May increase risk of heart block
- Calcium channel blockers: Additive hypotensive and cardiac effects
- Antibiotics (aminoglycosides, quinolones): May reduce absorption when taken orally
- Bisphosphonates: Magnesium may decrease absorption
- Potassium-sparing diuretics: May increase risk of hypermagnesemia
Adverse Effects
Common:- Diarrhea (oral administration)
- Nausea, vomiting
- Abdominal cramping
- Flushing, sweating
- Hypermagnesemia (>4.8 mg/dL)
- Hypotension
- Respiratory depression
- Complete heart block
- Muscle weakness
- Hypocalcemia
- Cardiac arrest (levels >15 mg/dL)
Monitoring Parameters
- Serum magnesium levels (therapeutic range: 1.5-2.5 mg/dL)
- Deep tendon reflexes (for IV therapy)
- Respiratory rate
- Blood pressure and cardiac rhythm
- Renal function (BUN, creatinine)
- Electrolytes (calcium, potassium)
- Fluid balance
- Neurological status
Patient Education
- Take oral magnesium with food to reduce gastrointestinal upset
- Do not exceed recommended doses without medical supervision
- Report signs of toxicity: muscle weakness, dizziness, confusion, slow heartbeat
- Laxative formulations should not be used for more than 1 week without medical advice
- Separate oral magnesium from other medications by 2-3 hours to avoid interactions
- Maintain adequate fluid intake when using magnesium supplements
- Inform healthcare providers about all magnesium-containing products being taken
References
1. National Institutes of Health. Magnesium Fact Sheet for Health Professionals. 2022. 2. FDA prescribing information for magnesium sulfate injection. 2021. 3. Guerrera MP, Volpe SL, Mao JJ. Therapeutic uses of magnesium. Am Fam Physician. 2009;80(2):157-162. 4. Fawcett WJ, Haxby EJ, Male DA. Magnesium: physiology and pharmacology. Br J Anaesth. 1999;83(2):302-320. 5. Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1-187. 6. American College of Obstetricians and Gynecologists. Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol. 2020;135(6):e237-e260. 7. UpToDate. Magnesium sulfate drug information. 2023. 8. Micromedex® Solutions. Magnesium monograph. Truven Health Analytics. 2023.