Magnesium Hydroxide: From Antacid to Clinical Pharmacology Insight

When a 54‑year‑old patient presents to the emergency department with acute epigastric pain after a heavy meal, the first bedside intervention is often a quick dose of an over‑the‑counter antacid. In most practice settings that antacid is magnesium hydroxide, a simple salt that neutralizes gastric acid and, in larger doses, stimulates intestinal motility. While many clinicians use it for its soothing effect on heartburn, the underlying pharmacology is richer and more nuanced than most students realize. Understanding magnesium hydroxide’s mechanisms, pharmacokinetics, therapeutic uses, and safety considerations is essential for pharmacists, residents, and clinicians who prescribe or counsel patients on over‑the‑counter regimens.

Introduction and Background

Magnesium hydroxide (Mg(OH)₂) is the inorganic salt of magnesium and hydroxide, first isolated in the 19th century by chemists studying mineral waters. Its therapeutic use as an antacid dates back to the early 1900s, when it was marketed under brand names such as "Milk of Magnesia" and "Gaviscon". The compound’s dual role as a mild laxative emerged when clinicians observed that high‑dose preparations induced osmotic diarrhea, a phenomenon exploited in the treatment of constipation and bowel preparation for colonoscopy.

Epidemiologically, acid‑related disorders such as gastroesophageal reflux disease (GERD) affect nearly 20% of adults in the United States, and over 30% of those with GERD use over‑the‑counter antacids at least once a week. Magnesium hydroxide remains the most widely used antacid in the U.S. and Europe, with annual sales exceeding $1 billion. In addition to its antacid function, magnesium is an essential electrolyte involved in neuromuscular conduction, enzyme activation, and bone formation, making magnesium‑based preparations an attractive source of supplemental magnesium for patients with low dietary intake or increased requirements.

Pharmacologically, magnesium hydroxide falls under the class of inorganic salts that neutralize gastric acid. It is distinct from calcium carbonate and aluminum hydroxide, which have different buffering capacities and side‑effect profiles. The drug’s therapeutic effects arise from both local acid neutralization and systemic magnesium absorption, which has implications for patients with renal impairment, heart failure, and electrolyte disorders.

Mechanism of Action

Acid Neutralization

Magnesium hydroxide acts as a weak base that reacts with hydrochloric acid (HCl) in the stomach to form magnesium chloride (MgCl₂) and water:

Mg(OH)₂ + 2HCl → MgCl₂ + 2H₂O

Because the reaction is limited by the solubility of Mg(OH)₂ (≈ 0.0013 g/mL at 25 °C), the drug provides a modest buffering effect, raising gastric pH to approximately 3–5 when administered at therapeutic doses. This pH shift reduces irritation of the esophageal mucosa, decreases pepsin activity, and alleviates heartburn and dyspepsia.

Osmotic Laxative Effect

At higher concentrations, magnesium hydroxide remains largely insoluble, acting as an osmotic agent in the colon. Unabsorbed magnesium ions bind water molecules, increasing luminal fluid volume and stimulating peristalsis. The resultant accelerated transit time produces loose stools within 30–60 minutes after ingestion. This mechanism is the basis for its use as a bowel cleanser before colonoscopy and for treating functional constipation.

Systemic Magnesium Absorption

Small amounts of magnesium chloride formed in the stomach are absorbed in the small intestine via both passive diffusion and active transport through the TRPM6/7 channels. The absorbed magnesium contributes to systemic magnesium levels, which modulate voltage‑gated calcium channels, ATPase activity, and the N-methyl-D-aspartate (NMDA) receptor. These interactions influence cardiac conduction, neuromuscular excitability, and bone mineralization.

Clinical Pharmacology

Pharmacokinetics

Absorption: Magnesium hydroxide is poorly soluble in aqueous media, resulting in limited gastric absorption (<10%). The absorbed fraction is primarily in the form of magnesium chloride, which is rapidly dissolved and absorbed in the small intestine. Peak plasma concentrations (Cmax) are typically reached within 1–2 hours after oral administration.

Distribution: Magnesium distributes to extracellular fluid and interstitial spaces; the volume of distribution (Vd) is approximately 0.6 L/kg. Because it is an ion, it does not cross the blood–brain barrier in significant amounts under normal conditions.

Metabolism: Magnesium hydroxide is not metabolized; it is excreted unchanged.

Excretion: Renal elimination is the primary route. The glomerular filtration rate (GFR) determines the rate of magnesium clearance; in patients with impaired renal function, serum magnesium can rise, leading to hypermagnesemia.

Pharmacodynamics

The antacid effect is dose‑dependent, with a typical over‑the‑counter dose of 500 mg (equivalent to 1 g of Mg(OH)₂) providing symptomatic relief for mild heartburn. The laxative effect requires higher doses (≥ 1.5 g), producing stool within 1 hour in 70% of patients.

Therapeutic window: The therapeutic index is narrow for systemic magnesium exposure; doses > 2 g increase the risk of serum magnesium > 2.5 mmol/L, especially in renal impairment.

Therapeutic Applications

• Acute heartburn and GERD relief: 500 mg PO q6–8 h as needed; maximum 4 g/day.
• Constipation (osmotic laxative): 1.5–2 g PO once daily; onset 30–60 min.
• Bowel preparation for colonoscopy: 1.5 g PO every 6 h for 3 days; final dose 2 h before procedure.
• Supplemental magnesium for deficiency: 1–2 g PO daily; monitor serum Mg.

Off‑label uses include pre‑operative bowel cleansing for certain endoscopic procedures and as a component of electrolyte replacement in patients with hypomagnesemia. Evidence from randomized trials shows that magnesium hydroxide is as effective as polyethylene glycol solutions for colon cleansing with fewer side effects.

Special populations:

• Pediatrics: 0.5 g/kg PO every 8 h for constipation; caution in infants <6 months.
• Geriatrics: Reduced renal clearance necessitates dose adjustment; monitor for hypermagnesemia.
• Renal/hepatic impairment: Contraindicated in advanced CKD (eGFR <30 mL/min); hepatic impairment has minimal impact.
• Pregnancy: Category B; generally safe for short‑term use; avoid high doses in the third trimester due to risk of preterm labor.

Adverse Effects and Safety

• Gastrointestinal: Nausea (≈5%), abdominal cramping (≈3%), diarrhea (≈20% at laxative doses).
• Systemic hypermagnesemia: Rare (<1%) in patients with normal renal function; incidence rises to 10–15% in CKD stages 4–5.
• Cardiac conduction abnormalities: Prolonged PR interval, hypotension, and in severe cases, respiratory depression.
• Allergic reactions: Anaphylaxis extremely rare; monitor for urticaria.

Drug Interactions

Monitoring Parameters

• Serum magnesium (baseline and every 48 h in CKD).
• Renal function (eGFR, creatinine).
• Electrocardiogram (baseline and if clinical symptoms).

Contraindications

• Severe renal impairment (eGFR <30 mL/min).
• Known hypersensitivity to magnesium salts.
• Pregnancy in the third trimester (high doses).

Clinical Pearls for Practice

• When in doubt, separate antacids from other oral meds by at least 2 hours. Magnesium can chelate cations, reducing absorption of many drugs.
• Use the “Milk of Magnesia” mnemonic: M‑L‑A‑C‑K‑S. M: Magnesium; L: Laxative; A: Antacid; C: Calcium; K: Kidney; S: Safety.
• For bowel prep, start at 1.5 g PO every 6 h; the last dose 2 h before colonoscopy. This schedule maximizes stool evacuation while minimizing cramping.
• Monitor serum Mg in patients on amiodarone or other Mg‑binding drugs. Hypermagnesemia can precipitate bradyarrhythmias.
• In elderly patients, start with half the adult dose and titrate upward while monitoring renal function. GFR declines with age, increasing hypermagnesemia risk.
• Do not use magnesium hydroxide as a laxative in patients with bowel obstruction. Osmotic agents can worsen obstruction.
• When treating constipation, consider magnesium hydroxide only if other laxatives (e.g., polyethylene glycol) are contraindicated or not tolerated.

Comparison Table

Exam‑Focused Review

Common question stems:

• “A 68‑year‑old man with CKD stage 4 is taking magnesium hydroxide for constipation. Which of the following is the most appropriate action?”
• “A patient on digoxin develops nausea after taking magnesium hydroxide. What is the most likely explanation?”
• “Which antacid is contraindicated in patients with severe renal insufficiency?”

Key differentiators students often confuse:

• Magnesium hydroxide vs. calcium carbonate: both buffer acid, but Mg can cause hypermagnesemia; Ca can cause hypercalcemia.
• Osmotic laxative vs. stimulant laxative: Mg hydroxide is osmotic; senna is stimulant.
• Use in bowel prep: Mg hydroxide is used in certain regimens; polyethylene glycol is the gold standard for colonoscopy prep.

Must‑know facts for NAPLEX/USMLE:

• Mg hydroxide has a low solubility product, limiting absorption.
• Hypermagnesemia signs: hypotension, bradycardia, loss of deep tendon reflexes.
• In patients with CKD, avoid high‑dose Mg hydroxide; monitor serum Mg.
• Mg hydroxide can interfere with absorption of drugs that require acidic pH.
• When used as a laxative, onset is rapid (30–60 min).

Key Takeaways

1. Magnesium hydroxide is a weak base that neutralizes gastric acid and acts as an osmotic laxative.
2. It is poorly absorbed; systemic effects depend on renal clearance.
3. Therapeutic uses include heartburn relief, constipation, bowel prep, and magnesium supplementation.
4. Hypermagnesemia is the most serious adverse effect, especially in CKD.
5. Drug interactions mainly involve reduced absorption of cationic drugs and increased Mg levels with Mg‑binding agents.
6. Separate dosing from other antacids and medications to avoid chelation.
7. Monitoring of serum Mg and renal function is essential in at-risk populations.
8. Clinical pearls help avoid common pitfalls in prescribing and counseling.
9. Comparison with other antacids clarifies indications and safety profiles.
10. Exam questions often test differentiation from calcium and aluminum antacids and recognition of hypermagnesemia signs.

Always counsel patients on the importance of adhering to dosing schedules and reporting any signs of dizziness, flushing, or muscle weakness promptly—early recognition of hypermagnesemia can prevent serious complications.