Monograph of Magnesium Hydroxide

Introduction

Magnesium hydroxide (chemical formula Mg(OH)₂) is a white, insoluble inorganic compound widely employed in clinical practice as an antacid and osmotic laxative. Since its first therapeutic use in the early 20th century, it has become a staple in over‑the‑counter preparations for the management of dyspepsia, gastro‑oesophageal reflux disease (GERD), and constipation. Its dualistic pharmacologic profile—neutralization of gastric acid and stimulation of colonic motility—renders it uniquely valuable in both acute and chronic therapeutic regimens. The present chapter is intended to provide a comprehensive understanding of magnesium hydroxide from a chemical, pharmacokinetic, and clinical perspective, thereby equipping medical and pharmacy students with the knowledge necessary to integrate this agent into evidence‑based practice.

Learning objectives

• Describe the physicochemical properties and synthesis of magnesium hydroxide.
• Explain the mechanisms underlying its antacid and laxative actions.
• Summarize the pharmacokinetic profile and factors influencing its absorption and elimination.
• Identify clinical indications, dosing considerations, and potential drug interactions.
• Apply case‑based reasoning to optimize magnesium hydroxide therapy in diverse patient populations.

Fundamental Principles

Core Concepts and Definitions

Magnesium hydroxide is an inorganic salt consisting of divalent magnesium cations and hydroxide anions. Its crystalline structure confers limited solubility in water (≈0.0008 g / 100 mL at 25 °C), a property that underpins its therapeutic actions. The compound is available in various dosage forms, including loose tablets, chewable tablets, effervescent granules, and liquid suspensions. In pharmaceutical preparations, magnesium hydroxide may be combined with sodium bicarbonate, citric acid, or other buffering agents to enhance palatability and pH modulation.

Theoretical Foundations

Upon ingestion, magnesium hydroxide undergoes limited dissolution in the acidic environment of stomach. The equilibrium reaction Mg(OH)₂ + 2H₊ ⇌ Mg²⁺ + 2H₂O liberates magnesium cations, which exhibit a weakly basic character. This process elevates gastric pH, thereby reducing mucosal irritation and acid‑mediated peptic ulceration. In the colon, the unabsorbed magnesium hydroxide acts as a hyperosmotic agent, drawing water into the lumen through osmosis (Δπ = C₁ − C₂), thereby softening stool and accelerating transit. The minimal dissolution also limits systemic absorption, mitigating the risk of hypermagnesemia in patients with normal renal clearance.

Key Terminology

• pH buffering: The capacity of a compound to modulate hydrogen ion concentration.
• Osmotic laxative: A medication that retains water in the intestinal lumen, promoting stool softening.
• Hypermagnesemia: Elevated serum magnesium concentration, potentially leading to neuromuscular and cardiac toxicity.
• Clearance (Cl): The volume of plasma from which a substance is completely removed per unit time.
• Half‑life (t_1/2): The time required for plasma concentration to decrease by 50 %.

Detailed Explanation

Synthesis and Manufacturing

Commercial production of magnesium hydroxide typically proceeds via neutralization of magnesium salts, such as magnesium chloride or magnesium sulfate, with calcium hydroxide or sodium hydroxide. The reaction is conducted in aqueous solution, followed by filtration, washing, and drying to remove soluble impurities. Particle size reduction via milling or grinding enhances surface area, thereby improving dissolution rate in the gastric milieu. Quality control measures include assessment of purity, particle size distribution, and residual moisture content, all of which influence the drug’s physicochemical behavior and therapeutic performance.

Pharmacokinetics

Absorption of magnesium hydroxide is limited due to its low solubility. The fraction of absorbed magnesium (f_a) is typically less than 1 %. Consequently, systemic exposure is minimal, with peak plasma concentrations (C_max) occurring within 1–2 hours post‑dose. The bioavailability (F) can be approximated by the integral of the absorption rate over time, represented in the equation C(t) = C₀ × e^−kt, where k is the elimination rate constant. Clearance (Cl) is predominantly renal, with an estimated value of 10–15 mL min⁻¹ in healthy adults. The elimination half‑life (t_1/2) is approximately 4–6 hours for the absorbed fraction, whereas the unabsorbed portion remains in the gastrointestinal tract until excreted with feces.

Mechanisms of Action

Magnesium hydroxide exerts antacid effects through direct neutralization of gastric hydrochloric acid. The neutralization reaction produces magnesium chloride, water, and a rise in intragastric pH. In patients with GERD, the resulting increase in pH reduces esophageal mucosal damage and alleviates heartburn symptoms. As an osmotic laxative, the compound’s insoluble nature allows it to remain in the intestinal lumen. The high concentration of magnesium ions creates an osmotic gradient that draws water from the plasma into the bowel, softening stool and facilitating defecation. The laxative effect is dose‑dependent, with typical therapeutic ranges of 15–45 g per day for adults, divided into multiple administrations.

Factors Affecting the Process

• Dosage form: Liquid suspensions provide a faster onset of action compared to tablets, due to enhanced surface area and dissolution.
• Particle size: Smaller particles increase dissolution rate, potentially improving antacid efficacy.
• Gastrointestinal transit time: Delayed gastric emptying, as seen in diabetic gastroparesis, may prolong exposure to gastric acid, thereby reducing antacid effectiveness.
• Food intake: Meals can buffer gastric acid and alter the pH profile, influencing the neutralization capacity of magnesium hydroxide.
• Renal function: Impaired glomerular filtration rate (GFR) diminishes magnesium clearance, elevating the risk of hypermagnesemia, particularly in chronic kidney disease (CKD) stages 4–5.

Clinical Significance

Relevance to Drug Therapy

Magnesium hydroxide’s dual action renders it suitable for managing both acid‑related disorders and constipation. In the antacid domain, it is frequently prescribed for mild to moderate heartburn, dyspepsia, and post‑prandial reflux episodes. Its rapid onset, coupled with minimal systemic absorption, makes it a safe alternative to proton pump inhibitors (PPIs) for short‑term symptom relief. Within the constipation spectrum, magnesium hydroxide is often used as a first‑line osmotic laxative before progressing to stimulant laxatives or bulk‑forming agents. The low cost and wide availability further contribute to its prominence in outpatient settings.

Practical Applications

Therapeutic dosing of magnesium hydroxide is tailored to the clinical indication and patient characteristics. For antacid therapy, a typical dose is 1–2 g (containing 0.6–1.2 g of elemental magnesium) taken after meals or at bedtime. For laxative purposes, a dose of 15–30 g orally, divided into 3–4 administrations per day, is commonly employed. Pediatric dosing follows a weight‑based approach, generally 2–4 mg kg⁻¹ per dose, with a maximum of 30 mg per day. In elderly patients or those with renal impairment, dose reduction or avoidance is advised to prevent accumulation.

Clinical Examples

Case 1: A 52‑year‑old male presents with nocturnal heartburn. After ruling out alarm symptoms, a trial of magnesium hydroxide 1 g at bedtime is initiated. Symptom resolution within 1 hour suggests adequate acid neutralization. The patient is advised to monitor for loose stools; if diarrhea occurs, the dose is reduced to 0.5 g.

Case 2: A 65‑year‑old female with CKD stage 3 experiences chronic constipation. A low‑dose trial of magnesium hydroxide 15 g daily is started, with close monitoring of serum magnesium and renal function. Over four weeks, stool frequency improves from once every 3 days to twice weekly, without evidence of hypermagnesemia.

Clinical Applications/Examples

Case Scenarios

Scenario A: A 30‑year‑old woman with a history of peptic ulcer disease is prescribed magnesium hydroxide for intermittent dyspepsia. She reports transient nausea and loose stools. The clinician considers switching to a combination antacid that includes a smaller magnesium load or adding a proton pump inhibitor for sustained acid suppression.

Scenario B: A 75‑year‑old man with osteoporosis and reduced bone mineral density is on chronic bisphosphonate therapy. He experiences constipation and is prescribed magnesium hydroxide 30 g daily. The patient develops mild muscle weakness, prompting laboratory evaluation that reveals serum magnesium of 2.8 mmol L⁻¹ (upper limit of normal). The dosage is reduced to 15 g per day, and stool frequency improves without additional symptoms.

Problem‑Solving Approaches

When selecting magnesium hydroxide for a patient, the following steps are recommended:

1. Assess the primary indication (antacid vs. laxative) and determine the appropriate therapeutic dose range.
2. Review comorbid conditions, particularly renal function, to evaluate the risk of hypermagnesemia.
3. Consider concomitant medications that may alter gastric pH (e.g., PPIs, H2‑receptor antagonists) or magnesium absorption (e.g., diuretics, antacids containing calcium).
4. Educate the patient on the expected onset of action and potential side effects, such as transient gastrointestinal discomfort or diarrhea.
5. Monitor serum magnesium and renal parameters in high‑risk populations, adjusting the dose accordingly.

Summary/Key Points

• Magnesium hydroxide is an insoluble inorganic salt with antacid and osmotic laxative properties.
• Its antacid action is mediated by neutralization of gastric acid, while its laxative effect results from osmotic water retention in the colon.
• Limited dissolution leads to minimal systemic absorption; thus, hypermagnesemia is uncommon in patients with intact renal function.
• Clinical dosing ranges: 1–2 g for antacid use; 15–30 g for laxative effect; weight‑based dosing in pediatrics.
• Renal impairment, advanced age, and concurrent medications require dose adjustment or alternative therapies.
• Monitoring of serum magnesium is prudent in patients at high risk for accumulation.

References

1. Rang HP, Ritter JM, Flower RJ, Henderson G. Rang & Dale's Pharmacology. 9th ed. Edinburgh: Elsevier; 2020.
2. Trevor AJ, Katzung BG, Kruidering-Hall M. Katzung & Trevor's Pharmacology: Examination & Board Review. 13th ed. New York: McGraw-Hill Education; 2022.
3. Golan DE, Armstrong EJ, Armstrong AW. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. 4th ed. Philadelphia: Wolters Kluwer; 2017.
4. Whalen K, Finkel R, Panavelil TA. Lippincott Illustrated Reviews: Pharmacology. 7th ed. Philadelphia: Wolters Kluwer; 2019.
5. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 14th ed. New York: McGraw-Hill Education; 2023.
6. Katzung BG, Vanderah TW. Basic & Clinical Pharmacology. 15th ed. New York: McGraw-Hill Education; 2021.
7. Trevor AJ, Katzung BG, Kruidering-Hall M. Katzung & Trevor's Pharmacology: Examination & Board Review. 13th ed. New York: McGraw-Hill Education; 2022.
8. Rang HP, Ritter JM, Flower RJ, Henderson G. Rang & Dale's Pharmacology. 9th ed. Edinburgh: Elsevier; 2020.