Aluminum Hydroxide, Magnesium Hydroxide and Calcium Carbonate

Mechanism

Mechanism of action and acid neutralization

When dissolving in the gastric medium, the molecules react chemically with the free protons (H⁺) of the cellular hydrochloric acid to form water and insoluble salts or those with little intestinal absorption:

Direct acid neutralization immediately increases gastric pH above 4.0. This increase in pH reversibly inhibits the conversion of pepsinogen to gastric pepsin (pepsin is completely inactivated at pH 5.0). In addition, aluminum salts have astringent properties that protect the mucosa through the formation of topical protective colloidal complexes.

💩 Aluminum Hydroxide

• Intestinal action: astringent and constipant.
• Mechanism: Free aluminum ions (Al³⁺) relax gastric and intestinal smooth muscle, delaying gastric emptying and colonic transit.
• Bounds phosphates in the intestinal lumen forming insoluble aluminum phosphate, reducing intestinal absorption of phosphorus (causing hypophosphatemia).

💧 Magnesium Hydroxide

• Intestinal action: osmotic laxative.
• Mechanism: Unabsorbed magnesium salts retain water in the lumen of the colon by osmotic gradient, stimulating the release of cholecystokinin and promoting peristalsis.
• Causes transient osmotic watery diarrhea.

Commercial Formulas Association

Because aluminum causes marked constipation and magnesium induces osmotic diarrhea, most commercial antacid preparations (such as Almax or Maalox) combine aluminum hydroxide and magnesium hydroxide (almagate or magaldrate) in an equimolar manner. In this way, the opposing gastrointestinal effects on intestinal transit are counteracted, minimizing colonic ADRs.

Pharmacokinetics

Pharmacokinetics

• Absorption: The majority of aluminum and magnesium salts are not absorbed systemically. However, in the presence of acidity, a small fraction of the cation is solubilized and systemically absorbed (Magnesium ≈ 15% - 30%, Aluminum < 0.1%). Calcium carbonate is absorbed at ≈ 10%.
• Distribution: Limited at the plasma level in healthy subjects. The absorbed calcium is deposited in the bone or circulates attached to albumin.
• Metabolism: Purely luminal inorganic chemical reaction. Does not require hepatic biotransformation.
• Excretion: The resulting insoluble salts and the non-neutralized fraction are eliminated via the fecal route. Systemically absorbed cations are obligately excreted by renal filtration.

Indicators and dose

Approved and Off-label indications

• Rapid symptomatic relief of heartburn, heartburn, dyspepsia and mild gastroesophageal reflux.
• Hyperphosphatemia associated with chronic renal failure: Aluminum hydroxide is used in a controlled manner as a chelator of intestinal dietary phosphates.

Dosage and Clinical Adjustment

Adults:

• 10 mL or 1 to 2 chewable tablets taken orally symptomatically, preferably between 1 and 3 hours after main meals and at bedtime (when rebound heartburn is maximum).
• Do not exceed the recommended daily doses or use continuously for more than 14 days without medical supervision.

Adjustment in Renal Failure: Contraindicated or strictly not recommended in moderate to terminal renal failure (eGFR < 30 mL/min). Its continued use in this population increases the risk of neurotoxicity and fatal arrhythmias due to ionic deposition.

Security

Contraindications

• Absolute: Hypersensitivity to the components. Severe renal failure (Child-Pugh renal / eGFR < 30 mL/min): Imminent danger of systemic accumulation of cations causing severe hypermagnesemia (cause of heart block and muscle paralysis of central origin) and aluminum encephalopathy.
• Relative: Pre-existing severe hypophosphatemia (aluminum exacerbates free phosphorus depletion). Chronic constipation or previous fecal impaction.

Adverse effects (ADRs)

• Frequent (>1/10): Diarrhea (preparations with excess magnesium) or marked constipation (preparations with excess aluminum).
• Uncommon / Rare: Severe hypophosphatemia in chronic use, manifested by extreme muscle weakness and osteomalacia.
• Milk-Alkali Syndrome (with Calcium Carbonate): Transient hypercalcemia, moderate metabolic alkalosis and secondary acute renal failure. It occurs due to massive and chronic consumption of calcium carbonate combined with milk or other dietary sources rich in calcium.

Drug interactions

• Direct Chemical Chelation: Free polyvalent cations (Al³⁺, Mg²⁺, Ca²⁺) act as chelators and irreversibly insolubilize multiple drugs in the gastrointestinal lumen: tetracyclines, quinolones (ciprofloxacin), levothyroxine, iron salts and digoxin. Golden rule: Administer the antacid at least 2 hours after these medications.
• Due to alteration of urinary pH: The alkalinization of urine induced by the absorption of calcium carbonate can reduce the excretion and raise plasma levels of basic drugs (quinidine, amphetamines) and increase the excretion of weak acids (salicylates).

Use in Pregnancy

They are considered safe in low and intermittent doses during pregnancy for the symptomatic management of heartburn in the third trimester (preferably compounds that combine aluminum and magnesium). Prolonged or high-dose use of calcium carbonate should be avoided due to the risk of subsequent fetal hypercalcemia and compensatory hypocalcemia.