ATC Class:A02A

VA Class:GA209

AHFS Class:

• Antacids and Adsorbents 56:04

Generic Name(s):

• Aluminum Carbonate, Basic

• Aluminum Hydroxide

• Calcium Carbonate, Precipitated

• Dihydroxyaluminum Aminoacetate

• Dihydroxyaluminum Sodium Carbonate

• Magaldrate

• Magnesium Carbonate

• Magnesium Hydroxide

• Magnesium Oxide

• Magnesium Trisilicate

• Potassium Bicarbonate

• Sodium Bicarbonate

Antacids are inorganic salts that dissolve in acid gastric secretions releasing anions that partially neutralize gastric hydrochloric acid.

Antacids are used as an adjunct to other drugs for the relief of peptic ulcer pain and to promote the healing of peptic ulcers. Antacids also are used for the relief of esophageal reflux, acid indigestion, heartburn, dyspepsia, and sour stomach; for the prevention of stress ulceration and GI bleeding; to reduce the risk associated with gastric aspiration; and for the management of hyperphosphatemia.

Considerations in Choosing an Antacid

The choice of a specific antacid preparation depends on palatability, cost, adverse effects, acid neutralizing capacity, the sodium content of the antacid, and the patient's renal and cardiovascular function. Because of its high sodium content, sodium bicarbonate generally is used only for occasional heartburn or indigestion and not for chronic high-dose management of peptic ulcer disease. The role of calcium carbonate in the management of peptic ulcers is controversial because this antacid may cause acid rebound, which is especially important when the drug is administered at bedtime. Most clinicians believe that calcium carbonate should not be used in the management of peptic ulcers. However, some clinicians postulate that frequent administration of calcium carbonate may ameliorate acid rebound and reduce the clinical importance of gastric hypersecretion and believe that calcium carbonate is useful because it has a rapid onset of action, high acid neutralizing capacity, and a prolonged effect and is relatively inexpensive. Magnesium and/or aluminum antacids are the most commonly used and are often administered concurrently or in commercially available combinations to control the frequency and consistency of bowel movements. In any antacid combination product, each active antacid ingredient must contribute at least 25% of the in vitro acid neutralizing capacity. With administration of fixed combinations, ideal regulation of bowel function is seldom achieved, and patients should be taught to supplement their antacid therapy with appropriate doses of magnesium, calcium, or aluminum antacids to regulate bowel function.

Fixed combinations of antacids and histamine H₂-receptor antagonists can be used for relief of occasional symptoms of heartburn (pyrosis) associated with acid indigestion (hyperchlorhydria) and sour stomach, with the antacid providing intital rapid relief and the histamine H₂-receptor antagonist providing more prolonged relief.

Fixed combinations of antacids with nonantacid laxatives are rational only if the laxative is used to counteract the constipating effect of the antacid. Antacid combinations containing analgesics or simethicone should be administered only when concurrent symptoms require the effects of both an antacid and the nonantacid drug. However, fixed combinations of antacids and analgesics are not indicated for the management of peptic ulcers. Antacid combinations containing an anticholinergic, sedative-hypnotic, antiemetic, antipepsin, or proteolytic agents, bile, or bile salts are irrational, unsafe, and ineffective. Optimal use of antacids and anticholinergics or sedative-hypnotics requires that the dosage of each drug be adjusted by administering each drug separately. Bismuth salts and milk have no appreciable acid neutralizing activity.

Peptic Ulcers

Few well-designed clinical studies are available demonstrating the efficacy or inefficacy of antacids in the healing of peptic ulcers or for the relief of peptic ulcer pain. However, most clinicians believe that based upon the ability of antacids to increase gastric pH these drugs are useful in the management of peptic ulcers. In one well-controlled 4-week trial in outpatients, placebo was compared with 1- and 3-hour postprandial and bedtime administration of a suspension containing magnesium and aluminum hydroxides and simethicone (about 144 mEq of acid neutralizing capacity per dose); the antacid regimen was more effective than placebo in healing duodenal ulcer craters (endoscopically proven), but the antacid was no more effective than placebo in relieving ulcer pain.

In another study in outpatients with gastric or duodenal ulcers, calcium carbonate (about 8.2 mEq of acid neutralizing capacity) in tablet form administered every hour while the patient was awake and as necessary for abdominal discomfort produced a greater incidence of radiologically confirmed healing and pain relief in patients with gastric ulcers but not in those with duodenal ulcers after 30 days as compared with placebo. In a third well-controlled 3-week trial in hospitalized gastric ulcer patients, placebo was compared to administration of 30 mL of a suspension containing magnesium and aluminum hydroxides and simethicone (acid neutralizing capacity not specified) every 2 hours while the patient was awake; gastric ulcer healing and pain relief were not different in antacid-treated and placebo-treated patients. In a 5-day clinical study, 15 mL of an antacid (30 mEq of acid neutralizing capacity per dose) was alternately administered every 30 minutes with placebo as needed to relieve duodenal ulcer pain; antacid was not different from placebo. In the same study, a single 30-mL dose of the antacid was not more effective than placebo in relieving duodenal ulcer pain.

In one well-controlled study, 4 weeks of oral therapy with 1.2 g of cimetidine daily was compared to that with 1- and 3-hour postprandial and bedtime administration of magnesium and aluminum hydroxides antacid suspension (about 123 mEq of acid neutralizing capacity per dose); cimetidine and antacid did not differ significantly (64 vs 52%) in healing of duodenal ulcer craters and erosions or pain relief. Well-controlled clinical studies are not available comparing the efficacy of anticholinergic agents to antacids in the management of peptic ulcers.

Current epidemiologic and clinical evidence supports a strong association between gastric infection with Helicobacter pylori and the pathogenesis of duodenal and gastric ulcers;200,201,208,220,221,233,235,238,240,242,243,244,248,249,250,251,252,253 long-term H. pylori infection also has been implicated as a risk factor for gastric cancer.201,208,209,210,211,212,213,214,215,216,217,220,221,234 For additional information on the association of this infection with these and other GI conditions, see Helicobacter pylori infection, under Uses, in Clarithromycin 8:12.12.92.

Conventional antiulcer therapy with antacids, H₂-receptor antagonists, proton-pump inhibitors, and/or sucralfate heals ulcers but generally is ineffective in eradicating H. pylori , and such therapy is associated with a high rate of ulcer recurrence (e.g., 60-100% per year).200,220,234,238,242,243,252 The American College of Gastroenterology (ACG), the National Institutes of Health (NIH), and most clinicians currently recommend that all patients with initial or recurrent duodenal or gastric ulcer and documented H. pylori infection receive anti-infective therapy for treatment of the infection.228,234,242,243,244 Although 3-drug regimens consisting of a bismuth salt (e.g., bismuth subsalicylate) and 2 anti-infective agents (e.g., tetracycline or amoxicillin plus metronidazole) administered for 10-14 days have been effective in eradicating the infection, resolving associated gastritis, healing peptic ulcer, and preventing ulcer recurrence in many patients with H. pylori -associated peptic ulcer disease,200,201,202,218,220,221,223,234,235,236,237,239,240,241,242,243,244,245,247,251,253,254,255,256,257 current evidence principally from studies in Europe suggests that 1 week of such therapy provides comparable H. pylori eradication rates.234,243,244 Other regimens that combine one or more anti-infective agents (e.g., clarithromycin, amoxicillin) with a bismuth salt and/or an antisecretory agent (e.g., omeprazole, lansoprazole, H₂-receptor antagonist) also have been used successfully for H. pylori eradication,200,201,202,203,204,205,206,207,218,219,220,221,222,223,227,230,233,234,244,246,259,260,261,262,263,264 and the choice of a particular regimen should be based on the rapidly evolving data on optimal therapy, including consideration of the patient's prior exposure to anti-infective agents, the local prevalence of resistance, patient compliance, and cost of therapy.228,234,243,257,258,259

Current evidence suggests that inclusion of a proton-pump inhibitor (e.g., omeprazole, lansoprazole) in anti- H. pylori regimens containing 2 anti-infectives enhances effectiveness, and limited data suggest that such regimens retain good efficacy despite imidazole (e.g., metronidazole) resistance.234,243,260 Therefore, the ACG and many clinicians234,245,246 currently recommend 1 week of therapy with a proton-pump inhibitor and 2 anti-infective agents (usually clarithromycin and amoxicillin or metronidazole), or a 3-drug, bismuth-based regimen (e.g., bismuth-metronidazole-tetracycline) concomitantly with a proton-pump inhibitor, for treatment of H. pylori infection.234,246,259 For a more complete discussion of H. pylori infection, including details about the efficacy of various regimens and rationale for drug selection, see Helicobacter pylori Infection, under Uses, in Clarithromycin 8:12.12.92.

Acid Indigestion

Although the efficacy of antacids for the relief of acid indigestion, heartburn, sour stomach, and pressure and/or bloating (commonly referred as gas), generally has not been established systematically by well-designed studies, most experts believe that, since these symptoms may be caused by gastric acid, antacids are probably useful.267

Gastroesophageal Reflux

Antacids also may be useful to increase gastric pH and to increase lower esophageal sphincter pressure in the management of esophageal reflux. The ACG states that antacids and antirefluxants such as alginic acid are more effective than placebo in relieving symptoms of heartburn induced by a meal, and are useful for self-medication as initial therapy for milder forms of gastroesophageal reflux disease (GERD). However, suppression of gastric acid secretion with a proton-pump inhibitor or histamine H₂- receptor antagonist to control symptoms and prevent complications of the disease is considered by the ACG to be the principal therapeutic goal in the management of GERD. Other measures such as avoidance of constrictive clothing, treatment of obesity, reducing meal size and dietary fat intake, avoidance of foods that increase reflux, avoiding recumbency after meals, and elevating the head of the bed should be initiated and continued throughout the course of treatment. For further information on the treatment of GERD, see Uses: Gastroesophageal Reflux, in Omeprazole 56:28.36.

Upper GI Bleeding

Antacids may be effective in the prevention of stress ulceration and GI bleeding. In one randomized controlled study in critically ill patients, antacids administered prophylactically to maintain gastric pH above 3.5 decreased the incidence of acute GI bleeding.

Gastric Aspirations

Antacids have been administered prophylactically as an adjunct to reduce the risk of gastric acid aspiration in patients undergoing cesarean section or emergency surgery.

Hyperphosphatemia

The hypophosphatemic effect of aluminum-containing antacids (except aluminum phosphate) has been used in conjunction with a low phosphate diet in the management of calcinosis universalis, in hyperparathyroidism secondary to chronic hemodialysis, and to prevent recurrent phosphatic renal calculi. Since aluminum carbonate reportedly binds phosphate more than does aluminum hydroxide, aluminum carbonate is generally preferred.

Calcium Replacement

For the use of calcium carbonate as replacement therapy, see Calcium Salts 40:12. For the use of magnesium preparations as laxatives, see the Cathartics and Laxatives General Statement 56:12. For the use of sodium bicarbonate as an alkalinizing agent, see Sodium Bicarbonate 40:08.

Antacids are administered orally. The dose of antacids should be expressed in terms of mEq of acid neutralizing capacity. Dose and frequency of administration depend on the acid secretory rate of the stomach, gastric emptying time, and the disorder being treated. The duration of action of antacids is determined principally by gastric emptying time. In fasting subjects, antacids have a duration of action of 20-60 minutes. However, if the drugs are administered 1 hour after meals, acid neutralizing effects may persist up to 3 hours. Sodium bicarbonate generally has a shorter duration of action than other antacids. Antacids should be used for longer than 2-week periods only under the management of a physician and as part of a carefully planned therapeutic regimen.

There is considerable variation in in vivo acid neutralizing capacity of equal volumes of different antacids and antacid products. Since suspensions are more rapidly and effectively solubilized than powders or tablets, antacid suspensions have a greater ability to react with and neutralize gastric acid. Antacid suspensions have a smaller particle size than do tablets and drying of antacid suspensions to prepare powders and tablets causes substantial loss of ability to neutralize acid. In general, an antacid suspension is preferable to a tablet or powder; tablets should be reserved for chronic use in patients who refuse suspensions because they are inconvenient or unpalatable. Tablets should be thoroughly chewed before swallowing.

The US Food and Drug Administration (FDA) requires that antacids have a minimum in vitro acid neutralizing capacity of 5 mEq per dose and that antacid labeling contain the in vitro acid neutralizing capacity; however, this FDA in vitro test does not correlate with in vivo acid neutralizing capacity.

For peptic ulcer disease, dosages of antacids are empirical and various antacid dosages have been used. In patients with uncomplicated duodenal ulcers or gastric ulcers, an antacid is administered 1 and 3 hours postprandially and at bedtime. In patients with duodenal ulcers, antacids are usually given for 4-6 weeks, and in patients with gastric ulcers, antacids are administered until healing is complete. If symptoms of duodenal ulcer recur, some clinicians recommend that antacids be administered 1 and 3 hours postprandially and at bedtime for 1 week and, if pain is relieved, less frequently for an additional 1-2 weeks; these patients should consult their physicians if pain worsens or is not relieved after the first week of therapy. Additional doses of antacids may be administered to relieve ulcer pain which occurs between regularly scheduled doses.

For the acute management of moderate or severe esophageal reflux, an antacid suspension is administered every hour; if symptoms persist, antacids may be given every 30 minutes. For long-term therapy of esophageal reflux, antacids are administered 1 and 3 hours postprandially and at bedtime and whenever symptoms recur.

In the management of GI bleeding and stress ulceration, antacids are usually administered every hour and, for GI bleeding, the antacid dosage should be titrated to maintain the nasogastric aspirate above pH 3.5. For severe symptoms, antacid suspensions may be diluted with water or milk and given by continuous intragastric infusion.

To reduce the risk of anesthesia-induced gastric acid aspiration, an antacid suspension has been given 30 minutes before anesthesia.

In conjunction with dietary phosphate restriction in the management of hyperphosphatemia, 30-40 mL of aluminum hydroxide or aluminum carbonate suspension is administered 3 or 4 times daily.

Precautions and Contraindications

Most antacids contain sodium as an impurity, and antacid products must be labeled with their sodium content if they contain more than 0.2 mEq of sodium per dose. Sodium bicarbonate is contraindicated and use of other sodium-containing antacids should be restricted in patients on low-sodium diets and in those with congestive heart failure, renal failure, edema, or cirrhosis. Antacid products containing more than 25 mEq of potassium in the recommended daily dosage should be used cautiously in patients with renal disease and only under the supervision of a physician.

Since antacids may alter the absorption of certain concomitantly administered oral drugs, patients taking oral drugs should be advised to consult their physician or other health professional before taking concomitant antacids. (See Drug Interactions.)

The most common adverse effects associated with prolonged administration of antacids are constipation and diarrhea. Although fixed-combination antacid products are frequently administered to balance the laxative and cathartic effects of each, bowel function must often be regulated by administering supplemental doses of an antacid with constipating (i.e., aluminum salt) or laxative (i.e., magnesium salt) action.

Some commercially available antacids contain the dye tartrazine (FD&C yellow No. 5), which may cause allergic reactions including bronchial asthma in susceptible individuals. Although the incidence of tartrazine sensitivity is low, it frequently occurs in patients who are sensitive to aspirin. Individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine should be warned that some antacids may contain aspartame, which is metabolized in the GI tract to phenylalanine following oral administration.

Serious medication errors have been reported to the US Food and Drug Administration (FDA) in which consumers used Maalox^® Total Relief (bismuth subsalicylate) when they intended to use traditional Maalox^® liquid antacid products containing aluminum hydroxide, magnesium hydroxide, and simethicone (e.g., Maalox^® Advanced Regular Strength, Maalox^® Advanced Maximum Strength).266,267,268 Because of the potential for serious adverse effects associated with accidental use of bismuth subsalicylate (which is chemically related to aspirin), the manufacturer of Maalox^® Total Relief initially agreed to change the trade name of the product to one that did not include “Maalox”; however, the manufacturer instead discontinued the bismuth subsalicylate preparation in the summer of 2010.267,269

Aluminum Antacids

The most frequent adverse effect of aluminum antacids is constipation. Decreased bowel motility, dehydration, or fluid restriction may predispose patients to intestinal obstruction. Hemorrhoids and fissures or fecal impaction may occur.

Long-term administration of aluminum antacids in patients with renal failure or chronic renal failure may result in hyperaluminemia since small amounts of aluminum are absorbed from the GI tract and excretion of aluminum is decreased in patients with renal failure. Absorbed aluminum becomes bound to serum proteins (e.g., albumin, transferrin) and therefore is not easily dialyzed; aluminum may then accumulate in bones, lungs, and nerve tissue. Aluminum accumulation in the CNS may be the cause of dialysis encephalopathy, while aluminum accumulation in the bones may result in or worsen dialysis osteomalacia. Dialysis dementia also may occur in patients with renal failure receiving long-term aluminum antacid therapy for hyperphosphatemia. Several cases of dialysis encephalopathy have been associated with increased aluminum concentrations in the dialysate water. Aluminum intoxication with severe osteomalacia and extensive aluminum deposition at the junction between calcified and noncalcified bone has been reported in several young children who were receiving large dosages of aluminum hydroxide for the management of hyperphosphatemia associated with azotemia; the children were not undergoing hemodialysis during aluminum hydroxide therapy.

Aluminum salts may cause phosphorus depletion which is generally negligible. However, with prolonged administration or large doses, hypophosphatemia may occur, especially in patients with inadequate dietary intake of phosphorus; hypercalciuria secondary to bone resorption and increased intestinal absorption of calcium results. This phosphorus depletion syndrome is characterized by anorexia, malaise, and muscle weakness, and prolonged aluminum antacid therapy may cause urinary calculi, osteomalacia, and osteoporosis. A low-phosphorus diet, diarrhea, excessive phosphorus losses from malabsorption, and restoration of renal function after a kidney transplant increase the likelihood of the syndrome. Serum phosphate concentrations should be monitored at monthly or bimonthly intervals in patients on maintenance hemodialysis who are receiving chronic aluminum antacid therapy.

Calcium Carbonate

The major limiting factor to the chronic use of calcium carbonate is gastric hypersecretion and acid rebound. Increased gastric acid secretion begins within 2 hours after administration of the drug and has occurred following a single 500-mg dose of calcium carbonate. In one study in peptic ulcer patients receiving large doses of calcium carbonate (500 mg/kg daily), hypercalcemia occurred in 14% of patients within 3 days of initiating therapy. Calcium carbonate may cause the milk-alkali syndrome which is characterized by hypercalcemia, metabolic alkalosis and, rarely, renal insufficiency; hypercalcemia may cause nausea, vomiting, anorexia, weakness, headache, dizziness, and change in mental status. Patients with renal impairment or dehydration and electrolyte imbalance are predisposed to developing the milk-alkali syndrome. Hypercalcemia has also been reported in chronic hemodialysis patients receiving calcium carbonate. Serum calcium concentrations should be monitored weekly and whenever symptoms of hypercalcemia occur in patients receiving large doses of calcium carbonate. Calcium carbonate reportedly causes constipation. Belching and flatulence may occur. When dietary phosphate is low, hypophosphatemia may occur.

Magnesium Antacids

Magnesium-containing antacids commonly cause a laxative effect and frequent administration of these antacids alone often cannot be tolerated; repeated doses cause diarrhea which may cause fluid and electrolyte imbalances. Chronic administration of magnesium trisilicate infrequently produces silica renal stones.

In patients with severe renal impairment, hypermagnesemia characterized by hypotension, nausea, vomiting, ECG changes, respiratory or mental depression, and coma has occurred after administration of magnesium-containing antacids. Magnesium-containing antacids should not be administered in patients with renal failure, and antacid products containing more than 50 mEq of magnesium in the recommended daily dosage should be used cautiously and only under the supervision of a physician who should monitor electrolytes in patients with renal disease.

Sodium Bicarbonate

Gastric distension and flatulence may occur with sodium bicarbonate preparations. Sodium bicarbonate, when given in large doses or in patients with renal insufficiency, may cause metabolic alkalosis. Chronic administration of bicarbonate with milk or calcium may cause the milk-alkali syndrome which is characterized by hypercalcemia, renal insufficiency, metabolic alkalosis, nausea, vomiting, headache, mental confusion, and anorexia. During the acute phase of the milk-alkali syndrome, the condition is reversible when the calcium and alkali are withdrawn. However, in patients with chronic milk-alkali syndrome, reduced renal function may persist even after calcium and alkali are discontinued. Patients with a salt-losing nephropathy have an increased risk of developing the milk-alkali syndrome.

The maximum daily dosage of sodium or bicarbonate is 200 mEq in patients younger than 60 years of age and 100 mEq in patients older than 60 years of age. Sodium bicarbonate is contraindicated for prolonged therapy because it may cause metabolic alkalosis or sodium overload.

All antacids potentially may increase or decrease the rate and/or extent of absorption of concomitantly administered oral drugs by changing GI transit time or by binding or chelating the drug. In vitro studies indicate that magnesium hydroxide or trisilicate has the greatest potential for drug binding and aluminum hydroxide and calcium carbonate are intermediate. Antacid-induced increases in GI pH may affect the disintegration, dissolution, solubility, or ionization of enteric-coated preparations and weakly acidic or basic drugs.

Simultaneous administration of aluminum-, calcium-, or magnesium-containing antacids with orally administered tetracyclines reduces the absorption of the tetracycline, probably because of chelation of these antacids by the tetracycline. Therefore, doses of tetracyclines should be spaced 1-2 hours from doses of antacids.

Concurrent administration of antacids and orally administered digoxin, indomethacin, or iron salts may decrease the absorption of these drugs. Doses of these drugs should be spaced as far apart as possible from doses of antacids. Concurrent administration of isoniazid and aluminum hydroxide gel may decrease the absorption of isoniazid; therefore, isoniazid should be administered at least 1 hour before aluminum-containing antacids. Absorption of buffered or enteric-coated aspirin is increased by simultaneous administration of antacids. Antacid-induced changes in urine pH increase urinary excretion and decrease blood concentrations of salicylates. Concurrent administration of dicumarol and an aluminum and magnesium hydroxides preparation reportedly increases the absorption of dicumarol; patients receiving antacids and oral anticoagulants should probably use warfarin rather than dicumarol. Concurrent administration of aluminum hydroxide and pseudoephedrine or diazepam increases the rate of absorption of the latter drugs. Administration of a magnesium and aluminum hydroxide preparation with chlordiazepoxide decreases the rate of chlordiazepoxide absorption. Administration of sodium bicarbonate with naproxen increases the rate of naproxen absorption, while concurrent administration of magnesium oxide or aluminum hydroxide with naproxen decreases the rate of naproxen absorption.

Antacid-induced increases in urine pH may decrease excretion of weakly basic drugs and increase excretion of weakly acidic drugs. Urinary excretion of amphetamines and quinidine are markedly decreased in patients whose urine is alkalinized with sodium bicarbonate and patients receiving these drugs concomitantly may have increased amphetamine or quinidine effects.

Pharmacology

The clinical use of antacids is based on their ability to increase the pH of gastric secretions. With usual doses, antacids generally do not increase and maintain gastric pH above 4-5. Although antacids do not neutralize all gastric acid, increasing gastric pH from 1.3 to 2.3 neutralizes 90% and increasing pH to 3.3 neutralizes 99% of gastric acid. Consequently, the amount of gastric acid back-diffusing through the gastric mucosa and the amount of acid reaching the duodenum is decreased. It is not known how much or for how long neutralization is required for optimal healing of peptic ulcers, but most clinicians believe that gastric pH should be maintained at about 3-3.5 for as many of the 24 hours as is possible. Antacids, in decreasing order of their ability to neutralize a given amount of acid, are calcium carbonate, sodium bicarbonate, magnesium salts, and aluminum salts. Magnesium hydroxide and aluminum hydroxide are the most potent magnesium and aluminum salts. Magnesium oxide has essentially the same acid neutralizing effect as magnesium hydroxide. Because magnesium trisilicate is slowly solubilized, it is a less effective buffer than magnesium hydroxide, carbonate, or phosphate.

Sodium bicarbonate rapidly reacts with hydrochloric acid to form sodium chloride, carbon dioxide, and water; excess bicarbonate that does not neutralize gastric acid rapidly empties into the small intestine and is absorbed. When sodium bicarbonate is given orally, gastric acid is neutralized by exogenous bicarbonate instead of intestinal bicarbonate. The net effect of administering sodium bicarbonate whether it reacts with gastric acid or reaches the small intestine is that all of a dose reaches the extracellular fluid. Mild metabolic alkalosis occurs; in patients with normal renal function, the kidneys excrete the excess sodium and bicarbonate ions and the urine becomes alkaline.

Antacids other than sodium bicarbonate neutralize gastric secretions but generally do not cause metabolic alkalosis, because the cation formed in the stomach is minimally absorbed and regains a basic anion in the small intestine. However, to the extent that the cation is absorbed and does not react with intestinal bicarbonate, the extracellular fluid receives a bicarbonate load; urinary pH is usually increased.

Calcium carbonate is slowly solubilized in the stomach and reacts with hydrochloric acid to form calcium chloride, carbon dioxide, and water. About 90% of the calcium chloride formed is converted to insoluble calcium salts (mainly calcium carbonate and to a lesser extent calcium phosphate) and calcium soaps in the small intestine and is not absorbed. When calcium carbonate is administered orally, a limited amount of calcium and intestinal bicarbonate are absorbed and hypercalcemia may occur. In some patients, metabolic alkalosis and the milk-alkali syndrome may occur. Calcium is excreted by the kidneys and hypercalciuria frequently occurs in patients receiving calcium carbonate.

Aluminum hydroxide or oxide is slowly solubilized in the stomach and reacts with hydrochloric acid to form aluminum chloride and water. In addition to forming aluminum chloride, dihydroxyaluminum sodium carbonate and aluminum carbonate form carbon dioxide, and aluminum phosphate forms phosphoric acid. About 17-30% of the aluminum chloride formed is absorbed and is rapidly excreted by the kidneys in patients with normal renal function. In the small intestine, aluminum chloride is rapidly converted to insoluble, poorly absorbed basic aluminum salts which are probably a mixture of hydrated aluminum oxide, oxyaluminum hydroxide, various basic aluminum carbonates, and aluminum soaps. Aluminum-containing antacids (except aluminum phosphate) also combine with dietary phosphate in the intestine forming insoluble, nonabsorbable aluminum phosphate which is excreted in the feces. If phosphate intake is limited in patients with normal renal function, aluminum antacids (except aluminum phosphate) decrease phosphate absorption and hypophosphatemia and hypophosphaturia occur; calcium absorption is increased. In vitro studies indicate that aluminum hydroxide binds bile salts with an affinity and capacity similar to that of cholestyramine; aluminum phosphate binds bile salts, but to a much lesser degree than does aluminum hydroxide.

Magnesium hydroxide rapidly reacts with hydrochloric acid to form magnesium chloride and water. In addition, magnesium carbonate forms carbon dioxide. Magnesium trisilicate is slowly solubilized and reacts with hydrochloric acid to form magnesium chloride, silicon dioxide, and water. About 15-30% of the magnesium chloride formed is absorbed and is rapidly excreted by the kidneys in patients with normal renal function. Any magnesium hydroxide that is not converted to magnesium chloride in the stomach is presumably subsequently changed in the small intestine to soluble but poorly absorbed salts. Magnesium hydroxide binds bile salts in vitro, but to a much lesser extent than does aluminum hydroxide. Magnesium-containing antacids have a laxative action. (See Saline Laxatives 56:12.)

Antacid-induced increases in gastric pH inhibit the proteolytic action of pepsin, an effect which is particularly important in patients with peptic ulcer disease. The optimum pH for pepsin activity is 1.5-2.5 and progressive inhibition occurs as gastric pH increases; above pH 4, the proteolytic activity of pepsin is minimal. Although some investigators have reported that aluminum- or calcium-containing antacids adsorb pepsin and thus have direct antipepsin effects, one study in which pH was controlled indicates that the antipepsin effects of antacids are due entirely to increased pH. Antacids do not coat the lining of peptic ulcers or the GI mucosa. Although some antacids, such as aluminum hydroxide, have astringent and demulcent actions, these effects are probably not important in the treatment of peptic ulcers.

In patients with peptic ulcers, antacids increase serum gastrin concentrations probably by increasing gastric pH. Single dose studies indicate that calcium carbonate causes gastric acid hypersecretion and acid rebound probably as a result of a local effect of calcium on gastrin-producing cells. Other antacids also increase secretion of gastric acid but do not cause acid rebound after the antacid has left the stomach. Aluminum-containing antacids delay gastric emptying time, an effect that is related to the concentration of aluminum in the stomach.

Chemistry and Stability

Chemistry

Antacids are inorganic salts that dissolve in acid gastric secretions releasing anions that partially neutralize gastric hydrochloric acid.

Aluminum Antacids

Aluminum Carbonate

Dried basic aluminum carbonate gel occurs as a white powder and is insoluble in water and in alcohol. Aluminum carbonate suspension is a white, creamy, thixotropic gel and contains the equivalent of 4.9-5.3% aluminum oxide and not less than 2.4% carbon dioxide.

Aluminum Hydroxide

Dried aluminum hydroxide gel occurs as a white, odorless, tasteless, amorphous powder and is insoluble in water and in alcohol. The powder contains 50-57.5% aluminum oxide as the hydrated oxide and may contain varying amounts of aluminum carbonate and bicarbonate. Tablets of dried aluminum hydroxide gel contain 62-72% of the labeled amount of aluminum hydroxide as aluminum oxide. Aluminum hydroxide gel is a white, viscous suspension. The suspension contains the equivalent of 3.6-4.4% w/w aluminum oxide in the form of aluminum hydroxide and hydrated oxide. The suspension also may contain basic aluminum carbonate and bicarbonate, flavoring agents, sweeteners and antimicrobial agents. Aluminum hydroxide gel suspension should not be frozen.

Aluminum Phosphate

Aluminum phosphate gel is a white, viscous suspension. The suspension contains 4-5% w/w aluminum phosphate and may contain preservatives.

Dihydroxyaluminum Aminoacetate

Dihydroxyaluminum aminoacetate occurs as a white, odorless powder that has a faintly sweet taste and is insoluble in water. The powder contains 35.5-38.5% aluminum oxide calculated on a dried basis and may contain small amounts of aluminum oxide or aminoacetic acid.

Calcium Carbonate

Precipitated calcium carbonate occurs as a fine, white, odorless, tasteless, microcrystalline powder and is practically insoluble in water and insoluble in alcohol.

Magnesium Antacids

Magnesium Carbonate

Magnesium carbonate occurs as light, white, friable masses (heavy magnesium carbonate) or as a bulky, white powder (light magnesium carbonate). The drug is odorless and is practically insoluble in water and insoluble in alcohol. Magnesium carbonate contains the equivalent of 40-43.5% magnesium oxide.

Magnesium Hydroxide

Magnesium hydroxide occurs as a bulky, white powder which is practically insoluble in water and in alcohol. Milk of Magnesia, Double-strength Milk of Magnesia, and Triple-strength Milk of Magnesia are suspensions containing 80, 160, and 240 mg of magnesium hydroxide per mL, respectively. Milk of Magnesia USP occurs as a white, opaque, more or less viscous suspension.

Magnesium Oxide

Magnesium oxide occurs as a very bulky, white, powder (light magnesium oxide) or as a relatively dense, white powder (heavy magnesium oxide). Magnesium oxide is practically insoluble in water and insoluble in alcohol. Light magnesium oxide suspends more readily in liquids than does heavy magnesium oxide.

Magnesium Trisilicate

Magnesium trisilicate, a compound of magnesium oxide and silicon dioxide, occurs as a fine, white, odorless, tasteless powder free from grittiness. The powder is insoluble in water and in alcohol. The powder contains not less than 20% magnesium oxide and not less than 45% silicon dioxide.

Miscellaneous Antacids

Dihydroxyaluminum Sodium Carbonate

Dihydroxyaluminum sodium carbonate is a single molecule that reportedly combines the antacid properties of aluminum hydroxide and sodium bicarbonate. Dihydroxyaluminum sodium carbonate occurs as a fine, white, odorless powder that is slightly hygroscopic at room temperature. The powder is practically insoluble in water and contains the equivalent of 34.8-38.2% aluminum oxide.

Sodium Bicarbonate

Sodium bicarbonate occurs as a white, crystalline powder with a saline and slightly alkaline taste. The drug is soluble in water and insoluble in alcohol. Aqueous solutions of sodium bicarbonate, when freshly prepared, are alkaline to litmus; alkalinity increases as the solutions stand, are agitated, or are heated.

Magaldrate

Magaldrate, a chemical combination of aluminum and magnesium hydroxides and sulfate, occurs as a white, odorless, crystalline powder and is insoluble in water and in alcohol. The powder contains the equivalent of 34-46% magnesium oxide, the equivalent of 21-30% aluminum oxide, and 13.3-17.5% sulfur trioxide, calculated on the dried basis. Each gram of magaldrate in the oral suspension and tablets contains the equivalent of 340-460 mg of magnesium oxide and 210-300 mg of aluminum oxide.

Stability

Aluminum Antacids

Aluminum Hydroxide

Aluminum hydroxide gel suspension should not be frozen. On standing, small amounts of clear liquid may separate from aluminum hydroxide gel suspension.

Aluminum Phosphate

On standing, small amounts of water may separate from aluminum phosphate gel suspension.

Magnesium Antacids

Magnesium Hydroxide

Milk of Magnesia USP should preferably be stored at less than 35°C; however, freezing should be avoided. On standing, varying proportions of water usually separate from Milk of Magnesia USP suspension.

Magnesium Oxide

Magnesium oxide readily absorbs water and carbon dioxide when exposed to air and, in the presence of a limited amount of water, forms a cement-like mass. In water, magnesium oxide is converted to magnesium hydroxide.

Only references cited for selected revisions after 1984 are available electronically.

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