Antacids

Antacids are a group of drugs that have been on the market for many years. They were initially first-line defense against peptic ulcer disease; however, the discovery of proton pump inhibitors revolutionized the treatment of peptic ulcer disease. Currently, antacid use is restricted to the relief of mild intermittent gastroesophageal reflux disease (GERD) associated heartburn.[1] The estimated prevalence of heartburn at least once per week in North America ranges from 18% to 28%, with 25% adults reporting heartburn daily.[2][3][4][5]

Antacids are medications that do not require a prescription; in other words, they are self-prescribed. Antacids are a combination of various compounds with various salts of calcium, magnesium, and aluminum as the active ingredients. The antacids act by neutralizing the acid in the stomach and by inhibiting pepsin, which is a proteolytic enzyme. Each of these cationic salts has a characteristic pharmacological property that determines its clinical use. Antacids have therapeutic use for the following[6]:

• Heartburn symptoms in GERD
• Duodenal and gastric ulcers
• Stress gastritis
• Pancreatic insufficiency
• Non-ulcer dyspepsia
• Diarrhea caused by bile-acid
• Biliary reflux
• Constipation
• Osteoporosis
• Urinary alkalinization 
• Phosphate binding in chronic renal failure

The antacids reduce the acid reaching the duodenum by neutralizing the acid present in the stomach. The main objectives are:

• Alleviating pain
• Relieving pylorospasms
• Avoid digestion and corrosion by acid chyme

The salts' mechanism of neutralization of acid varies, and each salt has a different mechanism with the ultimate goal of acid neutralization.

Aluminum Hydroxide

The formulation of aluminum hydrochloride and water results in the neutralization of the acid in the stomach. It is also known to inhibit pepsin activity.[7] Aluminum hydroxide is complexed with a sulfated polysaccharide sucrose octasulfate to form sucralfate. This complex does not have a significant buffering action against the acid or has no effect on the pepsin secretion and does not alter the gastric acid production in any way.[8][9] Nevertheless, it is known to heal chronic ulcers and prevent acute mucosal damage induced chemically by reducing access to pepsin and acid. Sucralfate, like its aluminum hydroxide component, is known to stimulate angiogenesis and granulation tissue formation.[8]

Aluminum hydroxide is also useful in hyperphosphatemia due to its ability to bind phosphate in the gastrointestinal (GI) tract and subsequently prevent the absorption of phosphate.[10]

Calcium Salts

Calcium salts neutralize gastric acidity resulting in increased gastric and duodenal bulb pH; they additionally inhibit the proteolytic activity of pepsin if the pH is greater than 4 and increase lower esophageal sphincter tone. The calcium released from calcium carbonate is known to increase peristalsis in the esophagus, pushing the acid into the stomach and provide relief from symptoms of heartburn. The calcium salts also form combined insoluble compounds with dietary phosphate and prevent the absorption of later.[11]

The acid-neutralizing mechanism of the antacids is well understood, as mentioned above. In addition to this, other mechanisms add to the ulcer healing properties of this class of drugs. The exact mechanism is still unclear, but it is believed to be a combination of[12][7]:

• Ability to promote angiogenesis
• Bind to bile acids
• Inhibit peptic activity
• Suppress Helicobacter pylori growth

The dose for antacids depends upon the age of the patient, the purpose of administration (neutralization of acid or off-label use), and the presence of other comorbidities like renal or hepatic impairment. As all the forms of these medications are available as over the counter medication, the dosing recommendation varies by product/and or manufacturer. 

 Aluminum Hydroxide (Antacid) 

• Oral: Usually taken daily after meals and at bedtime at a dose of  640 mg up to 5 to 6 times a day with a maximum dose of 3840 mg per 24 hours.
• Suspension  The dose for suspension form is 320 mg/5 mL (473 mL). The suspension is to be shaken before use and is to be followed by water.

Hyperphosphatemia

• Oral:  Use is reserved for patients with serum phosphorus levels greater than 7 mg/dl. It is to be taken with meals at a dose of 300  to 600 mg three times a day, with use limited to a short period (4 weeks).[13]

Calcium Carbonate (Antacid)

It is used up to a maximum dose of 8000 mg per day up to 2 weeks with 1 to 4 tablets for symptomatic relief.

Hyperphosphatemia

The total dose is not to exceed 2000 mg per day.[13]

Pregnancy and Breastfeeding

Antacids containing aluminum salts are safe to be used in pregnant women as well as for women during labor for aspiration prophylaxis.  The information regarding the use of aluminum-containing antacids in breastfeeding females has not been studied, but aluminum is known to be endogenous to breast milk.[14][15] In the case of calcium-containing antacids, excessive use is to be avoided in pregnant women as calcium crosses the placenta. The amount of calcium reaching the fetus is dependent on the physiological changes in the mother. Maternal calcium intake also affects the amount of calcium excreted in breast milk; the currently prevailing opinion is that the use of calcium-containing antacids is safe during breastfeeding.[16]

Adverse effects are prominent in the infant and the elderly populations. The chronic use of antacids in this population is not a recommendation due to safety concerns.

Aluminum Hydroxide

Aluminum use is associated with an increased risk of toxicity in individuals with renal failure and infants. It presents as[17][18][19][20]:

• Osteopenia
• Microcytic anemia
• Neurotoxicity
• Osteomalacia
• Constipation 
• Fecal impaction
• Nausea
• Vomiting
• Abdominal cramps
• Hypomagnesemia
• Hypophosphatemia

Calcium Carbonate

The adverse reactions often seen with this  group of antacids are[20][21]:

• Abdominal pain
• Anorexia
• Constipation
• Acid rebound
• Nausea
• Vomiting
• Flatulence
• Xerostomia
• Headache
• Hypercalcemia
• Hypophosphatemia
• Milk-alkali syndrome

The absolute contraindication is hypersensitivity to any component of the formulation. Also, antacid agents require caution in patients with:

• Renal  failure
• Heart failure
• Edema 
• Cirrhosis
• Low-sodium diets
• Uremia
• GI hemorrhages
• Hyperparathyroidism
• Renal calculus
• Achlorhydria