HEALTH AND MEDICAL PRODUCTS:ANTACIDS

ANTACIDS

The stomach, a J-shaped organ located between the esophagus and the small intestine within the gastrointestinal tract, performs many important body functions, including bulk storage of ingested food, mechanical breakdown of ingested food, production of a specialized glycoprotein called intrinsic factor that allows the body to absorb vitamin B12, and disruption of chemical bonds within food material (e.g., proteins) through the action of acids and enzymes. The inner mucosal tissue layer of the stomach contains many deep gastric pits, which in turn lead into the gastric glands that collectively produce stomach secretions called gastric juice. Parietal cells, specialized secretory cells, are especially common along the proximal portions of each gastric gland. These cells secrete intrinsic factor and hydrochloric acid (HCl). The secretory activities (i.e., release of HCl) of parietal cells maintain the inner stomach contents at a relatively low pH between 1.5 and 2.0, whereas normal body extracellular fluid pH ranges between 7.35 and 7.45 (relatively neutral). The acidic pH of gastric juices within the stomach allows for the destruction of ingested potentially harmful microorganisms within food, the denaturing of pro- teins within food, the inactivation of food enzymes, the destruction of ingested plant cell wall materials and meat connective tissues, and the proper activation and function of pepsin, a protein-digesting enzyme secreted by other cells (chief cells) within the gastric glands.

“Indigestion” refers to any number of gastrointestinal complaints that can include excess gas production and upset/sour stomach. “Heart- burn” is a symptom; it refers to a burning sensation that is often caused by the regurgitation of stomach acid from the stomach, up through the cardiac sphincter (the ring of smooth muscle that normally regulates the movement of food from the esophagus to the stomach), into the esophagus (the muscular tube that connects the stomach to the throat), which is positioned within the chest cavity. The sensation of heartburn is often the result of a medical condition known as acid reflux; it generally in- cludes symptoms such as a burning or discomfort behind the chest that moves upward toward the throat and tends to worsen after eating, while lying down or bending over, a bitter or sour taste of acid at the back of the throat, and/or frequent burping or bloating. In some cases, such ex- cess acid production may lead to a condition called gastritis, inflamma- tion of the underlying layers of stomach wall tissue. Persistent damage to this tissue may promote the formation of peptic ulcers, erosions of the esophagus and/or stomach wall. A common predisposing factor for ulcer formation is hypersecretion of HCl by the parietal cells lining the stom- ach (also called hyperchlorhydria). Antacids/acid blockers are technically used to treat hyperchlorhydria.

Over-the-counter oral antacids/acid blockers are a family of different drugs that include antacids, histamine receptor-2 blockers, and proton pump inhibitors. Antacids help prevent damage to the inner mucosal tis- sue layer of the gastrointestinal tract (e.g., stomach, esophagus) by assist- ing in neutralizing excess highly acidic gastric juices. While mineral-based antacids have been in world use since the third century, the first commercial stomach antacid seltzer was manufactured in the United States by Captain I. Emerson in 1891. Modern antacids do not completely neutralize stomach acid, as this would compromise digestive processes and potentially cause “acid rebound,” in which additional HCl is secreted to counteract such a dramatic change in stomach pH. However, these drugs can increase the pH level within the stomach from approximately 2 to a more alkaline level between 3 and 4. This increase neutralizes nearly 99 percent of stomach acid and provides significant relief from minor heart- burn for many individuals. All of these products provide effective relief within a minute or less, and the duration of action is usually between ten minutes and two hours after treatment.

Most antacid products contain one or more of four active alkaline in- gredients: aluminum salts [e.g., aluminum hydroxide; Al(OH)3], magne- sium salts [e.g., magnesium carbonate; MgCO3 and magnesium hydroxide (milk of magnesia); Mg(OH)2], calcium carbonate (chalk; limestone; CaCO3), and sodium bicarbonate (baking soda; NaHCO3). Several ant- acids are formulated with combinations of magnesium and aluminum salts [e.g., magaldrate; AlMg(OH)5] to neutralize stomach acid, to de- crease the action of pepsin (a digestive enzyme), and to prevent deleteri- ous side effects, including constipation and diarrhea. In addition, many types of bismuth mineral salts (e.g., bismuth subsalicylate), which are multipurpose intestinal medicinal agents, are also used as antacids be- cause they increase alkaline secretion to counteract any acid production in the stomach. As an antiulcer agent, bismuth subsalicylate also coats and protects irritated and inflamed gastrointestinal lumen tissue.

Effervescent antacids are those products that contain sodium bicar- bonate and citric acid. These products give an effervescent action when dissolved in water because of the evolution of carbon dioxide (CO2) gas when sodium bicarbonate and citric acid react in a hydrated environ- ment. It has been suggested that the release of carbon dioxide by sodium bicarbonate during this reaction may provide relief from the discomfort of overeating by inducing belching, which aids in the expulsion of swallowed air. Sodium citrate, which is also produced in the reaction of so- dium bicarbonate and citric acid, may also accept hydrogen ions (H+) and revert back to citric acid. Thus, the sodium citrate, which is pro- duced when effervescent antacids are dissolved in water, also acts as a stomach acid-neutralizing antacid.

Some antacids contain additional active ingredients, including analge- sics (e.g., aspirin) to treat headaches and antigas/antibloating products (e.g., simethicone, magnesium trisilicate) to treat uncomfortable feelings often associated with heartburn as a result of overeating.

Histamine receptor-2 (H2) blockers include chemicals such as cimeti- dine (N-cyano-N'-methyl-N''-[2-[[(5-methyl-1H-imidazol-4-yl)methyl] thio]ethyl]guanidine; C10H16N6S), famotidine (3-[[[2-[(aminoiminomethyl) amino]-4-thiazolyl]methyl]thio]-N-(aminosulfonyl)propanimidamide; C8 H15N7O2S3), nizatidine (N-[2-[[[2-[(dimethylamino)methyl]-4-thiazolyl] methyl]thio]ethyl]-N '-methyl-2-nitro-1,1-ethenediamine; C12H21N5O2S2), and ranitidine (N-[2-[[[5-[(dimethylamino)methyl]-2-furanyl]methyl]

thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine; C13H22N4O3S). These four individual drugs act as histamine antagonists (antihistamines) by compet- itively inhibiting the binding of histamine at histamine H2 receptors. Such receptors are located in HCl-secreting parietal cells within the stomach and in the heart. Histamine (2-(4-imidazolyl)-ethyl-amine) is a chemical mediator produced by the decarboxylation of histidine by the enzyme histidine decarboxylase. Within the gastric glands of the stomach, specialized enteroendocrine cells called histaminocytes release histamine, which binds to H2 receptors and aids in the stimulation of HCl secretion by parietal cells. Oral H2 receptor blockers typically require at least thirty minutes to one hour to initiate gastric acid secretion inhibition but then usually provide heartburn relief for up to six hours after treatment. In ad- dition, these drugs are used in the management of peptic ulcers to allow for an increase in tissue healing and to prevent recurrences.

Proton pump inhibitors (PPIs) are a class of drugs that decrease the production of gastric acid by targeting structures located within the stomach parietal cells called proton pumps. Omeprazole (5-methoxy-2- [[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimida- zole; C17H19N3O3S) is an example of a chemically active ingredient found in oral over-the-counter PPI products. Histamine, the neurotransmitter acetylcholine, and the hormone gastrin all work through the proton pump to allow the parietal cells to produce HCl. This active transport (which requires energy in the form of adenosine triphosphate) proton pump moves hydrogen ions (H+) produced within the parietal cells into the stomach lumen and pumps potassium ions (K+) back into the pari- etal cell from the lumen. As hydrogen ions are secreted into the stomach lumen, a different active transport pump moves chloride ions (Cl-) into the lumen to maintain an electrical equilibrium (balance) within the stomach. However, PPIs prevent the H+/K+ pump from functioning; thus, the movement of H+ into the stomach lumen to form HCl is blocked. Overall, the onset of action of an oral PPI is approximately one hour after treatment. However, the duration of heartburn relief and inhibition of HCl production may extend for as long as sixteen hours.