Antiulcer drugs

Definition

Antiulcer drugs are a class of drugs, exclusive of the antibacterial agents, used to treat ulcers in the stomach and the upper part of the small intestine.

Purpose

Recurrent gastric and duodenal ulcers are caused by Helicobacter pylori infections, and are treated with combination treatments that incorporate antibiotic therapy with gastric acid suppression. Additionally, bismuth compounds have been used. The primary class of drugs used for gastric acid suppression are the proton pump inhibitors, omeprazole, lansoprazole, pantoprazole and rabeprazole. The H2 receptor blocking agents, cimetidine, famotidine, nizatidine, and ranitidine have been used for this purpose, but are now more widely used for maintenance therapy after treatment with the proton pump inhibitors. Sucralfate, which acts by forming a protective coating over the ulcerate lesion, is also used in ulcer treatment and may be appropriate for patients in whom other classes of drugs are not indicated, or those whose gastric ulcers are caused by non-steroidal anti-inflammatory drugs (NSAIDs) rather than H. pylori infections.

Description

The proton pump inhibitors block the secretion of gastric acid by the gastric parietal cells. The extent of inhibition of acid secretion is dose related. In some cases, gastric acid secretion is completely blocked for over 24 hours on a single dose. In addition to their role in treatment of gastric ulcers, the proton pump inhibitors are used to treat syndromes of excessive acid secretion (Zollinger-Ellison Syndrome) and gastroesophageal reflux disease (GERD).

Histamine H2 receptor blockers stop the action of histamine on the gastric parietal cells, inhibiting the secretion of gastric acid. These drugs are less effective than the proton pump inhibitors, but may achieve a 75-79% reduction in acid secretion. Higher rates of acid inhibition may be achieved when the drug is administered by the intravenous route. The H2 receptor blockers may also be used to treat heartburn and hypersecretory syndromes. When given before surgery, the H2 receptor blockers are useful in prevention of aspiration pneumonia.

Sucralfate (Carafate), a substituted sugar molecule with no nutritional value, does not inhibit gastric acid, but rather, reacts with existing stomach acid to form a thick coating that covers the surface of an ulcer, protecting the open area from further damage. A secondary effect is to act as an inhibitor of the digestive enzyme pepsin. Sucralfate does not bind to the normal stomach lining. The drug has been used for prevention of stress ulcers, the type seen in patients exposed to physical stress such as burns and surgery. It has no systemic effects.

Recommended dosage

The doses of the proton pump inhibitors and H2 receptor blockers vary depending on the drug and condition being treated. Consult individual references.

The dose of sucralfate for acute ulcer therapy is 1 gram four times a day. After the ulcer has healed, maintenance treatment may continue at 1 gram two times daily.

Precautions

The proton pump inhibitors are generally well tolerated, and the most common adverse effects are diarrhea, itching, skin rash, dizziness, and headache. Muscle aches and a higher than normal rate of respiratory infections are among the other adverse reactions reported. Omeprazole is classed as pregnancy category C due to an increased rate of fetal deaths in animal studies. The other drugs in this group are pregnancy category B. It is not known if these drugs are excreted in human milk, but because of reported adverse effects to infants in animal studies, it is recommended that proton pump inhibitors not be used by nursing mothers.

The H2 receptor blockers vary widely in their adverse effects. Although they are generally well tolerated, cimetidine may cause confusion in elderly patients, and has an antiandrogenic effect that may cause sexual dysfunction in males. Famotidine has been reported to cause headache in 4.7% of patients. Nizatidine is pregnancy category C, the others are schedule B. It is advisable that mothers not take H2 receptor blockers while nursing.

Sucralfate is well tolerated. It is poorly absorbed, and its most common side effect is constipation in 2% of patients. Diarrhea, nausea, vomiting, gastric discomfort, indigestion, flatulence, dry mouth, rash, pruritus (itching), back pain, headache, dizziness, sleepiness, and vertigo have been reported, as well as rare allergic responses. Because sucralfate releases small amounts of aluminum into the system, it should be used with caution in patients with renal insufficiency. Sucralfate is category B in pregnancy. There is no information available about its safety in breastfeeding.

Interactions

Proton pump inhibitors may increase the pH of the stomach. This will inactivate some antifungal drugs that require an acid medium for effectiveness, notable itraconazole and ketoconazole.

H2 receptor blocking agents have a large number of drug interactions. Consult individualized references.

Sucralfate should not be used with aluminum containing antacids, because of the risk of increased aluminum absorption. Sucralfate may inhibit absorption and reduce blood levels of anticoagulants, digoxin, quinidine, ketoconazole, quinolones, and phenytoin.

Key Terms

AntibioticMedicine used to treat infections.

EnzymeA type of protein, produced in the body, that brings about or speeds up chemical reactions.

Gastrointestinal tractThe stomach, small intestine and large intestine.

HypersecretoryExcessive production of a bodily secretion. The most common hypersecretory syndrome of the stomach is Zollinger-Ellison Syndrome, a syndrome consisting of fulminating intractable peptic ulcers, gastric hypersecretion and hyperacidity, and the occurrence of gastrinomas of the pancreatic cells of the islets of Langerhans.

InflammationPain, redness, swelling, and heat that usually develop in response to injury or illness.

MucousThick fluid produced by the moist membranes that line many body cavities and structures.

Nonsteroidal anti-inflammatory drug (NSAID)A type of medicine used to relieve pain, swelling, and other symptoms of inflammation, such as ibuprofen or ketoprofen.

Pregnancy category A system of classifying drugs according to their established risks for use during pregnancy. Category A: Controlled human studies have demonstrated no fetal risk. Category B: Animal studies indicate no fetal risk, but no human studies; or adverse effects in animals, but not in well-controlled human studies. Category C: No adequate human or animal studies; or adverse fetal effects in animal studies, but no available human data. Category D: Evidence of fetal risk, but benefits outweigh risks. Category X: Evidence of fetal risk. Risks outweigh any benefits.