New Research:
Overview:
Risk Factors Include:
A peptic ulcer is an open sore or raw area that tends to develop in one of two places:
In the U.S., duodenal ulcers are three times more common than gastric ulcers.

Ulcers average between one-quarter and one-half inch in diameter. They develop when digestive juices produced in the stomach, intestines, and digestive glands damage the lining of the stomach or duodenum.
The two important components of digestive juices are hydrochloric acid and the enzyme pepsin. Both substances are critical in the breakdown and digestion of starches, fats, and proteins in food. They play different roles in ulcers:
Fortunately, the body has a defense system to protect the stomach and intestine against these two powerful substances:
Disrupting any of these defense mechanisms makes the lining of the stomach and intestine susceptible to the actions of acid and pepsin, increasing the risk for ulcers.
In 1982, two Australian scientists identified H. pylori as the main cause of stomach ulcers. They showed that inflammation of the stomach, and stomach ulcers, result from an infection of the stomach caused by H. pylori bacteria. This discovery was so important that the researchers were awarded the Nobel Prize in Medicine in 2005. The bacteria appear to trigger ulcers in the following way:
Even if ulcers do not develop, H. pylori bacteria are considered to be a major cause of active chronic inflammation in the stomach (gastritis) and the upper part of the small intestine (duodenitis).
H. pylori are also strongly linked to stomach cancer and possibly other non-intestinal problems.
Factors that Trigger Ulcers in H. pylori Carriers. Only around 10 to 15% of people who are infected with H. pylori develop peptic ulcer disease. H. pylori infections, particularly in older people, may not always predict whether there are peptic ulcers. Other variables must also be present to actually trigger ulcers. These may include:
When H. pylori were first identified as the major cause of peptic ulcers, these bacteria were found in 90% of people with duodenal ulcers and in about 80% of people with gastric ulcers. As more people are being tested and treated for the bacteria, however, the rate of H. pylori- associated ulcers has declined. Currently, H. pylori are found in about 50% of people with peptic ulcer disease.
Some researchers now believe that duodenal ulcers are not caused by H. pylori, but that the presence of the bacteria simply delays healing. This fact, they say, may explain why up to half of acute duodenal perforation cases show no evidence of H. pylori, and why duodenal ulcers can come back even after H. pylori has been eradicated.
Long-term use of NSAIDs is the second most common cause of ulcers. More than 30 million people take prescription NSAIDs regularly, and more than 30 billion tablets of over-the-counter brands are sold each year in the U.S. alone. The most common NSAIDs are aspirin, ibuprofen (Advil, Motrin), and naproxen (Aleve, Naprosyn), although many others are available.
Patients with NSAID-caused ulcers should stop taking these drugs. However, patients who require these medications on a long-term basis can reduce their risk of ulcers by taking drugs in the proton pump inhibitor (PPI) group, such as omeprazole (Prilosec). Famotidine (Pepcid -- an H2 blocker) may protect people who are taking low-dose aspirin for cardiovascular prevention, at least in the short-term. However, PPIs provide much better protection.
There is no doubt that NSAIDs increase the risk of ulcers and gastrointestinal (GI) bleeding. The risk of bleeding continues for as long as a patient takes these drugs and may persist for about 1 year after stopping. Short courses of NSAIDs for temporary pain relief should not cause major problems, because the stomach has time to recover and repair any damage that has occurred.
Some NSAIDs pose greater risks than others for ulcers and bleeding. No NSAID, even an over-the-counter brand, should be used long-term without a doctor's supervision.
Certain drugs other than NSAIDs may aggravate ulcers. These include warfarin (Coumadin) -- an anticoagulant that increases the risk of bleeding, oral corticosteroids, some chemotherapy drugs, spironolactone, and niacin.
Bevacizumab, a drug used to treat colorectal cancer, may increase the risk of GI perforation. Although the benefits of bevacizumab outweigh the risks, GI perforation is very serious. If it occurs, patients must stop taking the drug.
Rarely, certain conditions may cause ulceration in the stomach or intestine, including:
What is ZES? Zollinger-Ellison syndrome (ZES) is the least common major cause of peptic ulcer disease. In this condition, tumors in the pancreas and duodenum (called gastrinomas) produce excessive amounts of gastrin, a hormone that stimulates gastric acid secretion. These tumors are usually cancerous, so proper and prompt management of the disease is essential.

Another cause of peptic ulcer, although far less common than H. pylori or NSAIDs, is Zollinger-Ellison syndrome. A large amount of excess acid is produced in response to the overproduction of the hormone gastrin, which in turn is caused by tumors on the pancreas or duodenum. These tumors are usually cancerous and must be removed. Acid production should also be suppressed to prevent ulcers from returning.
Who Gets ZES? An estimated 1 out of every million people per year gets ZES. The incidence is 0.1 - 1% among patients with peptic ulcers. Typically the disease starts in people ages 45 - 50, and men are affected more often than women.
How Is ZES Diagnosed? ZES should be suspected in patients with ulcers who are not infected with H. pylori and who have no history of NSAID use. Diarrhea may occur before ulcer symptoms. Ulcers occurring in the second, third, or fourth portions of the duodenum or in the jejunum (the middle section of the small intestine) are signs of ZES. Gastroesophageal reflux disease (GERD) is more common, and often more severe in patients with ZES. Complications of GERD include ulcers and narrowing (strictures) of the esophagus.
How Is ZES Treated? Peptic ulcers associated with ZES are typically persistent and difficult to treat. Treatment consists of removing the tumors and suppressing acid with an intravenous PPI (Protonix). In the past, removing the stomach was the only option.
Dyspepsia. The most common symptoms of peptic ulcer are known collectively as dyspepsia. However, peptic ulcers can occur without dyspepsia or any other gastrointestinal symptom, especially when they are caused by NSAIDs. Dyspepsia may be persistent or recurrent and can lead to a variety of upper abdominal symptoms, including:
Many patients with the above symptoms do not have peptic ulcer disease or any other diagnosed condition. In that case, they have what is called functional dyspepsia.
Older patients are less likely to have symptoms than younger patients. A lack of symptoms may delay diagnosis, which may put older patients at greater risk for severe complications.
Recurrent abdominal pain and other gastrointestinal symptoms are common in children, and it is becoming the norm for pediatricians to screen for H. pylori infection in children with these symptoms. However, researchers have not been able to confirm a link between regular abdominal pain and H. pylori infection in children.
Ulcer Pain. Some symptoms are similar to those of gastric ulcers, although not everyone with these symptoms has an ulcer. The pain of ulcers can be in one place, or it can be diffuse (all over the abdomen). The pain is described as a burning, gnawing, or aching in the upper abdomen, or as a stabbing pain penetrating through the gut. The symptoms may vary depending on the location of the ulcer:
Ulcer pain may be particularly confusing or disconcerting when it radiates to the back or to the chest behind the breast bone. In such cases it can be confused with other conditions, such as a heart attack.
Because ulcers can cause hidden bleeding, patients may experience symptoms of anemia, including fatigue and shortness of breath.
Severe symptoms that begin suddenly may indicate a blockage in the intestine, perforation, or hemorrhage, all of which are emergencies. Symptoms may include:
Anyone who experiences any of these symptoms should go to the emergency room immediately.

Peptic ulcers may lead to emergency situations. Severe abdominal pain, with or without evidence of bleeding, may indicate that the ulcer has perforated the stomach or duodenum. Vomiting of a substance that resembles coffee grounds or the presence of black tarry stools may indicate serious bleeding.
Most people with severe ulcers experience significant pain and sleeplessness, which can have a dramatic and adverse impact on their quality of life.
Peptic ulcers caused by H. pylori or NSAIDs can be very serious if they cause hemorrhage or perforate the stomach or duodenum. Up to 15% of people with ulcers experience some degree of bleeding, which can be life-threatening. Ulcers that form where the small intestine joins the stomach can swell and scar, resulting in a narrowing or closing of the intestinal opening. In such cases, the patient will vomit the entire contents of the stomach, and emergency treatment is necessary.
Complications of peptic ulcers cause an estimated 6,500 deaths each year. These figures, however, do not reflect the high number of deaths associated with NSAID use. Ulcers caused by NSAIDs are more likely to bleed than those caused by H. pylori.
Because there are often no GI symptoms from NSAID ulcers until bleeding begins, doctors cannot predict which patients taking these drugs will develop bleeding. The risk for a poor outcome is highest in people who have had long-term bleeding from NSAIDs, blood clotting disorders, low systolic blood pressure, mental instability, or another serious and unstable medical condition. Populations at greatest risk are the elderly and those with other serious conditions, such as heart problems.
H. pylori is strongly associated with certain cancers. Some studies have also linked it to a number of non-gastrointestinal illnesses, although the evidence is inconsistent.
Stomach Cancers. Stomach cancer, also called gastric cancer, is the second leading cause of cancer death worldwide. In developing countries where the rate of H. pylori is very high, the risk of stomach cancer is six times higher than in the U.S. Evidence now suggests that H. pylori may be as carcinogenic to the stomach as cigarette smoke is to the lungs.
Infection with H. pylori promotes a precancerous condition called atrophic gastritis. The process most likely starts in childhood. It may lead to cancer through the following steps:
When H. pylori infection starts in adulthood it poses a lower risk for cancer, because it takes years for atrophic gastritis to develop, and an adult is likely to die of other causes first. Other factors, such as specific strains of H. pylori and diet, might also influence the risk for stomach cancer. For example, a diet high in salt and low in fresh fruits and vegetables has been associated with a greater risk. Some evidence suggests that the H. pylori strain that carries the cytotoxin-associated gene A (CagA) may be a particular risk factor for precancerous changes.
Although the evidence is mixed, some research suggests that early elimination of H. pylori may reduce the risk of stomach cancer to that of the general population. It is important to follow patients after treatment for a long period of time.
People with duodenal ulcers caused by H. pylori appear to have a lower risk of stomach cancer, although scientists do not know why. It may be that different H. pylori strains affect the duodenum and the stomach. Or, the high levels of acid found in the duodenum may help prevent the spread of the bacteria to critical areas of the stomach.
Other Diseases. H. pylori have also been weakly associated with other nonintestinal disorders, including migraine headache, Raynaud's disease (which causes cold extremities), and skin disorders such as chronic hives.
Men with gastric ulcers may face a higher risk for pancreatic cancer, although duodenal ulcers do not seem to pose the same risk.
About 10% of people in the U.S. are expected to develop peptic ulcers at some point in their lives. Peptic ulcer disease affects all age groups, but is rare in children. Men have twice the risk of ulcers as women. The risk of duodenal ulcers tends to rise, beginning around age 25, and continues until age 75. The risk of gastric ulcers peaks at ages 55 - 65.
Peptic ulcers are less common than they once were. Research suggests that ulcer rates have even declined in areas where there is widespread H. pylori infection. The increased use of proton pump inhibitor (PPI) drugs may be responsible for this trend.
H. pylori bacteria are most likely transmitted directly from person to person. Yet little is known about exactly how these bacteria are transmitted.
Who Is Infected with H. pylori? About 50% of the world's population are infected with H. pylori. The bacteria are nearly always acquired during childhood and persist throughout life if not treated. The prevalence in children is around 0.5% in industrialized nations, where rates continue to decline. Even in industrialized countries, however, infection rates in regions with crowded, unsanitary conditions are equal to those in developing countries.
How Do the Bacteria Pass from Person to Person? It is not entirely clear how the bacteria are transmitted. Suggested, but not clearly proven methods of transmission include: intimate contact, GI tract illness (particularly when vomiting occurs), and contact with oral secretions. The bacteria may also be passed in stools. Because H. pylori can live in water, but apparently not in food, the bacteria may also be transmitted through sewage-contaminated water.
Who Is at Risk for Ulcers from H. pylori? Although H. pylori infection is common, ulcers in children are very rare, and only 5% to 10% of H. pylori-infected adults develop ulcers. Some known risk factors include smoking, alcohol use, having a relative with peptic ulcers, being male, and having the cytotoxin-associated gene A (CagA). Experts do not know of any single factor or group of factors that can determine which infected patients are most likely to develop ulcers.
Between 15 - 25% of patients who have taken NSAIDs regularly will have evidence of one or more ulcers, but in most cases these ulcers are very small. Given the widespread use of NSAIDs, however, the potential total number of people who can develop serious problems may be very large. Long-term NSAID use can damage the stomach and, possibly, the small intestine.
The FDA has asked manufacturers of prescription NSAIDs and the COX-2 inhibitor celecoxib (Celebrex) to include with their products a boxed warning emphasizing the increased risk for cardiovascular events and GI bleeding in people taking these drugs. (Pharmaceutical companies are trying to develop new COX-2 inhibitors without these dangerous side effects. Early safety studies of the new COX-2 inhibitor CS-706 showed it to have the same effects on gastric mucosa as a placebo.)
The FDA also requested that manufacturers of over-the-counter NSAIDs revise their labels to include more specific language concerning potential cardiovascular and GI risks. Due to its proven heart benefits, aspirin was excluded from these labeling revisions.
Frequent Users
NSAIDs. Anyone who uses NSAIDs regularly is at risk for gastrointestinal problems. Even low-dose aspirin (81 mg) may pose some risk, although the risk is lower than with standard doses. The highest risk is among people who require long-term use of very high-dose NSAIDs, especially patients with rheumatoid arthritis. Other people who take high doses of NSAIDs include those with chronic low back pain, fibromyalgia, and chronic headaches.
Compared to NSAIDs, COX-2 inhibitors may pose less risk for uncomplicated ulcers, but these medications do not seem to reduce the risk of more serious events, such as bleeding or perforation.
Contributing Factors. Certain factors may increase the risk for ulcers in NSAID users:
Stress and Psychological Factors. Although stress is no longer considered a cause of ulcers, some studies still suggest that stress may predispose a person to ulcers or prevent existing ulcers from healing.
Smoking. Smoking increases acid secretion, reduces prostaglandin and bicarbonate production, and decreases mucosal blood flow. However, the results of studies on the actual effect of smoking on ulcers are mixed. Some evidence suggests that smoking delays the healing of gastric and duodenal ulcers. Other studies have found no increased risk for ulcers in smokers.

Tobacco use and exposure may accelerate coronary artery disease and peptic ulcer disease. It is also linked to reproductive problems, esophageal reflux, hypertension, fetal illness and death, and delayed wound healing.
Peptic ulcers are always suspected in patients with persistent dyspepsia (bloating, belching, and abdominal pain). Symptoms of dyspepsia occur in 20% - 25% of people who live in industrialized nations, but only about 15% - 25% of those with dyspepsia actually have ulcers. A number of steps are needed to accurately diagnose ulcers.
The doctor will ask for a thorough report of a patient's dyspepsia and other important symptoms, such as weight loss or fatigue, present and past medication use (especially chronic NSAID use), family members with ulcers, and drinking and smoking habits.
In addition to peptic ulcers, a number of conditions, notably gastroesophageal reflux disease (GERD) and irritable bowel syndrome, cause dyspepsia. Often, however, no cause can be determined. In such cases, the symptoms are referred to collectively as functional dyspepsia.
Peptic ulcer symptoms, particularly abdominal pain and chest pain, may resemble those of other conditions, such as gallstones or a heart attack. Certain features may help to distinguish these different conditions. However, symptoms often overlap, and it is impossible to make a diagnosis based on symptoms alone. A number of tests are needed.
The following disorders may be confused with peptic ulcers:
Dyspepsia may also occur with gastritis, stomach cancer, or as a side effect of certain drugs, including NSAIDs, antibiotics, iron, corticosteroids, theophylline, and calcium blockers.
When ulcers are suspected, the doctor will order tests to detect bleeding. These may include a rectal exam, complete blood count, and fecal occult blood test (FOBT). The FOBT tests for hidden (occult) blood in stools. Typically, the patient is asked to supply up to six stool specimens in a specially prepared package. A small quantity of feces is smeared on treated paper, which is then exposed to hydrogen peroxide. If blood is present, the paper turns blue.
Simple blood, breath, and stool tests can now detect H. pylori with a fairly high degree of accuracy. It is not entirely clear, however, which individuals should be screened for H. pylori.
Candidates for Screening. Experts recommend testing for H. pylori in all patients with peptic ulcer disease. Some doctors currently test for H. pylori only in individuals with dyspepsia who also have high-risk conditions, such as:
Smokers and those who experience regular and persistent pain on an empty stomach may also be good candidates for screening tests. Some doctors argue that testing for H. pylori may be beneficial for patients with dyspepsia who are regular NSAID users. In fact, given the possible risk for stomach cancer in H. pylori- infected people with dyspepsia, some experts now recommend that any patient with dyspepsia lasting longer than 4 weeks should have a blood test for H. pylori. This is a subject of considerable debate, however.
Tests for Diagnosing H. pylori. The following tests are used to diagnose H. pylori infection. Testing may also be done after treatment to ensure that the bacteria have been completely eliminated.
Endoscopy is a procedure used to evaluate the esophagus, stomach, and duodenum using an endoscope -- a long, thin tube equipped with a tiny video camera. When combined with a biopsy, endoscopy is the most accurate procedure for detecting the presence of peptic ulcers, bleeding, and stomach cancer, or for confirming the presence of H. pylori.
Appropriate Candidates for Endoscopy. Because endoscopy is invasive and expensive, it is unsuitable for screening everyone with dyspepsia. Most individuals with these symptoms are managed effectively without endoscopy. Endoscopy is usually reserved for patients with dyspepsia who also have risk factors for ulcers, stomach cancer, or both. Risk factors include the following:
The decision about whether endoscopy should be performed on patients who do not respond to initial medication should be individualized. It may be recommended for patients with gastric ulcers who continue to have symptoms despite treatment, or for those who have ulcers without a clear cause. There is some debate about whether patients under age 45 who have persistent dyspepsia but no alarm symptoms should have an endoscopy.
The Procedure. Endoscopy may be performed in a hospital, doctor's office, or outpatient surgery center, and typically involves the following:

An upper GI series was the standard method for diagnosing peptic ulcers until endoscopy and tests for detecting H. pylori were introduced. In an upper GI series, the patient drinks a solution containing barium. X-rays are then taken, which may reveal inflammation, active ulcer craters, or deformities and scarring due to previous ulcers. Endoscopy is more accurate, although it is also more invasive and expensive.
Stool tests may show traces of blood that are not visible to the naked eye, and blood tests may reveal anemia in those who have bleeding ulcers. If Zollinger-Ellison syndrome is suspected, blood levels of gastrin should be measured.
Deciding which treatment is best for patients with symptoms of dyspepsia or peptic ulcer disease depends on a number of factors. An endoscopy to identify any ulcers and test for H. pylori probably gives the best guidance for treatment. However, dyspepsia is such a common reason for a doctor's visit that many people are treated initially based on their symptoms and blood or breath H. pylori test results. This approach (called test and treat) is considered an appropriate option for most patients. Patients who do not have any evidence of bleeding or other alarm symptoms, and who are over age 55 should have an endoscopy performed first.
If an endoscopy is performed soon after the patient first visits a doctor for symptoms, treatment is based on the results of the endoscopy:
As mentioned above, most patients who do not have risk factors for additional complications are treated without first having an endoscopy. The decision of which treatment to use is based on the types of symptoms patients have, and on the results of their H. pylori blood or breath tests.
Patients who are not infected with H. pylori are given a diagnosis of functional (non-ulcer) dyspepsia. These patients are most commonly given 4 to 8 weeks of a PPI. If this dose is not effective, doubling the dose will occasionally relieve symptoms. If there is still no symptom relief, patients may have an endoscopy. However, it is unlikely that an ulcer is present. In this group of patients, symptoms may not fully improve.
There is considerable debate about whether to test for H. pylori and treat infected patients who have dyspepsia but no clear evidence of ulcers.
Reported cure rates for H. pylori range from 70% - 90% after antibiotic treatment. The standard treatment regimen uses two antibiotics and a PPI:
Patients typically take this combination treatment for at least 14 days. A 7-day regimen is another option, but some research suggests that 14 days of therapy with antibiotics and PPIs is more effective at eradicating H. pylori.
Follow-Up. Follow-up testing to check that the bacteria have been eliminated should be done no sooner than 4 weeks after therapy is completed. Test results before that time may not be accurate.
In most cases, drug treatment relieves ulcer symptoms. However, symptom relief does not always indicate treatment success, just as persistent dyspepsia does not necessarily mean that treatment has failed. Heartburn and other GERD symptoms can get worse and require acid-suppressing medication.
Failure. Treatment fails in about 10 - 20% of patients, typically when they do not follow their prescribed treatment. Compliance with standard antibiotic regimens may be poor for the following reasons:
Treatment may also fail if patients harbor strains of H. pylori that are resistant to antibiotics. When this happens, different drugs are tried.
Reinfection after Successful Treatment. Studies in developed countries indicate that once the bacteria are eliminated, recurrence rates are below 1% per year. Reinfection with the bacteria is possible, however, in areas where the incidence of H. pylori is very high and sanitary conditions are poor. In such regions, reinfection rates are 6 - 15%.
If patients are diagnosed with NSAID-caused ulcers or bleeding, they should:
Healing Existing Ulcers. A number of drugs are used to treat NSAID-caused ulcers. PPIs -- omeprazole (Prilosec), lansoprazole (Prevacid), or esomeprazole (Nexium) -- are used most often. Other drugs that may be useful include H2 blockers, such as famotidine (Pepcid AC), cimetidine (Tagamet), and ranitidine (Zantac). Sucralfate is another drug used to heal ulcers and reduce the stomach upset caused by NSAIDs.
People with chronic pain may try a number of other medications to minimize the risk of ulcers associated with NSAIDs:
The American College of Gastroenterology has made recommendations about the prevention of ulcers in patients using NSAIDs. A patient's physician must consider whether they are at high, moderate, or low risk for gastrointestinal and cardiovascular problems. Depending on your risk factors, your doctor may recommend any NSAID, naproxen only, a COX-2 inhibitor, one of these, or none of the three. Some patients take either a PPI or misoprostol along with their NSAID. Before starting a patient on long-term NSAID therapy, a physician should consider testing for H. pylori.
The following drugs are sometimes used to treat peptic ulcers caused by either NSAIDs or H. pylori.
Many antacids are available without a prescription, and they are the first drugs recommended to relieve heartburn and mild dyspepsia. Antacids are not effective for preventing or healing ulcers, but they can help in the following ways:
Liquid antacids are thought to work faster and be more potent than tablets, although some evidence suggests that both forms work equally well.
Basic Salts Used in Antacids. There are three basic salts used in antacids:
Interactions with Other Drugs. Antacids can reduce the absorption of a number of drugs. Conversely, some antacids increase the potency of certain drugs. The interactions can be avoided by taking other drugs 1 hour before or 3 hours after taking the antacid.
Drug Interactions with Antacids (such as Maalox, Mylanta) | |
Drugs that are not absorbed as well if taken with antacids | Drugs that are made more potent by antacids |
Tetracycline Ciprofloxacin (Cipro) Propranolol (Inderal) Captopril (Capoten) Ranitidine (Zantac) Famotidine (Pepcid AC) | Valproic acid Sulfonylureas Quinidine Levodopa |
H. pylori is usually highly sensitive to certain antibiotics, particularly amoxicillin, and to antibiotics in the macrolide class, such as clarithromycin. Either class of antibiotics is an effective second antibiotic in a three-drug regimen. Other antibiotics that are sometimes used include tetracycline, metronidazole, and ciprofloxacin.
Side Effects of Antibiotics.
Compounds that contain bismuth are often used in the three-drug treatment programs. They destroy the cell walls of H. pylori bacteria. The only bismuth compound available in the U.S. has been bismuth subsalicylate (Pepto-Bismol), although a drug combination of the H2 blocker ranitidine and bismuth citrate (Tritec) has been released. High doses can cause vomiting and depression of the central nervous system, but the doses given for ulcer patients rarely cause side effects.
Actions against ulcers. PPIs are the drugs of choice for managing patients with peptic ulcers, regardless of the cause. They suppress the production of stomach acid by blocking the gastric acid pump -- the molecule in the stomach glands that is responsible for acid secretion.
PPIs can be used either as part of a multidrug regimen for H. pylori, or alone for preventing and healing NSAID-caused ulcers. They are also useful for treating ulcers caused by Zollinger-Ellison syndrome. They are considered to be more effective than H2 blockers.
Some people carry a gene that reduces the effectiveness of PPIs. This gene is present in 18% - 20% of people who are of Asian descent.
Standard Brands. Most PPIs are available by prescription as oral drugs. There is no evidence that one brand of PPI works better than another. Brands approved for ulcer prevention and treatment include:
Possible Adverse Effects.
In theory, long-term use of PPIs by people with H. pylori may reduce acid secretion enough to cause atrophic gastritis (chronic inflammation of the stomach), a risk factor for stomach cancer. Long-term use of PPIs may also mask the symptoms of stomach cancer and delay diagnosis. At this time, however, there have been no reports of an increase in the incidence of stomach cancer with long-term use of these drugs.
H2 blockers interfere with acid production by blocking histamine, a substance produced by the body that encourages acid secretion in the stomach. H2 blockers were the standard treatment for peptic ulcers until PPIs and antibiotic regimens against H. pylori were developed. These drugs cannot cure ulcers, but they are useful in certain cases. They are effective only for duodenal ulcers, however.
Four H2 blockers are currently available over-the-counter in the U.S.: famotidine (Pepcid AC), cimetidine (Tagamet), ranitidine (Zantac), and nizatidine (Axid). All have good safety profiles and few side effects. There are some differences between these drugs:
PPIs are more effective than H2 blockers at healing ulcers in people who take NSAIDs. Treatment effectiveness for PPIs is between 65% and 100%, versus 50% and 85% for H2 blockers, depending on which specific drugs are being used.
Long-Term Concerns. In most cases, H2 blockers have good safety profiles and few side effects. Because H2 blockers can interact with other drugs, be sure to tell your doctor about any other medications you are taking. There are also some concerns about possible long-term effects -- for example, that long-term acid suppression with these drugs may cause cancerous changes in the stomach in patients who also have untreated H. pylori infection. More research is needed.
However, the following concerns are well documented:
Famotidine is removed from the body primarily by the kidney. This can pose a danger to people with kidney problems. The U.S. Food and Drug Administration (FDA) and Health Canada are now advising physicians to reduce the dose and increase the time between doses in patients with kidney failure. Use of the drug in those with impaired kidney function can affect the central nervous system and may result in anxiety, depression, insomnia or drowsiness, and mental disturbances.
Misoprostol (Cytotec) increases prostaglandin levels in the stomach lining, which protects against the major gastrointestinal side effects of NSAIDs.
Actions against ulcers. Misoprostol can reduce the risk of NSAID-induced ulcers in the upper small intestine by two-thirds, and in the stomach by three-fourths. It does not neutralize or reduce acid, so although the drug is helpful for preventing NSAID-induced ulcers, it is not useful for healing existing ulcers.
Side Effects.
Sucralfate (Carafate) seems to work by adhering to the ulcer crater and protecting it from further damage by stomach acid and pepsin. It also promotes the defensive processes of the stomach. Sucralfate has an ulcer-healing rate similar to that of H2 blockers. Other than constipation, which occurs in 2.2% of patients, the drug has few side effects. Sucralfate does interact with a wide variety of drugs, however, including warfarin, phenytoin, and tetracycline.
When a patient comes to the hospital with bleeding ulcers, endoscopy is usually performed. This procedure is critical for the diagnosis, determination of treatment options, and treatment of bleeding ulcers.
In high-risk patients or those with evidence of bleeding, options include watchful waiting with medical treatments or surgery. The first critical steps for massive bleeding are to stabilize the patient and support vital functions with fluid replacement and possibly blood transfusions. People on NSAIDs should stop taking these drugs, if possible.
Depending on the intensity of the bleeding, patients can be released from the hospital within a day or kept in the hospital for up to 3 days after endoscopy. Bleeding stops spontaneously in about 70 - 80% of patients, but about 30% of patients who come to the hospital for bleeding ulcers need surgery. Endoscopy is the surgical procedure most often used for treating bleeding ulcers and patients at high-risk for rebleeding. It is usually combined with medications such as epinephrine and intravenous proton pump inhibitors (PPIs).
Between 10 - 20% of patients require more invasive procedures for bleeding, such as major abdominal surgery.
Endoscopy is important for both diagnosing and treating bleeding ulcers.
Endoscopy for Diagnosing Bleeding Ulcers and Determining Risk of Rebleeding. With endoscopy, doctors are able to detect the signs of bleeding, such as active spurting or oozing of blood from arteries. Endoscopy can also detect specific features in the ulcers, referred to as stigmata, which indicate a higher or lower risk of rebleeding.
Endoscopy as Treatment. Endoscopy is usually used to treat bleeding from visible vessels that are less than 2 mm in diameter. This approach also appears to be very effective at preventing rebleeding in patients whose ulcers are not bleeding, but who have high-risk features (swollen blood vessels or clots adhering to ulcers).
The following is a typical endoscopy procedure:
Endoscopy is effective at controlling bleeding in most appropriate candidates. If rebleeding occurs, a repeat endoscopy is effective in about 75% of patients. Those who fail to respond require major abdominal surgery. The most serious complication from endoscopy is perforation of the stomach or intestinal wall.
Other Medical Considerations. Certain medications may be needed after endoscopy:
Major abdominal surgery for bleeding ulcers is now generally performed only when endoscopy fails or is not appropriate. Certain emergencies may require surgical repair, such as when an ulcer perforates the wall of the stomach or intestine, causing sudden intense pain and life-threatening infection.
Surgical Approaches. The standard major surgical approach (called open surgery) uses a wide abdominal incision and standard surgical instruments. Laparoscopic techniques use small abdominal incisions, through which are inserted tubes that contain miniature cameras and instruments. Laparoscopic techniques are increasingly being used for perforated ulcers. Research finds that laparoscopic surgery for a perforated peptic ulcer is comparable in safety with open surgery, and results in less pain after the procedure.
Major Surgical Procedures. There are a number of surgical procedures aimed at providing long-term relief of ulcer complications. These include:
Antrectomy and pyloroplasty are usually performed with vagotomy.
In the past, it was common practice to tell people with peptic ulcers to consume small, frequent amounts of bland foods. Exhaustive research conducted since that time has shown that a bland diet is not effective in reducing the incidence or recurrence of ulcers, and that eating numerous small meals throughout the day is no more effective than eating three meals a day. Large amounts of food should still be avoided, however, because stretching the stomach can result in painful symptoms.
Fruits and Vegetables. The good news is that a diet rich in fiber may cut the risk of developing ulcers in half and speed the healing of existing ulcers. Fiber found in fruits and vegetables is particularly protective; vitamin A contained in many of these foods may increase the benefit.
Milk. Milk actually encourages the production of acid in the stomach, although moderate amounts (2 - 3 cups a day) appear to do no harm. Certain probiotics, which are "good" bacteria added to yogurt and other fermented milk drinks, may protect the gastrointestinal system.
Coffee and Carbonated Beverages. Coffee (both caffeinated and decaffeinated), soft drinks, and fruit juices with citric acid increase stomach acid production. Although no studies have proven that any of these drinks contribute to ulcers, consuming more than 3 cups of coffee per day may increase susceptibility to H. pylori infection.
Spices and Peppers. Studies conducted on spices and peppers have yielded conflicting results. The rule of thumb is to use these substances moderately, and to avoid them if they irritate the stomach.
Garlic. Some studies suggest that large amounts of garlic may have some protective properties against stomach cancer, although one study concluded that garlic offered no benefits against H. pylori and, in large amounts, can cause considerable GI distress.
Olive Oil. Studies from Spain have shown that phenolic compounds in virgin olive oil may be effective against eight strains of H. pylori, three of which are antibiotic-resistant.
Vitamins. Although no vitamins have been shown to protect against ulcers, H. pylori appear to impair the absorption of vitamin C, which may play a role in the higher risk of stomach cancer.
Some evidence suggests that exercise may help reduce the risk for ulcers in some people.
Stress relief programs have not been shown to promote ulcer healing, but they may have other health benefits.
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