eMedicine Specialties > Gastroenterology > Stomach

Peptic Ulcer Disease

Tri H Le, MD, Assistant Professor of Medicine, Division of Gastroenterology and Hepatology, Penn State Milton S Hershey Medical Center
George T Fantry, MD, Director of Clinical Gastroenterology, Department of Internal Medicine, Division of Gastroenterology, Associate Professor, University of Maryland School of Medicine

Updated: Jul 17, 2008

Introduction

Background

Peptic ulcer disease (PUD) is a common disorder that affects millions of individuals in the United States each year. PUD has a major impact on our health care system by accounting for roughly 10% of medical costs for digestive diseases. In the last two decades, major advances have been made in the understanding of the pathophysiology of PUD, particularly regarding the role of Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs (NSAIDs). This has led to important changes in diagnostic and treatment strategies, with the potential for improving the clinical outcome and for decreasing health care costs.

Pathophysiology

Peptic ulcers are defects in the gastric or duodenal mucosa that extend through the muscularis mucosa. H pylori infection and NSAID use are the most common etiologic factors. Other less common causes are hypersecretory states, such as Zollinger-Ellison syndrome, G-cell hyperplasia, mastocytosis, and basophilic leukemias.

Under normal conditions, a physiologic balance exists between peptic acid secretion and gastroduodenal mucosal defense. Mucosal injury and, thus, peptic ulcer occur when the balance between the aggressive factors and the defensive mechanisms is disrupted. Aggressive factors, such as NSAIDs, H pylori, alcohol, bile salts, acid, and pepsin, can alter the mucosal defense by allowing back diffusion of hydrogen ions and subsequent epithelial cell injury. The defensive mechanisms include tight intercellular junctions, mucus, mucosal blood flow, cellular restitution, and epithelial renewal.

Frequency

United States

• One-year point prevalence is 1.8%. Lifetime prevalence is approximately 10%. PUD affects approximately 4.5 million people annually.

International

The frequency of PUD in other countries is variable and determined primarily by association with the major causes of PUD: H pylori and NSAIDs.

Mortality/Morbidity

Medical office visits and hospitalizations for PUD have decreased in the last few decades. The mortality rate has decreased modestly in the last few decades and is approximately 1 death per 100,000 cases. The hospitalization rate is approximately 30 patients per 100,000 cases.

Sex

• Prevalence has shifted from predominance in males to similar occurrences for both sexes.
• Lifetime prevalence is approximately 11-14% for men and 8-11% for women.

Age

• Age trends for ulcer occurrence reveal declining rates in younger men, particularly for duodenal ulcer, and increasing rates in older women.
• Trends reflect complex changes in risk factors for PUD, including age-cohort phenomena with the prevalence of H pylori infection and the use of NSAIDs in older populations.

Clinical

History

• Epigastric pain (the most common symptom)
  • Gnawing or burning sensation
  • Occurs 2-3 hours after meals
  • Relieved by food or antacids
  • Patient awakens with pain at night.
  • May radiate to the back (consider penetration)
• Nausea
• Vomiting, which might be related to partial or complete gastric outlet obstruction
• Dyspepsia, including belching, bloating, distention, and fatty food intolerance
• Heartburn
• Chest discomfort
• Anorexia, weight loss
• Hematemesis or melena resulting from gastrointestinal bleeding
• Dyspeptic symptoms that might suggest PUD are not specific because only 20-25% of patients with symptoms suggestive of peptic ulceration are found on investigation to have a peptic ulcer.

Physical

• In uncomplicated PUD, clinical findings are few and nonspecific.
  • Epigastric tenderness
  • Guaiac-positive stool resulting from occult blood loss
  • Melena resulting from acute or subacute gastrointestinal bleeding
  • Succussion splash resulting from partial or complete gastric outlet obstruction

Causes

•  H pylori infection
  • H pylori infection and NSAID use account for most cases of PUD.
  • The rate of H pylori infection for duodenal ulcers in the United States is less than 75% for patients who do not use NSAIDs. Excluding patients who use NSAIDs, 61% of duodenal ulcers and 63% of gastric ulcers are positive for H pylori in one study. This rate also depends on the demographic, which appears to be less frequent in whites as compared to nonwhites.
  • Prevalence in complicated ulcers (ie, bleeding, perforation) is significantly lower than that found in uncomplicated ulcer disease.
• Nonsteroidal anti-inflammatory drugs
  • Similar to H pylori infection, NSAID use is a common cause for PUD.
  • Corticosteroids alone do not increase the risk for PUD; however, they can potentiate the ulcer risk in patients who use NSAIDs concurrently.
• Severe physiologic stress
  • Burns
  • CNS trauma
  • Surgery
  • Severe medical illness
• Hypersecretory states (uncommon)
  • Gastrinoma (Zollinger-Ellison syndrome) or multiple endocrine neoplasia (MEN-I)
  • Antral G cell hyperplasia
  • Systemic mastocytosis
  • Basophilic leukemias
• Diseases associated with an increased risk of PUD include cirrhosis, chronic obstructive pulmonary disease, renal failure, and organ transplantation.
• Additional rare, miscellaneous causes include radiation-induced or chemotherapy-induced ulcers, vascular insufficiency (crack cocaine), and duodenal obstruction.

Differential Diagnoses

Other Problems to Be Considered

Crohn disease with gastric or duodenal involvement
Drug-induced dyspepsia
Duodenitis
Functional (nonulcerous) dyspepsia
Gastric infections
Infiltrative diseases of the stomach

Workup

Laboratory Studies

• In most patients with uncomplicated PUD, routine laboratory tests usually are not helpful. Documentation of PUD depends on radiographic and endoscopic confirmation.
• If the diagnosis of PUD is unclear or complicated and PUD is suspected, obtaining CBC, liver function tests (LFTs), amylase, and lipase might be useful.

Imaging Studies

• Upper gastrointestinal series
  
  
  • Double-contrast radiography performed by an experienced radiologist might approach the diagnostic accuracy of upper GI endoscopy. However, it has been replaced largely by diagnostic endoscopy, when available.
  • It is not as sensitive as endoscopy for establishing a diagnosis of small ulcers (<0.5 cm).
  • It also does not allow for obtaining a biopsy to rule out malignancy in the setting of a gastric ulcer or to assess for H pylori infection in the setting of a gastroduodenal ulcer.

Other Tests

• Detection of H pylori infection is essential in all patients with peptic ulcers.
• Endoscopic or invasive tests include a rapid urease test, histopathology, and culture.
  
  
  • Rapid urease tests are considered the endoscopic diagnostic test of choice. The presence of H pylori in gastric mucosal biopsy specimens is detected by testing for the bacterial product urease. Three kits (ie, CLOtest, Hp-fast, Pyloritek) are commercially available, each containing a combination of a urea substrate and a pH sensitive indicator. One or more gastric biopsy specimens are placed in the rapid urease test kit. If H pylori is present, bacterial urease converts urea to ammonia, which changes pH and produces a color change.
  • Obtain histopathology, often considered the criterion standard to establish a diagnosis of H pylori infection , if the rapid urease test result is negative and a high suspicion for H pylori persists (presence of a duodenal ulcer).
  • Culture primarily is used in research studies and is not available routinely for clinical use.
• Nonendoscopic or noninvasive tests include serum H pylori antibody detection, fecal antigen tests, and urea breath tests.
  
  
  • Antibodies (immunoglobulin G [IgG]) to H pylori can be measured in serum, plasma, or whole blood. Results with whole blood tests obtained from finger sticks are less reliable.
  • Urea breath tests detect active H pylori infection by testing for the enzymatic activity of bacterial urease. In the presence of urease produced by H pylori, labeled carbon dioxide (heavy isotope, carbon-13, or radioactive isotope, carbon-14) is produced in the stomach, absorbed into the bloodstream, diffused into the lungs, and exhaled.
  • Fecal antigen testing identifies active H pylori infection by detecting the presence of H pylori antigens in stools. This test is more accurate than antibody testing and is less expensive than urea breath tests.
• Special studies
  
  
  • A fasting serum gastrin level should be obtained in certain cases to screen for Zollinger-Ellison syndrome. Such cases include the following: patients with multiple ulcers; ulcers occurring distal to the duodenal bulb; strong family history of PUD; peptic ulcer associated with diarrhea, steatorrhea, or weight loss; peptic ulcer not associated with H pylori infection or NSAID use; peptic ulcer associated with hypercalcemia or renal stones; ulcer refractory to medical therapy; and ulcer recurs after surgery.
  • A secretin stimulation test may be used if the diagnosis of Zollinger-Ellison syndrome cannot be made with the gastrin level alone. This test can distinguish Zollinger-Ellison syndrome from other conditions with a high serum gastrin level, such as antisecretory therapy with a proton pump inhibitor, renal failure, or gastric outlet obstruction.
  • Measurement of acid secretion is not useful in the routine evaluation of PUD.

Procedures

• Upper GI endoscopy
  
  
  • Preferred diagnostic test in the evaluation of patients with suspected PUD
  • Highly sensitive for the diagnosis of gastric and duodenal ulcers
  • Allows for biopsies and cytologic brushings in the setting of a gastric ulcer to differentiate a benign ulcer from a malignant lesion
  • Allows for detection of H pylori infection with antral biopsies for a rapid urease test and/or histopathology in patients with PUD

Treatment

Medical Care

• Given the current understanding of the pathogenesis of PUD, most patients with PUD are treated successfully with cure of H pylori infection and/or avoidance of NSAIDs, along with the appropriate use of antisecretory therapy.
• A number of treatment options exist for patients presenting with symptoms suggestive of PUD or ulcerlike dyspepsia, including empiric antisecretory therapy, empiric triple therapy for H pylori infection, endoscopy followed by appropriate therapy based on findings, and H pylori serology followed by triple therapy for patients who are infected. Breath testing for active H pylori infection may be used.
• Computer models have suggested that obtaining H pylori serology followed by triple therapy for patients who are infected is the most cost-effective approach; however, no direct evidence from clinical trials provides confirmation.
• Perform endoscopy early in patients older than 45-50 years and in patients with associated so-called alarm symptoms, such as dysphagia, recurrent vomiting, weight loss, or bleeding.
• See also American College of Gastroenterology Issues Guidelines for Treatment of Helicobacter pylori Infection and Recommendations for Treating Peptic Ulcer Disease Reviewed.

Surgical Care

With the success of medical therapy, surgery has a very limited role in the management of PUD.

• Potential indications for surgery include refractory disease. Complications of PUD include the following:
  • Refractory, symptomatic peptic ulcers, though rare with the cure of H pylori infection and the appropriate use of antisecretory therapy, are a potential complication of PUD.
  • Perforation usually is managed emergently with surgical repair. However, this is not mandatory for all patients.
  • Obstruction can complicate PUD, particularly if PUD is refractory to aggressive antisecretory therapy, H pylori eradication, or avoidance of NSAIDs. Obstruction may persist or recur despite endoscopic balloon dilation.
  • Penetration, particularly if not walled off or if a gastrocolic fistula develops, is a potential complication of PUD.
  • Bleeding can complicate PUD, particularly in patients with massive hemorrhage and hemodynamic instability, recurrent bleeding on medical therapy, and failure of therapeutic endoscopy to control bleeding.
• The appropriate surgical procedure depends on the location and nature of the ulcer.
  • Many authorities recommend simple oversewing of the ulcer with treatment of the underlying H pylori infection or cessation of NSAIDs for bleeding PUD.
  • Additional surgical options for refractory or complicated PUD include vagotomy and pyloroplasty, vagotomy and antrectomy with gastroduodenal reconstruction (Billroth I) or gastrojejunal reconstruction (Billroth II), or a highly selective vagotomy.

Consultations

Consult a general surgeon if the clinical presentation suggests a complicated peptic ulcer.

Diet

No special diet is required.

Medication

Treat all patients with peptic ulcers and associated H pylori infection with proton pump inhibitor (PPI)-based triple therapy, which results in a cure rate of infection and healing in approximately 85-90% of cases. Ulcers can relapse in the absence of successful H pylori eradication.

Dual therapies, which are alternative regimens for treating H pylori infection, are usually not recommended as first-line therapy because of a variable cure rate that is significantly less than the cure rate achieved with triple therapy.

Active ulcers associated with NSAID use are treated with an appropriate course of PPI therapy and the cessation of NSAIDs. For patients with a known history of ulcer, and in whom NSAID use is unavoidable, the lowest possible dose and duration of the NSAID and co-therapy with a PPI or misoprostol are recommended.

PPI-based triple therapies for H pylori are considered the first-line therapies for the treatment of H pylori in the United States with a cure rate of 85-90%. These regimens consist of a PPI, amoxicillin, and clarithromycin for 7-14 days. A longer duration of treatment (14 d vs 7 d) appears to be more affective and is currently the recommended duration of treatment. Amoxicillin should only be substituted by metronidazole in penicillin-allergic patients because of the high rate of metronidazole resistance.

In the setting of active ulcers caused by H pylori, treatment with a PPI beyond the 14-day course of antibiotics and until the confirmation for the eradication of H pylori is recommended for complicated ulcers.

PPI-based triple therapies consist of a 14-day treatment of the following:

Omeprazole (Prilosec): 20 mg PO bid or

Lansoprazole (Prevacid): 30 mg PO bid or

Rabeprazole (Aciphex): 20 mg PO bid or

Esomeprazole (Nexium): 40 mg PO qd

Plus:

Clarithromycin (Biaxin): 500 mg PO bid and

Amoxicillin (Amoxil): 1 g PO bid

The alternative combination therapy consists of the following treatments administered for 14 days:

Omeprazole (Prilosec): 20 mg PO bid or

Lansoprazole (Prevacid): 30 mg PO bid or

Rabeprazole (Aciphex): 20 mg PO bid or

Esomeprazole (Nexium): 40 mg PO qd

Plus:

Clarithromycin (Biaxin): 500 mg PO bid and

Metronidazole (Flagyl): 500 mg PO bid

Quadruple therapies for H pylori infection are generally reserved for patients who have failed a course of treatment and are administered for 14 days. The treatment includes the following drugs:

PPI PO bid and

Bismuth 525 mg PO qid and

Metronidazole 500 mg PO qid and

Tetracycline 500 mg PO qid

Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Amoxicillin (Amoxil, Biomox, Trimox)

Derivative of ampicillin and has similar antibacterial spectrum, namely certain gram-positive and gram-negative organisms. Superior bioavailability and stability to gastric acid and has broader spectrum of activity than penicillin. Somewhat less active than that of penicillin against Streptococcus pneumococcus. Penicillin-resistant strains also resistant to amoxicillin, but higher doses may be effective. Interferes with synthesis of cell wall mucopeptides during active multiplication resulting in bactericidal activity against susceptible bacteria. Used in combination with other antimicrobial agents.
If H pylori is identified as the underlying cause of gastritis, subsequent eradication now is almost generally accepted practice. Protocols for H pylori eradication require a combination of antimicrobial agents and antisecretory agents, such as PPIs, ranitidine bismuth citrate, or bismuth subsalicylate. Despite the combinatorial effect of drugs in regimens used to treat H pylori infection, cure rates remain, at best, 80-95%.

Dosing

Adult

1 g PO bid

Pediatric

Not established

Interactions

Reduces the efficacy of oral contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment; may enhance chance of candidiasis

Clarithromycin (Biaxin)

Semisynthetic macrolide antibiotic that reversibly binds to P site of 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, causing bacterial growth inhibition. If H pylori is identified as the underlying cause of gastritis, subsequent eradication now is almost generally accepted practice. Protocols for H pylori eradication require a combination of antimicrobial agents and antisecretory agents, such as PPIs, ranitidine bismuth citrate, or bismuth subsalicylate. Despite the combinatorial effect of drugs in regimens used to treat H pylori infection, cure rates remain, at best, 80-95%.

Dosing

Adult

500 mg PO bid

Pediatric

Not established

Interactions

Toxicity increases with coadministration of fluconazole and pimozide; effects decrease and GI adverse effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, carbamazepine, ergot alkaloids, triazolam, and HMG-CoA reductase inhibitors; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increases in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents; decreases metabolism of repaglinide, thus increasing serum levels and effects

Contraindications

Documented hypersensitivity; coadministration of pimozide

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; give half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies

Metronidazole (Flagyl)

Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents. If H pylori is identified as the underlying cause of gastritis, subsequent eradication now is almost generally accepted practice. Protocols for H pylori eradication require a combination of antimicrobial agents and antisecretory agents, such as PPIs, ranitidine bismuth citrate, or bismuth subsalicylate. Despite the combinatorial effect of drugs in regimens used to treat H pylori infection, cure rates remain, at best, 80-95%.

Dosing

Adult

500 mg PO bid

Pediatric

Not established

Interactions

May increase toxicity of anticoagulants, cyclosporine, lithium, phenytoin, tacrolimus, and carbamazepine; cimetidine may increase toxicity of metronidazole; disulfiram reaction may occur with orally ingested ethanol; coadministration increases amiodarone toxicity (QT prolongation); increases disulfiram toxicity (psychotic symptoms) with concurrent use; phenobarbital and rifampin may increase metabolism of metronidazole

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution with liver impairment, blood dyscrasias, CNS disease; reduce dosage with severe hepatic disease; monitor for seizures and development of peripheral neuropathy

Tetracycline (Sumycin)

Inhibits bacterial growth by binding to the 30S ribosomal unit, preventing protein synthesis.
Component of drug combination therapy that effectively treats duodenal ulcer or gastric ulcer associated with H pylori infection. Treats gram-positive and gram-negative organisms and mycoplasmal, chlamydial, and rickettsial infections. Used in combination with other antimicrobial agents.
If H pylori is identified as the underlying cause of gastritis, subsequent eradication now is almost generally accepted practice. Protocols for H pylori eradication require a combination of antimicrobial agents and antisecretory agents, such PPIs, ranitidine bismuth citrate, or bismuth subsalicylate. Despite the combinatorial effect of drugs in regimens used to treat H pylori infection, cure rates remain, at best, 80-95%.

Dosing

Adult

500 mg PO qid

Pediatric

Not established

Interactions

Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants

Contraindications

Documented hypersensitivity; severe hepatic dysfunction

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one-half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Proton pump inhibitors (PPIs)

Proton pump inhibitors bind to and inhibit the H⁺/K⁺ -adenosine triphosphatase (ATPase) pump of the parietal cell, resulting in a marked decrease in acid secretion. These drugs are an important part of triple therapy, the treatment of choice for H pylori infection. Proton pump inhibitors have some direct antibacterial effect, and their antisecretory properties aid in ulcer healing. Can be used as primary therapy to heal ulcers not associated with H pylori infection.

Lansoprazole (Prevacid)

Decreases gastric acid secretion by inhibiting parietal cell H⁺/K⁺ -ATP pump. Might decrease the incidence of NSAID-induced peptic ulcers and can be used to help prevent peptic ulcers in chronic NSAID users at high risk

Dosing

Adult

15-30 mg PO qd for 4 wk

Pediatric

Not established

Interactions

May decrease effects of ketoconazole and itraconazole; may increase theophylline clearance

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Consider adjusting dose in liver impairment

Esomeprazole (Nexium)

Inhibits gastric acid secretion by inhibiting H⁺/K⁺ -ATPase enzyme system at secretory surface of gastric parietal cells.

Dosing

Adult

20-40 mg PO qd for 4-8 wk

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Symptomatic relief with proton pump inhibitors may mask symptoms of gastric malignancy

Rabeprazole (Aciphex)

Inhibits gastric acid secretion by inhibiting H⁺/K⁺ -ATPase enzyme system at secretory surface of gastric parietal cells.

Dosing

Adult

20 mg PO qd for 4 wk

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Symptomatic relief with proton pump inhibitors may mask symptoms of gastric malignancy

Omeprazole (Prilosec)

Decreases gastric acid secretion by inhibiting parietal cell H⁺/K⁺ -ATP pump. Might decrease the incidence of NSAID-induced peptic ulcers and can be used in preventing peptic ulcers in high-risk chronic NSAID users

Dosing

Adult

20 mg PO qd for 4 wk

Pediatric

Not established

Interactions

May decrease effects of itraconazole and ketoconazole; may increase toxicity of warfarin, digoxin, and phenytoin

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Bioavailability might increase in elderly patients

Cytoprotectants

These agents have the ability to induce prostaglandin synthesis and, thus, cytoprotective effects in the GI tract.

Misoprostol (Cytotec)

Prostaglandin analog can be used to decrease incidence of peptic ulcers and complications in chronic NSAID users

Dosing

Adult

200 mcg PO qid

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; do not use in women of childbearing age unless patient requires NSAID therapy and is at high risk for complications of PUD

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Caution in renal impairment and elderly patients; adverse gastrointestinal effects (eg, abdominal pain, diarrhea) are common; lower doses have fewer adverse effects but are slightly less effective; the dose can be titrated to optimal therapeutic dose

H2-receptor blockers

These agents selectively block H2-receptors on parietal cells, resulting in diminished acid secretion and ulcer healing. Long-term use can have tachyphalaxis.

Cimetidine (Tagamet)

Can be used as primary therapy to heal ulcers not associated with H pylori infection.
Treatment duration is 6-8 wk. A longer treatment course might be required for gastric ulcers

Dosing

Adult

400 mg PO bid or 800 mg PO qhs for 6-8 wk

Pediatric

Not established

Interactions

Can increase blood levels of theophylline, warfarin, tricyclic antidepressants, triamterene, phenytoin, quinidine, propranolol, metronidazole, procainamide, and lidocaine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Elderly patients might experience confusional states; might cause impotence and gynecomastia in young males; might increase levels of many drugs; adjust dose or discontinue treatment if changes in renal function occur

Ranitidine (Zantac)

Inhibits histamine stimulation of the H2 receptor in gastric parietal cells, which, in turn, reduces gastric acid secretion, gastric volume, and reduced hydrogen concentrations

Dosing

Adult

150 mg PO bid or 300 mg PO qhs

Pediatric

Not established

Interactions

May decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment

Famotidine (Pepcid)

Competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, reduced gastric volume, and reduced hydrogen concentrations

Dosing

Adult

20 mg PO bid or 40 mg PO qhs

Pediatric

Not established; suggested dose is 1-2 mg/kg/d PO/IV divided q6h; not to exceed 40 mg per dose

Interactions

May decrease effects of ketoconazole and itraconazole

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

If changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment

Nizatidine (Axid)

Competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, reduced gastric volume, and reduced hydrogen concentrations

Dosing

Adult

150 mg PO bid or 300 mg PO qhs

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal or liver impairment (if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment)

Follow-up

Further Outpatient Care

• Endoscopy is required to document healing of gastric ulcers and to rule out gastric cancer. This usually is performed 6-8 weeks after the initial diagnosis of PUD.
• Documentation of H pylori cure with a noninvasive test, such as the urea breath test or fecal antigen test, is appropriate in patients with complicated ulcers.

Inpatient & Outpatient Medications

• Consider maintenance therapy with half standard doses of H2-receptor antagonists at bedtime in patients with recurrent, refractory, or complicated ulcers, particularly if cure of H pylori has not been documented or if an H pylori -negative ulcer is present.

Deterrence/Prevention

• Primary prevention of NSAID-induced ulcers includes the following:
  • Avoid unnecessary use of NSAIDs.
  • Use acetaminophen or nonacetylated salicylates when possible.
  • Use the lowest effective dose of an NSAID and switch to less toxic NSAIDs, such as the newer NSAIDs or cyclooxygenase-2 (COX-2) inhibitors, in high-risk patients without cardiovascular disease.
• Consider prophylactic or preventive therapy for the following patients:
  • Patients with NSAID-induced ulcers who require chronic, daily NSAID therapy
  • Patients older than 60 years
  • Patients with a history of PUD or a complication such as gastrointestinal bleeding
  • Patients taking concomitant steroids or anticoagulants or patients with significant comorbid medical illnesses
• Prophylactic regimens that have been shown to dramatically reduce (prevent) the risk of NSAID-induced gastric and duodenal ulcers include the use of a prostaglandin analogue or a PPI.
  • Misoprostol 100-200 mcg PO 4 times per day
  • Omeprazole 20-40 mg PO every day
  • Lansoprazole 15-30 mg PO every day

Complications

• Perforation
• Penetration
• Obstruction
• Bleeding

Prognosis

• When the underlying cause is addressed, the prognosis is excellent. Most patients are treated successfully with the cure of H pylori infection, avoidance of NSAIDs, and the appropriate use of antisecretory therapy.
• Cure of H pylori infection changes the natural history of the disease, with a decrease in the ulcer recurrence rate from 60-90% to approximately 10-20%. However, this is a higher recurrence rate than previously reported, suggesting an increased number of ulcers not caused by H pylori infection.

Patient Education

• Stop smoking.
• Avoid NSAID and aspirin use.
• Avoid heavy alcohol use.
• Stress reduction counseling might be helpful in individual cases but is not needed routinely.
• For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education articles Peptic Ulcers, Heartburn, and Understanding Heartburn/GERD Medications.

Miscellaneous

Medicolegal Pitfalls

• Failure to assess for H pylori infection in patients with PUD is a potential pitfall.
• Choosing an inadequate treatment regimen for patients with H pylori infection, such as the wrong combination of drugs, wrong dosage, or too short duration of treatment, is a potential pitfall.
• Failure to obtain a detailed medical history regarding potential NSAID use is a potential pitfall.

References

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Keywords

PUD, Helicobacter pylori infection, H pylori infection, nonsteroidal anti-inflammatory drugs, NSAIDs, mucosal break, dyspepsia, heartburn, smoking, stress, epigastric pain, belching, bloating, distention, fatty food intolerance, hematemesis, melena, gastrointestinal bleeding, Guaiac-positive stool, occult blood loss, succussion splash, gastric outlet obstruction, duodenal ulcers, perforation, gastrinoma, Zollinger-Ellison syndrome, multiple endocrine neoplasia syndrome, MEN-I, antral G cell hyperplasia, systemic mastocytosis, basophilic leukemias, cirrhosis, chronic pulmonary disease, renal failure, renal transplantation, radiation-induced ulcers, chemotherapy-induced ulcers, vascular insufficiency, crack cocaine, duodenal obstruction

Contributor Information and Disclosures

Author

Tri H Le, MD, Assistant Professor of Medicine, Division of Gastroenterology and Hepatology, Penn State Milton S Hershey Medical Center
Tri H Le, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society of Gastrointestinal Endoscopy, and Crohns and Colitis Foundation of America
Disclosure: Nothing to disclose.

Coauthor(s)

George T Fantry, MD, Director of Clinical Gastroenterology, Department of Internal Medicine, Division of Gastroenterology, Associate Professor, University of Maryland School of Medicine
George T Fantry, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

Medical Editor

Terence David Lewis, MBBS, FRACP, FRCPC, FACP, Program Director, Internal Medicine Residency, & Assistant Chairman, Associate Professor, Department of Internal Medicine, Division of Gastroenterology, Loma Linda University Medical Center
Terence David Lewis, MBBS, FRACP, FRCPC, FACP is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, California Medical Association, Royal College of Physicians and Surgeons of Canada, and Sigma Xi
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Noel Williams, MD, Professor Emeritus, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; Professor, Department of Internal Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
Noel Williams, MD is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Assistant Dean for Medical Curriculum, Associate Professor of Medicine, Division of General Internal Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

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