Peptic Ulcer Disease Management

Last updated: 19 June 2026
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Principles of Therapy

PUD treatment should be guided by the underlying cause, and when an etiology other than H pylori or NSAID use is identified, the primary disorder should be treated. The treatment of both gastric and duodenal ulcers involves suppression of acid secretion and eradication of H pylori (if present). Antisecretory therapy speeds up the healing process and allows faster relief of symptoms. It must be noted that most peptic ulcers heal within 8 weeks of initiation of antisecretory therapy. The eradication of H pylori in high-risk patients has been shown to greatly lower the risk of subsequent ulceration and prevent recurrent bleeding in patients with bleeding peptic ulcers. For patients initiating Aspirin for primary prevention, guidelines recommend H pylori eradication because of the associated bleeding risk.

It is important to suppress nocturnal acid secretion in patients with duodenal ulcers. A maintenance antisecretory therapy may be recommended in patients at high risk for ulceration (ie history of ulcer complications, frequent recurrences) and for H pylori infection unresponsive to repeat treatment. Consider primary prophylaxis with antisecretory agents in patients with a prior history of PUD and on steroids or who are >65 years old, those with severe physiologic stress, hypoperfusion or extensive burns, patients at high risk of GI complications from NSAIDs, or those with concomitant high-dose steroid, antithrombotic or anticoagulant use. Secondary prophylaxis could be considered for patients with prior complications from PUD (eg bleeding, obstruction and perforation). The management of refractory peptic ulcers includes a prolonged course of antisecretory therapy, often with the proton pump inhibitor (PPI) dose increased to twice the previous dose. PPI, histamine2-receptor antagonist (H2RA) and Sucralfate are drugs for stress ulcer prophylaxis.

Pharmacological therapy

Antacids  

Antacids neutralize gastric acid and lower pepsin activity. This is effective in relieving symptoms of PUD, promoting healing of ulcers, and reducing recurrence. It is used for short-term relief of symptoms. Antacids may be absorbable (eg Sodium bicarbonate, Calcium bicarbonate) or non-absorbable (eg Aluminum or Magnesium hydroxide). Absorbable antacids may provide fast and complete neutralization but may cause alkalosis and should only be used for 1-2 days. Non-absorbable antacids are preferred due to lesser systemic side effects.



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Colloidal Bismuth Preparations

Example drugs: Bismuth subcitrate, Bismuth subsalicylate   

Bismuth subcitrate has high affinity for damaged tissue. Bismuth salts form mucus-bound complexes that coat the ulcer base, protecting it from gastric acid, pepsin and bile. Treatment efficacy is comparable with H2RAs and other ulcer-healing agents.  

Histamine2-Receptor Antagonists (H2RAs)  

Example drugs: Cimetidine, Famotidine, Lafutidine, Nizatidine, Ranitidine, Roxatidine  

Histamine2-receptor antagonists markedly suppress basal and meal-stimulated acid secretion by blocking histamine action at the H2-receptors in the parietal cells of the stomach. All H2RAs are equally effective in healing duodenal ulcers. Healing rates were 70-80% after 4 weeks of therapy and 87-95% after 8 weeks. Conventional doses of H2RAs are more effective in healing NSAID-related duodenal ulcers than gastric ulcers.    

Double doses of H2RAs are effective in decreasing the risk of NSAID-induced gastric ulcer. H2RAs given with NSAIDs may be a cost-effective way of preventing ulcer bleeding secondary to NSAID use; however, no clinical data is available that proves that this strategy prevents ulcer complications. No study has evaluated the efficacy of H2RAs in chronic NSAID users. This is less effective than PPIs. H2RAs are generally safe and well tolerated but can cause mild central nervous system (CNS) effects due to their ability to cross the blood-brain barrier and react with CNS histamine receptors. Cimetidine and Ranitidine both interact with the hepatic cytochrome P-450 mixed oxidase system and can inhibit the elimination of other drugs that are metabolized through the same system. H2RAs are well absorbed after oral administration and absorption is not affected by food; unlike other agents in this class, Nizatidine does not undergo first-pass hepatic metabolism and has nearly 100% oral bioavailability. 

Potassium-Competitive Acid Blockers (PCABs)  

Example drugs: Revaprazan, Tegoprazan, Vonoprazan  

Potassium-competitive acid blockers reversibly inhibit the activity of H+/K+-ATPase by competing for potassium on the luminal side of the parietal cells at the final stage of the acid secretory pathway. They are acid stable and do not need an acidic environment for activation (ie a prodrug is not necessary). The full effect is achieved with the first dose due to its rapid onset of action and with similar effects seen on succeeding doses. A comparable safety profile and similar efficacy in healing and prevention of NSAID-induced ulcers with PPIs. Tegoprazan and Vonoprazan, in combination with antibiotics, are effective for the eradication of H pylori associated with PUD.

Prostaglandin Analogues  

Example drug: Misoprostol  

Prostaglandin analogues protect the gastroduodenal mucosa by promoting the secretion of bicarbonate and mucus, and by augmenting mucosal blood flow and cell restoration in the gastric mucosa. These also have an antisecretory effect when given in high doses. These are useful in healing ulcers and preventing ulcer recurrence. These are primarily recommended for the prevention of NSAID-induced gastroduodenal ulceration. Prostaglandin analogues need frequent dosing and are associated with more side effects than H2Ras; hence, these are generally not used for the treatment of PUD. The major drawback is the incidence of diarrhea and its abortifacient property; hence, these are not for use by pregnant women and women of childbearing age.  

Proton Pump Inhibitors (PPIs)  

Example drugs: Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole  

PPIs are the most potent inhibitors of gastric acid secretion. They are most effective if they are administered immediately before meals; for once-daily dosing, it is recommended that PPIs be taken immediately before breakfast. These irreversibly inhibit the activity of the H+/K+-ATPase pump of gastric parietal cells. These have a similar safety profile to H2RAs but heal peptic ulcers faster than H2Ras. These have an 80-100% healing rate after 4 weeks of therapy in patients with duodenal ulcers and 8 weeks for patients with gastric ulcers. Co-medication with PPIs is better than with H2RAs in preventing ulcer bleeding in patients on antiplatelet or anticoagulant therapy.  

PPIs are preferred over standard-dose H2RAs for healing NSAID-induced peptic ulcer and are widely used in combination with NSAIDs to prevent ulcer development. These are associated with significant risk reduction for upper GI bleeding in patients who use NSAIDs. These are the main agents for prophylaxis and treatment of NSAID-related upper GI injury. PPI in combination with COX-2 inhibitors is associated with the highest risk reduction for recurrent complications of ulcers and may be given for primary prophylaxis or if long-term NSAIDs are needed.  

In high-risk patients with a non-variceal peptic ulcer bleed, high-dose IV or oral PPIs may be given after endoscopic hemostasis is achieved to decrease the incidence of rebleeding and possible need for surgery. Oral PPIs are recommended to be given for 6-8 weeks after endoscopic treatment of bleeding peptic ulcer for mucosal healing. Refractory PUD may be treated with double-strength PPIs to achieve healing. Long-term PPI use without a strong indication should be avoided; long-term PPI therapy may be offered to patients with idiopathic ulcers. These may also be used in patients with gastric outlet obstruction to heal any active ulcers. PPIs may be incorporated with calcium supplements to mitigate increased risk of bone fractures associated with long-term use.

Sucralfate  

Sucralfate has been used to treat PUD and has similar healing rates as antacids and H2Ras. This protects the gastroduodenal mucosa by adhering to the base of the ulcer, adsorbing bile acids, inactivating pepsin, and stimulating bicarbonate and mucus secretion without affecting gastric acid secretion. This may also be used in preventing duodenal ulcer relapse. Sucralfate has an excellent safety profile and is generally well tolerated. The treatment duration for PUD is 4 weeks.

Nonpharmacological

Patient Education  

Alcohol  

Alcohol is a strong promoter of acid secretion. It is an independent risk factor for PUD. Chronic alcohol drinkers develop ulceration, while occasional drinkers may only have gastritis. The recurrence rates of patients who consume alcohol were significantly higher in patients with gastric ulcer recurrence compared to duodenal ulcer recurrence with ulcers reappearing at the same or adjacent sites as the previous ulcers. Patients should be advised to limit their alcohol intake to 1 alcoholic drink/day.  

Diet  

There is limited evidence that changing the diet hastens ulcer healing or prevents recurrence. Patients should be advised to avoid specific foods that may precipitate dyspepsia, eg coffee, caffeinated soda, fatty and spicy foods. Milk has been shown to be a potent gastric acid secretion stimulus.  

Medication Use  

Aspirin, NSAIDs and corticosteroids can cause peptic ulceration. Cardiologists should carefully assess the need for Aspirin in patients with a history of PUD. Patients should be advised to discontinue NSAID use; if not possible, alternative agents may be considered to prevent the development of peptic ulceration and mucosal injury. Prolonged NSAID use should be given with a PPI, high-dose (2x) histamine2-receptor antagonists (H2RAs), or Misoprostol. A selective cyclooxygenase-2 (COX-2) inhibitor should be substituted for a traditional NSAID. COX-2 inhibitors cause a significantly lower incidence of ulceration and ulcer complications, but their use has been decreased due to their association with myocardial infarction and thrombotic cardiovascular (CV) events. Current studies suggest that both coxibs and NSAIDs, with the possible exception of full-dose Naproxen, increase CV risk. NSAID use should be based on assessment of an individual patient’s GI and CV risks. In patients with low CV risk, use an NSAID at the lowest effective dose for low GI risk and Celecoxib plus a PPI for high GI risk. In patients with high CV risk, use Naproxen or Celecoxib plus a PPI for low GI risk, and Celecoxib plus a PPI only if simple analgesics have failed for high GI risk. 



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Smoking  

Smoking increases the risk of ulcer recurrence and slows healing. The risk of PUD is correlated with the number of cigarettes smoked per day. The recurrence rates of patients who smoked were significantly higher in patients with gastric ulcer recurrence compared to duodenal ulcer recurrence, with ulcers reappearing at the same or adjacent sites as the previous ulcers. Patients should be advised to stop smoking.  

Psychosocial Factors  

Inability to tolerate stress and depressive symptoms increases the risk of ulcer development. Work-related stress, social problems, and post-traumatic stress disorder are also predictive of subsequent ulcer disease. Counseling patients regarding stress reduction can be helpful.

Surgery

Surgery is recommended in patients with emergent ulcer-related complications (eg hemorrhage, perforation, gastric outlet obstruction), PUD refractory to medical and/or endoscopic management, or rare causes of ulcer disease (eg gastrinoma, Zollinger-Ellison syndrome). The most common indication for surgery is bleeding. Surgical hemostasis is recommended for patients with bleeding peptic ulcers after failure of repeated endoscopy or after initial endoscopy in patients with >2 cm ulcers, hypotension, and/or unstable hemodynamic status. Peritonitis resulting from perforation is a surgical emergency that needs patient resuscitation, laparotomy and peritoneal toilette, or omental patch placement.  

Definitive ulcer surgeries include truncal vagotomy, selective vagotomy, highly selective vagotomy, or partial gastrectomy for duodenal ulcer and partial gastrectomy with gastroduodenal or gastrojejunal anastomosis for gastric ulcer. Chronic obstruction may be relieved by vagotomy and pyloroplasty, antrectomy, or gastroenterostomy. The indications for elective peptic ulcer surgery include resection of ulcers suspected to be malignant, failure to heal despite maximal medical therapy (intractability), intolerance or non-compliance with medical regimen, and relapse while on maximal medical therapy.