Peptic%20ulcer%20disease Treatment
Principles of Therapy
- The most appropriate therapy for peptic ulcer disease (PUD) depends on the cause
- Treatment of both gastric and duodenal ulcers involves suppression of acid secretion, eradication of H pylori (if present) and avoidance of nonsteroidal anti-inflammatory drugs (NSAIDs)
- Antisecretory therapy speeds up the healing process and allows faster relief of symptoms
- 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 ulcer
- It is important to suppress nocturnal acid secretion in patients with duodenal ulcers
- Maintenance antisecretory therapy may be recommended in patients at high risk for ulceration (ie history of ulcer complications, have frequent recurrences) and for H pylori infection unresponsive to repeat treatment
Pharmacotherapy
Antacids
- Neutralize gastric acid and lower pepsin activity
- Effective in relieving symptoms of PUD, promoting healing of ulcers and reducing recurrence
- Used only for short-term relief of symptoms
- 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 be used only for 1-2 days
- Non-absorbable antacids are preferred due to lesser systemic side effects
Bismuth subcitrate
- Has high affinity for damaged tissue
- Coats the base of the ulcer crater that provides protection against gastric acid, pepsin and bile
- Treatment efficacy is comparable with histamine2-receptor antagonists (H2RAs) and other ulcer healing agents
Histamine2-Receptor Antagonists (H2RAs)
- Eg Cimetidine, Famotidine, Lafutidine, Nizatidine, Ranitidine, Roxatidine
- Decrease gastric 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
- 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 complication
- No study has evaluated the efficacy of H2RAs in chronic NSAID users
- Less effective than proton pump inhibitors (PPIs)
- H2RAs are generally well tolerated but can cause mild central nervous system effects due to their ability to cross the blood-brain barrier and react with central nervous system (CNS) histamine receptors
- Cimetidine and Ranitidine both interact with hepatic cytochrome P-450 mixed oxidase system, hence can alter the metabolism of different drugs
Potassium-Competitive Acid Blockers (PCABs)
- Eg Revaprazan, Vonoprazan
- Reversibly inhibit the activity of H+/K+-ATPase by competing for potassium on the luminal side of the parietal cell
- Full effect is achieved with the first dose due to its rapid onset of action and with similar effect seen on repeated doses
- Similar efficacy in terms of ulcer healing and prevention of NSAID-induced ulcers and comparable safety profile to PPIs
- Studies have shown that Vonoprazan may also be effective for the eradication of H pylori in combination with antibiotics
Prostaglandin Analogues
- Eg Misoprostol
- 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
- Also has antisecretory effect when given in high doses
- Useful in healing ulcers and preventing ulcer recurrence
- Primarily recommended for prevention of NSAID-induced gastroduodenal ulceration
- Needs frequent dosing and associated with more side effects than H2RAs, hence, generally not used for the treatment of PUD
- Major drawback is the incidence of diarrhea and its abortifacient property, hence, not for use by pregnant women and women of childbearing age
Proton Pump Inhibitors (PPIs)
- Eg Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole
- Most potent inhibitor of gastric acid secretion
- Irreversibly inhibit the activity of H+/K+-ATPase pump of the gastric parietal cells
- Have similar safety profile as with H2RAs but PPIs heal peptic ulcers faster than H2RAs
- Has 80-100% healing rate after 4 weeks of therapy in patients with duodenal ulcer and 8 weeks for patients with gastric ulcer
- Co-medication with PPIs is better than with H2RAs in preventing an ulcer bleed in patients on antiplatelet therapy
- Extensively used in combination with NSAIDs to prevent NSAID-induced peptic ulcer
- Associated with significant risk reduction for upper GI bleeding in patient who uses NSAIDs
- Main agent for prophylaxis and treatment of NSAID-related upper GI injury
- Recent studies suggest that PPIs in combination with COX-2 inhibitors is associated with the highest risk reduction for recurrent complication of ulcer
- In high-risk patients with a non-variceal peptic ulcer bleed, high-dose intravenous (IV) or oral PPIs may be given after endoscopic hemostasis is achieved to decrease 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
- May also be used in patients with gastric outlet obstruction to heal any active ulcers
Sucralfate
- Has been used to treat PUD and has healing rates same as with antacids and H2RAs
- Protects the gastroduodenal mucosa by adhering to the base of the ulcer, adsorbing bile acids, inactivating pepsin, and stimulating bicarbonate and mucus secretion; however, has no effect on gastric acid secretion
- May also be used in preventing duodenal ulcer relapse
- Has an excellent safety profile and is generally well tolerated
- Treatment duration for PUD is 4 weeks