Peptic%20ulcer%20disease Treatment

• 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

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