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IV/4.7: Therapy
The therapy of peptic ulcer is aimed at reducing the effects of the aggressive factors (primarily the gastric acid), strengthening the defensive factors, as well as treating the H. pylori infection. Food rich in energy and fibers promote healing of the ulcer; fats and sugars slow down the emptying of the stomach and lessen the effects of the medicines.
Inhibition of the proton pump (H+/K+ ATPase) located on the basolateral membrane of the parietal cells is the base of pharmacologic therapy due to inhibition of gastric acid secretion (omeprazole, esomeprazole, pantoprazole, lansoprazole, rabeprazole). A treatment of 8 weeks results in a healing of the ulcer in 80 to 100%. Antacids neutralize the hydrochloric acid produced in the stomach and strengthen the protective mechanisms of the mucosa. Histamine H2 receptor antagonists (ranitidine, famotidine, nizatidine, roxatidine) decrease histamine-induced acid production. A treatment of 8 weeks results in healing of the ulcer in 87 to 94%. Of the active substances promoting mucous membrane protection, misoprostol, a prostaglandin analog, is not marketed in Hungary; its use is limited by the gastrointestinal side effects which occur at higher doses. The defensive capacity of mucosa is strengthened and the healing of the ulcer is promoted by sucralfate.
Treatment (eradication) of the H. pylori infection includes the administration of a proton pump inhibitor and a double antibiotic combination (amoxicillin and clarithromycin or metronidazole) for a week. If the eradication is unsuccessful, second-line therapy consisting of a proton pump inhibitor and amoxicillin or, depending on the first-line treatment, metronidazole or clarithromycin, or proton pump inhibitor + metronidazole + clarithromycin is recommended. In patients who are unresponsive also to the second treatment, single or double antibiotic resistance is present. The guidelines take no firm stand on the third-line treatment. In Europe bacterial culture and susceptibility tests are recommended prior to the start of a further therapy.
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Ulcers in patients negative to H. pylori and NSAID (idiopathic ulcers) heal more difficultly and recur more frequently, therefore the therapy of idiopathic ulcers and the prevention of their recurrence is usually a more difficult task as compared to the H. pylori positive ulcers. An effective inhibition of acid secretion can be attained more difficultly in patients with H. pylori negative ulcers; therefore a treatment with doses higher than usual (often maximal doses) is required and it should be administered for a longer time. A part of patients require also maintaining, continuous acid secretion inhibiting therapy.
In patients with duodenal ulcer a follow up based on clinical observation is sufficient, while in patients with gastric ulcer one has to strive for a confirmation of the healing by endoscopic and histological examinations in order to exclude any malignant processes; therefore follow up endoscopies are recommended at 4 to 6 weeks and at the end of the 3rd month. An effective inhibition of acid secretion is indicated for 1 to 3 months by taking basic or elevated doses of a proton pump inhibitor. After a successful ulcer healing and eradication complaints may remain in 30 to 40% of the patients (reflux, ulcer-type dyspepsia), requiring a prolonged (3 to 6 months) inhibition of acid secretion (1x standard dose proton pump inhibitor, 0.5x standard dose histamine H2 receptor antagonist). Maintenance therapy is indicated in patients whose ulcers are associated with complications, recur frequently, are not responsive to therapy, or they are giant or fibrotic. In patients with NSAID-induced ulcers the drug should possibly be discontinued in addition to an effective inhibition of acid secretion and, depending on the H. pylori status, eradication.
In patients with a hemorrhage it is important to monitor the hemodynamic parameters, and to apply appropriate circulatory support as well as fluid and blood replacement. Hemostasis may be attained by pharmacologic or endoscopic techniques (electrocoagulation, electro-thermo-hydro probe, laser coagulation, argon beam laser, placing of an endoclip, sclerotization). In case of a hemorrhage not responding to conservative (pharmacologic, endoscopic) therapy, surgical intervention is necessary. Since the introduction of the inhibitors of acid secretion, the number of ulcer surgeries has decreased. Surgical solution is also required (due to a presumed malignancy) in patients whose gastric ulcers yet persist after 12 weeks; or in case of a perforation or an advanced stricture.
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