Peptic ulcers are mainly ulcers that occur in the stomach and duodenum. In recent years, with the in-depth research on the cause and pathogenesis of peptic ulcer, a common and frequent disease, the progress of drugs for the treatment of peptic ulcer has provided many new drugs for the treatment of peptic ulcer. the introduction of H2 receptor antagonists in the 1970s significantly reduced the incidence of peptic ulcer comorbidity and was a milestone in the therapeutics of peptic ulcer disease. the 1980s saw the introduction of H2 receptor blockers, which are more powerful and longer lasting than histamine H2 receptor blockers. The introduction of H+-K+ ATPase (proton pump) inhibitors, which have a more powerful and long-lasting acid-suppressive effect than histamine H2 receptor blockers, greatly improved the healing rate of ulcers; there is a worldwide consensus that H. pylori is the main cause of ulcers. Based on Schwartz’s classical theory, the new concept of “no H. pylori, no ulcer recurrence” has been added. The ensuing treatment of H. pylori effectively reduces the chances of ulcer recurrence, leading to a major change in the treatment strategy for ulcer disease. This has led to a significant change in the treatment strategy for ulcer disease, not only improving the cure rate of ulcers but also reducing the recurrence rate. This has opened a new era in the treatment of peptic ulcers.
At the same time, the proposed theory of gastric mucosal attack-defense factor balance and recent studies have also led pathophysiologists and clinicians to a new understanding that weakened gastric mucosal protection is an important factor in ulcer formation, i.e., strengthening gastric mucosal protection and promoting mucosal repair is one of the important aspects in the treatment of peptic ulcer. Gastric mucosal protective agents developed to enhance the protective effect of gastric mucosa have also been developed. Modern pharmacological treatment therapeutics for peptic ulcer disease have been greatly enriched. Pharmacological treatment aims at eliminating or weakening the aggressive factors and restoring or enhancing the defensive factors. In order to achieve symptom relief, cure ulcers, and prevent recurrence and complications (of course, drug safety and effectiveness/price ratio are also factors to be considered in clinical treatment of any disease).
A. Principles of the selection of drugs for peptic ulcer
1. Acid-suppressing drugs are the mainstay: histamine H2 receptor antagonists and proton pump inhibitors can be the drugs of choice for gastric and duodenal ulcer disease. It is generally believed that PPI is better than H2RAs for healing and maintenance treatment of bulbar ulcers.
2. Selecting drugs according to different types of ulcers: The pathogenesis of gastric ulcer and duodenal ulcer is not exactly the same. The pathogenesis of gastric ulcer is mainly based on impaired mucosal barrier mechanism, and drugs to strengthen the gastric mucosal barrier should be selected mainly, supplemented with acid-suppressing drugs. The patients with duodenal ulcers are mostly accompanied by pathological hyper-secretion of gastric acid and pepsin, and the treatment should be based on drugs that inhibit gastric acid secretion.
3, eradication of Helicobacter pylori (Hp) treatment: Hp infection is currently the world’s most widespread chronic bacterial infection in humans. In developing countries Hp infection rate is about 50-90%, and Hp infection rate increases with age. The infection is most likely through the “mouth bite” and “fecal bite” route, so Hp infection often has family clustering, eradication therapy is one of the most effective, cheapest and simplest ways to treat peptic ulcer.
A single drug cannot eradicate Hp. a triple regimen containing bismuth or a triple regimen containing a proton pump inhibitor, or even a quadruple regimen. However, drug resistance has been a popular current research problem.
4, NSAIDs-related ulcers because they can inhibit mucosal synthesis of prostaglandins (PG), weakening the mucosal cytoprotective effect and enhancing the sensitivity of the mucosa to injury. NSAIDs should be discontinued or reduced if possible, or replaced with other drugs. is the key to treatment. The treatment of such ulcers with H2 receptor antagonists or proton pump inhibitors will help the ulcers heal.
5. The course of drug therapy should be regular, and long-term acid control therapy is required in the following cases.
(1) Ulcer disease without Hp infection (PUD).
(2) Those for whom Hp eradication therapy is ineffective.
(3) Refractory ulcers.
(4) Hypergastrinemia, gastrinoma, hypergastrinemia, hypercalcemia and rapid gastric emptying.
(5) Patients with peptic ulcer who must take Aspirin or other NSAIDs for a long time, and patients who apply NSAIDs prior to eradication of H. pylori can effectively prevent the occurrence of NSAID-related ulcers.
II. Classification and application of peptic ulcer drugs
(i) Drugs that reduce the invasiveness to the mucosa
1. H2 receptor antagonists: H2 receptor antagonists can prevent histamine from binding to H2 receptors on the gastric mucosa, resulting in a decrease in gastric acid secretion from the wall cells. There are three kinds of drugs commonly used in China, cimetidine, ranitidine and famotidine. The treatment of duodenal ulcer requires 4-8 weeks for meclizine and 8-12 weeks for gastric ulcer.
2. Proton pump inhibitor: The final process of gastric acid secretion is the activation of H+-K+-ATPase (proton pump) in the wall cell membrane, which causes H+ (HCL) to be secreted into the gastric lumen. Therefore proton pump inhibitors can inhibit gastric acid secretion caused by any stimulus. Currently listed in China and clinically used are omeprazole, lansoprazole, pantoprazole, and rabeprazole have been listed in China.
Now commonly used proton pump inhibitors are omeprazole, nexin, lansoprazole (lansoprazole), pantoprazole, rabeprazole, commonly used dose in the order of 20mg/day; 20mg/day; 30mg/day; 40mg/day; 10mg/day, can control the symptoms within 1 to 3 days, DU in two weeks after taking the drug healing rate of up to 70%, after 4 weeks to more than 90%, 6 ～The healing effect of GU is not as good as that of DU, and the time of taking the drug should be extended appropriately.
3, the acid making agent: the treatment of peptic ulcer before the 70s mainly rely on these drugs. There has been nearly a century of application history. Mainly some inorganic weak bases, after oral intake can directly neutralize the gastric acid, can reduce or lift the gastric acid on the ulcer surface stimulation and corrosion effect. Cheaper, common sodium bicarbonate (baking soda), aluminum hydroxide, magnesium hydroxide, calcium carbonate, etc.. These drugs are mostly made into compound preparations, such as: gastric soothing (containing aluminum hydroxide, magnesium trisilicate, belladonna infusion), etc. Sodium bicarbonate has tended to be eliminated due to too many adverse reactions. Now still in use for the colloidal aluminum magnesium combination and compound calcium carbonate, the rest have been abandoned. Magnesium aluminum carbonate for a new generation of antacids and mucosal protective effect.
(B) enhance the mucosal defense drugs
Gastric mucosal protective drugs It is known that the weakening of the protective effect of gastric mucosa is an important factor in the formation of ulcers, and recent studies have concluded that strengthening the protective effect of gastric mucosa and promoting the repair of mucosa is one of the important aspects of the treatment of peptic ulcer. At the same time, gastric mucosal protective agents developed to enhance the protective effect of gastric mucosa have been continuously developed. Such as various dosage forms of colloidal bismuth, aluminum thioglycollate, magnesium aluminum carbonate, Schweser, Metsulin-S granules, etc. and prostate derivatives. It can be used externally as well as internally. In recent years, it has been reported that it is used internally for bleeding stomach pain and gastric and duodenal ulcers. Combined with H2 receptor antagonist treatment, the efficacy of Kangfu Xin oral solution for the treatment of peptic ulcer is comparable to that of Loxac.
1.Colloidal bismuth subcitrate (CBS): the clinical dosage is 120mg, 4 times/day, eight weeks of treatment, the healing rate of DU and GU is similar to that of H2 receptor antagonist.
2, aluminum thioglycollate (sucralfate): the dosage is 1g, 3-4 times / day.
3, aluminum magnesium carbonate (Taicid): dosage of 1g, 3-4 times / day
4.Prostaglandin (prostaglandine
E): now the clinical application of 2, misoprostol (misoprostol) and enprostil (enprostil), dosage of 200ug, 4 times / day and 35ug, 2 times / day, a course of 4 weeks, the efficacy is similar to the cimetidine
5, rehabilitation of new oral liquid: dosage of 10-20ml, 3-4 times / day
(C) kill Helicobacter pylori
(1) Bismuth-containing triplet: CBS 240mg, 2 times/day + metronidazole 400mg, 2 times/day + tetracycline 500mg, 2 times/day, or CBS 240mg, 2 times/day + metronidazole 400mg, 2 times/day + amoxicillin 500mg,
2 times/day, or CBS 240mg, 2 times/day + metronidazole 400mg, 2 times/day + clarithromycin 250mg, 2 times/day, for 1~2 weeks, the eradication rate of H.pylori is more than 85%;
(2) Triplex containing proton pump inhibitor: omeprazole 20mg (or other PPI preparation), 2 times/day + metronidazole 400mg, 2 times/d + clarithromycin 250mg, 2 times/day, or omeprazole 20mg (or other PPI preparation)
2 times/d + metronidazole 400mg.
2 times/d + amoxicillin 1000mg, 2 times/d, or omeprazole 20mg (or other PPI preparations), 2 times/d + clarithromycin 250mg, 2 times/d + amoxicillin 1000mg, 2 times/d, for 1 week, the eradication rate of H. pylori is more than 90%;
(3) In case of failure of triple therapy eradication, quadruple therapy can be used: for bismuth-containing triple + proton pump inhibitor, a course of 1 week.
(D) The problem of drug resistance of H. pylori
With the in-depth understanding of H. pylori and the development of treatment and the widespread use of antibiotics, the rate of bacterial resistance to antibiotics is increasing. The rate of drug resistance of H. pylori varies from one country region to another. The resistance rate to metronidazole and clarithromycin is on the rise worldwide, ranging from 20% to 80% (average 30%-40%) for metronidazole and 1%-20% for clarithromycin. Irregularity of treatment protocols, poor patient compliance, and misuse of antibiotics are important causes of antibiotic resistance.
The following measures can reduce the occurrence of drug resistance and improve the therapeutic effect, as recommended by the Eradication of Helicobacter pylori Group in China.
1, strictly grasp the indications for eradication, the choice of formal and effective treatment programs.
2, combination of drugs, avoiding the use of a single antibiotic or antibacterial drugs.
3, strengthening the knowledge of primary care physicians on H. pylori treatment and updating.
4, for patients who have failed eradication treatment, drug sensitivity testing before re-treatment in units where available to avoid the use of antibiotics that are resistant to them.
5, the continuous development of new drugs for the treatment of H. pylori, including combined Chinese and Western medicine treatment.
6. the use of the PPI triplet regimen for 2 weeks if necessary due to the drug resistance of H. pylori.
7, for those who fail in first-line therapy and switch to remedial therapy, try to avoid nitroimidazoles and should switch to other drugs, such as furazolidone and intragastric retention-type gentamicin extended-release tablets
8. Efforts should be made to research and develop H. pylori vaccines to make immune control of the infection a reality.
For the choice of treatment regimen, principles should be followed to avoid the occurrence of drug resistance.