Gastroesophageal reflux disease (GERD) - Conservative treatment

The success of therapy lies not only in adequate drug correction, but also in changing the patient’s lifestyle and dietary habits.

Recommendations for a certain lifestyle for the patient:

• changes in body position during sleep;
• changes in nutrition;
• abstinence from smoking;
• abstinence from alcohol abuse;
• if necessary, weight loss;
• refusal of medications that induce the development of GERD;
• avoiding loads that increase intra-abdominal pressure, wearing corsets, bandages and tight belts, lifting weights over 8-10 kg on both hands, work that involves bending the torso forward, physical exercises that involve overexertion of the abdominal muscles.

To restore muscle tone of the diaphragm, special exercises that do not involve bending the torso are recommended.

Avoiding a strictly horizontal position during sleep helps reduce the number of reflux episodes and their duration, as esophageal cleansing is enhanced by gravity. The patient is advised to raise the head of the bed by 15 cm .

The following dietary changes are recommended:

• it is necessary to avoid overeating and snacking at night;
• lying down after eating;
• after eating, avoid bending forward and lying down;
• foods rich in fat (whole milk, cream, fatty fish, goose, duck, pork, fatty beef, lamb, cakes, pastries), drinks containing caffeine (coffee, strong tea or cola), chocolate, products containing peppermint and pepper (all of them reduce the tone of the lower esophageal sphincter);
• citrus fruits and tomatoes, fried foods, onions and garlic, as they have a direct irritating effect on the sensitive esophageal mucosa;
• consumption of butter and margarine is limited;
• It is recommended to eat 3-4 meals a day, a diet with a high protein content, since protein foods increase the tone of the lower esophageal sphincter;
• last meal - no less than 3 hours before bedtime, after meals 30-minute walks.
• sleep with the head of the bed elevated; avoid loads that increase intra-abdominal pressure: do not wear tight clothing and tight belts, corsets, do not lift weights more than 8-10 kg on both hands, avoid physical activity associated with overstraining the abdominal muscles; quit smoking; maintain normal body weight;

For preventive purposes, it is necessary to prescribe cocktails suggested by G.V. Dibizhevoy for 2-3 weeks: cream or fermented baked milk 0.5 liters + whipped protein of one egg + 75 ml. 3% tannin. Use 8-10 times a day, several sips through a straw before and after meals.

Avoid taking medications that reduce the tone of the lower esophageal sphincter (anticholinergics, tricyclic antidepressants, sedatives, tranquilizers, calcium antagonists, beta-agonists, medications containing L-dopamine, narcotics, prostaglandins, progesterone, theophylline).

Treatment in most cases should be carried out on an outpatient basis. Treatment should include general measures and specific drug therapy.

Indications for hospitalization

Antireflux treatment in complicated cases of the disease, as well as in case of ineffectiveness of adequate drug therapy. Endoscopic or surgical intervention (fundoplication) in case of ineffectiveness of drug therapy, in the presence of complications of esophagitis: strictures of Barrett's esophagus, bleeding.

Drug therapy

Includes the administration of prokinetics, antisecretory agents and antacids.

Brief description of drugs used in the treatment of gastroesophageal reflux disease:

1. Antacid drugs

Mechanism of action: neutralize hydrochloric acid, inactivate pepsin, adsorb bile acids and lysolicitin, stimulate the secretion of bicarbonates, have a cytoprotective effect, improve esophageal cleansing and alkalization of the stomach, which helps to increase the tone of the lower esophageal sphincter.

For the treatment of gastroesophageal reflux disease, it is better to use liquid forms of antacid drugs. It is better to use conditionally insoluble (non-systemic) antacid drugs, such as those containing non-absorbable aluminum and magnesium, antacids (Maalox, Phosphalugel, Gastal, Rennie), as well as antacid drugs that contain substances that eliminate the symptoms of flatulence (Protab, Daigin, Gestid).

Of the great variety of antacid drugs, one of the most effective is Maalox. It is distinguished by a variety of forms, the highest acid-neutralizing capacity, as well as the presence of a cytoprotective effect due to the binding of bile acids, cytotoxins, lysolecithin and activation of the synthesis of prostaglandins and glycoproteins, stimulation of the secretion of bicarbonates and protective mucopolysaccharide mucus, a virtually complete absence of side effects and a pleasant taste.

Preference should be given to third-generation antacid drugs such as Topalkan, Gaviscon. They contain: colloidal aluminum oxide, magnesium bicarbonate, hydrated silicic anhydrite and alginic acid. When dissolved, Topalkan forms a foamy antacid suspension that not only adsorbs HCI, but also, accumulating above the layer of food and liquid and getting into the esophagus in case of gastroesophageal reflux, has a therapeutic effect, protecting the mucous membrane of the esophagus from aggressive gastric contents. Topalkan is prescribed 2 tablets 3 times a day 40 minutes after meals and at night.

2. Prokinetics

The pharmacological action of these drugs consists of enhancing antropyloric motility, which leads to accelerated evacuation of gastric contents and increased tone of the lower esophageal sphincter, a decrease in the number of gastroesophageal refluxes and the time of contact of gastric contents with the esophageal mucosa, improved esophageal cleansing and the elimination of delayed gastric evacuation.

One of the first drugs in this group is the central dopamine receptor blocker Metoclopramide (Cerucal, Reglan). It enhances the release of acetylcholine in the gastrointestinal tract (stimulates the motility of the stomach, small intestine and esophagus), blocks central dopamine receptors (affects the vomiting center and the center regulating gastrointestinal motility). Metoclopramide increases the tone of the lower esophageal sphincter, accelerates evacuation from the stomach, has a positive effect on esophageal clearance and reduces gastroesophageal reflux.

The disadvantage of Metoclopramide is its undesirable central action (headache, insomnia, weakness, impotence, gynecomastia, increased extrapyramidal disorders). Therefore, it cannot be used for a long time.

A more successful drug from this group is Motilium (Domperidone), which is an antagonist of peripheral dopamine receptors. The effectiveness of Motilium as a prokinetic agent does not exceed that of Metoclopramide, but the drug does not penetrate the blood-brain barrier and has virtually no side effects. Motilium is prescribed 1 tablet (10 mg) 3 times a day 15-20 minutes before meals. As a monotherapy, it can be used in patients with grades I-II GERD. It is important to note that Motilium intake cannot be combined in time with antacids, since an acidic environment is necessary for its absorption, and with anticholinergic drugs that neutralize the effect of Motilium. The most effective for the treatment of GERD is Prepulsid (Cisapride, Coordinax, Peristil). It is a gastrointestinal prokinetic agent devoid of antidopaminergic properties. Its mechanism of action is based on indirect cholinergic effects on the neuromuscular apparatus of the gastrointestinal tract. Prepulsid increases the tone of the LES, increases the amplitude of esophageal contractions and accelerates the evacuation of stomach contents. At the same time, the drug does not affect gastric secretion, so Prepulsid is best combined with antisecretory drugs for reflux esophagitis.

The prokinetic potential of a number of other drugs is being studied: Sandostatin, Leuprolide, Botox, as well as drugs that act through serotonin receptors 5-HT ₃ and 5-HT ₄.

3. Antisecretory drugs

The goal of antisecretory therapy for GERD is to reduce the damaging effects of acidic gastric contents on the esophageal mucosa. H2-histamine receptor blockers and proton pump inhibitors are used in the treatment of GERD.

_{4. H2} -histamine receptor blockers

Currently, 5 classes of H2-blockers are available _: Cimetidine (1st generation), Ranitidine (2nd generation), Famotidine (3rd generation), Nizatidine (Axid) (4th generation) and Roxatidine (5th generation).

The most widely used drugs are from the Ranitidine (Ranisan, Zantac, Ranitin) and Famotidine (Quamatel, Ulfamid, Famosan, Gastrosidin) groups. These drugs effectively reduce basal, night, food- and drug-stimulated secretion of hydrochloric acid in the stomach, and inhibit pepsin secretion. If possible, preference should be given to Famotidine, which, due to its greater selectivity and lower dosage, acts longer and does not have the side effects inherent in Ranitidine. Famotidine is 40 times more effective than Cimetidine and 8 times more effective than Ranitidine. In a single dose of 40 mg, it reduces night secretion by 94%, basal by 95%. In addition, Famotidine stimulates the protective properties of the mucous membrane by increasing blood flow, bicarbonate production, prostaglandin synthesis, and enhancing epithelial reparation. The duration of action of 20 mg Famotidine is 12 hours, 40 mg - 18 hours. The recommended dose for the treatment of GERD is 40-80 mg per day.

5. Proton pump inhibitors

Proton pump inhibitors are currently considered the most powerful antisecretory drugs. Drugs in this group are virtually devoid of side effects, since they exist in active form only in the parietal cell. The action of these drugs is to inhibit the activity of Na ⁺ /K ⁺ -ATPase in the parietal cells of the stomach and block the final stage of HCI secretion, while almost 100% inhibition of hydrochloric acid production in the stomach occurs. Currently, 4 chemical varieties of this group of drugs are known: Omeprazole, Pantoprazole, Lansoprazole, Rabeprazole. The progenitor of the proton pump inhibitors is Omeprazole, first registered as the drug Losek by Astra (Sweden). A single dose of 40 mg of Omeprazole completely blocks the formation of HCI for 24 hours. Pantoprazole and Lansoprazole are used in a dosage of 30 and 40 mg, respectively. The drug from the Rabiprazole group Pariet has not yet been registered in our country; clinical trials are underway.

Omeprazole (Losec, Losek-maps, Mopral, Zoltum, etc.) at a dose of 40 mg allows healing of esophageal erosions in 85-90% of patients, including patients who do not respond to therapy with histamine H2-receptor blockers _. Omeprazole is especially indicated for patients with GERD stages II-IV. Control studies with Omeprazole showed earlier attenuation of GERD symptoms and more frequent cures compared to conventional or double doses of H2 _- blockers, which is associated with a greater degree of suppression of acid production.

Recently, a new improved form of the drug "Losec", produced by the company "Astra", "Losec-maps", appeared on the market of medicinal products. Its advantage is that it does not contain allergens of fillers (lactose and gelatin), is smaller in size than a capsule, and is covered with a special shell to facilitate swallowing. This drug can be dissolved in water and, if necessary, used in patients with a nasopharyngeal tube.

Currently, a new class of antisecretory drugs is being developed that do not inhibit the proton pump, but only prevent the movement of Na ⁺ /K ⁺ -ATPase. A representative of this new group of drugs is ME - 3407.

6. Cytoprotectors.

Misoprostol (Cytotec, Cytotec) is a synthetic analogue of PG E2. It has a broad protective effect on the gastrointestinal mucosa:

• reduces the acidity of gastric juice (suppresses the secretion of hydrochloric acid and pepsin, reduces the reverse diffusion of hydrogen ions through the gastric mucosa;
• increases the secretion of mucus and bicarbonates;
• increases the protective properties of mucus;
• improve blood flow in the esophageal mucosa.

Misoprostol is prescribed at 0.2 mg 4 times a day, usually for stage III gastroesophageal reflux disease.

Venter (Sucralfate) is an ammonium salt of sulfated sucrose (disaccharide). Accelerates the healing of erosive and ulcerative defects of the esophagogastroduodenal mucosa by forming a chemical complex - a protective barrier on the surface of erosions and ulcers and prevents the action of pepsin, acid and bile. It has an astringent property. Prescribed 1 g 4 times a day between meals. The administration of Sucralfate and antacid drugs should be separated by time.

In gastroesophageal reflux caused by the reflux of duodenal contents into the esophagus (alkaline, bile reflux variant), usually observed in cholelithiasis, a good effect is achieved by taking non-toxic ursodeoxycholic bile acid (Ursofalk) 250 mg at night, which in this case is combined with Koordinax. The use of Cholestyramine is also justified (an ammonium anion exchange resin, a non-absorbable polymer, binds to bile acids, forming a strong complex with them, excreted with feces). Taken at 12-16 g / day.

Dynamic observation of the detected secretory, morphological and microcirculatory disorders in GERD confirms the various currently proposed regimens for drug correction of gastroesophageal reflux disease.

The most common are (A.A. Sheptulin):

• a "stepwise increasing" therapy scheme, which involves prescribing drugs and combinations of varying strengths at different stages of the disease. Thus, at the first stage, the main focus of treatment is on lifestyle changes and, if necessary, taking antacids. If clinical symptoms persist, prokinetics or H2-histamine receptor blockers are prescribed at the second stage of treatment _. If such therapy is ineffective, then at the 3rd stage, proton pump inhibitors or a combination of H2-blockers and prokinetics are used ₍ in particularly severe cases, a combination of proton pump blockers and prokinetics);
• The "step-down" therapy scheme involves the initial administration of proton pump inhibitors, followed by a transition to H2-blockers or prokinetics after achieving a clinical effect _. The use of such a scheme is justified in patients with severe disease and pronounced erosive and ulcerative changes in the esophageal mucosa.

Options for drug therapy taking into account the stage of development of GERD (P.Ya. Grigoriev):

1. For gastroesophageal reflux without esophagitis, Motilium or Cisapride is prescribed orally for 10 days, 10 mg 3 times a day in combination with antacids, 15 ml 1 hour after meals, 3 times a day and the 4th time before bedtime.
2. In case of reflux esophagitis of the 1st degree of severity, H2-blockers are prescribed orally _: for 6 weeks - Ranitidine 150 mg 2 times a day or Famotidine 20 mg 2 times a day (for each drug, take in the morning and evening with an interval of 12 hours). After 6 weeks, if remission occurs, drug treatment is stopped.
3. For reflux esophagitis of the 2nd degree of severity - Ranitidine 300 mg 2 times a day or Famotidine 40 mg 2 times a day or Omeprazole 20 mg after lunch (at 2-3 p.m.) is prescribed for 6 weeks. After 6 weeks, drug treatment is stopped if remission has occurred.
4. For grade III reflux esophagitis, Omeprazole 20 mg is prescribed orally for 4 weeks, 2 times a day, in the morning and in the evening with a mandatory interval of 12 hours, and then, in the absence of symptoms, continue taking Omeprazole 20 mg per day or another proton pump inhibitor 30 mg 2 times a day for up to 8 weeks, after which they switch to taking H2-histamine receptor blockers _in a maintenance half dose for a year.
5. In case of grade IV reflux esophagitis, Omeprazole 20 mg is prescribed orally for 8 weeks, 2 times a day, in the morning and in the evening with a mandatory interval of 12 hours, or another proton pump inhibitor, 30 mg 2 times a day, and when remission occurs, switch to permanent intake of H2- _histamine blockers. Additional means of therapy for refractory forms of GERD include Sucralfate (Venter, Sukratgel), 1 g 4 times a day 30 minutes before meals for 1 month.

G. Tytgat recommended adhering to the following rules in the treatment of gastroesophageal reflux disease:

• a mild disease (reflux esophagitis grade 0-1) requires a special lifestyle and, if necessary, taking antacids or H2 _- receptor blockers;
• at a moderate degree of severity (reflux esophagitis grade II), along with constant adherence to a special lifestyle and diet, long-term use of H2-receptor blockers _in combination with prokinetics or proton pump inhibitors is necessary;
• in severe cases (grade III reflux esophagitis), a combination of H2-receptor blockers _and proton pump inhibitors or high doses of H2-receptor blockers _and prokinetics are prescribed;
• the lack of effect of conservative treatment or complicated forms of reflux esophagitis are indications for surgical treatment.

Considering that one of the main reasons leading to increased spontaneous relaxation of the lower esophageal sphincter is an increase in the level of neuroticism in patients suffering from GERD, testing to assess the personality profile and correct the identified disorders seems extremely relevant. To assess the personality profile in patients with pathological gastroesophageal refluxes identified by pH-metry, we conduct psychological testing using a computer modification of the Eysenck, Shmishek, MMPI, Spielberger questionnaires, and the Luscher color test, which allows us to identify the dependence of the nature and severity of gastroesophageal refluxes on individual personality traits and, accordingly, taking this into account, develop effective treatment regimens. Thus, it is possible to achieve not only a reduction in treatment time, but also to significantly improve the quality of life of patients. Along with standard therapy, depending on the identified anxious or depressive personality type, patients are prescribed Eglonil 50 mg 3 times a day or Grandaxin 50 mg 2 times a day, Teralen 25 mg 2 times a day, which improves the prognosis of the disease.

Treatment of gastroesophageal reflux disease in pregnant women

It has been established that the main symptom of GERD - heartburn - occurs in 30-50% of pregnant women. Most (52%) pregnant women experience heartburn in the first trimester. The pathogenesis of GERD is associated with hypotension of the LES under basal conditions, increased intra-abdominal pressure and slow evacuation function of the stomach. Diagnosis of the disease is based on clinical data. Endoscopic examination (if necessary) is considered safe. Lifestyle changes are of particular importance in treatment. At the next stage, "non-absorbable" antacids are added (Maalox, Phosphalugel, Sucralfate, etc.). Considering that Sucralfate (Venter) can cause constipation, the use of Maalox is more justified. In case of treatment refractoriness, H2-blockers such as Ranitidine or Famotidine can be _used.

The use of Nizatidine during pregnancy is not indicated, since in the experiment the drug showed teratogenic properties. Taking into account the experimental data, the use of Omeprazole, Metoclopramide and Cisapride is also undesirable, although there are isolated reports of their successful use during pregnancy.

Anti-relapse treatment of gastroesophageal reflux disease

Currently, there are several options for anti-relapse treatment of GERD (permanent therapy):

• H2 _- blockers in a full daily dose twice a day (Ranitidine 150 mg 2 times a day, Famotidine 20 mg 2 times a day, Nizatidine 150 mg 2 times a day).
• Treatment with proton pump inhibitors: Omeprazole (Losec) 20 mg in the morning on an empty stomach.
• Taking prokinetics: Cisapride (Coordinax) or Motilium in half the dose compared to the dose used during the exacerbation period.
• Long-term treatment with non-absorbable antacids (Maalox, Phosphalugel, etc.).

The most effective anti-relapse drug is omeprazole 20 mg in the morning on an empty stomach (88% of patients maintain remission for 6 months of treatment). When comparing Ranitidine and placebo, this figure is 13 and 11%, respectively, which casts doubt on the advisability of long-term use of Ranitidine for anti-relapse treatment of GERD.

Retrospective analysis of prolonged permanent use of small doses of Maalox suspension 10 ml 4 times a day (acid-neutralizing capacity 108 mEq) in 196 patients with stage II GERD showed a fairly high anti-relapse effect of this regimen. After 6 months of permanent therapy, remission was maintained in 82% of patients. No patient experienced side effects that forced them to stop prolonged treatment. No data on the presence of phosphorus deficiency in the body were obtained.

American specialists have calculated that a five-year full antireflux therapy costs patients more than $6,000. At the same time, when stopping taking even the most effective drugs and their combinations, there is no long-term remission. According to foreign authors, relapse of GERD symptoms occurs in 50% of patients 6 months after stopping antireflux therapy, and in 87-90% after 12 months. There is an opinion among surgeons that adequately performed surgical treatment of GERD is effective and cost-effective.

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