Gastroesophageal Reflux Disease (GERD): Conservative Treatment

The success of therapy is not only in the adequately conducted drug correction, but also in changing the lifestyle and dietary habits of the patient.

Recommendations for a patient of a certain lifestyle:

• changes in the position of the body during sleep;
• changes in nutrition;
• refraining from smoking;
• abstaining from alcohol abuse;
• if necessary, weight loss;
• refusal of medications that induce the onset of GERD;
• exclusion of loads increasing intra-abdominal pressure, wearing corsets, bandages and tight belts, lifting weights of more than 8-10 kg on both hands, work involving a torso bending forward, physical exercises associated with overstrain of abdominal muscles.

To restore the muscle tone of the diaphragm, special exercises are recommended that are not related to the torso of the trunk.

Exclusion of a strictly horizontal position during sleep can reduce the number of reflux episodes and their duration, as esophageal cleansing increases due to the action of gravity. Patient is advised to raise the head end of the bed on15 centimeters.

The following changes in the diet are recommended:

• it is necessary to exclude overeating, "snacking" at night;
• lying down after eating;
• after eating, avoid tilting forward and horizontal position;
• foods rich in fat (whole milk, cream, fatty fish, goose, duck, pork, fat beef, lamb, cakes, cakes), drinks containing caffeine (coffee, strong tea or cola), chocolate, peppermint and peppermint products pepper (they all reduce the tone of the lower esophageal sphincter);
• citrus and tomatoes, fried, onions and garlic, as they have a direct irritant effect on the sensitive esophageal mucosa;
• limited consumption of butter, margarine;
• it is recommended 3-4 meals a day, a diet with high protein content, as protein food increases the tone of the lower esophageal sphincter;
• the last meal - at least 3 hours before bedtime, after meals 30-minute walks.
• to sleep with the raised head end of the bed; eliminate the stresses that increase intra-abdominal pressure: do not wear tight clothes and tight belts, corsets, do not lift weights over 8-10 kg on both hands, avoid the physical stress associated with overstrain of the abdominal press; to give up smoking; maintaining normal body weight;

With a prophylactic goal, it is necessary for 2-3 weeks to appoint cocktails, proposed by G.V. Dibizhevoy: cream or fermented milk 0.5 liters + whipped egg white + 75 ml. 3% tannin. Apply 8-10 times a day for a few sips through the straw before and after eating.

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

Treatment in most cases should be performed on an outpatient basis. Treatment should include general interventions and specific drug therapy.

Indications for hospitalization

Antireflux treatment in case of complicated course of the disease, as well as in case of ineffectiveness of adequate medication. Conducting endoscopic or surgical intervention (fundoplication) in case of ineffectiveness of drug therapy, in the presence of complications of esophagitis: stricture of Barrett's esophagus, bleeding.

Drug therapy

Includes the appointment of prokinetics, antisecretory drugs and antacids.

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

1. Antacid preparations

Mechanism of action: neutralize hydrochloric acid, inactivate pepsin, adsorb bile acids and lysolycine, stimulate bicarbonate secretion, exert a cytoprotective effect, improve esophageal cleansing and alkalization of the stomach, which increases the tone of the lower esophagic sphincter.

For the treatment of gastroesophageal reflux disease, it is better to use liquid forms of antacid preparations. It is better to use conditionally insoluble (non-systemic) antacid preparations, such as those containing nonabsorbable aluminum and magnesium, antacids (Maalox, Fosfalugel, Gastal, Rennie), as well as antacid preparations, which include substances that eliminate sy, metoplasmia (Protab, Dajin, Gestid).

Of the vast number of antacid preparations, one of the most effective is Maalox. It is characterized by a variety of forms, the highest acid neutralizing ability, as well as the presence of cytoprotective action due to the binding of bile acids, cytotoxins, lysolecithin and activation of the synthesis of prostaglandins and glycoproteins, stimulation of bicarbonate secretion and protective mucopolysaccharide mucus, almost complete absence of side effects and pleasant taste.

Preference should be given to antacid preparations of the third generation such as Topalcan, Gaviscon. They include: colloidal alumina, magnesium hydrogencarbonate, hydrated silicic anhydrite and alginic acid. When dissolved, Topalcan forms a foamy antacid suspension that not only adsorbs HCI but also accumulates over the food and liquid layer and, if it occurs in the case of gastroesophageal reflux into the esophagus, has a therapeutic effect, protecting the esophageal mucosa from aggressive gastric contents. Topalcane appoint 2 tablets 3 times a day 40 minutes after meals and at night.

2. Prokinetics

The pharmacological action of these drugs is to enhance the anthropyloric motility, which leads to an accelerated evacuation of the gastric contents and an increase in the tone of the lower esophageal sphincter, a decrease in the number of gastroesophageal refluxes and the time of contact of the gastric contents with the esophageal mucosa, an improvement in esophageal cleansing and the elimination of delayed gastric evacuation.

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

Disadvantage of Metoclopramide is its undesirable central effect (headache, insomnia, weakness, impotence, gynecomastia, exacerbation of extrapyramidal disorders). Therefore, it can not 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 for 15-20 minutes before meals. As a monotherapy, it can be used in patients with grade I-II GERD. It is important to note that the use of Motilium can not be combined in time with the use of antacids, since it requires an acidic medium for its absorption, and with anticholinergic drugs that neutralize the effect of Motilium. The most effective treatment for GERD is Prepulsid (Cisapride, Coordix, Peristil). It is a gastrointestinal prokinetic, devoid of antidopaminergic properties. At the heart of its mechanism of action is an indirect cholinergic effect on the neuromuscular apparatus of the gastrointestinal tract. Prepulsed increases the tone of the NPS, increases the amplitude of the esophagus and accelerates the evacuation of the contents of the stomach. At the same time, the drug does not affect gastric secretion, therefore, it is better to combine Prepulcide with reflux esophagitis with antisecretory drugs.

Prokinetic potential of a number of other drugs is studied: Sandostatin, Leuprolide, Botox, and also drugs acting through serotonin receptors 5-HT ₃ and 5-HT ₄.

3. Antisecretory drugs

The goal of antisecretory therapy of GERD is to reduce the damaging effect of acidic gastric contents on the mucosa of the esophagus. In the treatment of GERD, blockers of histamine H2-receptors and proton pump inhibitors are used.

4. H ₂ -receptor blockers of histamine

Currently, 5 classes of H ₂ -blockers are available: cimetidine (1st generation), Ranitidine (2nd generation), famotidine (3rd generation), Nizatidine (axide) (IV generation) and Roxatidine (V generation).

The most widely used drugs from the groups Ranitidin (Ranisan, Zantak, Ranitin) and Famotidine (Kwamatel, Ulfamid, Famosan, Gastrosidin). These drugs effectively reduce basal, night, food-induced and drug-induced secretion of hydrochloric acid in the stomach, inhibit the secretion of pepsins. If a choice is possible, Famotidine should be given preference, which, due to its greater selectivity and lower dosage, acts longer and does not have the side effects inherent in Ranitidine. Famotidine is more effective than tsimitidine 40 times and ranitidine 8 times. In a single dose of 40 mg, he reduces night secretion by 94%, basal by 95%. In addition, famotidine stimulates the protective properties of the mucous membrane, by increasing blood flow, production of bicarbonates, the synthesis of prostaglandins, reinforcement of epithelial repair. The duration of action of 20 mg of famotidine is 12 hours, 40 mg is 18 hours. The recommended dose for treatment of GERD is 40-80 mg per day.

5. Proton Pump Blockers

Proton pump blockers are currently considered to be the strongest antisecretory drugs. Preparations of this group are practically devoid of side effects, since in active form they exist only in the parietal cell. The effect of these drugs is inhibition of Na ⁺ / K ⁺ -ATPase in the parietal cells of the stomach and blockade of the final stage of HCI secretion, with almost 100% inhibition of production of hydrochloric acid in the stomach. Currently, four chemical species of this group of drugs are known: omeprazole, pantoprazole, lansoprazole, rabeprazole. The progenitor of proton pump inhibitors is Omeprazole, first registered as a drug Losek by the company "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 group Rabiprazole Pariet in our country has not yet been registered, clinical trials are under way.

Omeprazole (Losek, Losek-Maps, Mopral, Zoltum, etc.) in a dose of 40 mg allows to achieve healing of erosions of the esophagus in 85-90% of patients, including patients who do not respond to therapy with histamine H ₂ -receptor blockers . Especially Omeprazole is indicated in patients with GERD II-IV stage. In control studies with omeprazole, there was an earlier stagnation of GERD symptoms and a more frequent cure compared with conventional or doubled doses of H ₂ -blockers, which is associated with a greater degree of suppression of acid production.

Recently, a new improved form of the drug "Losek", produced by the company "Astra", "Losek-maps" appeared on the market of medicines. Its advantage lies in the fact that it does not contain allergenic fillers (lactose and gelatin), smaller in size than the capsule, covered with a special coating to facilitate swallowing. This preparation can be dissolved in water and, if necessary, used in patients with a nasopharyngeal probe.

At present, a new class of antisecretory drugs is being developed that do not inhibit the operation of the proton pump, but only interfere with the movement of Na ⁺ / K ⁺ -ATPase. Representative of this new group of drugs is ME - 3407.

6. Cytoprotectors.

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

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

Misoprostol is prescribed 0.2 mg 4 times a day, usually with grade 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 mucous membrane by forming a chemical complex - a protective barrier on the surface of erosion and ulcers and prevents the action of pepsin, acid and bile. It has an astringent property. Assign 1 g 4 times a day between meals. The administration of sucralfate and antacid preparations should be divided in time.

In gastroesophageal reflux caused by casting of duodenal contents (alkaline, bilious variant of reflux) observed in the esophagus, usually observed with cholelithiasis, a good effect is achieved when taking non-toxic ursodeoxycholic bile acid (Ursofalk) at 250 mg per night, which in this case is combined with Coordix. Also, the use of cholestyramine is justified (ammonium anion exchange resin, a nonabsorbable polymer, binds to bile acids, forming a solid complex with them, excreted with feces). It is taken at 12-16 g / day.

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

The most common are (AA Sheptulin):

• a scheme of "phased-up" therapy, which involves the appointment at different stages of the disease of different strength drugs and combinations. So, at the first stage, the main place in treatment is given to lifestyle changes and, if necessary, taking antacids. If clinical symptoms persist, prokinetic or H ₂ -blockers of histamine receptors are prescribed at the second stage of treatment . If such therapy is ineffective, then in the third stage, proton pump inhibitors or a combination of H ₂ -blockers and prokinetics (in particularly severe cases, a combination of proton pump blockers and prokinetics) are used;
• the scheme of "gradually decreasing" therapy assumes from the very beginning the appointment of proton pump inhibitors with the subsequent transition after achieving a clinical effect on the reception of H ₂ -blockers or prokinetics. The use of such a scheme is justified in patients with severe disease and pronounced erosive and ulcerative changes in the mucosa of the esophagus.

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

1. If gastroesophageal reflux without esophagitis for 10 days is prescribed inside Motilium or Cisapride 10 mg 3 times a day in combination with antacids of 15 ml 1 hour after meals, 3 times a day and 4 th time before bedtime.
2. When reflux esophagitis I-st grade - prescribed inside _2- blockers: for 6 weeks - Ranitidine 150 mg twice a day or famotidine 20 mg twice a day (for each drug taken in the morning and evening at intervals of 12 hours). After 6 weeks, if there is a remission, the drug treatment is stopped.
3. With reflux esophagitis II degree of severity - for 6 weeks appoint Ranitidine 300 mg 2 times a day or famotidine 40 mg 2 times a day or Omeprazole 20 mg after lunch (14-15 hours). After 6 weeks, the drug treatment stops if there is a remission.
4. When reflux-esophagitis III degree of severity - for 4 weeks is prescribed inside Omeprazole 20 mg 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 twice a day for up to 8 weeks, then go on to receive H ₂ -receptor blockers for histamine in a maintenance half dose for a year.
5. With reflux esophagitis IV grade - for 8 weeks, prescribe omeprazole 20 mg 2 times a day, morning and evening with a mandatory interval of 12 hours or another proton pump inhibitor at 30 mg 2 times a day and when the remission goes to a permanent intake of H ₂ -blockers of histamine. Additional drugs for the treatment of refractory forms of GERD include Sucralfate (Venter, Sukratgel) 1 g 4 times a day for 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 0-1 degree) requires a special life regimen and, if necessary, the use of antacids or H ₂ -receptor blockers ;
• at an average degree of severity (reflux esophagitis of the 2nd degree), along with constant observance of a special mode of life and diet, a long-term use of H ₂ -receptor blockers in combination with prokinetics or proton pump inhibitors is necessary ;
• In severe illness (reflux esophagitis III degree), a combination of H ₂ -receptor blockers and proton pump inhibitors or high doses of H ₂ -receptor blockers and prokinetics is prescribed;
• absence of the 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 with the purpose of assessing the personal profile and correcting the revealed violations is extremely topical. To assess the personal profile in patients with pathological gastroesophageal refluxes revealed at pH-metry, we perform psychological testing using computer modification of the Eysenck, Shmishek, MMPI, Spielberger, Lusher color test, which allows us to reveal the dependence of the character and severity of gastroesophageal refluxes on individual personality characteristics and accordingly, taking this into account, develop effective treatment regimens. Thus, it is possible to achieve not only a shortening of treatment time, but also significantly improve the quality of life of patients. Along with standard therapy, depending on the detected anxious or depressive personality type, Eglonil 50 mg 3 times a day or Grandaxin 50 mg 2 times a day, Teralen 25 mg 2 times a day is prescribed to patients, which improves the prognosis of the disease.

Treatment of gastroesophageal reflux disease in pregnant women

It was found that the main symptom of GERD - heartburn - occurs in 30-50% of pregnant women. Most (52%) of pregnant women experience heartburn in the first trimester. The pathogenesis of GERD is associated with hypotension of NPS in basal conditions, increased intra-abdominal pressure and delayed evacuation function of the stomach. Diagnosis of the disease is based on clinical data. Conducting (if necessary) endoscopic examination is considered safe. In the treatment of particular importance is the change in lifestyle. At the next stage "nonabsorbable" antacid preparations (Maalox, Phosphalugel, Sucralfate, etc.) are added. Given that Sucralfate (Venter) can cause constipation, the use of Maalox is more justified. In the case of refractory treatment, such H ₂ -blockers as Ranitidine or Famotidine may be used .

The use of Nizatidine during pregnancy is not shown, since in the experiment the drug exhibited teratogenic properties. In view of the experimental data, the use of omeprazole, metoclopramide and cisapride is also undesirable, although there are isolated reports of their successful use during pregnancy.

Antiretroviral treatment of gastroesophageal reflux disease

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

• H ₂ -blockers in a full daily two-time dose (Ranitidine 150 mg twice daily, Famotidine 20 mg twice daily, Nizatidine 150 mg 2 times a day).
• Treatment with proton pump inhibitors: Omeprazole (Losek) 20 mg in the morning on an empty stomach.
• Admission prokinetics: Cisapride (Coordix) or Motilium in a half dose compared with the dose used in the period of exacerbation.
• Long-term treatment with nonabsorbable antacids (Maalox, Fosfalugel, etc.).

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

A retrospective analysis of prolonged permanent application of small doses of Maalox suspension on 10 ml 4 times a day (acid neutralizing capacity of 108 meq) in 196 patients with GERD of stage II showed a rather high antirecordance effect of this regimen. After 6 months of permanent therapy, remission persisted in 82% of patients. None of the patients had any side effects that caused the prolonged treatment to stop. Data on the presence of phosphorus deficiency in the body is not obtained.

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

[1], [2], [3], [4], [5], [6], [7], [8],