Technologies for drug suppression of gastric secretion

What is low stomach acid?

05.05.2021

Low stomach is an eating disorder associated with a decrease in the amount of hydrochloric acid (HCL) in the gastric juice. Hydrochloric acid is vital for proper digestion. It converts pepsinogen into pepsin, an enzyme that breaks down proteins into smaller, more easily digestible substances. In addition, hydrochloric acid prevents the migration and colonization of bacteria from the intestines to the stomach and is an important part of the immune system , since it serves as an acidic barrier to the development of a number of microorganisms that enter the stomach with food.

People suffering from stomach and digestive problems often think that they are caused by too much stomach acid. The reason may be that the symptoms of excess and lack of stomach acid are almost the same. Therefore, research is needed before any conclusions can be drawn on this issue.

Symptoms of low stomach acid

Symptoms of low stomach acid may include flatulence, belching , nausea and vomiting, bloating , burning or heaviness in the stomach , especially after eating, indigestion , bad breath , chronic candidiasis , diarrhea or constipation , undigested food in stool, food allergies , abdominal , itching around the rectum , weak and brittle nails, skin rashes and disorders, acne , chronic intestinal parasites, iron deficiency, hair loss, increased incidence of parasitic infections, etc.

It is important to note! All of these symptoms could be the result of other problems related to your health - these are quite early warning signs that are worth keeping in mind. As your symptoms worsen, you'll know where the problem might be and how to solve it.

Gastric juice is a “natural killer” of bacteria

Decreased production of hydrochloric acid is called hypochlorhydria or achlorhydria. This deficiency condition can be caused by atrophic gastritis , chronic gastritis , autoimmune thyroiditis , pernicious anemia, parasitic infection (worms), mucopolysaccharidosis IV, Ménétrier's disease (hypertrophic gastritis ), Helicobacter pylori infection and Helicobacter pylori.

This deficiency should not be ignored because it increases the risk of developing certain bacterial and parasitic infections and aggravates existing ones. In a healthy person, the amount of acid in the stomach is enough to kill bacteria, but as we age, acid production may decrease and this can lead to lower pepsin levels. This in turn leads to indigestion . In people with low levels of hydrochloric acid, bacterial colonies are often observed in the stomach .

How can we deal with the problem?

First of all, you need to consult with a specialist after carrying out the necessary tests. The second step is to improve your diet . This should be done first, since adjusting your eating habits is based on the principles of healthy eating. According to studies, people on a diet have normal levels of stomach and do not suffer from bacteria in the small intestine. Thus, a diet rich in fruits, vegetables, nuts and seeds would alleviate stomach and digestive problems. Additionally, people suffering from hypochlorhydria can take an additional source of hydrochloric acid - betaine hydrochloride. This will support pepsin production and improve and regulate digestion, especially of protein-rich foods, which are usually difficult for people suffering from low acidity to process.

What is betaine hydrochloride - betaine HCL?

Betaine HCL is the acidic form of betaine, a vitamin-like substance found in grains and other foods. It is actually a vitamin derived from choline, which is extracted from sugar beets. It contains organically bound nitrogen and has a pronounced lipotropic effect. Betaine hydrochloride also helps neutralize lactic acid and reduce the toxicity of harmful homocysteine, a protein intermediate formed during the conversion of the amino acid methionine.

As with any supplement, it is recommended that you consult a physician .

Published in Gastroentorology Premium Clinic

Technologies for drug suppression of gastric secretion

1. M1-anticholinergics

Historically, M-anticholinergics were among the first drugs used to treat patients with peptic ulcers. The “progenitors” of this group of drugs were belladonna extract and atropine, which served as the basis of antiulcer therapy for decades. However, the colossal number of serious side effects, directly and naturally related to the effect of drugs on the heart, bronchi, blood vessels, and brain receptors, forced the search for new drugs. This is how platiphylline and metacin appeared, which have less pronounced side effects, but are fundamentally inferior to atropine in terms of the severity of the antisecretory effect. Like atropine, platiphylline and metacin are non-selective M-cholinergic agents, that is, they have a blocking effect on M1, M2 and M3 cholinergic receptors. Pirenzepine has a selective effect on M1-cholinergic receptors, selectively inhibiting the secretion of acid and pepsin, which is under the control of the vagus nerve, suppressing gastric secretion caused by conditioned reflex stimulation, stretching of the fundus of the stomach and amino acids, without affecting the motor-evacuation function of the stomach. The inhibition of hydrochloric acid secretion by pirenzepine is indirect. Pirenzepine blocks M1-cholinergic receptors located on the membrane of ECL cells, and thereby inhibits the release of histamine, which stimulates the secretion of HCl by parietal cells. It should be borne in mind that pirenzepine does not act directly on parietal cells, since only M3 cholinergic receptors are located on their membrane, and there are no M1 cholinergic receptors. The structure of pirenzepine is a tricyclic benzodiazepine compound. The drug differs from typical tricyclic benzodiazepines with neurotropic activity in its high hydrophilicity, which causes, on the one hand, insignificant penetration through the blood-brain barrier, weak interindividual fluctuations in absorption, distribution and elimination of the drug, but on the other hand, low bioavailability. Pirenzepine suppresses the secretion of hydrochloric acid much weaker than atropine, without affecting the quantitative production of protective gastric mucus. A study of the nature of the suppression of gastric secretion by pirenzepine showed a decrease in secretion on an empty stomach both in patients with gastric ulcer and in patients with duodenal ulcer. At the same time, basal secretion decreased in 62.9% of patients with gastric ulcers and in 64.3% with duodenal ulcers; stimulated – in 51.8 and 71.4% of patients, respectively. When taken 2 times a day, gastrocepin equally reduces both daytime and nighttime secretion. It should be noted that if atropine in patients with peptic ulcer causes a noticeable increase in the concentration of gastrin in the blood, then pirenzepine significantly reduces it during the gastric phase of digestion induced by distension of the fundus of the stomach or amino acids. It was noted that pirenzepine enhances the protective properties of mucus only in the interdigestive phase of gastric functioning: in a portion of gastric contents taken on an empty stomach and reflecting interdigestive processes, an increase in the content of fucose and N-acetylneuraminic acid in the mucus was noted, while in basal portions (mechanical stimulation secretion), the increase in the production of these mucus components was less pronounced, and in the stimulated ones, the mucus production did not change at all. An important property of pirenzepine is the ability to increase the volumetric velocity of blood flow in the mucous-submucosal layer of the gastroduodenal complex. Pirenzepine increases blood flow in a dose-dependent manner, which may be explained by the involvement of muscarinic receptors in both vasoconstriction and vasodilation. It is assumed that the drug selectively inhibits the function of M1 receptors involved in vasoconstriction. Information about the effect of pirenzepine on the tone of the lower esophageal sphincter and pyloric tone is very contradictory. Data is provided that when the drug is administered intravenously to patients with cardiospasm at a dose of 10 mg every 4 minutes. There is a significant decrease in pressure in the lower esophageal sphincter within approximately 50 minutes. This effect was not observed when the drug was administered orally. However, according to other data, gastrocepin reduces pressure in the lower esophageal sphincter, slows down the swallowing movements of the esophagus, gastric emptying and duodenal motility. Pirenzepine reduces the volume of basal pancreatic secretion and the content of chymotrypsin without affecting the concentration of bicarbonate ions. The latter circumstance can be considered very important for the treatment of both diseases of the duodenum and pancreas. It is necessary to remember the possibility of the formation of antibodies to the drug with a decrease in effectiveness with prolonged use. Thus, M1 anticholinergics can be used in cases of increased gastric secretion, especially in the case of proven vagotonia. It should be noted that for a drug similar in structure to tricyclic antidepressants, the possibility of side effects such as dry mouth, vestibular disorders, impaired accommodation, and drowsiness is completely natural.

Despite the fact that the antisecretory activity of M1-anticholinergics is in many ways inferior to the activity of H2-blockers and proton pump inhibitors, pirenzepine, nevertheless, has been used in the practice of emergency surgery for a very long time precisely due to the existence of a dosage form for parenteral administration. Historically, the route of pharmaceutical action on muscarinic receptors was the earliest. But at the present time, as N.A. rightly emphasizes. Yaitsky (2002), non-selective and selective M-anticholinergic blockers have actually lost their original significance in the treatment of both gastroduodenal ulcers and their complications. M1 anticholinergics have been replaced by drugs that act at the molecular level and block subcellular processes - H2 receptor blockers and proton pump inhibitors.

2. H2 blockers

Histamine H2 receptor blockers (H2 blockers) are still one of the most popular classes of drugs used to treat acid-related diseases. In the 70s and 80s of the twentieth century, H2 blockers truly revolutionized gastroenterology, forcing us to reconsider the existing concepts of pharmaceutical potential in the treatment of peptic ulcers. With the introduction of H2-blockers into clinical practice, it became possible, if not to cure a patient of a peptic ulcer, then at least to achieve its stable remission. Therapy with H2-blockers, referred to by many as “medical vagotomy,” also forced us to reconsider the issue of indications for surgical treatment of patients with peptic ulcer disease, on the one hand, narrowing the indications for planned operations to a minimum, and on the other, calling into question the feasibility of performing interventions that have basically different options for vagotomy. The appearance of H2-histamine receptor blockers in clinical practice is due to a number of scientific discoveries. At the beginning of the twentieth century, the physiologist H. Dale isolated an unknown biologically active substance from ergot, identified as beta-imidazolylethylamine and later named “histamine”. In 1936, H. Dale was awarded the Nobel Prize for a series of experimental studies that established a connection between increased gastric secretion after intravenous administration of histamine and the formation of gastric ulcers. Much later, in 1972, pharmacologist J. Black established the presence of H2-histamine receptors in the stomach and isolated a substance that selectively acts on H2 receptors and does not affect H1 receptors - burimamide. This substance inhibited gastric secretion stimulated by pentagastrin and histamine, which made it possible to identify histamine as the final link in the chain of transmission of stimulating impulses to the parietal cell. For the identification of H2 receptors and the development of drugs that block them, J. Black was awarded the Nobel Prize in 1988.

According to their chemical structure, H2 blockers can be considered as modified histamine derivatives. The difference lies in the presence of a modified side chain of the imidazole part of the molecule in H2-blockers. The action of H2 blockers is based on a competitive effect on histamine H2 receptors in parietal cells with respect to histamine. The inhibition of hydrochloric acid secretion by H2 blockers is indirect and is caused by the inactivation of parietal cell adenylate cyclase when blocking H2 receptors. Inactivation of adenylate cyclase, in turn, leads to a decrease in the concentration of cAMP in the parietal cell and a sharp decrease in the activity of H+/K+-ATPase, which ultimately leads to a decrease in the secretion of H+ into the lumen of the tubules of the parietal cell. H2 blockers inhibit both stimulated and basal gastric secretion. The secretion of pepsin is inhibited to a much lesser extent.

Despite the fact that the first representatives of H2-blockers were synthesized already in 1972, their widespread clinical use was limited by a number of serious side effects. Thus, cimetidine can cause gynecomastia (due to stimulation of prolactin secretion) and impaired glucose tolerance (due to a decrease in plasma insulin concentrations). Cimetidine also blocks peripheral receptors of male sex hormones, which can lead to a decrease in libido and potency; may have a hepatotoxic effect (decreased blood flow in the liver, increased transaminase levels); interacts with the cytochrome P450 system; can cause an increase in creatinine levels in the blood, damage to the central nervous system, hematological changes, have cardiotoxic effects and immunosuppressive effects. In this regard, the description of cimetidine in various manuals is nothing more than a tribute to history; the drug itself is now practically not used in clinical practice.

Currently, therapy with H2-blockers in the vast majority of cases is carried out by prescribing famotidine. The widespread use of famotidine in the form for parenteral administration in the practice of emergency surgical gastroenterology in the 90s of the twentieth century is associated with the relatively favorable tolerability profile of this drug. Famotidine has no hepatotoxic effect, does not interact with the cytochrome P450 system, does not increase plasma creatinine levels, does not penetrate the blood-brain barrier and does not cause neuropsychiatric disorders. It is known that the antisecretory activity of famotidine is 20-60 times higher than the activity of cimetidine and 3-20 times higher than the activity of ranitidine. Compared with ranitidine, famotidine is more effective at increasing gastric pH and reducing gastric volume. According to JL Smith (1997), in healthy volunteers, a single dose of famotidine at a dose of 5 to 20 mg caused a decrease in basal acid production by 94% and 97%, respectively. The production of hydrochloric acid after stimulation with pentagastrin decreased by 41-90%, respectively. The duration of action of drugs in this group is determined by the strength of binding to histamine H2 receptors. With famotidine, this connection is the strongest, therefore, among the H2-histamine receptor blockers, it provides the longest reduction in basal secretion - for about 12 hours, which allows in clinical practice to use low doses of the drug and increase the frequency of dosing to 1 time per day at night.

Unfortunately, there is a group of patients who are resistant to H2 blockers. Resistance to H2 blockers is observed, according to clinical data, in 15-25% of all patients with peptic ulcer disease. According to a drug test with ranitidine with intragastric pH-metry, this phenomenon was observed in 11.5% of patients with duodenal ulcer and chronic gastroduodenitis. The effectiveness of H2 blockers varies among different groups of patients. In particular, smoking is a serious factor reducing the effectiveness of these drugs.

3. Proton pump inhibitors

Today, proton pump inhibitors (PPIs) - blockers of H+/K+-ATPase of the parietal cell - occupy a central place among the drugs that suppress the secretion of hydrochloric acid, and are the “gold standard” in the treatment of acid-related diseases. According to their chemical structure, PPIs are benzimidazole derivatives. PPIs themselves, which are weak bases, are ineffective at neutral pH. But in the acidic environment of the parietal cell tubules (only at pH < 4), benzimidazole derivatives are converted into the active form - sulfenamide, which irreversibly, due to the formation of covalent disulfide bridges, interacts with the SH groups of the H+/K+-ATPase of the parietal cell membranes, leading to to a change in conformation and suppression of enzyme activity, thereby stopping the secretion of H+ into the lumen of the stomach. This circumstance explains the high selectivity of the action of PPI on parietal cells, where there is an acidic environment for the formation of sulfenamide, which occurs within 2–4 minutes. Secretion of H+ by parietal cells is restored only after the synthesis of new H+/K+-ATPase molecules in their membrane, which takes 18–20 hours. It is obvious that the effect of PPIs on the process of H+ secretion itself determines the suppression of acid formation by these drugs, which does not depend on the stimulation or blocking of cholinergic, gastrin and histamine receptors of the parietal cell.

In 1974, a prototype of this group of drugs was synthesized, in 1975, the first industrial prototype of a PPI, timoprazole, appeared, and in 1979, omeprazole was synthesized. Currently, the family of proton pump inhibitors includes several drugs - pantoprazole, omeprazole, lansoprazole, rabeprazole, esomeprazole. A characteristic feature of the pharmacodynamics of PPIs is the ability to suppress both basal and stimulated secretion of hydrochloric acid by parietal cells for 24 hours or more (Fig. 4.3). The antisecretory effect with a single oral dose of PPI reaches a maximum after 2-3 hours and decreases by the end of 3 days. Suppression of hydrochloric acid production under the influence of PPI occurs regardless of vagal influences or the presence of amino acids in the gastric lumen, that is, in both phases I and II of gastric secretion. At the same time, long-term therapy with PPIs does not lead to the development of tolerance; after discontinuation of these drugs, “rebound syndrome” does not develop. On the contrary, PPIs are characterized by a state of functional cumulation, that is, a long aftereffect, when the effect “accumulates”, not the drug. In this case, the return to the original acidity levels occurs no earlier than 4–5 days after the end of therapy.

In addition, an important feature of PPIs that distinguishes them from other antisecretory drugs is the absence of pronounced side effects during short-term or long-term courses of treatment. In this regard, back in 1988, PPIs were recognized as the main group of acid-controlling drugs at the World Congress of Gastroenterology in Rome. It is well known that there is a direct relationship between the healing of ulcers and the ability of drugs to suppress acidity. But, as it has become obvious, it is possible to achieve reparation of an ulcerative defect not only and not so much by the long-term administration of drugs that suppress acid secretion, but also by the use of drugs that can maintain the level of intragastric pH above 4 for a given time. Numerous studies have established that when intragastric pH is maintained above 4 for at least 18-20 hours a day, a chronic duodenal ulcer passes into the white scar stage in 100% of cases within 4 weeks, and a chronic gastric ulcer within 8 weeks. Similarly, for patients with erosive and ulcerative damage to the esophageal mucosa resulting from GERD, it is possible to achieve complete repair by suppressing gastric secretion for at least 14 hours a day. It is possible to achieve a guaranteed reduction in gastric secretion in terms of strength and duration only through the use of PPIs.

Taking into account the widespread use of both H2-blockers and PPIs in modern clinical practice, it is natural to compare these groups of drugs. Most researchers point to the fundamentally greater antisecretory activity of PPIs, which exceeds that of H2-blockers by 5 to 10 times. A single dose of PPI in an average therapeutic dose leads to inhibition of acid production by 80–98%, while taking H2 blockers – only by 50–75%. According to J. Breiter (2000), against the background of two-week PPI therapy, clinical remission in patients with duodenal ulcer was achieved in 72% of cases, in patients with gastric ulcer - in 66% of cases. In a similar situation, when using H2 blockers, clinical remission was observed in 56% of cases and 41% of cases, respectively.

Currently, it is a generally accepted postulate that, in addition to excess production of hydrochloric acid, one of the key positions in the development of the inflammatory process in the mucous membrane of the stomach and duodenum and in the pathogenesis of gastroduodenal ulcers is played by the infectious factor. In 1983, in biopsy samples of the mucous membrane of the antrum of the stomach, a microorganism was identified, later named Helicobacter pylori (HP), living on the surface of the mucosa in an aggressive acidic environment. The studies carried out made it possible to recognize this microorganism as the main cause of the development of the inflammatory process and ulcer formation in the gastroduodenal zone. The main goal in the treatment of diseases associated with HP infection is eradication (complete destruction) of the microorganism from the surface of the mucous membrane. When HP disappears from the surface of the stomach, the ulcer defect is repaired and the structure of the mucous membrane is restored. To achieve eradication, combination therapy is currently used, aimed at reducing the acid-forming function of the stomach and destroying HP on the surface of the mucous membrane. Currently, proton pump inhibitors, for example, omeprazole (Losec®), esomeprazole (Nexium®), are used as antisecretory drugs in first- and second-line eradication therapy regimens (see Table 4.1) in both adults and children. It is obvious that these drugs themselves do not have anti-Helicobacter activity in vivo; during HP infection, their effect is aimed only at changing the intragastric pH. Under the influence of PPIs, the production of hydrochloric acid decreases, which leads to a sharp increase in pH in the antrum of the stomach. To protect against the effects of acid, vegetative forms of HP that exist on the surface of the mucous membrane release ammonia. In a neutral environment, these bacteria die under the influence of the ammonia they themselves produce. Bacteria that are preserved in the fundus in the form of cocci, with an increase in pH in the stomach, pass into a vegetative form and become accessible to antibiotics or other drugs (for example, bismuth preparations). Thus, proton pump inhibitors, without having a direct effect on HP, create conditions for the effect of antibiotics on them. When using a combination of omeprazole with macrolides (clarithromycin), there is an increase in the bioavailability of both groups of drugs, which increases the effectiveness of the macrolide on HP. That is why the most effective and at the same time the shortest (7 days) treatment regimens are those that include PPIs and macrolides (Table).

Eradication therapy regimens (Maastricht 2000).

According to S.I. Pimanova (2000), the effectiveness of triple therapy in terms of HP eradication reaches 90%. When conducting quadruple therapy, indicated in the presence of HP strains resistant to the action of known antibiotics, the eradication efficiency reaches 98% (in case of preservation of sensitivity to metronidazole) and 82% (in case of resistance to metronidazole). It is especially emphasized that the effectiveness of eradication therapy regimens that include an H2-blocker as an antisecretory drug does not exceed 50%, as a result of which it is not recommended for use by the Maastricht consensus.

Considering the cause-and-effect relationship between the persistence of HP and ulcer formation established by many authors, a large number of works are devoted to eradication therapy for acute gastroduodenal ulcerative bleeding. Some authors (O.V. Kokueva, 1995, D. Graham, 1996), pointing to the fundamental role of HP in the genesis of ulcerative hemorrhage and its relapse, provide data on the high effectiveness of eradication therapy in terms of preventing relapses of acute gastroduodenal ulcerative bleeding. Other researchers (M.G. Gonchar et al., 1999, Yu.S. Vinnik et al., 2002), noting the close connection between the persistence of HP and the development of complications of peptic ulcer disease, speak of the effectiveness of anti-Helicobacter therapy only in terms of preventing relapses of peptic ulcer disease.

Various drugs from the PPI group have different antisecretory activity and clinical effectiveness. Thus, G. Hasselgren (2004), who studied the duration of the antisecretory effect of omeprazole, rabeprazole, lansoprazole and pantoprazole with a single oral dose of 40 mg PPI, found that the duration of intragastric pH > 4 when taking omeprazole or rabeprazole was 14 hours, when taking lansoprazole - 12 hours, pantoprazole – 10 hours. Assessing the clinical effectiveness of PPIs for GERD and exacerbation of peptic ulcer disease both by the dynamics of clinical symptoms and by the endoscopically verified dynamics of reparative processes, G. Armstrong (2004), H. Lauritsen (2003), R. Miner (2003) ranked the drugs according to the reducing the severity of the antisecretory effect (the ability to maintain intragastric pH > 4) and reducing clinical effectiveness in the following sequence: omeprazole, rabeprazole, lansoprazole, pantoprazole.

A turning point in the history of PPIs was the introduction by AstraZeneca of an intravenous formulation of omeprazole (Losec®). This circumstance made it possible to use PPIs in emergency gastroenterology and surgery: for acute gastroduodenal ulcer bleeding, after suturing perforated gastroduodenal ulcers, for acute pancreatitis and, finally, in the case of bleeding from erosions and ulcers of the esophagus. Intravenous administration of omeprazole has a dose-dependent inhibition of hydrochloric acid secretion. The volume of distribution, regardless of the functional state of the kidneys, is 0.3 l/kg; the average half-life in the terminal phase does not depend on the duration of therapy and is 40 minutes. When administered intravenously, the bioavailability of omeprazole is 100%, i.e. all drug molecules reach the parietal cells. The median time to achieve a pH of more than 4 with bolus administration of 40 and 80 mg of omeprazole is 39 and 20 minutes, respectively. To achieve a persistent and long-term increase in intragastric pH, the optimal method of administration is a continuous infusion of the drug with the initial administration of a high bolus dose. Since proton pumps are constantly formed in parietal cells, and the half-life of proton pump inhibitors from the bloodstream is quite short (1 - 2 hours), the meaning of continuous infusion of omeprazole is the primary inactivation of all actively secreting proton pumps by bolus administration, followed by inactivation of newly formed proton pumps by constant introduction. After an initial bolus dose of 80 mg, the drug is administered continuously at a dose of 8 mg/hour, which allows the pH level in the stomach to be constantly maintained above 6.0.

More than ten years of experience in using the parenteral form of omeprazole has revealed the advantages of the drug, primarily in the case of a life-threatening complication of gastroduodenal ulcers - acute bleeding. In prospective randomized studies, Hwan-Jeng Lin (1998), P. Netzer (1999) showed that the use of omeprazole is significantly more effective than cimetidine and famotidine in increasing the pH of gastric juice and reducing the number of recurrent bleeding from gastroduodenal ulcers. Thus, already 1 hour after a bolus administration of omeprazole, the intragastric pH value was above 6 and was maintained at this level throughout the day. At the same time, after a bolus administration of famotidine, the intragastric pH value reached 4.5 only after 5 hours and tended to decrease during the first day of observation. Analysis of the results of the use of drugs of various pharmaceutical groups in terms of ensuring stable hemostasis in OGDAC, carried out over the past 15 years by a large number of authors, shows that omeprazole for intravenous administration has the greatest effectiveness in gastroduodenal bleeding from chronic, acute and NSAID-induced ulcers. The least effectiveness in OGDAC of various etiologies (except for acute ulcers) was observed with pirenzepine and famotidine for intravenous administration. In the case of acute ulcers, the combined use of intravenous forms of omeprazole with misoprostol is most effective. In patients with bleeding from NSAID-induced ulcers, there were no cases of unstable hemostasis during intravenous use of omeprazole as monotherapy or in combination with misoprostol. At the same time, during the treatment of bleeding NSAID-induced ulcers with drugs of the pirenzepine and famotidine group, a state of unstable hemostasis was noted in approximately 20% of patients, which indicates a significantly lower effectiveness of the use of these drugs in this category of patients. The lowest effectiveness of pirenzepine should be explained by its lowest antisecretory activity compared to drugs of other groups. On the other hand, the different effectiveness of intravenous forms of famotidine and omeprazole cannot be explained only by the fundamental difference in the antisecretory activity of these drugs, since parenteral administration of these drugs in adequate dosages allows maintaining intragastric pH above 4 for 48–72 hours in most patients, which is sufficient to exclude the influence acid-peptic factor on the progression of fibrinoid necrosis and ensuring ulcer repair. In everyday clinical practice, the following dosage regimen for IV omeprazole is used: 1) 80 mg of the drug is administered once as an intravenous bolus over 15-20 minutes; 2) after bolus administration, the drug is administered intravenously through an infusion pump at a rate of 4-8 mg/hour for 96 hours.

For chronic gastritis with decreased secretion

For those suffering from chronic gastritis with reduced secretion, which makes it difficult to digest food, a special diet No. 2
developed, which has two basic principles: - nutrition should be as complete as possible and contain all the substances necessary for the body, - you need to eat in small portions - four to five times a day so as not to create unnecessary stress on the stomach and improve the process of digestion and absorption. On top of that, introduce foods into your diet that stimulate the production of enzymes responsible for digesting food. These are meat, vegetables, vegetable and animal fats. And also try to consume enough calories daily to restore the body after illness. Diet No. 2 assumes a daily diet of about 3000 kcal.

Causes of gastritis of the stomach

Based on their occurrence, they are divided into acute and chronic gastritis.

Acute gastritis is an acute inflammation of the gastric mucosa due to exposure to an irritant, i.e. chemically active substances (acids, alkalis) entering the stomach, taking medications (NSAIDs), poisoning with poor-quality food and/or contaminated with infected microorganisms.

The appearance and development of chronic gastritis is influenced by many factors. The main ones are exogenous.

Exogenous factors are:

• The presence in the stomach of bacteria such as Helicobacter pylori, which are the main etiological factor in the occurrence of chronic gastritis. The influence of other bacteria has not been proven
• Eating disorder
• Alcohol and tobacco abuse
• Long-term use of drugs that affect the gastric mucosa, the main ones being: NSAIDs and glucocorticosteroids (prednisolone)
• Emotional overstrain, stress

Along with exogenous factors, there are also internal factors (endogenous) that contribute to the occurrence of chronic gastritis:

• Genetic predisposition
• Duodenogastric reflux
• Endogenous intoxications
• Chronic infectious diseases
• Metabolic disorders
• Hypovitaminosis
• For other diseases of the gastrointestinal tract, for example, chronic pancreatitis, chronic cholecystitis, which reflexively affect the gastric mucosa

The use of antacids in gastroenterology

Mamedova L.D., Loranskaya I.D., Rakitskaya L.G.

When it comes to antacids, for some reason they only mean alkalis. This is not entirely correct. Antacids are substances or a group of substances that have an anti-acid effect. This, naturally, includes alkalis that have a predominantly neutralizing effect on acidic gastric juice, substances that bind free hydrochloric acid directly in the stomach and thereby average its contents, as well as hydrochloric acid adsorbents; substances that reduce the acidity of gastric contents not directly, but by inhibiting the intensity of gastric juice secretion (for example, atropine).

Anti-acid agents may also include water and some solutions that dilute gastric juice, temporarily reduce the acidity of gastric contents and alleviate the patient’s condition. It is known that some patients get significant relief from the pain of peptic ulcers after drinking a glass of cold water.

Antacids are widely used in the treatment of gastroesophageal reflux disease, peptic ulcers of the esophagus, peptic ulcer disease, erosive gastritis with preserved and increased gastric secretion, symptomatic and peptic ulcers of the stomach, duodenum, anastomositis, in the prevention of reflux esophagitis with hiatal hernia, to eliminate pyloric hypertonicity syndrome with a sharp increase in gastric secretion (increased Mehring-Hirsch-Serdyukov reflex) and other similar conditions.

In the pathogenesis of these diseases, the primary role is played by the influence of aggressive factors and a decrease in the compensatory capabilities of the gastroduodenal mucosa. The most aggressive factors are hydrochloric acid and pepsin.

Soluble absorbable antacids (alkalis) are also used for acidosis (diabetes mellitus, typhoid fever, scarlet fever, arsenic and phosphorus poisoning), and for the treatment of urolithiasis with the formation of urate and oxalate stones.

The Department of Gastroenterology of the Russian Medical Academy of Postgraduate Education has developed a working classification of antacids [2].

Antacids:

• Drugs that directly affect the acidity of gastric contents.
  Agents that have a neutralizing effect: sodium bicarbonate, magnesium oxide, magnesium carbonate.
• Agents that have a neutralizing, adsorbing and enveloping effect: aluminum hydroxide, Maalox, etc.
• Food antacids: meat, dairy, egg dishes.
• Means that reduce the acidity of gastric juice due to neutralization and dilution: low-mineralized alkaline waters of Zheleznovodsk (Smirnovsky and Slavyansky springs), Essentukov (springs No. 4, 20), Pyatigorsk (warm “Narzan”), etc.

Characteristics of the main antacids

Drugs that directly affect the acidity of gastric contents

Agents that have a neutralizing effect

One of the most popular antacids in this group is sodium bicarbonate (bicarbonate of soda). The neutralizing effect of taking bicarbonate of soda occurs quite quickly - after 2-3 seconds. When the drug is taken orally, a rapid reaction occurs to neutralize the hydrochloric acid of the gastric contents with the formation of table salt, water and carbon dioxide. The resulting carbon dioxide causes a reflex stimulation of the secretion of hydrochloric acid.

The negative side of this antacid is that when taken frequently, the bicarbonates of the duodenal contents remain unneutralized, which under physiological conditions are neutralized by the hydrochloric acid of the gastric contents. All this can lead to disruption of the acid-base balance towards alkalosis. The development of metabolic alkalosis can be observed with prolonged oral intake of sodium bicarbonate, especially against the background of dairy and plant foods.

The duration of the antiacid action is determined by the dose of the drug and the typological characteristics of gastric secretion. Thus, in individuals with an excitable type of gastric secretion, the antacid effect will be shorter than in individuals with an inhibitory type.

Magnesium oxide has a rapid neutralizing effect against hydrochloric acid in the gastric contents. In this case, magnesium chloride is formed, which, when leaving the stomach, neutralizes the bicarbonates of the duodenal contents, and, therefore, does not lead to disruption of the acid-base balance. Magnesium carbonate formed in the intestines is not absorbed and has a laxative effect.

Side effects of magnesium-containing antacids:

• Dyskinesia of the gastrointestinal tract: large amounts of magnesium enhance the evacuation of intestinal contents.
• The accumulation of Mg2+ ions in the body during long-term use of antacids leads to hypermagnesemia with the development of bradycardia and renal failure.
• Changes in the bioavailability of drugs.

When calcium carbonate interacts with hydrochloric acid of the gastric contents, a rapid neutralization reaction occurs with the formation of calcium chloride, which, when passing into the intestine, neutralizes bicarbonates and again turns into calcium carbonate, causing constipation.

Side effects of calcium-containing antacids:

• Gastrointestinal dyskinesia: large amounts of calcium slow down the evacuation of intestinal contents.
• The accumulation of Ca2+ ions in the body during long-term use of antacids causes: hypercalcemia, milk-alkali syndrome, and in patients with urolithiasis increases stone formation.
• Changes in the bioavailability of drugs. Antacids of this group provide an immediate therapeutic effect.

A combination of drugs from this group is advisable. As for the duration of their action, it depends on the dose of the drug and the typological characteristics of the secretory activity of the gastric glands. In persons with an inhibitory type of secretion it is the greatest (20-40 min), in persons with an excitable type of secretion it is the smallest (10-15 min). This is a group of short-acting antacids; it is advisable to prescribe them not before meals (“hunger” pains can be relieved with food antacids), but after meals, more precisely at the time of the onset of “late” pains. In these cases, alkalis eliminate pathological evacuation and alleviate the patient’s condition.

Agents that have a neutralizing, adsorbing and enveloping effect - non-absorbable antacids

The antacid effect of aluminum hydroxide is mainly associated with the adsorption and neutralization of hydrochloric acid. Aluminum salts can also inactivate pepsin and gastricin and have a cytoprotective effect. The time of the anti-acid action of aluminum hydroxide does not exceed 30-40 minutes.

Maalox is a well-balanced combination of aluminum hydroxide and magnesium hydroxide. Available in the form of tablets and suspension. The drug is well tolerated and has no side effects. The mechanism of action of Maalox is as follows:

• neutralization of hydrochloric acid;
• adsorption of hydrochloric acid;
• cytoprotective effect;
• decrease in proteolytic activity of gastric juice;
• enveloping effect, binding of lysolycetin and bile acids.

The protective effect of Maalox is due to stimulation of prostaglandin synthesis. The ability to bind epithelial growth factor and fix it in the area of ​​the ulcerative defect was discovered, which stimulates local repair and regenerative processes, cell proliferation and angiogenesis (Fig. 1).

In a number of studies, Maalox was not inferior in effectiveness to histamine H2-blockers [3,4,7].

Gaviscon quickly interacts with the acidic contents of the stomach. This forms an alginate gel, which prevents the occurrence of gastroesophageal reflux. Alginates, creating a thick foam on the surface of the gastric mucosa, have a therapeutic effect due to their acid-neutralizing effect and the formation of a protective film. During regurgitation, the gel is more likely than stomach contents to enter the esophagus and reduce irritation of the mucous membrane [1,3,6].

Drugs in this group should be prescribed between meals, i.e. 1-1.5 hours after eating.

Contraindications for non-absorbable antacids are severe renal impairment and Alzheimer's disease [6].

Nutritional antacids

When creating dietary regimens for patients with peptic ulcers and chronic gastritis, it is necessary to take into account not only the soda effect of a particular product, but also the antacid effect of food. The magnitude and duration of the antacid effect of food on acidic gastric contents depend not only on the type of food product, but also on the typological characteristics of the secretory apparatus of the stomach: with an excitable type of secretion, the pH of the gastric contents increases to 3.5-4.0 for 20-30 minutes, and with the braking type up to 5.0-6.2 - for 80-100 minutes.

Meals every 2-3 hours support long-term averaging of gastric contents, especially with an inhibitory type of secretion, which protects the mucous membrane from acid-peptic damage and provides adequate nutrition to the patient.

The use of food antacids is necessary, since they are much superior to medicinal ones in strength and duration of action. The introduction into the diet of products containing protein, which has a pronounced anti-acid effect, makes the diet more complete and improves the taste of dietary dishes [2].

Agents that reduce the acidity of stomach contents through neutralization and dilution.

This group of antacid agents includes low-mineralized alkaline waters. In patients with an excitable type of gastric secretion, the duration of the antiacid effect ranges from 10-20 minutes, while the pH in the gastric cavity increases to 5.0; in patients with an inhibitory type of secretion it reaches 40 minutes or more, i.e. The antacid effect of mineral water under basal conditions is short.

If alkaline mineral waters are taken 15-20 minutes after a meal, then, as our studies have shown, it is possible to achieve a rather long state of averaging in the stomach cavity - up to 1.5 hours. Thus, the anti-acid effect of alkaline mineral water depends not only on the typological features the functioning of the secretory apparatus of the stomach, but also on the time of its administration in relation to food intake.

Agents that reduce the acidity of gastric contents by inhibiting the intensity of gastric juice secretion or directly inhibiting the secretion of hydrochloric acid

Cholinoretic (anticholinergic) drugs acting primarily in the area of ​​peripheral M- and N-cholinoreactive systems

This group of drugs, reducing the secretory activity of the stomach, pancreas, reducing or completely eliminating pain caused by excessive peristalsis, increased tone of the smooth muscles of the stomach, intestines, gall bladder, etc., has become widely used in the treatment of patients with peptic ulcers, cholecystitis, cardiospasm, intestinal or biliary colic, etc.

Atropine and atropine-like drugs, inhibiting the process of gastric juice secretion, thereby reduce acidity. Under the influence of these drugs, the amount of gastric juice released per unit of time sharply decreases, and this contributes to the manifestation of the activity of mediating factors and, as a result, to a decrease in the acidity of gastric contents.

A more pronounced anti-acid effect of atropine and other drugs of this group was observed in patients who had an inhibitory type of gastric secretion. M-anticholinergics have a pronounced effect on various organs and systems, which leads to adverse reactions such as impaired accommodation, tachycardia, difficulty urinating, increased intraocular pressure, etc. [6]. Therefore, the creation of drugs that have an anticholinergic effect and an isolated effect on gastric secretion deserves great attention. Such a drug was gastrocepin, a selective blocker of muscarinic receptors (M1) of acetylcholine in the parietal cells of the gastric mucosa.

Histamine H2 receptor blockers and proton pump inhibitors

In clinical settings, it was found that H2-histamine receptor blockers have a strong blocking effect on gastric secretion. Being specific competitive antagonists of histamine H2 receptors, they reduce the secretion of hydrochloric acid by parietal cells and pepsin, promote scarring of gastric and duodenal ulcers, and relieve pain in peptic ulcers [6]. These drugs affect the level of histamine in the blood and tissues of the periulcerous area, changing the intensity of the inflammatory reaction and accelerating the process of scarring of the ulcerative defect. The stimulating effect of drugs of this group on the process of ulcer scarring is due to the adaptive restructuring of the neurohumoral regulatory apparatus and the restoration of tissue homeostasis. Observations have shown that the optimal time frame for establishing adaptive relationships in the neurohumoral regulatory apparatus is 10-15 days. Further continuation of the course of treatment activates the synthesis of tissue histamine, which can lead to destructive changes and the formation of erosions on the mucous membrane of the gastroduodenal zone. The combination of H2 blockers with an H1 histamine receptor blocker increases the effectiveness of treatment and prevents the development of erosions, which allows for prolonged therapy [2].

Proton pump inhibitors effectively control the pH level in the gastric cavity. The mechanism of action of proton pump blockers is associated with blocking the activity of H+, K+-ATPase of the parietal cell. Powerful suppression of acidity is the main therapeutic factor in the treatment of acid-related diseases [5,7]. Proton pump inhibitors are more preferable for antisecretory therapy.

Other drugs that inhibit gastric secretion

Secretin is one of the peptide gastrointestinal hormones. The release of the hormone begins in the duodenum at a pH of about 4.5. Secretin enhances the secretion of bicarbonates by the pancreas; choleresis, potentiating cholecystokinin-pancreozymin, inhibits the secretion of hydrochloric acid. Somatostatin is a hormone of the anterior pituitary gland. In the stomach it is secreted by specific endocrine D-cells of the mucous membrane of the fundus and antrum. Somatostatin plays a role in regulating the secretion of hydrochloric acid in the stomach. Its inhibitory effect on the release of gastrin and the secretion of hydrochloric acid occurs both in the basal and stimulated phases of gastric secretion.

Prostaglandins are biologically active substances whose actions are diverse. One of the main biological effects of prostaglandins is their pronounced effect on the tone of the smooth muscles of various organs and a decrease in gastric secretion. They inhibit the formation of hydrochloric acid, improve blood flow, and increase the production of bicarbonates and mucus in the stomach.

Thus, the classification of antacids, in which drugs are divided into groups depending on their mechanism of action in relation to acidic gastric juice, allows for the correct choice of one or another drug or their combinations when carrying out complex treatment.

Literature 1. Alginates are new agents based on natural compounds in the treatment of gastroesophageal reflux disease and other acid-related diseases of the digestive system. Guidelines. St. Petersburg, 2008. 33 p. 2. Belousov A.S., Vodolagin V.D., Zhakov V.P. Differential diagnosis and treatment of diseases of the digestive system. M: Medicine, 2002. 424 p. 3. Diagnosis and treatment of gastroesophageal reflux disease: A manual for doctors / Comp. V.T. Ivashkin, A.A. Sheptulin, A.S. Trukhmanov, O.A. Sklyanskaya, M.Yu. Konkov. M., 2005. 30 p. 4. Minushkin O.N. et al. Modern aspects of antacid therapy. M., 1998. 5. Minushkin O.N., Ivashkin V.T., Trukhmanov A.S., Vasiliev Yu.V., Maslovsky L.V. Pariet in Russia: results of a multicenter clinical trial // Ros. Journal of gastroenterology, hepatology, coloproctology. 2000. No. 6. P. 43-46. 6. Fundamentals of clinical pharmacology and rational pharmacotherapy: A guide for practicing physicians / Ed. Yu.B. Belousova, M.V. Leonova. M.: Bionics, 2002. T. 1. P. 254-258.

For acute gastritis

During the period of exacerbation of gastritis, doctors prescribe a special diet that is as gentle as possible on
the irritated gastric mucosa. The diet consists of liquid, pureed and non-spicy foods. As you feel better, the diet gradually expands and becomes similar to the diet of a completely healthy person - minus indigestible fatty meats and fish, smoked meats, hot, salty and overly spicy dishes. But nutritionists do not recommend abusing these products even for people with a still healthy stomach - in order to avoid digestive disorders.

MEDICINES THAT LOWER THE SECRETION OF HOLARIC ACID (Part 1)

Preferanskaya Nina Germanovna Associate Professor of the Department of Pharmacology, Institute of Pharmacy named after. A.P. Nelyubin First Moscow State Medical University named after. THEM. Sechenov (Sechenov University), Ph.D.

The activity of parietal cells that produce hydrochloric acid is controlled by a number of biologically active substances. Acetylcholine, histamine, and gastrin occupy an important place among them.

Receptors of these mediators are localized on the basolateral membrane of the cell: M3-cholinergic receptors, H2-histamine receptors and cholecystokinin CCK receptors, stimulation of which leads to increased gastric secretion.

There are three phases of triggering the secretion of hydrochloric acid. The initial phase - “brain” , is activated conditionally by irritation of distant receptors, excited not so much by thoughts about food, stimuli that form appetite, but by the sight, smell and taste of food. Impulses arising in the central nervous system (CNS) reach the stomach through the cholinergic fibers of the vagus nerves (parasympathetic division). Neurons release the mediator acetylcholine, which acts on parietal cells not only directly, but also indirectly.

The direct pathway of action of acetylcholine occurs through the interaction of the mediator with M3-cholinergic receptors on the basolateral membrane of glandulocytes and stimulation of enterochromaffin-like cells of the stomach. Enterochromaffin-like cells in the fundus of the stomach are a source of histamine.

The indirect route of action of acetylcholine is associated with the effect on specialized cells of the gastric mucosa that produce gastrin and histamine. As a result, paracrine cells, located mainly in the pyloric part of the stomach, release histamine, and in the antrum, gastrin is released by G cells of the stomach. Histamine-producing cells are located in the fundus of the stomach. Receptors for gastrin on histamine-producing and parietal cells. The action of gastrin increases the activity of histidine decarboxylase, which converts it into histamine.

The second phase is “neurohumoral” and begins when food enters the stomach. Distension of the stomach increases the release of histamine and gastrin. Histamine secretion is stimulated by calcium (Ca2+), the intracellular concentration of which increases and the formation of cAMP increases. A key role in the regulation of hydrochloric acid secretion is played by histamine, which is a paracrine factor. Histamine is released into the intercellular fluid, acts locally and affects the functions of cells located near it. Activation of calcium channels leads to increased acid production by the proton pump. The energy-dependent ion pump transfers the hydrogen ion into the lumen of the gastric gland to the outer side of the secretory cytoplasmic membrane, and the potassium ion rushes into the parietal cell.

The enzyme H+/K+-adenosine triphosphatase (H+/K+-ATPase - proton pump) is responsible for the secretion of hydrogen ions in the apical secretory membrane of the parietal cells of the gastric mucosa. The transport of chlorine ions is influenced by both the concentration gradient of these ions between the blood plasma and gastric juice, and the difference in electrical charges on both sides of the gastric mucosa. The release of hydrogen (H+) and chloride (Cl¯) ions into the stomach cavity forms hydrochloric acid (HCl).

The third phase, the “ intestinal” phase, occurs when food enters the duodenum, which causes the release of cholecystokinin from the pancreas. Cholecystokinin stops the driving activity of the stomach, contracts the pylorus and blocks the secretion of hydrochloric acid.

Increased secretion of gastric juice can lead to damage to the stomach wall, the occurrence of peptic ulcers, which causes the development of gastric or duodenal ulcers, hyperacid gastritis, reflux esophagitis and other diseases. Irritation of existing ulcers causes spasm of the stomach muscles and pain.

Drugs that reduce the secretory function of the stomach and reduce the production of hydrochloric acid include anticholinergic blockers, histamine blockers, synthetic prostaglandins and proton pump inhibitors (proton pump).

Cholinergic receptor blockers are divided into:

• selective M1 anticholinergic blockers - Pirenzepine (Gastrocepin);
• non-selective M1,2,3 anticholinergic blockers - Atropine, Platiphylline and a combined preparation of belladonna (belladonna) - Besalol, consisting of belladonna leaf extract and phenyl salicylate;
• ganglion blockers, blockers of Mn-cholinergic receptors of the ganglia of the autonomic nervous system - Azamethonium bromide.

M-anticholinergics of plant origin: atropine, platyphylline and belladonna preparations are non-selective drugs. M-anticholinergics are one of the long-used drugs to reduce gastric secretion. However, it is not possible to achieve a deep blockade of secretion when administered, so they are prescribed as an addition to the main treatment with antacids and diets. In addition, drugs of the atropine group have a number of undesirable effects: dry mouth, tachycardia, impaired accommodation. Platiphylline, which does not have so many disadvantages, is less effective. It is more rational to use anticholinergics before bedtime in order to influence the nocturnal secretion of hydrochloric acid, which especially increases with peptic ulcer disease.

Besalol is a combination drug containing belladonna extract and phenyl salicylate. Belladonna extract, by blocking M-cholinergic receptors, reduces the secretion of the salivary and bronchial glands, as well as the gastric glands, relaxes the tone of the smooth muscle organs. Phenyl salicylate does not decompose in an acidic environment, but is broken down in the alkaline environment of the small intestine into phenol and salicylic acid. The drug does not have an irritating effect on the gastric mucosa and does not cause dysbacteriosis. The resulting salicylic acid has analgesic, antipyretic and anti-inflammatory effects.

The active ingredients of the drug have not only anticholinergic, antisecretory, anti-inflammatory and antiseptic effects, but also exhibit antispasmodic and analgesic effects.

The drug is used for mild forms of diseases to treat the gastrointestinal tract (enteritis, colitis, enterocolitis), as well as the urinary tract (cystitis, pyelitis, pyelonephritis).

Azamethonium bromide is a ganglion blocker, although it has an antisecretory effect, but it is not used in medical practice for this purpose, because There are selective drugs with fewer side effects.

Pirenzepine /Gastrocetin is the most effective selective drug among M-anticholinergics. Release form: tab. 0.025 mg; 10 mg amp. with solvent 2 ml. The drug selectively blocks M1-cholinergic receptors at the level of the intramural ganglia and turns off the stimulating effect of the vagus nerve on gastric secretion.

When using the drug, microcirculation of the gastric mucosa improves due to the dilation of blood vessels, intragastric proteolysis is suppressed (the process of enzymatic decomposition of proteins), gastric mucus formation is stimulated, the resistance of cells of the gastric mucosa to damage increases, thereby having a gastroprotective and antiulcer effect. The maximum concentration in the blood plasma is achieved after 3–4 hours. To a small extent, Pirenzepine reduces the secretion of the salivary glands, which is manifested by dry mouth. Side effects with pirenzepine occur less frequently than with non-selective anticholinergic drugs, because it does not affect the receptors of the myocardium (M2 cholinergic receptors) and smooth muscles (M3 cholinergic receptors).

The drug does not cross the BBB and the placenta, so it can be prescribed to nursing mothers. Contraindicated in the first trimester of pregnancy. Use with caution in patients with glaucoma and prostatic hypertrophy. With rapid subjective improvement, you should not stop taking it due to a possible deterioration of the condition. When administered intravenously, it is necessary to monitor the state of the cardiovascular system. However, in terms of acid-blocking properties, pirenzepine is much inferior not only to proton pump inhibitors, but also to H2-histamine blockers.

H2-HISTAMINE RECEPTOR BLOCKERS

The mechanism of action of histamine is to stimulate histamine receptors in cells of various organs. There are two types of histamine receptors: H1 and H2 (from the first letter Histaminum). Excitation of H1-histamine receptors leads to contraction of the muscles of the bronchi, gastrointestinal tract, uterus, and dilation of small blood vessels. Drugs that block H1-histamine receptors are used in medical practice as antihistamines and antiallergic agents. When H2-histamine receptors are stimulated, an increase in the secretion of gastric juice is observed, and its acidity also increases. H2-histamine receptors are localized in the gastric glands, in the parietal cells. It is believed that in case of gastric ulcer and hyperacid gastritis (high acidity), the activity of H2-histamine receptors is sharply increased. Histamine blockers block H2-histamine receptors and thereby suppress excessive secretion of gastric juice and reduce its acidity, which has a beneficial effect in the treatment of acid-related diseases. These drugs cause “rebound syndrome” and cannot be abruptly discontinued due to a sharp increase in the production of hydrochloric acid. It is not recommended to use drugs for the treatment of Helicobacter pylori infection.

H2-histamine receptor blockers are distinguished by generation:

• the first generation - Cimetidine (Neuronorm) - is currently not produced or used;
• second generation - Ranitidine (TN "Zantac" , tablet 150 mg, 300 mg, tablet spike. 150 mg/300 mg; TN "Acylok" , tablet 150 mg, tablet 300 mg, injection solution. 25 mg/ml, amp. 2 ml for IM and IV administration; TN "Ranisan" , table 75 mg/150 mg);
• third generation - Famotidine (TN "Kvamatel" , tablet 20 mg, 40 mg, portioned lyophilis. 20 mg d/d. solution; TN "Famosan" , tablet 20 mg, 40 mg).

Ranitidine (Ranitidinum) - suppresses the secretion of gastric juice by 70%, has a long-lasting effect (more than 12 hours), so the usual dosage is 1 tablet. (0.150) is used 2 times a day, 300 mg tablets - 1 time at night. When using the drug, the volume and acidity of gastric juice decreases. The maximum concentration is reached after 2 hours. The drug passes through the histohematic and placental barriers, the BBB is poor. Determined in breast milk. The half-life is 2–3 hours.

Important! The main undesirable effects of the drug are allergic reactions (in the form of redness and itching), dizziness, and dry mouth.

In children, it is approved for use from 12 years of age; for the treatment of peptic ulcers, 2–4 mg/kg is used 2 times a day. When used, the drug can enter into numerous drug interactions, increasing the concentration in the blood and increasing the toxicity of other drugs.

The Food and Drug Administration (FDA) has identified a potential carcinogen in Ranitidine. The issue of recalling the drug from the pharmaceutical market is being discussed due to the content of the carcinogenic substance N-nitrosodimethylamine (NDMA), which gets into the drug from the substance of some manufacturing companies. However, recent studies have found low levels of NDMA and the risk to patients is currently being assessed.

Famotidine (Famotidinum) was more effective. Third-generation drugs are distinguished by their ability to block gastric secretion up to 80%, suppress basal and histamine-, gastrin- and acetylcholine-stimulated production of hydrochloric acid. Simultaneously with the increase in pH, the activity of pepsin decreases. After oral administration, it is quickly absorbed from the gastrointestinal tract. The maximum concentration in blood plasma is achieved within 3 hours. Metabolized in the liver, weakly inhibits the oxidase system of cytochrome P 450. T½ is 4 hours. Elimination mainly occurs through the kidneys, 40% of the drug is excreted unchanged in the urine. The duration of action of the drug after a single dose depends on the dose and ranges from 12 to 24 hours. The risk of drug interactions is significantly lower than with Ranitidine.

The drug is available with a prescription!

Important! The drug's side effects are mild and extremely rare. It is contraindicated in case of hypersensitivity, during pregnancy and breastfeeding. During treatment with the drug, dry mouth and skin, loss of appetite, drowsiness, increased fatigue, headache, muscle pain, and allergic reactions may occur. It is not recommended to prescribe the drug to children; use it with caution in case of liver dysfunction. During the treatment period, it is necessary to refrain from driving and other activities that require increased concentration and reaction speed.

SYNTHETIC ANALOGUES OF PROSTAGLANDINS

Misoprostol (Misoprostolum) - TN "Cytotec" , table. 200 mcg (0.2 mg) - used for the treatment of erosive and ulcerative lesions of the stomach and duodenum resulting from taking drugs that have an ulcerogenic effect (for example, NSAIDs, corticosteroids). This drug has an inhibitory effect on the secretion of hydrochloric acid, protects the gastrointestinal mucosa from the effects of various irritants, while providing a cytoprotective effect, stimulates the secretion of mucus and bicarbonates, increases blood flow and prevents the formation of ulcers in the gastrointestinal tract.

Important! The drug is contraindicated during pregnancy. Side effects: headache, cramping abdominal pain, nausea, diarrhea, uterine bleeding (we will tell you more about this drug in the article on gastroprotectors).

Drugs used for decreased secretion of gastric glands

The secretion of the gastric glands is under the control of the vagus nerve, as well as a number of gastrointestinal hormones and other endogenous substances.
An increase in the tone of the vagus nerve, as well as the release of gastrin and histamine, enhance the secretory activity of the stomach. The main enzymes of gastric juice are pepsin, chymosin, lipases. Pepsin and chymosin are proteolytic enzymes that break down proteins into polypeptides and amino acids. Gastric juice lipases break down fats into glycerol and fatty acids.

In case of insufficiency of the gastric glands, substances that stimulate secretion or replacement therapy are used.

1- Substitution therapy

If there is insufficient production of hydrochloric acid, drugs containing enzymes of gastric juice and hydrochloric acid are used, which compensate for their deficiency in the stomach.

Natural gastric juice is obtained by imaginary feeding of dogs. Artificial gastric juice is obtained by infusing dried pig stomachs in diluted hydrochloric acid. Medicines contain all enzymes and acid. Used internally for hypo- and anacid gastritis, Achilles, dyspepsia. Prescribe 1-2 tablespoons during or after meals for adults, 1-2 teaspoons for children.

Pepsin is obtained from the gastric mucosa of pigs. It is usually used in combination with diluted 1-3% hydrochloric acid for digestive disorders. Take 1-2 tablespoons before or during meals.

If there is insufficient secretion of hydrochloric acid, use hydrochloric acid diluted 20-40 drops with water before meals or during meals (through a straw).

Acidin-pepsin (betacid) - tablets containing 1 part pepsin and 4 parts acidin (betaine hydrochloride), which separates free hydrochloric acid in the stomach. Take 1-2 tablets. in dissolved form during or after meals.

Abomin is obtained from the gastric mucosa of calves and contains a sum of proteolytic enzymes. Prescribe 1 tablet. while eating.

Citropepsin contains pepsin in combination with citric acid.

2-Means of stimulant therapy.

To enhance the secretory activity of the gastric glands, plantain drugs are used: Plantain juice and Plantaglucid granules. They contain the sum of polysaccharides from plantain and flea. They stimulate secretion in the presence of functionally capable cells in the gastric mucosa, and have an antispasmodic and anti-inflammatory effect. Prescribed for gastritis, gastric and duodenal ulcers with low acidity.

Bitterness, carbonated mineral waters, and sour fruit juices have a sonic effect.

Histamine is used to diagnose the functional state of the stomach. It stimulates the H2-histamine receptors of the stomach, which leads to significant secretion of gastric juice while maintaining secretory activity. In case of overdose, shock and collapse may develop.

The secretion of the gastric glands is under the control of the vagus nerve, as well as a number of gastrointestinal hormones and other endogenous substances. An increase in the tone of the vagus nerve, as well as the release of gastrin and histamine, enhance the secretory activity of the stomach.

The main enzymes of gastric juice are pepsin, chymosin, lipases. Pepsin and chymosin are proteolytic enzymes that break down proteins into polypeptides and amino acids. Gastric juice lipases break down fats into glycerol and fatty acids.

In case of insufficiency of the gastric glands, substances that stimulate secretion or replacement therapy are used.

1- Substitution therapy

If there is insufficient production of hydrochloric acid, drugs containing enzymes of gastric juice and hydrochloric acid are used, which compensate for their deficiency in the stomach.

Natural gastric juice is obtained by imaginary feeding of dogs. Artificial gastric juice is obtained by infusing dried pig stomachs in diluted hydrochloric acid. Medicines contain all enzymes and acid. Used internally for hypo- and anacid gastritis, Achilles, dyspepsia. Prescribe 1-2 tablespoons during or after meals for adults, 1-2 teaspoons for children.

Pepsin is obtained from the gastric mucosa of pigs. It is usually used in combination with diluted 1-3% hydrochloric acid for digestive disorders. Take 1-2 tablespoons before or during meals.

If there is insufficient secretion of hydrochloric acid, use hydrochloric acid diluted 20-40 drops with water before meals or during meals (through a straw).

Acidin-pepsin (betacid) - tablets containing 1 part pepsin and 4 parts acidin (betaine hydrochloride), which separates free hydrochloric acid in the stomach. Take 1-2 tablets. in dissolved form during or after meals.

Abomin is obtained from the gastric mucosa of calves and contains a sum of proteolytic enzymes. Prescribe 1 tablet. while eating.

Citropepsin contains pepsin in combination with citric acid.

2-Means of stimulant therapy.

To enhance the secretory activity of the gastric glands, plantain drugs are used: Plantain juice and Plantaglucid granules. They contain the sum of polysaccharides from plantain and flea. They stimulate secretion in the presence of functionally capable cells in the gastric mucosa, and have an antispasmodic and anti-inflammatory effect. Prescribed for gastritis, gastric and duodenal ulcers with low acidity.

Bitterness, carbonated mineral waters, and sour fruit juices have a sonic effect.

Histamine is used to diagnose the functional state of the stomach. It stimulates the H2-histamine receptors of the stomach, which leads to significant secretion of gastric juice while maintaining secretory activity. In case of overdose, shock and collapse may develop.