Omeprazole (Omeprasolum; caps. 0.02 each) - is a racemic mixture of two enantiomers, reduces acid secretion due to specific inhibition of the acid pump of parietal cells. With a single appointment, the drug acts quickly and provides a reverse inhibition of acid secretion. Omeprazole is a weak alkali, concentrated and converted into an active form in acidic environment tubular cells of the parietal layer of the gastric mucosa, where it is activated and inhibits H + , K + -ATPase of the acid pump. The drug has a dose-dependent effect on the last stage of acid synthesis, inhibits both basal and stimulating secretion, regardless of the stimulating factor. Intravenous administration of omeprazole has a dose-dependent suppression of hydrochloric acid in humans. In order to achieve a rapid decrease in intragastric acidity, intravenous administration of 40 mg of omeprazole is recommended, after which there is a rapid decrease in intragastric secretion, which is maintained for 24 hours.

The degree of suppression of acid secretion is proportional to the area under the curve (AUC concentration-time) of omeprazole and is not proportional to the actual concentration of the drug in the blood at a given time. During treatment with omeprazole, tachyphylaxis was not observed. Decreased gastric acid secretion by proton pump inhibitors or other acid-inhibiting agents leads to an increase in the growth of normal intestinal microflora, which in turn may lead to a slight increase in the risk of intestinal infections caused by bacteria such as Salmonella and Campylobacter.

The volume of distribution in healthy subjects is 0.3 l / kg, a similar figure is determined in patients with renal insufficiency. In elderly patients and in patients with renal insufficiency, the volume of distribution is slightly reduced. The rate of binding of omeprazole to plasma proteins is about 95%. After administration, the mean terminal elimination half-life is 0.3 to 0.6 L/min. During treatment, there are no changes in the duration of the half-life. Omeprazole is completely metabolized by cytochrome P-450 (CYP) in the liver. The metabolism of the drug is mainly dependent on the specific isoenzyme CYP2C19 (S-mefinitone hydroxylase), which is responsible for the formation of the main metabolite hydroxyomeprazole. Metabolites affect gastric acid secretion. About 80% of the intravenously administered dose is excreted as metabolites in the urine, and the rest in the faeces. In patients with impaired renal function, the excretion of omeprazole does not undergo any changes. An increase in the half-life in patients with impaired liver function is determined, however, omeprazole does not accumulate. Indications for use: duodenal ulcer, peptic ulcer, reflux esophagitis, treatment of Zollinger-Ellison syndrome.

Side effects - Omeprazole is generally well tolerated. Side effects have been reported, however, in most cases the actual relationship between effect and treatment has not been established.

Integuments - skin rashes and skin itch. In some cases, photosensitivity reaction, erythema multiforme, alopecia. Musculoskeletal system - in some cases, arthralgia, muscle weakness, myalgia.

Central and peripheral nervous systems: headache, hyponatremia, dizziness, paresthesia, drowsiness, insomnia. In some cases, patients with severe comorbidities may experience depression, agitation, aggressiveness, and hallucinations.

Gastrointestinal: diarrhea, constipation, abdominal pain, nausea, vomiting, flatulence. In some cases, dry mouth, stomatitis, gastrointestinal candidiasis.

Liver system: in some cases, an increase in the activity of liver enzymes, encephalopathy may develop in patients with severe liver disease.

Endocrine system: in some cases, gynecomastia.

Circulatory system: in some cases, leukopenia, thrombocytopenia, agranulocytosis and pancytopenia.

Others: general malaise, hypersensitivity reaction in the form of urticaria (rarely), in some cases, angioedema, fever, bronchospasm, interstitial nephritis, anaphylactic shock.

Antacids. This group includes agents that neutralize hydrochloric acid and those that reduce the acidity of gastric juice. These are anti-acid drugs. Usually these are chemical compounds with the properties of weak alkalis, they neutralize hydrochloric acid in the lumen of the stomach. The decrease in acidity is of great therapeutic importance, since the activity of pepsin and its digestive effect on the gastric mucosa depend on its amount. The optimum pH for pepsin activity is in the range of 1.5 to 4.0. At pH = 5.0, pepsin is active. Therefore, it is desirable that antacids raise the pH no higher than 4.0 (optimally, when taking antacids, the pH of gastric juice should be 3.0 - 3.5), which does not disturb the digestion of food. Usually, the pH of gastric contents normally ranges from 1.5 to 2.0. Pain syndrome begins to subside when the pH becomes more than 2.

There are systemic and non-systemic antacids. Systemic antacids are agents that can be absorbed, and therefore have effects not only in the stomach, but can also lead to the development of alkalosis in the body as a whole. Non-systemic antacids are not absorbed, and therefore are able to neutralize acidity only in the stomach, without affecting the acid-base state of the body. Antacids include sodium bicarbonate (baking soda), calcium carbonate, aluminum and magnesium hydroxide, magnesium oxide. Typically, these substances are used in various dosage forms and in various combinations. Systemic antacids include sodium bicarbonate and sodium citrate, all other of the above agents are non-systemic.

Sodium bicarbonate (baking soda) is a compound that is highly soluble in water, quickly reacting in the stomach with hydrochloric acid. The reaction proceeds with the formation of sodium chloride, water and carbon dioxide. The drug works almost instantly. Although sodium bicarbonate acts quickly, its effect is short and weaker than that of other antacids. The carbon dioxide formed during the reaction stretches the stomach, causing bloating and belching. In addition, taking this drug may be accompanied by a "recoil" syndrome. The last one is that rapid rise pH in the stomach leads to the activation of parietal G-cells of the central part of the stomach, producing gastrin. Gastrin also stimulates the secretion of hydrochloric acid, which leads to the development of hyperacidity after the termination of the antacid. Usually the syndrome of "recoil" develops in 20-25 minutes. Due to good absorption from the gastrointestinal tract, sodium bicarbonate can cause systemic alkalosis, which is clinically manifested by decreased appetite, nausea, vomiting, weakness, abdominal pain, muscle cramps and cramps. This is a rather dangerous complication requiring immediate discontinuation of the drug and assistance to the patient. Given the severity of the side effects, sodium bicarbonate as an antacid is used extremely rarely.

Non-systemic antacids, as a rule, are insoluble, act in the stomach for a long time, are not absorbed, and are more effective. When they are consumed, the body does not lose either cations (hydrogen) or anions (chlorine), and there is no change in the acid-base state. The action of non-systemic antacids develops more slowly, but lasts longer.

Aluminum hydroxide (aluminum hydroxide; Aluminii hydroxydum) is a drug with a moderate antacid effect, acts quickly and effectively, shows a significant effect after about 60 minutes.

The drug binds pepsin, reduces its activity, inhibits the formation of pepsinogen and increases the secretion of mucus. One gram of aluminum hydroxide neutralizes 250 ml of decinormal hydrochloric acid to pH = 4.0. In addition, the drug has an astringent, enveloping and adsorbing effect. Side effects: not all patients tolerate the astringent effect of the drug well, which can be manifested by nausea, taking aluminum preparations is accompanied by constipation, therefore, aluminum-containing preparations are combined with magnesium preparations. Aluminum hydroxide promotes the excretion of phosphates from the body. The drug is indicated for diseases with increased secretion of gastric juice (hydrochloric acid): ulcer, gastritis, gastroduodenitis, food poisoning, flatulence. Assign aluminum hydroxide orally in the form of a 4% aqueous suspension, 1-2 teaspoons per reception (4-6 times a day

Magnesium oxide (Magnesii oxydum; powder, gel, suspension) - burnt magnesia - a strong antacid, more active than aluminum hydroxide, acts faster, longer and has a laxative effect. Each of these antacids has both advantages and disadvantages. In this regard, their combinations are used. The combination of aluminum hydroxide in the form of a special balanced gel, magnesium oxide and D-sorbitol made it possible to obtain one of the most common and effective, at present, antacid preparations - Almagel (Almagel; 170 ml; the drug got its name from the words al-aluminum, ma-magnesium , gel-gel). The drug has an antacid, adsorbing and enveloping effect. The gel-like dosage form contributes to the uniform distribution of the ingredients over the surface of the mucous membrane and the prolongation of the effect. D-sorbitol promotes bile secretion and relaxation.

Indications for use: gastric and duodenal ulcers, acute and chronic hyperacid gastritis, gastroduodenitis, esophagitis, reflux esophagitis, Zollinger-Ellison syndrome, pregnancy heartburn, colitis, flatulence, etc. There is a drug Almagel-A, which additionally contains Almagel anestezin is also added, which gives both a local anesthetic effect and suppresses the secretion of gastrin.

Almagel is usually used 30-60 minutes before a meal, and also within an hour after a meal. The drug is prescribed individually, depending on the localization of the process, the acidity of gastric juice, etc. Preparations similar to Almagel: - gastrogel; - phosphalugel contains aluminum phosphate and colloidal gels of pectin and agar-agar, which bind and absorb toxins and gases, as well as bacteria, reduce the activity of pepsin; - megalac; - Milanta contains aluminum hydroxide, magnesium oxide and simethicone; - gastal - tablets, which include: 450 mg of aluminum hydroxide - magnesium carbonate gel, 300 mg of magnesium hydroxide.

Currently, the most popular drug from the group of antacids is the drug Maalox (Maalox). The composition of the drug includes aluminum hydroxide and magnesium oxide. Maalox is available as a suspension and tablets; 5 ml of Maalox suspension contain 225 mg of aluminum hydroxide, 200 mg of magnesium oxide and neutralize 13.5 mmol of hydrochloric acid; the tablets contain 400 mg of aluminum hydroxide and magnesium oxide, so they have the highest acid-neutralizing activity (up to 18 mmol of hydrochloric acid). Maalox-70 is even more active (up to - 35 mmol of hydrochloric acid).

The drug is indicated for gastritis, duodenitis, peptic ulcer of the stomach and duodenum, reflux esophagitis.

MEDICINES PROTECTING THE GASTRIC MUCOSA FROM ACID-PEPTIC ACTION AND IMPROVING REPARATIVE PROCESSES

1. Bismuth preparations (vikalin, vikair, de-nol).

2. Venter.

3. Preparations of prostaglandins.

4. Dalargin.

Bismuth preparations are used as astringents and antiseptics in the treatment of patients with peptic ulcer. Most often, these are combined tablets - vikalin (basic bismuth nitrate, sodium bicarbonate, calamus rhizome powder, buckthorn bark, rutin and quelin). IN last years In medical practice, drugs have entered that protect the mucous membrane from acid-peptic action more strongly. These are colloidal preparations of bismuth of the second generation, one of which is de-nol (De-nol; 3-potassium dicitrate bismuthate; each tablet contains 120 mg of colloidal bismuth subcitrate). This drug envelops the mucous membrane, forming a protective colloid-protein layer on it. It does not have an antacid effect, but exhibits antipeptic activity by binding pepsin. The drug also has an antimicrobial effect, it is much more effective than bismuth-containing antacids increases the resistance of the mucous membrane. De-nol cannot be combined with antacids. The drug is used for any localization of the ulcer, it is highly effective for: gastric and duodenal ulcers that do not scar for a long time; peptic ulcer in smokers; prevention of recurrence of peptic ulcer; chronic gastritis.

Assign 1 tablet three times a day half an hour before meals and 1 tablet at bedtime. De-nol is contraindicated in severe renal failure.

Venter (sucralfate; in tab. 0.5) is the basic aluminum salt of sucrose octasulfate. The antiulcer action is based on binding to the proteins of dead tissue, into complex complexes that form a strong barrier. Gastric juice is locally neutralized, the action of pepsin slows down, the drug also absorbs bile acids. At the site of the ulcer, the drug is fixed for six hours. Venter and de-nol cause scarring of duodenal ulcers after three weeks. Sucralfate is used 1.0 four times a day before meals, and also at bedtime. Side effect: constipation, dry mouth.

Solcoseryl (Solcoseryl) - protein-free extract from the blood of cattle. Protects tissues from hypoxia and necrosis. It is used for trophic ulcers of any localization. Apply 2 ml 2-3 times a day, intravenously and intramuscularly, until the ulcer heals.

Prostaglandin preparations: misoprostol (cytotec), etc. Under the action of these drugs, the acidity of gastric juice decreases, the motility of the stomach and intestines increases, and favorable effects on the ulcerative niche in the stomach are determined. The drugs also have a reparative, hypoacid (by increasing mucus formation), hypotensive effect. Misoprostol (Misoprostol; in tab. 0.0002) is a preparation of prostaglandin E2, which is obtained from plant materials. Synonym - sitetech. Prostaglandin preparations are indicated for acute and chronic gastric and duodenal ulcers. Side effects: transient diarrhea, mild nausea, headache, abdominal pain.

Dalargin (Dalarginum; in amps and vials, 0.001 each) is a peptide drug that promotes the healing of gastric and duodenal ulcers, reduces the acidity of gastric juice, and has a hypotensive effect. The drug is indicated for exacerbation of peptic ulcer of the stomach and duodenum.

ATMOSPHERIC CORROSION INHIBITOR « H-M-1 »

Atmospheric corrosion inhibitor "N-M-1" is intended for to protect products from atmospheric and microbiological corrosion during operation, storage, conservation and transportation in various climatic conditions (continental, marine, tropical, arctic). It is also used to protect equipment from parking corrosion and interoperational conservation of heat and power equipment.

"N-M-1" is an analogue of the inhibitor M-1. For its manufacture, instead of synthetic fatty acids of the C 10 -C 13 fraction, fatty acids C 10 -C 18 were used.

Protects products from biodamage by inhibiting the growth of the most common types of mold fungi.

To obtain inhibited anti-corrosion primers with enhanced protective properties and extended service life of the paintwork.

Joint research work of NPP NOTECH LLC with the developer of inhibitors M-1 and N-M-1 - the laboratory of corrosion inhibitors JSC VNIIneftekhim (St. Petersburg) under the guidance of Honored Scientist of the Russian Federation, Professor A. AND. Altsybeeva - ensured the maximum approximation of the technological and protective properties of the inhibitor "N-M-1" to the properties of the inhibitor M-1.

The H-M-1 inhibitor is not a precursor.

Specifications:

Appearance- pasty substance

Color- brown

It is a high molecular weight adduct of fatty acids of the C 10 -C 18 fraction and a cyclic amine.

Solubility(% mass at +25 o C):

In water up to 3;

In gasoline up to 80;

In industrial oils - at least 20;

In organic solvents up to 50%.

Protects steel, cast iron, zinc, nickel, chromium, aluminium, copper and its alloys.

Packing: euro bucket 18 kg.

Technological and protective properties of the inhibitor "N-M-1" are similar to the properties and composition of the inhibitor M-1. Inhibitor "N-M-1" is included in GOST 9.014-78 "Temporary anti-corrosion protection of products. General requirements".

Preparation of inhibited preservation oils and solutions, production of anti-corrosion coatings.

Atmospheric corrosion inhibitor "N-M-1" is used:

1. in the form of 5 ... 10% solutions in volatile solvents (gasoline, ethanol, etc.);
2. in the form of 1 ... 3% solutions in water (condensate);
3. in the form of additives to mineral oils and fuels (diesel, jet, kerosene), rust converters, detergents in the amount of 0.1 ... 3% of the mass;
4. in the form of 0.2…3% wt. aqueous solutions when combining hydrotesting and conservation with the additional use of volatile corrosion inhibitors;
5. by introducing into anticorrosive epoxy, vinyl, vinyl-epoxy and other primers in an amount of up to 2.5% of the mass of paintwork materials at the stage of their manufacture.

The preparation of inhibitor oils and solutions can be carried out by introducing the inhibitor without heating or by heating (avoid sources of open fire) up to 40-50 ° C, depending on the consistency of the inhibitor and inhibitor oil, with thorough mixing, until a homogeneous mixture is obtained. If necessary, warming up to +80°С in the mass of the inhibitor is allowed before use. For the preparation of aqueous solutions, condensate is used, because. Tap water solutions tend to be cloudy.

Warranty period of storage: 24 months from the date of manufacture.

Specifications:

Solubility (% mass at +25°C):

In water not less than 3%;

In gasoline 82.9%;

In industrial oils not less than 50%.

Surface preparation

Items must be delivered clean. Preparation for conservation is carried out in accordance with sections 4.5 of GOST 9.014 ESZKS.

Conservation

Preservation of products (parts, components, mechanisms, etc.) using inhibited oils, fuels, as well as solutions of "N-M-1" in volatile solvents is carried out by applying them to the metal surface by dipping, brushing, spraying or any other method , so that there are no unmoistened places on the products. After applying the solution (oil) to the surface of the equipment, allow excess oil to drain or the solvent to evaporate. Preservation of the internal cavities of mechanisms (fuel systems, etc.) without their disassembly is carried out by short-term study (pumping) at a temperature not exceeding 70 ° C or by filling the mechanism with inhibited oil (fuel, solution).

The consumption rates of inhibited materials (oils, solutions, etc.) are set depending on the design of the products, the method of application, storage conditions and periods.

Preserved for long periods of storage with solutions of "N-M-1" in oils and volatile solvents, products, components and parts of equipment are wrapped in waxed or wrapping paper.

Precautionary measures: Atmospheric corrosion inhibitor "N-M-1" is a low-toxic substance. When working with the N-M-1 inhibitor, it is necessary for the personnel to use special footwear, overalls, safety devices in accordance with standard industry standards. When working with inhibitor solutions in oils, fuels and volatile solvents, the general rules for working with flammable or explosive substances must be observed. In case of contact with skin or mucous membranes, rinse with warm water or a weak solution of soda.

Application of corrosion inhibitor "N-M-1"

Without reliable corrosion protection, equipment quickly fails. Anti-corrosion protection is especially important in situations where the operation of metal structures or mechanisms is carried out in an aggressive chemical environment, and they are constantly exposed to vapors and high temperatures.

We take part in the reconstruction of the water supply system of the fountains of the Peterhof State Museum-Reserve, which has no analogues in the world. Corrosion inhibitor "N-M-1" preserves pipes and water shut-off devices for the winter period. NOTECH rust converter is used for painting metal structures and external protection of pipe joints.

Corrosion inhibitors "FMT" and "N-M-1" were used for the conservation of the weapons collection of the State Hermitage.

You can send an application for the purchase of corrosion inhibitor "N-M-1" to e-mail: . We look forward to collaborating.

Application for purchase xchemical rust converter "NOTECH" you can send to e-mail:. We look forward to collaborating.

This group is among pharmacological preparations one of the leading, belongs to the means of choice in the treatment of peptic ulcers. The discovery of H2 histamine receptor blockers over the past two decades is considered the largest in medicine, helping to solve economic (affordable cost) and social problems. Thanks to H2-blockers, the results of therapy for peptic ulcers have improved significantly, surgical interventions began to be used as rarely as possible, the quality of life of patients improved. "Cimetidine" was called the "gold standard" in the treatment of ulcers, "Ranitidine" in 1998 became the sales record holder in pharmacology. A big plus is the low cost and at the same time the effectiveness of drugs.

Usage

Histamine H2 receptor blockers are used to treat acid-dependent gastrointestinal diseases. The mechanism of action is the blocking of H2 receptors (otherwise they are called histamine) cells of the gastric mucosa. For this reason, the production and entry into the lumen of the stomach of hydrochloric acid is reduced. This group of drugs belongs to antisecretory

Most often, H2 histamine receptor blockers are used in cases of manifestations of peptic ulcer. H2 blockers not only reduce the production of hydrochloric acid, but also suppress pepsin, while gastric mucus increases, the synthesis of prostaglandins increases here, and the secretion of bicarbonates increases. The motor function of the stomach is normalized, microcirculation improves.

Indications for the use of H2-blockers:

• gastroesophageal reflux;
• chronic and acute pancreatitis;
• dyspepsia;
• Zollinger-Ellison syndrome;
• respiratory reflux-induced diseases;
• chronic gastritis and duodenitis;
• Barrett's esophagus;
• ulcers of the esophageal mucosa;
• stomach ulcer;
• ulcers medicinal and symptomatic;
• chronic dyspepsia with retrosternal and epigastric pain;
• systemic mastocytosis;
• for the prevention of stress ulcers;
• Mendelssohn's syndrome;
• prevention of aspiration pneumonia;
• bleeding of the upper gastrointestinal tract.

Histamine H2 receptor blockers: classification of drugs

There is a classification of this group of drugs. They are divided by generation:

• The I generation includes "Cimetidine".
• "Ranitidine" is a blocker of H2 histamine receptors of the II generation.
• The III generation includes "Famotidine".
• Nizatidine belongs to the IV generation.
• The V generation includes "Roxatidin".

"Cimetidine" is the least hydrophilic, due to this, the half-life is very short, while liver metabolism is significant. The blocker interacts with cytochromes P-450 (a microsomal enzyme), while the rate of hepatic metabolism of the xenobiotic changes. "Cimetidine" is a universal inhibitor of hepatic metabolism among most drugs. In this regard, it is able to enter into pharmacokinetic interaction, therefore, cumulation and increased risks of side effects are possible.

Among all H2 blockers, Cimetidine penetrates tissues better, which also leads to increased side effects. It displaces endogenous testosterone from its connection with peripheral receptors, thereby causing sexual dysfunction, leads to a decrease in potency, develops impotence and gynecomastia. "Cimetidine" can cause headaches, diarrhea, transient myalgia and arthralgia, increased blood creatinine, hematological changes, CNS lesions, immunosuppressive effects, cardiotoxic effects. Blocker H2 histamine receptors III generation - "Famotidine" - less penetrates into tissues and organs, thereby the amount side effects decreases. Do not cause sexual disorders and drugs of subsequent generations - "Ranitidine", "Nizatidin", "Roxatidin". All of them do not interact with androgens.

Comparative characteristics of drugs

There were descriptions of H2 blockers of histamine receptors (preparations of the extra-class generation), the name is "Ebrotidine", "Ranitidine bismuth citrate" is singled out, this is not a simple mixture, but complex compound. Here, the base - ranitidine - binds to trivalent bismus citrate.

Blocker H2 histamine receptors III generation "Famotidine" and II - "Ranitidine" - have greater selectivity than "Cimetidine". Selectivity is a dose-dependent and relative phenomenon. "Famotidine" and "Ranitidine" more selectively than "Cinitidine", affect H2 receptors. For comparison: "Famotidine" is eight times more powerful than "Ranitidine", "Cinitidine" - forty times. Differences in potency are determined by dose equivalence data of different H2 blockers that affect hydrochloric acid suppression. The strength of connections with receptors also determines the duration of exposure. If the drug is strongly bound to the receptor, dissociates slowly, the duration of the effect is determined. On the basal secretion "Famotidine" affects the longest. Studies show that "Cimetidine" provides a decrease in basal secretion for 5 hours, "Ranitidine" - 7-8 hours, 12 hours - "Famotidine".

H2 blockers belong to the group of hydrophilic drugs. Among all generations, Cimetidine is less hydrophilic than others, while moderately lipophilic. This allows him to easily penetrate into various bodies, effects on H2 receptors, which leads to many side effects. "Famotidine" and "Ranitidine" are considered highly hydrophilic, they penetrate poorly through tissues, their predominant effect on the H2 receptors of parietal cells.

The maximum number of side effects in "Cimetidine". "Famotidine" and "Ranitidine", due to changes in the chemical structure, do not affect metabolizing liver enzymes and give fewer side effects.

Story

The history of this group of H2-blockers began in 1972. English company in laboratory conditions under the leadership of James Black, she investigated and synthesized a huge number of compounds that were similar in structure to the histamine molecule. Once safe compounds were identified, they were transferred to clinical trials. The very first buriamid blocker was not entirely effective. Its structure was changed, methiamide turned out. Clinical studies have shown greater efficacy, but greater toxicity has manifested itself in the form of granulocytopenia. Further work led to the discovery of "Cimetidine" (I generation of drugs). The drug passed successful clinical trials, in 1974 it was approved. It was then that histamine H2 receptor blockers began to be used in clinical practice, it was a revolution in gastroenterology. James Black received the Nobel Prize in 1988 for this discovery.

Science does not stand still. Due to the multiple side effects of Cimetidine, pharmacologists began to focus on finding more effective compounds. So other new H2 blockers of histamine receptors were discovered. Drugs reduce secretion, but do not affect its stimulants (acetylcholine, gastrin). Side effects, "acid rebound" orient scientists to search for new means to reduce acidity.

outdated medicine

There is a more modern class of drugs called proton pump inhibitors. They are superior in acid suppression, in the minimum of side effects, in the time of exposure to histamine H2 receptor blockers. The drugs whose names are listed above are still used quite often in clinical practice due to genetics, for economic reasons (more often it is Famotidine or Ranitidine).

Antisecretory modern facilities, used to reduce the amount of hydrochloric acid, are divided into two large classes: proton pump inhibitors (PPIs), as well as histamine H2 receptor blockers. The latter drugs are characterized by the effect of tachyphylaxis, when repeated administration causes a decrease in the therapeutic effect. PPIs do not have this disadvantage and therefore, unlike H2 blockers, they are recommended for long-term therapy.

The phenomenon of the development of tachyphylaxis when taking H2-blockers is observed from the beginning of therapy within 42 hours. In the treatment of ulcers, it is not recommended to use H2-blockers, preference is given to proton pump inhibitors.

resistance

In some cases, histamine H2 blockers are listed above), as well as PPI preparations sometimes cause resistance. When monitoring the pH of the stomach environment in such patients, no changes in the level of intragastric acidity are detected. Sometimes cases of resistance to any group of H2 blockers of the 2nd or 3rd generation or to proton pump inhibitors are detected. Moreover, increasing the dose in such cases does not give a result, it is necessary to choose a different type of drug. The study of some H2-blockers, as well as omeprazole (PPI) shows that from 1 to 5% of cases have no changes in daily pH-metry. With dynamic monitoring of the process of treatment of acid dependence, the most rational scheme is considered, where daily pH-metry is studied on the first, and then on the fifth and seventh day of therapy. The presence of patients with complete resistance indicates that in medical practice there is no drug that would have absolute effectiveness.

Side effects

Histamine H2 receptor blockers cause side effects with varying frequency. The use of "Cimetidine" causes them in 3.2% of cases. Famotidine - 1.3%, Ranitidine - 2.7%. Side effects include:

• Dizziness, headaches, anxiety, fatigue, drowsiness, confusion, depression, agitation, hallucinations, involuntary movements, visual disturbances.
• Arrhythmia, including bradycardia, tachycardia, extrasystole, asystole.
• Diarrhea or constipation, abdominal pain, vomiting, nausea.
• Acute pancreatitis.
• Hypersensitivity (fever, rash, myalgia, anaphylactic shock, arthralgia, erythema multiforme, angioedema).
• Changes in liver function tests, mixed or holistic hepatitis with or without jaundice.
• Elevated creatinine.
• Hematopoietic disorders (leukopenia, pancytopenia, granulocytopenia, agranulocytosis, thrombocytopenia, aplastic anemia and cerebral hypoplasia, hemolytic immune anemia.
• Impotence.
• Gynecomastia.
• Alopecia.
• Decreased libido.

Famotidine has the most side effects on the gastrointestinal tract, with diarrhea often developing, in rare cases, on the contrary, constipation occurs. Diarrhea occurs due to antisecretory effects. Due to the fact that the amount of hydrochloric acid in the stomach decreases, the pH level rises. In this case, pepsinogen is more slowly converted to pepsin, which helps break down proteins. Digestion is disturbed, and diarrhea most often develops.

Contraindications

Histamine H2 receptor blockers include a number of drugs that have the following contraindications for use:

• Disorders in the work of the kidneys and liver.
• Cirrhosis of the liver (portosystemic encephalopathy in history).
• Lactation.
• Hypersensitivity to any drug of this group.
• Pregnancy.
• Children under 14 years of age.

Interaction with other means

H2 blockers of histamine receptors, the mechanism of action of which is now understood, have certain pharmacokinetic drug interactions.

absorption in the stomach. Due to antisecretory effects, H2 blockers are able to influence the absorption of those electrolyte drugs where there is a dependence on pH, since the degree of diffusion and ionization may decrease in drugs. "Cimetidine" is able to reduce the absorption of drugs such as "Antipyrin", "Ketoconazole", "Aminazin" and various iron preparations. To avoid such malabsorption, drugs should be taken 1-2 hours before the use of H2 blockers.

hepatic metabolism. Blockers of H2 histamine receptors (preparations of the first generation especially) actively interact with cytochrome P-450, which is the main oxidizer of the liver. At the same time, the half-life increases, the effect may be prolonged and an overdose of the drug, which is metabolized by more than 74%, may occur. Cimetidine reacts most strongly with cytochrome P-450, 10 times more than Ranitidine. Interaction with "Famotidine" does not occur at all. For this reason, when using Ranitidine and Famotidine, there is no violation of the hepatic metabolism of drugs, or it manifests itself to a small extent. When using Cimetidine, the clearance of drugs is reduced by about 40%, and this is clinically significant.

Hepatic blood flow rate. It is possible to reduce the rate of hepatic blood flow up to 40% when using Cimetidine, as well as Ranitidine, it is possible to reduce the systemic metabolism of high-clearance drugs. "Famotidine" in these cases does not change the rate of portal blood flow.

tubular excretion of the kidneys. H2-blockers are excreted with active secretion of the tubules of the kidneys. In these cases, interactions with parallel medicines if their excretion is carried out by the same mechanisms. "Imetidine" and "Ranitidine" are able to reduce renal excretion to 35% of novocainamide, quinidine, acetylnovocainamide. "Famotidine" does not affect the excretion of these drugs. In addition, its therapeutic dose is able to provide a low plasma concentration, which will not significantly compete with other agents at the levels of calcium secretion.

Pharmacodynamic interactions. The interaction of H2-blockers with groups of other antisecretory drugs can increase therapeutic efficacy (for example, with anticholinergics). The combination with drugs that act on Helicobacter (preparations of metronidazole, bismuth, tetracycline, clarithromycin, amoxicillin) accelerates the tightening of peptic ulcers.

Pharmacodynamic adverse interactions have been established when combined with drugs containing testosterone. "Cimetidine" hormone is displaced from its connection with receptors by 20%, while the concentration in the blood plasma increases. "Famotidine" and "Ranitidine" do not have a similar effect.

Trade names

In our country, registered and allowed for sale the following drugs H2 blockers:

"Cimetidine"

Trade names: Altramet, Belomet, Apo-cimetidine, Yenametidine, Histodil, Novo-cimetine, Neutronorm, Tagamet, Simesan, Primamet, Cemidin , "Ulcometin", "Ulkuzal", "Cymet", "Cimehexal", "Cygamet", "Cimetidine-Rivofarm", "Cimetidine Lannacher".

"Ranitidine"

Trade names: "Acilok", "Ranitidine Vramed", "Atsideks", "Asitek", "Histak", "Vero-ranitidin", "Zoran", "Zantin", "Ranitidine Sediko", "Zantak", "Ranigast" , "Raniberl 150", "Ranitidine", "Ranison", "Ranisan", "Ranitidine Akos", "Ranitidine BMS", "Ranitin", "Rantak", "Ranx", "Rantag", "Yazitin", "Ulran ", "Ulkodin".

"Famotidine"

Trade names: "Gasterogen", "Blokatsid", "Antodin", "Kvamatel", "Gastrosidin", "Lecedil", "Ulfamid", "Pepsidin", "Famonit", "Famotel", "Famosan", "Famopsin" , Famotidine Akos, Famocid, Famotidine Apo, Famotidine Akri.

"Nizatidin". Trade name "Axid".

"Roxatidin". Trade name "Roxan".

"Ranitidine bismuth citrate". Trade name "Pylorid".

(also called: proton pump inhibitors, proton pump inhibitors, proton pump blockers, H + / K + -ATPase blockers, hydrogen pump blockers, etc.) - antisecretory drugs intended for the treatment of acid-dependent diseases of the stomach, duodenum and esophagus blocking the proton pump (H + / K + -ATPase) of the lining (parietal) cells of the gastric mucosa and thus reducing the secretion of hydrochloric acid. The abbreviation IPP is most often used, less often - IPN.

Proton pump inhibitors are the most effective and modern drugs in the treatment of gastric ulcers, duodenal ulcers (including those associated with Helicobacter pylori infection) and the esophagus, providing a decrease in acidity and, as a result, the aggressiveness of gastric juice.

All proton pump inhibitors are benzimidazole derivatives and have a similar chemical structure. PPIs differ only in the structure of the radicals on the pyridine and benzimidazole rings. The mechanism of action of various proton pump inhibitors is the same, they differ mainly in their pharmacokinetics and pharmacodynamics.

Mechanism of action of a proton pump inhibitor

Proton pump inhibitors, after passing through the stomach, enter the small intestine, where they dissolve, after which they first enter the liver through the bloodstream, and then penetrate through the membrane into the parietal cells of the gastric mucosa, where they concentrate in the secretory tubules. Here, at an acidic pH, proton pump inhibitors are activated and converted into tetracyclic

The mechanism of action of inhibitors proton pump (Maev I.V. and others)

sulfenamide, which is charged and therefore unable to cross membranes and does not leave the acidic compartment within the secretory tubules of the parietal cell. In this form, proton pump inhibitors form strong covalent bonds with the mercapto groups of cysteine ​​residues of H + /K + -ATPase, which blocks the conformational transitions of the proton pump, and it becomes irreversibly excluded from the process of hydrochloric acid secretion. In order for acid production to resume, the synthesis of new H + /K + -ATPases is necessary. Half of the human H + /K + -ATPase is renewed in 30-48 hours and this process determines the duration of the therapeutic effect of PPIs. At the first or single dose of PPI, its effect is not maximal, since not all proton pumps are built into the secretory membrane by this time, some of them are in the cytosol. When these molecules, as well as newly synthesized H + /K + -ATPases appear on the membrane, they interact with subsequent doses of PPI, and its antisecretory effect is fully realized (Lapina T.L., Vasiliev Yu.V.).

Types of proton pump inhibitors

The Anatomical Therapeutic Chemical Classification (ATC) in section A02B Antiulcer and gastroesophageal reflux drugs contains two groups with proton pump inhibitors. Group A02BC 'Proton Pump Inhibitors' lists the International Nonproprietary Names (INNs) of seven PPIs (the first six types are approved in the US and Russian Federation, seventh, dexrabeprazole, has no permission for use): Esomeprazole, dexlansoprazole, and dexarabeprazole are optical isomers of omeprazole, lansoprazole, and rabeprazole, respectively, with greater biological activity. Also included in this group are combinations of:

A02BC53 Lansoprazole, combinations
A02BC54 Rabeprazole, combinations

In group A02BD Combinations of drugs for eradication Helicobacter pylori» lists proton pump inhibitors in combination with various antibiotics for treatment Helicobacter pylori-associated diseases of the digestive tract:

A02BD01 Omeprazole, amoxicillin and metronidazole
A02BD02 Lansoprazole, tetracycline and metronidazole
A02BD03 Lansoprazole, amoxicillin and metronidazole
A02BD04 Pantoprazole and amoxicillin and clarithromycin
A02BD05 Omeprazole, amoxicillin and clarithromycin
A02BD06 Esomeprazole, amoxicillin and clarithromycin
A02BD07 Lansoprazole, amoxicillin and clarithromycin
A02BD09 Lansoprazole, clarithromycin and tinidazole
A02BD10 Lansoprazole, amoxicillin and levofloxacin

There are a number of new proton pump inhibitors in various stages of development and clinical trials. The most famous of them and close to completion of the trials is tenatoprazole. However, some clinicians believe that it has no clear pharmacodynamic advantages over its predecessors and that the differences relate only to pharmacokinetics. active substance(Zakharova N.V.). Among the advantages of ilaprazol are the fact that it is less dependent on the polymorphism of the CYP2C19 gene and that its half-life (T 1/2) is 3.6 hours (Maev I.V. et al.)

In January 2009, the US Food and Drug Administration (FDA) approved for use in the treatment of GERD the sixth proton pump inhibitor - dexlansoprazole, which is an optical isomer of lansoprazole, in May 2014 it received permission in Russia.

In the Pharmacological index in the section Gastrointestinal drugs there is a group "Proton pump inhibitors".

By order of the Government of the Russian Federation dated December 30, 2009 No. 2135-r, one of the proton pump inhibitors is omeprazole (capsules; lyophilisate for preparing a solution for intravenous administration; lyophilisate for solution for infusion; film-coated tablets) is included in the List of Vital and Essential Medicines.

Currently 5 standard doses of proton pump inhibitors (esomeprazole 40 mg, lansoprazole 30 mg, omeprazole 20 mg, rabeprazole 20 mg) are currently licensed in Europe for the treatment of GERD.
pantoprazole 40 mg) and one double (omeprazole 40 mg). Standard doses of proton pump inhibitors are licensed for the treatment of erosive esophagitis for 4-8 weeks, and double dose for the treatment of refractory patients who have already been previously treated with standard doses given for up to 8 weeks. Standard doses are prescribed once a day, a double dose - twice a day (VD Pasechnikov et al.).

OTC proton pump inhibitors

In the first decades after their introduction, antisecretory drugs in general and proton pump inhibitors in the United States, Russia, and many other countries were prescription drugs. In 1995, the FDA approved the over-the-counter (Over-the-Coutne r) sale of the H2 blocker Zantac 75, in 2003 - the first OTC PPI Prilosec OTC (omeprazole magnesium). Later, over-the-counter PPIs were registered in the US: Omeprazole (omeprazole), Prevacid 24HR (lansoprazole),
Nexium 24HR (esomeprazole magnesium), Zegerid OTC (omeprazole + sodium bicarbonate). All over-the-counter forms are low in active ingredient and are intended to “treat frequent heartburn.”

Pantoprazole 20 mg is approved for OTC in the European Union (EU) 12.6.2009, in Australia - in 2008 Esomeprazole 20 mg - in the EU 26.8.2013 Lansoprazole - in Sweden since 2004, later allowed in a number of other EU countries, Australia and New Zealand. Omeprazole - in Sweden since 1999, later in Australia and New Zealand, other EU countries, Canada, a number of Latin American countries. Rabeprazole - in Australia since 2010, later - in the UK (Boardman H.F., Heeley G. The role of the pharmacist in the selection and use of over-the-counter proton-pump inhibitors. Int J Clin Pharm (2015) 37: 709–716 DOI 10.1007/s11096-015-0150-z).

In Russia, the following are allowed for OTC sale, in particular: dosage forms IPP
:

• Gastrozole, Omez, Ortanol, Omeprazole-Teva, Ultop, capsules containing 10 mg of omeprazole
• Beret, Noflux, Pariet, Rabiet, capsules containing 10 mg of rabeprazole sodium (or rabeprazole)
• Controloc , capsules containing 20 mg of pantoprazole

General rule when taking over-the-counter PPIs: if there is no effect within the first three days, a specialist consultation is necessary. The maximum duration of treatment with over-the-counter PPIs without contacting a doctor is 14 days (for Controloc - 4 weeks). The interval between 14-day courses should be at least 4 months.

Proton pump inhibitors in the treatment of gastrointestinal diseases

Proton pump inhibitors are the most effective hydrochloric acid suppressing drugs, although they are not without some disadvantages. As such, they have found wide application in the treatment of acid-related diseases. gastrointestinal tract, including, if necessary, eradication of Helicobacter pylori.

Diseases and conditions in the treatment of which the use of proton pump inhibitors is indicated (Lapina T.L.):

• gastroesophageal reflux disease (GERD)
• stomach and/or duodenal ulcer
• Zollinger-Ellison syndrome
• damage to the gastric mucosa caused by the use of non-steroidal anti-inflammatory drugs (NSAIDs)
• diseases and conditions in which Helicobacter pylori eradication is indicated.

Numerous studies have shown a direct relationship between the duration of maintenance of gastric acidity with pH> 4.0 and the speed of healing of ulcers and erosions in the esophagus, gastric and duodenal ulcers, the frequency of Helicobacter pylori eradication, and a decrease in symptoms characteristic of extraesophageal manifestations of gastroesophageal reflux. The lower the acidity of the contents of the stomach (i.e. the higher the pH value), the earlier the effect of the treatment is achieved. In general, it can be said that for most acid-related diseases, it is important that the pH level in the stomach be more than 4.0 for at least 16 hours a day. More detailed studies have established that each of the acid-dependent diseases has its own critical level of acidity, which must be maintained for at least 16 hours a day (Isakov V.A.):

Acid related diseases	The level of acidity required for healing, pH, not less
Gastrointestinal bleeding	6
GERD complicated by extraesophageal manifestations	6
Quad or triple therapy with antibiotics	5
Erosive GERD	4
Damage to the gastric mucosa caused by the use of non-steroidal anti-inflammatory drugs	4
functional dyspepsia	3
Maintenance Therapy for GERD	3

In the pathogenesis of gastric and / or duodenal ulcers, the decisive link is the imbalance between the factors of aggression and the factors of protection of the mucous membrane. Currently, among the factors of aggression, in addition to hypersecretion of hydrochloric acid, there are: hyperproduction of pepsin, Helicobacter piylori, impaired gastroduodenal motility, exposure to the mucous membrane of the stomach and duodenum of bile acids and lysolicetin, pancreatic enzymes in the presence of duodenogastric reflux, as well as ischemia of the mucous membrane, smoking, drinking hard liquor, taking certain medicines such as non-steroidal anti-inflammatory drugs. Protective factors include: secretion of gastric mucus, production of bicarbonates, which contribute to the neutralization of intragastric acidity at the surface of the gastric mucosa up to 7 units. pH, the ability of the latter to regenerate, the synthesis of prostaglandins, which have a protective effect and are involved in ensuring adequate blood flow in the mucous membrane of the stomach and duodenum. It is important that many of these factors of aggression and defense are genetically determined, and the balance between them is maintained by the coordinated interaction of the neuroendocrine system, including the cerebral cortex, hypothalamus, peripheral endocrine glands, and gastrointestinal hormones and polypeptides. The most important role of hyperacidity in the genesis of peptic ulcer is confirmed by the high clinical efficacy of antisecretory drugs that are widely used in modern therapy of peptic ulcer, among which proton pump inhibitors play a leading role (Maev I.V.).

Proton pump inhibitors in eradication regimens Helicobacter pylori

eradication Helicobacter pylori does not always reach the target. The very wide and misuse of common antibacterial agents led to an increase in resilience Helicobacter pylori. It is recognized that in different countries world (different regions), it is advisable to use different schemes. In the vast majority of regimens, one of the proton pump inhibitors is necessarily present in the so-called standard dosage (omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg, esomeprazole 20 mg, rabeprazole 20 mg 2 times a day). The presence of a proton pump inhibitor in the regimen significantly increases the effectiveness of antibiotics and dramatically increases the percentage of successful eradications. An exception when proton pump inhibitors are not used is atrophy of the gastric mucosa with achlorhydria, confirmed by pH-metry. The choice of one or another proton pump inhibitor affects the likelihood of eradication, but the replacement of other drugs (antibiotics, cytoprotectors) has a much greater impact than PPIs. Specific recommendations for the eradication of Helicobacter pylori are given in the Standards for the Diagnosis and Treatment of Acid-Dependent and Helicobacter pylori-Associated Diseases adopted by the Scientific Society of Gastroenterologists of Russia in 2010.

Proton pump inhibitors increase the risk of fractures, possibly causing Clostridium difficile-associated diarrhea and may cause hypomagnesaemia and dementia in old age, and likely increase the risk of pneumonia in the elderly

The US Food and Drug Administration (FDA) has issued a number of reports about the possible dangers of long-term or high doses of proton pump inhibitors:

• In May 2010, the FDA issued a warning about increased risk fractures of the hip, wrist and spine with long-term use or high doses of proton pump inhibitors (“FDA Warning”)
• in February 2012, an FDA announcement was issued warning patients and physicians that proton pump inhibitor therapy may increase the risk of Clostridium difficile -associated diarrhea(FDA Communication dated 8.2.2012).

In light of this and similar information, the FDA believes: When prescribing proton pump inhibitors, clinicians should select as many low dose or a shorter course of treatment that would be adequate for the patient's condition.

Several cases of life-threatening hypomagnesemia (lack of magnesium in the blood) associated with the use of proton pump inhibitors have been described (Yang Y.-X., Metz D.C.). Proton pump inhibitors, when taken with diuretics in elderly patients, slightly increase the risk of hospitalization for hypomagnesemia. However, this fact should not affect the rationale for prescribing proton pump inhibitors, and the small magnitude of risk does not require screening for magnesium levels in the blood (Zipursky J el al. Proton Pump Inhibitors and Hospitalization with Hypomagnesemia: A Population-Based Case-Control Study / PLOS Medicine - Sep 30, 2014).

According to studies conducted in Germany (German Center for Neurodegenerative Diseases, Bonn), long-term use of proton pump inhibitors increases the risk of dementia in old age by 44% (Gomm W. et al. Association of Proton Pump Inhibitors With Risk of Dementia. A Pharmacoepidemiological Claims Data Analysis JAMA Neurol Published online February 15, 2016 doi:10.1001/jamaneurol.2015.4791).

Researchers from the UK found that older people who received PPIs over a two-year period had a higher risk of pneumonia. The logic of the authors of the study is as follows: the acid in the stomach creates a barrier to the pathogenic intestinal microbiota for the lungs. Therefore, if acid production decreases due to the intake of PPIs, then due to high refluxes, a greater number of pathogens can enter the body. Airways(J. Zirk-Sadowski, et al. Proton-Pump Inhibitors and Long-Term Risk of Community-Acquired Pneumonia in Older Adults. Journal of the American Geriatrics Society, 2018; DOI: 10.1111/jgs.15385).

Taking proton pump inhibitors during pregnancy

Different proton pump inhibitors have different risk categories for the fetus according to the FDA: Taking proton pump inhibitors to treat gastroesophageal reflux disease during the first trimester of pregnancy more than doubles the risk of having a baby with a heart defect (GI & Hepatology News, August 2010).

There are also studies proving that taking proton pump inhibitors during pregnancy increases the risk of asthma in the unborn child by 1.34 times (taking H2 blockers by 1.45 times). Source: Lai T., et al. Acid-Suppressive Drug Use During Pregnancy and the Risk of Childhood Asthma: A Meta-analysis. Pediatrics. Jan 2018.

Selection of proton pump inhibitors

The acid-suppressing effect of proton pump inhibitors is strictly individual for each patient. In a number of patients, phenomena such as “resistance to proton pump inhibitors”, “nocturnal acid breakthrough”, etc. are noted. This is due to both genetic factors and the state of the body. Therefore, in the treatment of acid-dependent diseases, the appointment of proton pump inhibitors should be individually and timely adjusted taking into account the response to the treatment. It is advisable to determine the individual rhythm of taking and doses of drugs for each patient under the control of intragastric pH-metry (Bredikhina N.A., Kovanova L.A.; Belmer S.V.).

Daily pH-gram of the stomach after taking PPIs

Comparison of proton pump inhibitors

It is generally accepted that proton pump inhibitors are the most effective means for the treatment of acid-related diseases. The class of antisecretory agents that appeared before PPIs - H2-blockers of histamine receptors are gradually being replaced from clinical practice and PPIs compete only with each other. Among gastroenterologists, there are different points of view on the comparative effectiveness of specific types of proton pump inhibitors. Some of them argue that, despite some differences that exist between PPIs, today there are no convincing data that allow us to talk about the greater effectiveness of any PPI compared to the others (Vasilyev Yu.V. et al.) or that eradication Hp type of PPI included in the composition of triple (quadruple therapy) does not matter (Nikonov E.K., Alekseenko S.A.). Others write that, for example, esomeprazole is fundamentally different from the other four PPIs: omeprazole, pantoprazole, lansoprazole and rabeprazole (Lapina T.L., Demyanenko D. and others). Still others believe that rabeprazole is the most effective (Ivashkin V.T. et al., Maev I.V. et al.).

A group of scientists from Germany (Kirchheiner J. et al.) did a dose-response meta-analysis for the average 24-hour intragastric pH and the percentage of time with pH>4 in 24 hours for various PPIs. They obtained the following values ​​of the effectiveness of various PPIs to achieve an average value of intragastric pH=4:
The cost of generic omeprazole, pantoprazole and lansoprazole is much lower than original preparations esomeprazole and rabeprazole, which is of no small importance for the patient and often determines the choice of the drug based on financial capabilities, especially for long-term use (Alekseenko S.A.).

Trade names of drugs - proton pump inhibitors

A wide range of different drugs from the group of proton pump inhibitors is presented on the domestic pharmaceutical market:

• active substance omeprazole: Bioprazole, Vero-omeprazole, Gastrozole, Demeprazole, Zhelkizol, Zerocid, Zolsser, Krismel, Lomak, Losek, Losek Maps, Omegast, Omez, Omezol, Omecaps, Omepar, Omeprazole, Omeprazole pellets, Omeprazole-AKOS, Omeprazole- acri, Omeprazole-E.K., Omeprazole-OBL, Omeprazole-Teva, Omeprazole-Richter, Omeprazole-FPO, Omeprazole Sandoz, Omeprazole Stada, Omeprol, Omeprus, Omefez, Omizak, Omipiks, Omitox, Ortanol, Ocid, Pepticum, Pleom -20, Promez, Risek, Romesek, Sopral, Ulzol, Ultop, Helicid, Helol, Cisagast
• the active substance is omeprazole, in addition to which the drug contains a noticeable amount of sodium bicarbonate: Omez insta
• active substance omeprazole + domperidone: Omez-d
• active ingredient pantoprazole: Zipantola, Controloc, Krosatsid, Nolpaza, Panum, Peptazol, Pizhenum-Sanovel, Puloref, Sanpraz, Ultera
• active ingredient lansoprazole: Acrylanz, Helicol, Lanzabel, Lanzap, Lanzoptol, Lansoprazole, Lansoprazole pellets, Lansoprazole Stada, Lansofed, Lancid, Loenzar-Sanovel, Epikur
• active substance rabeprazole: Beret, Zolispan, Zulbex, Noflux (formerly called Zolispan), Ontime, Noflux, Pariet, Rabelok, Rabeprazole-OBL, Rabeprazole-SZ, Rabiet, Razo, Hairabezol
• active substance

proton pump(synonyms: proton pump, H + /K + -ATPase, hydrogen-potassium adenosine triphosphatase) is an enzyme that plays a crucial role in the secretion of hydrochloric acid in the stomach.

The proton pump consists of two subunits: α-subunit, which is a polypeptide chain of 1033 amino acid residues and β-subunit, which is a glycoprotein containing 291 amino acid residues, as well as carbohydrate cytoplasmic fragments.

The upper figure (from the article by Lapina O.D.) shows the structure of the proton pump: Polypeptide chainα -subunit crosses the membrane ten times, forming 5 transmembrane loops. N- and C-terminiα subunits are found in the cytoplasm. A significant part of the polypeptide chain (about 800 amino acids) forms a large cytoplasmic domain, in which the active center of the enzyme is located, where ATP hydrolysis occurs. Cations move across the membrane through a channel that is formed by transmembrane loops. N-terminusβ -subunit is located inside the cytoplasm, its polypeptide chain crosses the membrane only once. Most of the b-subunit is located on the extracellular side of the membrane. It contains areas that undergo glycosylation.

The proton pump (H + /K + -ATPase), which is present in large numbers in the parietal cells of the gastric mucosa, transports the hydrogen ion H + from the cytoplasm to the stomach cavity through the apical membrane of the parietal cells in exchange for the potassium ion K +, which it carries inside the cell. In this case, both cations are transported against the electrochemical gradient, and the energy source for this transport is the hydrolysis of the ATP molecule. Simultaneously with hydrogen protons, chloride anions Cl - are transferred into the lumen of the stomach against an electrochemical gradient. K + ions entering the cell leave it along the concentration gradient together with Cl - ions through the apical membrane of parietal cells. H + ions are formed in equivalent quantities with HCO 3 - during the dissociation of carbonic acid H 2 CO 3 with the participation of carbonic anhydrase. Ions HCO 3 - passively move into the blood along the concentration gradient through the basolateral membrane in exchange for the Cl - ion. Thus, hydrochloric acid is released into the lumen of the stomach with the participation of a proton pump in the form of H + and Cl - ions, and K + ions move through the membrane back into the parietal cell.

proton pump inhibitors

The action of proton pump inhibitors (PPIs), the most effective antiulcer class of drugs, is based on blocking the proton pump. Being absorbed in the small intestine and getting through the bloodstream into the gastric mucosa, proton pump inhibitors accumulate in the secretory tubules of parietal cells. Here, PPIs (at an acidic pH value) are activated and, due to acid-dependent transformation, are transformed into tetracyclic sulfenamide, which is covalently incorporated into the main cysteine ​​groups of the proton pump, thus excluding the possibility of its conformational transitions and thereby blocking the possibility of hydrochloric acid production by the parietal cell.

All proton pump inhibitors (omeprazole, pantoprazole, lansoprazole, rabeprazole and esomeprazole) are benzimidazole derivatives and have a similar chemical structure, differing only in the structure of the radicals on the pyridine and benzimidazole rings.

Potassium-competitive blockers

Like proton pump inhibitors, potassium competitive blockers also block the proton pump (H + /K + -ATPase). However, unlike proton pump inhibitors, which realize their acid-suppressing effect by covalently binding to the cysteine ​​groups of H + /K + -ATPase, K-CBA competitively interact with the ionic K + -binding domain of H + /K + -ATPase.

In 2006, the first potassium-competitive blocker