H to atpase. Proton pump inhibitors: an overview of the group of drugs

This group is among the leading pharmacological preparations, belongs to the means of choice in the treatment of peptic ulcers. The discovery of histamine H2 receptor blockers over the past two decades is considered the largest in medicine, helps in solving 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 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. motor function stomach normalizes, improves microcirculation.

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 first 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 changing the rate of hepatic metabolism of the xenobiotic. "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 histamine receptor blockers (preparations of the extra-class generation), the name is "Ebrotidine", "Ranitidine bismuth citrate" is singled out, this is not a simple mixture, but a 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 gives it the ability to easily penetrate into various organs, affect 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 under laboratory conditions under the guidance of James Black, she investigated and synthesized a huge number of compounds that were similar in structure to the histamine molecule. Once secure connections were identified, they were passed on to clinical researches. 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 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 gastric 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 functional tests liver, 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 tools

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 action may be prolonged and an overdose may occur. medicinal product, which is metabolized by more than 74%. 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, the following preparations of H2-blockers are registered and acceptable for sale:

"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".

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 "H-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, assemblies, 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, it is necessary to observe general rules work with flammable or explosive substances. 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 email: . We look forward to collaborating.

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

	Omeprazole is historically the first proton pump inhibitor
	Esomeprazole - S-isomer of omeprazole
	Pantoprazole
	Lansoprazole
	Rabeprazole
	Dexlansoprazole is an optical isomer of lansoprazole
	Tenatoprazole

According to the chemical structure, all proton pump inhibitors are derivatives of benzimidazole and have a single molecular core. Proton pump inhibitors differ only in chemical radicals, which give them individual properties regarding the duration of the latent period, the duration of the action of the drug, the features of pH selectivity, interactions with other drugs taken simultaneously, etc.

Molecules of proton pump inhibitors, accumulating in the intracellular tubules of parietal cells in close proximity to H + /K + -ATPase molecules, after some transformations are transformed into tetracyclic sulfenamide, which is covalently included in the cysteine ​​groups of H + /K + -ATPase, thereby making , the latter unable to participate in the process of transporting ions.

Composition and form of release. Lansoprazole. Capsules (30 mg).

Pharmachologic effect. Antiulcer agent. Specific inhibitor of H + -K + -ATPase. Acting in the final phase of hydrochloric acid secretion in the stomach, the drug reduces acid production, regardless of the nature of the stimulating factor.

Indications. peptic ulcer duodenum or stomach in the acute phase, reflux esophagitis.

Application. The daily dose is 30 mg in one dose. The course of treatment is 4 weeks, if necessary, treatment can be continued for 2-4 weeks. In patients receiving theophylline, lansoprazole should be administered with caution and under close medical supervision. The drug can cause the induction of various cytochrome P 450 enzyme systems. Antacids containing aluminum and magnesium hydroxides should be taken 2 hours after taking lansoprazole.

Side effect. Rarely - diarrhea, constipation; in isolated cases - skin rash.

Pharmachologic effect. H + -K + -ATPase inhibitor. Reduces the level of basal and stimulated (regardless of the type of stimulus) secretion of hydrochloric acid in the stomach. In duodenal ulcer associated with Helicobacter pylori, such a decrease in gastric secretion increases the sensitivity of the microorganism to antibiotics. Pantoprazole has its own antimicrobial activity against H. pylori.

Indications. Peptic ulcer of the stomach or duodenum in the acute phase, Zollinger-Ellison syndrome, eradication of Helicobacter pylori (in combination with antibiotic therapy), reflux esophagitis.

Application. The average therapeutic dose is 40 mg / day. The maximum dose is 80 mg / day. The duration of the course of therapy is set depending on the indications, but it should not exceed 8 weeks. Prior to initiation of therapy, the possibility of malignant neoplasm in the stomach and esophagus, since the use of pantoprazole reduces the severity of symptoms and may delay the establishment of a correct diagnosis.

Side effect. diarrhea, headache; rarely - nausea, pain in the upper abdomen, flatulence, rash, itching, weakness, dizziness; in isolated cases - edema, fever, initial manifestations depressive states, visual impairment.

Interaction with other drugs. With the simultaneous use of pantoprazole, it can change the absorption of drugs, the absorption of which depends on the pH of the gastric contents (ketocanazole). Due to the fact that pantoprazole is metabolized in the liver by the cytochrome P 450 enzyme system, the possibility cannot be ruled out. drug interaction with drugs metabolized by the same enzyme system.

1.4.4. Omeprazole (Omeprazole)

Pharmachologic effect. H + -K + -ATPase inhibitor. It inhibits the activity of H + -K + -ATPase in the parietal exocrinocytes of the stomach and thereby blocks the final stage of hydrochloric acid secretion. This leads to a decrease in basal and stimulated secretion, regardless of the nature of the stimulus. The effect of the drug occurs quickly, depends on the size of the dose taken and persists for 24 hours or more after a single dose of 20 mg of omeprazole.

Indications. Peptic ulcer of the stomach and duodenum in the acute phase, reflux esophagitis, Zollinger-Ellison syndrome.

Application. A single dose is 20-40 mg. The daily dose is 20-40 mg, the frequency of use is 1-2 times / day. In severe cases of the disease, 40 mg of the drug is administered intravenously 1 time / day. Duration of treatment - 2-8 weeks. Before starting therapy, it is necessary to exclude the presence of a malignant process (especially in patients with gastric ulcers), since treatment with the drug may mask the symptoms and delay the correct diagnosis. With exacerbation of peptic ulcer of the stomach and duodenum, the drug is prescribed at a dose of 20 mg 1 time / day in the morning on an empty stomach. Patients with poor healing of duodenal ulcers are recommended to prescribe omeprazole at a dose of 40 mg 1 time / day, which allows healing to be achieved within 4 weeks. For the prevention of recurrence of duodenal ulcer, 10 mg is prescribed 1 time / day. If necessary, the dose can be increased to 20-40 mg 1 time / day. For the prevention of recurrence of gastric ulcer in patients with poor healing, it is recommended to prescribe 20 mg 1 time / day. Patients with poor healing of gastric ulcers are recommended to prescribe omeprazole 40 mg / day, which will provide scarring for 8 weeks. For peptic ulcer associated with Helicobacter pylori, omeprazole is prescribed at a dose of 40 mg / day in combination with amoxicillin (1.5–3 g in 2 divided doses) for 2 weeks.

Side effect. On the nervous system: rarely - dizziness, headache, agitation, drowsiness, insomnia; paresthesia; in some cases - depression and hallucinations. On the digestive system: rarely - dry mouth, taste disturbance, diarrhea or constipation, stomatitis, abdominal pain; increased activity of liver enzymes in blood plasma. On the respiratory system: rarely - bronchospasm. On the musculoskeletal system: arthralgia, muscle weakness, myalgia. On the hematopoietic system: rarely - leukopenia, thrombocytopenia. Skin reactions: rash, urticaria, itching, erythema multiforme. Other: blurred vision, peripheral edema, increased sweating, fever.

Interaction with other drugs. Omeprazole can slow down the elimination of drugs metabolized by oxidation in the liver (in particular, warfarin, diazepam and phenytoin).

(they are also proton pump inhibitors, proton pump blockers, hydrogen pump blockers, blockers H + /K+ -ATPase, most often there is a reduction in PPI, sometimes - PPI) are drugs that regulate and suppress the secretion of hydrochloric acid. Intended for the treatment of gastritis, and other diseases associated with high acidity.

There are several generations of PPIs that differ from each other in additional radicals in the molecule, due to which the duration of the therapeutic effect of the drug and the speed of its onset change, the side effects of previous drugs are eliminated, and interaction with other drugs is regulated. 6 names of inhibitors are registered in Russia.

By generation

1 generation

2 generation

3rd generation

There is also Dexrabeprazole, an optical isomer of rabeprazole, but it does not yet have state registration in Russia.

By active ingredients

Omeprazole-based preparations

Lansoprazole-based preparations

Preparations based on rabeprazole

Preparations based on pantoprazole

esomeprazole preparations

Dexlansoprazole-based preparations

• Dexilant. It is taken to treat ulcers in the esophagus and to relieve heartburn. It is practically not popular with doctors as a drug for the treatment of stomach ulcers. The capsule contains 2 types of granules that dissolve at different times, depending on the pH level. USA.

When prescribing a certain group of "prazoles", the question always arises: "Which drug is better to choose - the original or its generic?" For the most part, original products are considered more effective, since they have been studied for many years at the molecular stage, then preclinical and clinical trials were carried out, interactions with other substances, etc. The quality of raw materials, as a rule, is better. Manufacturing technologies are more modern. All this directly affects the speed of the onset of the effect, the therapeutic effect itself, the presence of side effects, etc.

If you choose analogues, it is better to give preference to preparations made in Slovenia and Germany. They are sensitive to every stage of the production of the drug.

Indications for admission

All proton pump blockers are used to treat gastrointestinal diseases:

Features of the use of PPI in various pathologies

These drugs are used only in conditions where acidity gastric juice increased as they move into their active form only at a certain pH level. This should be understood in order not to self-diagnose and prescribe treatment without a doctor.

Gastritis with low acidity

In this disease, PPIs are useless if the pH of the gastric juice exceeds 4-6. With such values, the drugs do not pass into the active form and are simply excreted from the body, without bringing any relief to the condition.

stomach ulcer

For its treatment, it is extremely important to follow the rules for taking PPIs. If you systematically violate the regimen, then therapy can be delayed for a long time and the likelihood of side effects increases. Most importantly, take the medicine 20 minutes before meals so that the stomach has the right pH. Some generations of PPIs do not work well in the presence of food. It is better to drink the drug at the same time in the morning in order to develop a habit of taking it.

myocardial infarction

It would seem, what does he have to do with it? Quite often, after a heart attack, patients are prescribed an antiplatelet agent - clopidogrel. Almost all proton pump inhibitors reduce the effectiveness of this important substance by 40-50%. This is due to the fact that PPIs block the enzyme that is responsible for the transformation of clopidogrel into its active form. These drugs are often prescribed together because the antiplatelet drug can cause stomach bleeding, so doctors try to protect the stomach from side effects.

The only proton pump blocker that is safest in combination with clopidogrel is pantoprazole.

Systemic fungal diseases

Sometimes the fungus is treated with oral forms itraconazole. In this case, the drug does not act in one particular place, but on the whole organism as a whole. The antifungal substance is covered with a special shell, which dissolves in an acidic environment, with a decrease in pH values, the drug is absorbed worse. With their joint appointment, the drugs are taken at different times of the day, while itraconazole is best washed down with cola or other drinks that increase acidity.

Contraindications

Although the list is not very large, it is important to read this paragraph of the instructions carefully. And be sure to warn the doctor about any illnesses and other medications taken.

Side effects

Usually, unwanted effects are minimal if the course of treatment is short. But the following phenomena are always possible, which disappear with the withdrawal of the drug or after the course of treatment:

• pain in abdominal cavity, violation of the chair, bloating, nausea, vomiting, dry mouth;
• headache, dizziness, general malaise, insomnia;
• allergic reactions: itching, rash, drowsiness, swelling.

Alternative PPIs

There is another group of antisecretory drugs, which is also used for peptic ulcer and other syndromes - H2-histamine receptor blockers. Unlike PPIs, drugs block certain receptors in the stomach, while proton pump inhibitors inhibit the activity of enzymes that produce hydrochloric acid. The effect of H2 blockers is shorter and less effective.

The main representatives are famotidine and ranitidine. The duration of action is about 10-12 hours with a single application. Crosses the placenta and enters breast milk. They have the effect of tachyphylaxis - the body's reaction to repeated use of the drug is a noticeable decrease therapeutic effect sometimes even 2 times. Usually observed after 1-2 days after the start of the reception. In most cases, they are used when the question of the price of treatment is acute.

It can also be attributed to alternative means. They reduce the acidity of the stomach, but they do this for a very short time and are used only as emergency aids for stomach pain, heartburn, and nausea. They have an unpleasant effect - rebound syndrome. It lies in the fact that the pH rises sharply after the end of the drug, the acidity rises even more, the symptoms can worsen with double force. This effect is more often observed after taking antacids containing calcium. Acid rebound is neutralized by eating.

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 the acidic environment of the tubular cells of the parietal layer of the gastric mucosa, where it activates and inhibits the 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. To achieve a rapid reduction in intragastric acidity, it is recommended intravenous administration 40 mg of omeprazole, followed by rapid decline 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 increased growth normal microflora intestines, which in turn may lead to a slight increase in the risk of developing 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 kidney failure. 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.

Skin - skin rashes and pruritus. 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 value for pepsin activity is in the range from 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. The 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 latter is that a rapid increase in the 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. It's pretty dangerous complication requiring immediate discontinuation of the drug and assistance to the patient. Given the severity of these side effects, sodium bicarbonate is rarely used as an antacid.

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) - a drug with a moderate strength of antacid action, 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): ulcers, 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 has made it possible to obtain one of the most common and effective, currently, antacids- 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. Gelatinous dosage form promotes uniform distribution of ingredients over the surface of the mucous membrane and lengthening 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 (bismuth basic nitrate, sodium bicarbonate, calamus rhizome powder, buckthorn bark, rutin and quelin). AT 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 dead tissue proteins 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 effects: constipation, dry mouth.

Solcoseryl is a protein-free extract from the blood of cattle. Protects tissues from hypoxia and necrosis. Used for trophic ulcers 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 amp. and vial. 0.001 each) is a peptide drug that promotes the healing of stomach 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.