Groups of proton pump inhibitors. Treatment of heartburn with proton pump inhibitors

In gastroenterology, to stop the formation of hydrochloric acid in the stomach, hydrogen pump blockers are often used, drugs that effectively relieve heartburn.

Patients with pathologies of the gastrointestinal tract (gastrointestinal tract) know firsthand the pharmacological names of these drugs, but few people were interested in which group of drugs they belong to. Heartburn medications belong to the family of proton pump inhibitors. that have individual characteristics.

When antacids, drugs designed to suppress hydrochloric acid produced by the stomach through chemical neutralization, do not help the patient, doctors resort to hydrogen pump blockers. These heartburn drugs are able to suppress the activity of the proton pump to reduce the production of hydrochloric acid, which is produced in the cell membrane responsible for digestion.

Inhibitors penetrate into the perietal cells of the gastric mucosa

This is a new and modern approach in the treatment of diseases such as heartburn, reflux, ulcers, gastritis. When using drugs, the neutralization of biochemical processes is based on the level of secretory cells. The patient needs to know how hydrogen pump blockers affect the body.

New generation heartburn drugs, passing through the stomach, begin their action already in the small intestine, where the active process of dissolution and further transportation of the active substance through the bloodstream to the liver takes place. The effect of the drug does not end there, the inhibitors penetrate into the perietal cells of the gastric mucosa through the membrane and reach a peak concentration in the secretory type tubules.

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Further, the main task of PPI, with an increase in the acidity of the stomach, is to act on cell structures that are designed to produce acid. The functional work of these cells is reduced, therefore, with the subsequent entry of food into the stomach, the blockers eliminate the production of acid. At the same time, inhibitors can not only relieve heartburn, but also heal erosions, ulcers, and perform a protective function of the digestive system.

The drugs of the inhibitory group include:

• Omeprazole;
• pantoprazole;
• Rabeprozole;
• esomeprozole;
• Lansoprazole.

Above is the most famous list of medicines that are aimed at combating many diseases of the gastrointestinal tract.

Note! The first drug in the group of hydrogen pump blockers is omeprazole. He is considered the ancestor of drugs aimed at stopping the production of hydrochloric acid, due to the effect on the cell membranes of the stomach.

Top 5 effective drugs

Omeprazole

It belongs to the most famous and time-tested drugs. His can be used for the following pathologies:

• peptic ulcer of various etiologies;
• gastritis;
• duodenitis;
• Zollinger-Ellison syndrome;
• reflux esophagitis.

During observations of the effect of the drug on the patient's body, it was found that its use has a positive effect even with a malignant tumor.

Interesting fact! The drug, like many others from the group of blockers, has a phenomenon called in medicine "night acid breakthrough". It consists in the fact that during a night's sleep there is a high release of hydrochloric acid for an hour. Moreover, the phenomenon does not depend on the dose of the drug taken the day before. This fact leads to the fact that the recovery process slows down.

Omeprazole is available in various forms: enteric capsules, tablets and powder to prepare a solution. The medicine has earned its popularity also due to the minimum range of contraindications, which is impossible to say about side effects. When using the drug, it must be remembered that only the attending physician can prescribe the dosage.

Lansoprazole

It is an antiulcer agent. The drug differs from Omeprazole in the design of radicals, which provide an antisecretory effect. In pharmacies, you can see only one form of the drug - capsules. The list of contraindications for this medication is more extensive than that of its predecessor. Lansoprazole has an active effect on acidity in the last stage of secretion..

Depending on the stage of development of the pathology of the digestive system, the drug is recommended to be used at a dosage of 15, 30 and 60 mg per day. It shows a positive trend in the treatment of an ulcer that heals after 28 days of using the medication.

Pantoprazole

This medicine has an undeniable advantage - the possibility of long-term use to maintain a therapeutic effect in peptic ulcer disease. The drug can be used orally and intravenously. It is produced in the form of tablets. Studies that have been conducted over 10 years have proven that cases of relapse with the use of this drug are unlikely.

Carefully! During treatment with Pantoprazole, patients with severe liver failure should constantly measure the level of liver enzymes. So, with an increase in the indicators, the drug is prohibited to be used.

Rabeprazole

The drug, like its predecessors, blocks the formation of increased acid in the stomach. It can be used not only for heartburn, but also as a therapeutic agent in the fight against diseases associated with high acidity. Available in the form of enteric tablets.

Like omeprazole, Rabeprazole has 3 contraindications for use: pregnancy, lactation and individual intolerance. When using the drug in 95% of cases, peptic ulcer stopped within 1 month.

Esomeprazole

It is believed that on today it is the most effective drug, which is able to control the gastrointestinal tract for 14 hours. Available only in the form of tablets.

Experts generally recommend 20 mg per day before and during the examination for signs of acid-related disease. Further, the doctor independently prescribes the dosage. Long-term studies have shown that peptic ulcer can heal within 3-4 weeks of using the medication.

How to choose the right inhibitor

Modern pharmacology offers hydrogen pump blockers, drugs for heartburn and treatment of ulcers of various etiologies, in a wide range. These are 5 modern drugs that have been described above. All of them are similar in their chemical composition, side reactions and metabolic features. However, the choice of the drug depends on several factors that the attending physician takes into account when prescribing a prescription.

Gastroenterologists believe that all modern hydrogen pump blockers, like heartburn drugs do not have a strong discrepancy in the final effect on the body. Therapists are sure that it is extremely undesirable to choose a medication on your own, since there is still a difference between them, which, if used improperly, can affect the course of the disease.

The factors influencing the choice of medicine, the regimen of taking and dosage include:

• the presence of a Helicobacter pylori infection in the body;
• stage of the disease, severity;
• the importance of the rapid response of the drug;
• condition of the liver and other digestive organs;
• age features;
• interaction with other medicines.

Experts have developed an algorithm according to the rules for choosing inhibitors proton pump. First of all, both the physician and the patient must take into account the presence of parallel current pathologies not only from the digestive tract, but also from the entire body system as a whole.

Age is one of the main values ​​when choosing a medication, since after 60-65 years there is a risk of developing complications, in adolescence it is advisable to resort to less aggressive therapy and only if it is ineffective to prescribe hydrogen pump blockers. Preparations for heartburn in this group should be selected taking into account the individual reaction of the body to the acid-suppressing effect.

The choice of drug depends on several factors that the attending physician takes into account when prescribing a prescription.

Some patients may experience nocturnal acid breakthrough or resistance to proton pump inhibitors. These factors are affected by the state of the whole organism as a whole and the genetic characteristics of the patient. Therapy, which involves the use of hydrogen pump blockers as drugs for heartburn, of course, should be carried out under the supervision of a physician and adjusted during treatment.

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Any patient should approach the choice of inhibitors responsibly. and only with the help of a doctor. Before using the medication, it is necessary to read the instructions for use and pay special attention to the points on contraindications and side effects, since sometimes even specialists can lose sight of something. It is possible that the patient forgot to warn about the presence of any pathology that can play a cruel joke when taking blockers.

Contraindications

Contraindications are basically identical for all drugs, they relate to individual intolerance to the components of the drug, neoplasms of various etiologies in the gastrointestinal tract, pregnancy and lactation. These are the standard conditions under which therapy with inhibitors will not be possible.

Therapists recommend that you undergo an examination before taking medication for a long time. from this group of drugs, because disturbances in the work of the cardiac activity, the respiratory system can provoke complications.

Heartburn medications are frequent helpers during pregnancy, but the use of hydrogen pump blockers in this situation is not possible. This can lead to pathologies in the development of the fetus. All medicines belonging to this group are able to penetrate the placental barrier. To date, studies have been conducted regarding omeprazole and its effects on the body of a pregnant woman and child.

Scientists suggest relative safety of the drug, but only with the appointment of a specialist

Experiments were also conducted with the participation of Lansoprazole among animals. As a result, no abnormalities in the fetus as a result of the administration of the drug were detected. Despite all the ongoing studies, omeprazole and lansoprazole have a fundamental difference in the degree of safety and current clinical data do not recommend the use of these medications during the period of childbearing.

Possible consequences after taking inhibitors

Few people think about the consequences of using hydrogen pump blockers, heartburn drugs can not only help with pathologies of the digestive system, but also have a negative impact on the human body. This must be taken into account before you start taking medications. Proton pump inhibitors block the production of hydrochloric acid, but at the same time they significantly reduce the secretion of gastric juice.

If there is no problem with acid secretion in the stomach, taking inhibitors can lead to the development of an infection caused by C. difficile bacteria.

If a person starts self-administration of hydrogen pump blockers to get rid of heartburn, this may well lead to sad consequences.

For optimal intake of calcium in our body, the presence of an acidic environment in it is necessary, if inhibitors stop this process for a long time, a person may develop hyperparathyroidism, when all useful minerals are washed out of the bone system. This can lead to a decrease in bone mass and, as a result, fractures.

It is important to know! Studies conducted in this area have shown that the infection is most common in people who often use drugs from the group of hydrogen pump blockers as a therapy for the digestive system.

When using proton pump inhibitors, it must be remembered that they are considered effective and safe medicines. The risk of developing complications or side effects is always lower than the benefits that the drugs bring. The main thing, as in the treatment of other drugs, is not to self-medicate, but to seek help from specialists. Be healthy!

Useful information about inhibitors (hydrogen pump blockers) in this video:

Why heartburn occurs:

How to deal with heartburn during pregnancy:

... drugs that allow you to "grab the parietal cell by the throat", acting directly on the final stage of hydrochloric acid secretion.

proton pump inhibitors have the most powerful effect among all antisecretory drugs. The use of these drugs significantly improves the prognosis for diseases caused by excess acid production in the stomach (gastric and duodenal ulcers, gastroesophageal reflux disease, Zollinger-Ellison syndrome, NSAID gastropathy, functional dyspepsia). The first proton pump inhibitor was discovered omeprazole (Losek, Gastrozol, Omez, etc.), later lansoprazole (Lanzap, Lanzoptol), pantoprazole (Controloc) and rabeprazole (Pariet) were synthesized. Recently, the optical S-isomer of omeprazole, esomeprazole (Nexium), has been synthesized.

Key Benefits of Proton Pump Inhibitors, taking into account which patients are treated: (1) the effect of eliminating heartburn and / or pain behind the sternum and in the epigastric region, especially in the daytime, occurs relatively quickly in patients with various acid-dependent diseases; (2) more intense inhibition of gastric acid formation for a longer time compared to H2 receptor antagonists and antacids; (3) high efficiency of proton pump inhibitors in various H. pylori therapy schemes; (4) higher efficiency in the treatment of patients with hypersecretion of hydrochloric acid.

General Features of Proton Pump Inhibitors: (1) quite unstable to the effects of acidic stomach contents (except for esomeprazole); (2) are rapidly absorbed in the small intestine (including the duodenum); (3) have a similar mechanism of action; (4) have sufficiently high similar levels of activation at low pH; (5) due to the ability to increase the pH level of the contents of the stomach, may alter the absorption of certain drugs (for example, increase the absorption of acid-labile antibiotics); (6) have a short half-life (within 1 hour in most people) and negligible renal clearance.

Mechanism of action. Proton pump (or proton pump) inhibitors are substituted benzimidazole derivatives. Being chemically weak bases, they accumulate in the tubules of parietal cells, where they are converted into tetracyclic sulfenamide. Sulfenamide covalently binds via disulfide bonds to the cysteine ​​groups of the proton pump, which leads to inhibition of the enzyme (H+,K+)-ATPase located on the apical membrane of the parietal cells of the gastric mucosa. The enzyme (H+,K+)-ATPase carries out the transfer of hydrogen ions from the parietal cell into the lumen of the stomach. Accordingly, inhibition of this enzyme leads to inhibition of acid secretion. Suppression of acid production by these drugs does not depend on the state of receptors (H2, M3, etc.) on the basement membrane of parietal cells. It should be noted that the high selectivity of proton pump inhibitors is due to the fact that their activation is possible only at an acidic pH (<4), в то же время они не устойчивы в кислой среде, поэтому при пероральном введении ингибиторы протонного насоса должны быть защищены от воздействия кислоты желудка. Данная проблема решается покрытием капсул, содержащих действующее вещество - ингибитор протоновой помпы, оболочкой, которая растворяющейся в щелочной среде. Минуя желудок, они быстро всасываются в кишечнике в щелочной среде и перераспределяются между органами и тканями.

Dosing regimen. Inside: in the morning, before meals. Without chewing. Drinking a small amount of water. Intravenously: once a day. The use of proton pump inhibitors in elderly patients does not require dose adjustment. Since proton pump inhibitors are characterized by a slow onset of action (no earlier than 1 hour), they are not suitable for on-demand therapy (at the time of pain, heartburn).

Comparative characteristics of drugs. Omeprazole, pantoprazole and lansoprazole differ in chemical structure, bioavailability, half-life, etc., but the results of their clinical use are almost identical. The minimum inhibitory concentration for omeprazole is 25-50 mg/l, lansoprazole - 0.78-6.25 mg/l, pantoprazole - 128 mg/l. Treatment regimens with lansoprazole provide an earlier onset of clinical remission compared with omeprazole. The frequency of recurrence of peptic ulcers after treatment with lansoprazole is 55-62%, pantoprazole - 55%, omeprazole - 41%. Currently, only omeprazole and lansoprazole are approved for long-term maintenance therapy. Long-term use (more than 5.5 years) of omeprazole in patients does not lead to the development of neoplastic changes. In patients with peptic ulcer who received maintenance therapy with pantoprazole at a dose of 40-80 mg daily for more than 3 years, there was a slight and statistically insignificant increase in the number of ECL cells. Unlike omeprazole and lansoprazole, pantoprazole interacts much less with the cytochrome P-450 system. Antacids, like food, do not affect the pharmacokinetics of pantoprazole. Sucralfate and food intake may alter the absorption of lansoprazole. The pharmacokinetics of omeprazole may be altered by food intake but not by liquid antacids. Therefore, lansoprazole and omeprazole are taken 30 minutes before meals, and pantoprazole - regardless of the meal.

drug interaction. Omeprazole and its stereoisomer esomeprazole may somewhat slow down the excretion of drugs metabolized by the cytochrome P450 system (diazepam, warfarin, phenytoin). The absorption of ketaconazole and itraconazole may be reduced when co-administered with omeprozole and esomeprazole. The metabolism of caffeine, theophylline, propranolol, quinidine and other drugs is not disturbed. When using rabeprazole, the absorption of ketoconazole may decrease and the absorption of digoxin may increase. Lansoprazole increases the clearance of theophylline when taken orally.

Side effects. (1) Side effects observed in short courses of therapy: the most common side effects are from the central nervous system, such as headache, fatigue, dizziness, and from the gastrointestinal tract, such as diarrhea or constipation. In rare cases, allergic reactions (skin rash, bronchospasm) are noted. With intravenous administration of omeprazole, the possibility of visual and hearing impairments has been described. (2) Side effects observed with long-term use of drugs of the omeprazole, lansoprazole and pantoprazole groups: hyperplasia of enterochromaffin cells of the gastric mucosa, progression of atrophic gastritis phenomena (but the risk of malignancy does not increase); with prolonged use of high doses of proton pump inhibitors, a decrease in the level of absorption of vitamin B12 was noted. One of the unpleasant side effects with long-term use of proton pump inhibitors is the appearance in some patients of flatulence, manifested by significant bloating and involuntary discharge of gases through the anus in unforeseen situations (in transport, at work during office meetings, etc.), which is significant worsens the quality of life of patients. Against the background of long-term use of proton pump inhibitors, some patients of elderly and senile age have a significant deterioration in vision. For proton pump inhibitors, as well as for H2 receptor antagonists, a “withdrawal syndrome” is characteristic, more pronounced when esomeprazole is discontinued, which is prescribed to patients at a dose of 40 mg.

(!) Based on the analysis of long-term use of omeprazole, it was concluded that people who take proton pump inhibitors continuously for a long time do not experience any additional risk of cancer compared to those who did not take these drugs.

(!) Against the background of long-term treatment with various original proton pump inhibitors, acquired (secondary) resistance to certain proton pump inhibitors may appear. Such resistance becomes noticeable after long-term treatment with the same drug, when its effectiveness against the background of continuous treatment of patients (for a year or more) is significantly reduced, however, the "transfer" of patients to treatment with other proton pump inhibitors improves their condition.

Dosage and administration of omeprazole(Omeprazole). Inside: With gastric ulcer, duodenal ulcer and reflux esophagitis - 20 mg 1 time per day (if necessary - 40 mg). With a duodenal ulcer, the course of treatment is 2-4 weeks, with a stomach ulcer and reflux esophagitis - 4-8 weeks. For the prevention of peptic ulcer - 20 mg 1 time per day. With Zollinger-Ellison syndrome: the initial dose is 20-60 mg per day, if necessary, up to 120 mg / day (daily dose above 80 mg should be divided into two doses) for 2-8 weeks. The level of secretion in the stomach should be up to 10 mmol HCl/h in non-resected patients, up to 5 mmol HCl/h in resected patients. In combined eradication anti-Helicobacter therapy for peptic ulcer - omeprazole 20 mg for 7 days. Intravenously: 1 time per day. The substance (40 mg) is dissolved in 100 ml of physiological saline or 5% dextrose solution and injected within 20-30 minutes after dilution. The infusion must be completed within 12 hours if the diluent is saline and within 6 hours if diluted in dextrose. It is usually sufficient to carry out infusions for 2-5 days, after which the patient can be transferred to oral administration of the drug.

Dosage and administration of lansoprazole(Lansoprazole). Inside: Non-ulcerative dyspepsia: 15-30 mg per day for 2-4 weeks. Gastric ulcer: 30-60 mg per day for 4-8 weeks. Erosive and ulcerative esophagitis: 30-60 mg per day for 4-8 weeks. Reflux esophagitis: 30 mg daily for 4 weeks. Zollinger-Ellison syndrome: the dose is individually selected to provide basal acid production below 10 mmol / h. In combined eradication anti-Helicobacter therapy: 30 mg 2 times a day for 7 days.

Doses and use of pantoprazole(Panthoprazole). Inside: Monotherapy of peptic ulcer of the stomach and duodenum, gastroesophageal reflux disease - usually 40 mg / day, possibly (dose increase) up to 80 mg / day (especially with erosive and ulcerative forms of reflux esophagitis). The duration of the course for duodenal ulcer is 14 days (sometimes up to 2 weeks), for gastric ulcer and gastroesophageal reflux disease - 4 weeks (in some cases for up to 4 more weeks). In combined eradication anti-Helicobacter therapy, pantoprazole is used at 40 mg 2 times a day (before breakfast and before dinner or during meals, without chewing and without destroying the integrity of the tablet, drinking liquid).

Dosage and administration of rabeprazole(Rabeprazole): Inside, 20 mg 1 time per day; with peptic ulcer of the stomach and duodenum in the acute stage - within 4-6 weeks, if necessary - up to 12 weeks; with reflux esophagitis: 4-8 weeks, further maintenance therapy is possible: 10-20 mg 1 time per day; with Zollinger-Ellison syndrome, the dose is selected individually. As part of eradication anti-Helicobacter therapy, rabeprazole is used using appropriate combinations of antibiotics for 7 days.

Dosage and use of esomeprazole(Esomeprazol). inside. The tablet should be swallowed whole with liquid. Tablets should not be chewed or broken. Treatment of erosive reflux esophagitis: 40 mg once a day for 4 weeks. An additional 4-week course of treatment is recommended in cases where, after the first course, esophagitis is not cured or symptoms persist. Prevention of recurrence in patients with cured esophagitis: 20 mg 1 time per day. Symptomatic treatment of GERD: 20 mg 1 time per day - for patients without esophagitis. If after 4 weeks of treatment the symptoms do not disappear, an additional examination of the patient should be carried out. In combination with appropriate antibiotic therapy for eradication of Helicobacter pylori, treatment of duodenal ulcer associated with Helicobacter pylori, prevention of recurrence of peptic ulcers in patients with peptic ulcer associated with Helicobacter pylori: esomeprazole is used at a dose of 20 mg for 7 days. Patients with renal insufficiency and for elderly patients dose adjustment is not required. In severe liver failure, the dose should not exceed 20 mg / day.

More than 90% of the population suffers from digestive problems, heartburn and gastritis, but few people know that drugs designed to alleviate the condition have long existed and are actively used in medical practice in cases where antacids do not help. Let's figure out what a proton pump inhibitor is, we will also consider a list of drugs.

Where did the pump come from in the human body?

The proton pump, also known as the proton pump, is an enzymatic protein that promotes the production. This is a necessary and most important action for the process of digesting food. However, it often happens that acid begins to be produced in large quantities, which leads to unpleasant and painful sensations in the stomach.

Indications for use

A proton pump inhibitor (a list of drugs will be listed below) is used quite often.

Inhibitors, or proton pump blockers, are drugs that are used to treat diseases of the gastrointestinal tract associated with high acidity:

Gastritis, including erosive;

Ulcers of the stomach and duodenum;

Duodenitis - inflammation of the mucous membrane of the duodenum;

GERD - a reflux disease in which the contents of the stomach are regularly thrown into the esophagus, which eventually corrodes the mucous membrane of the esophagus, trachea and pharynx;

Dyspepsia - a violation of the digestive process, in which there is a feeling of stabbing / cutting pain in the epigastric region (solar plexus region) after eating;

The consequences of taking non-steroidal anti-inflammatory drugs (such as Diclofenac), which irritate the mucous membranes of the gastrointestinal tract;

Zollinger-Ellison syndrome - gastrinoma - a malignant tumor that causes increased secretion of hydrochloric acid.

In all these cases, the use of proton pump inhibitors is indicated.

Mechanism of action

PPI tablets or capsules are taken by mouth, dissolve in the small intestine, and are carried in the blood through the liver to the secretory tubules, where they begin to accumulate. Due to the impact directly on the tubules, which produce hydrochloric acid, inhibitors reduce its secretion, respectively, the aggressiveness of gastric juice decreases.

A proton pump inhibitor (a list of drugs is available at any pharmacy) is prescribed by a doctor.

The mechanism of operation of all drugs of this type is the same, but the concentration of the active substance, which maintains the required pH level, and the speed of exposure differ. Only a doctor can pick them up after taking measurements of acidity, it is performed within a day. Next, a suitable drug is prescribed, and its effectiveness is monitored. If relief does not occur, and this is possible in case of resistance to drugs of this kind, then a replacement should be sought.

In terms of pH, they are guided by the state of acidity of the gastrointestinal tract. There are 14 units in total, water is neutral, is in the middle of the acid-base balance and has a pH of 7. An acidic medium goes to the lower side from the water, and an alkaline one to the upper side.

Different types of diseases associated with increased production of hydrochloric acid are characterized by different pH values. For example, a duodenal ulcer can heal at a pH greater than 3 throughout the day, and in order to kill the Helicobacter pylori bacterium, a slightly acidic environment is needed, where the pH is greater than 5.

According to the pH norm and the established diagnosis, the doctor prescribes one or another drug from the group of proton pump blockers in a certain dosage for a certain period.

Duration of admission

The course of treatment can be several months and even years. For example, for the drug "Rabeprazole" the instruction describes the duration of the intake. safe for the body, because they act locally and are not addictive, that is, after the end of the course, you can not be afraid of the so-called "withdrawal syndrome". This type of medicine does not drown out the disease, but completely cures it.

Now it’s clear what a proton pump inhibitor is. The list of drugs is very extensive.

Group of proton pump blockers

"Omeprazole" is a well-known drug. Available for sale:

- "Omeprazole-Acre".

- Omeprazole-Richter is the most potent option.

- Omeprazole Sandoz. A combined agent used rather to regulate the production of hydrochloric acid and the functions of the gastrointestinal tract.

It has long been known that Omeprazole is a proton pump inhibitor, but today it is preferred to be prescribed less frequently, since new generation drugs differ for the better both in effectiveness and in the manifestation of side effects.

It is allowed to administer not only orally, but also intravenously, which contributes to obtaining a quick result. No disease recurrence was noted during 10 years of patient follow-up.

"Pantoprazole"

Each package contains instructions for use for the Pantoprazole preparation. The price of the drug is an average of 130 rubles.

"Pantoprazole" with great care, but prescribed during the 2nd and 3rd trimesters of pregnancy, if the potential benefit is expected to be much higher than the risk to the child. Tests on pregnant women have not been conducted, but no negative effects on the fetus have been noted in animals.

Before using Omeprazole and Pantoprazole, you should carefully read the extensive list of drug interactions and consult your doctor if you plan to take any drug from this list at the same time as other drugs. Analogue - "Nolpaza".

Why is this drug prescribed? It is also a proton pump inhibitor. Available in two forms - in tablets and ampoules for injection. But in fact, ampoules are a lyophilizate from which an injection solution is prepared. It is most often prescribed for peptic ulcer, but has been successfully used for other diseases of the gastrointestinal tract.

Thanks to the juice produced in a smaller volume, the mucous membrane is not so much irritated. If there are ulcers and erosion, then they gradually heal. Nolpaza copes with this perfectly. Why the drug is prescribed has become clearer. Analogs - Lanzap, Lansofed, Loenzar-sanovel, Epikur, Akrilanz, etc. It is limitedly used in the treatment of pregnant women and children, the use is undesirable if you can choose another a drug.

Rabeprazole is another drug from the group of proton pump blockers.

The instruction for the drug "Rabeprazole" indicates that it is incompatible with liquid antacids. The effect is enhanced when taken simultaneously with Warfarin, Diazepam, Theophylline and Phenytoin. Analogues - "Bereta", "Zolispan", "Noflux", "Pariet", "Rabelok", "Khairabezol", etc.

Lansoprazole is an effective drug for diseases of the gastrointestinal tract. It blocks the production of gastric juice. This confirms the instructions for the drug "Lansoprazole". In addition, the medication fights the bacterium Helicobacter pylori. Specific antibodies to it are produced intensively due to the action of the drug. The drug works as much as possible the first few days from the start of administration. Analogs - "Emanera", "Nexium", "Losek", "Sanpraz", etc. Some drugs taken simultaneously with "Lansoprazole" can increase its concentration in the blood plasma and enhance the effect. These are Imipramine, Clomipramine, Citalopram. "Diazepam" and "Phenytoin" increase the content slightly, and "Ketoconazole", "Itraconazole" and "Clarithromycin" help to reduce the effectiveness of the drug. This is how Lansoprazole describes the instructions for use.

"Esomeprazole" is a good drug for peptic ulcer of the stomach and duodenum. Can be used with antibiotics. It treats in the phase of exacerbation of diseases and is used for prevention. Suppresses the reproduction of Helicobacter pylori. The drug "Esomeprazole" (capsules and solution for injection) is used for a month at a dosage of 40 mg per day. For prevention, the dose can be halved.

Precautionary measures

Against the background of treatment with proton pump blockers, the symptoms of oncological diseases may become mild, therefore, before starting therapy, it is necessary to undergo an examination to exclude the occurrence of tumors. In addition, an urgent study will be required with frequent vomiting, especially with blood, stool disorder and a change in its color and smell, as well as a sharp weight loss. So, with caution it is worth taking "Rabeprazole sodium".

This group of drugs, according to recent studies, increases the fragility of bones, respectively, and the risk of fractures, and also provokes associated diarrhea (that is, caused by taking certain medications), hypomagnesemia, and the manifestation of dementia in old age.

For this reason, the doctor should first prescribe the lowest possible dosage or the shortest possible course of administration and observe the effect.

Application with antibiotics

Proton pump inhibitors (new generation drugs) are used in the complex treatment of diseases caused by the bacterium Helicobacter pylori, which can both contribute to the occurrence of problems in the gastrointestinal tract and provoke relapses of already seemingly cured diseases. In this case, antibiotics are added to the treatment, mainly of the tetracycline series.

This is a group of strong antibiotics, so in no case should you prescribe them yourself.

Side effects

Like any medication, proton pump blockers have a number of possible side effects:

• increased drowsiness - therefore, this type of drug is forbidden to be taken by persons whose activities require attention and speed of reactions, for example, drivers;

• headaches reaching migraines - anti-migraine drugs are not forbidden to be taken simultaneously with PPIs, but a doctor's consultation is desirable;

• dizziness and weakness;

• pain in the legs, spine, joints;

• indigestion - diarrhea or constipation, nausea;

• taste change;

• dry mouth;

• allergic reactions - urticaria, itching;

• slowing down the formation of blood cells - leukocytes and platelets;

• increased sweating, chills.

In these cases, the attending physician must be informed, who, as a rule, prescribes another suitable PPI preparation.

It should be taken into account that side effects are quite rare and most often mild, therefore, under the supervision of a doctor, further use is usually quite possible.

If proton pump inhibitors (new generation drugs) are used, then there are practically no side effects.

Contraindications

General contraindications for all proton pump inhibitors are:

The period of lactation and pregnancy, especially the 1st trimester, the use of some drugs of this group in the 2nd and 3rd trimesters is possible with the consent of the doctor. These drugs are extremely bioavailable, that is, they are able to penetrate tissues, including and accumulate in breast milk. And although there is no confirmed data on the harm of these drugs to the fetus, there is no reverse information, with the exception of animal experiments.

Children under 12 years of age, since the work of their endocrine glands is at the stage of development and formation, so any intervention can cause a failure.

Allergy or hypersensitivity to the components of the drug.

For example, all this is described for the preparation "Pantoprazole" instructions for use.

Price

Prices for proton pump blockers vary widely, but they are quite affordable. On average, the cost is from 90 rubles. for a package of "Omeprazole" up to 500 rubles. for the packaging of other new generation drugs.

The price also depends on the number of capsules / tablets in the package and the country of origin. For example, Russian generics can be bought for 20-100 rubles, but you need to understand that generics are not original products. They often have lower efficiency and worse tolerability, more likely to cause side effects.

Updated: 07/23/2019 18:29:34

Judge: Natalia Shneider

*Overview of the best in the opinion of the editors of the site. About selection criteria. This material is subjective, is not an advertisement and does not serve as a guide to the purchase. Before buying, you need to consult with a specialist.

Proton pump inhibitors (PPIs) are a group of drugs that reduce the production of hydrochloric acid in the stomach. Doctors recommend these funds for both therapeutic and prophylactic purposes.

When are proton pump inhibitors prescribed?

1. The main indication for drugs from this group is diseases caused by high acidity of gastric juice: peptic ulcer of the stomach or duodenum. As they wrote in old textbooks: "no acid - no ulcer." This position remains true even after the discovery of the true cause of peptic ulcer - a bacterium called Helicobacter Pilory (Helicobacter pylori).
2. To destroy this bacterium, proton pump inhibitors can also be prescribed in normal stomach acidity. Helicobacteria has adapted well to existence in an acidic environment, and with an increase in pH above 4, it becomes more sensitive to antibiotics. Therefore, for its eradication, a complex of PPIs is prescribed, and 2-3 antibacterial agents.
3. Another acid-dependent disease in which proton pump inhibitors are prescribed is complicated gastroesophageal reflux disease. When it disrupts the normal operation of the lower esophageal sphincter - a circular muscle that blocks the flow of stomach contents into the esophagus. Constantly getting on the unprotected mucous acid causes inflammation, ulcers, disrupts the normal structure of cells, which over time can lead to a malignant neoplasm. PPIs are recommended to protect the esophageal mucosa from the action of acid.
4. Another situation where drugs from this group are recommended for people with normal stomach acidity is chronic pancreatitis with excretory pancreatic insufficiency. Simply put, when the gland, depleted by constant inflammation, produces an insufficient amount of enzymes for normal digestion. In such cases, enzyme preparations are usually prescribed. But for them to work, you need an alkaline environment. Alkaline to neutralize the acidic food bolus that came from the stomach is synthesized by the same pancreas, and if it is insufficient, the tablets with enzymes taken may also be ineffective. To prevent this from happening, proton pump inhibitors are prescribed, reducing the acidity in the stomach, and, therefore, in the food bolus that comes out of it.
5. For preventive purposes, proton pump inhibitors are recommended for people who are forced to regularly take drugs from the group of non-steroidal anti-inflammatory drugs: diclofenac, ibuprofen, paracetamol, aspirin, etc. These drugs slow down the regeneration of the gastric mucosa and often cause silent, asymptomatic ulcers. To prevent this, PPIs are prescribed.

Rating of the best proton pump inhibitors

Nomination	place	Name of product	price
Best OTC Proton Pump Inhibitors	1		73 ₽
	2		162 ₽
	3		1 698 ₽
Best Prescription Proton Pump Inhibitors	1		132 ₽
	2		350 ₽
	3		898 ₽
The best combined drugs	1		1 030 ₽
	2		425 ₽

Best OTC Proton Pump Inhibitors

Speaking about drugs dispensed from pharmacies without a doctor's prescription, it should be noted that drugs with the same active ingredient may turn out to be both prescription and not. For example, Omez, which we will talk about in this section of the ranking of the best proton pump inhibitors, is available from pharmacies without a prescription. And its domestic counterpart Gastrozol is prescription. An even stranger situation has developed with Ultop, which contains a similar active ingredient: 10 mg capsules are available without a prescription, and 20 and 40 mg are prescription. Therefore, no matter how much we want to use only active substances in the rating, leaving readers to choose from the proposed analogues, taking into account financial possibilities, in this section of the ranking of the best proton pump inhibitors, we are forced to use the trade names of the drugs.

OTC PPIs can be taken on their own for 2 weeks, but if they don't provide relief in the first 3 days, it's best to see a doctor right away.

Active ingredient: Omeprazole.

A time-tested product that combines proven effectiveness and affordable price. Available in capsules of 10, 20 and 40 mg. Capsules are taken 1 time per day half an hour before meals with water. If necessary, the capsule can be opened and the contents mixed with water or food.

The dosage is selected individually, most often the therapeutic effect appears when taking 20 mg, but often 10 mg is enough (or, conversely, a higher dose is needed).

The most common side effects are headache, insomnia, dizziness, diarrhea or constipation, nausea, bloating, and abdominal pain.

The drug is contraindicated for use in children under 18 years of age (omeprazole is allowed in pediatrics from the age of 2, but there are separate forms for patients of this age), with individual intolerance.

Can be used during pregnancy.

Possible non-prescription analogues: Ultop.

Advantages

• economy,
• can be taken by pregnant women.

disadvantages

• does not combine with some antiviral and antifungal drugs (for more details, see the instructions)

Active ingredient: pantoprazole.

The combination of German quality and relatively affordable price. Available in tablets of 20 and 40 mg, without a prescription it is released only in the minimum dosage.

Take 20 mg once daily before meals with plenty of fluids (some patients may require a higher dose).

It is effective from the first days of admission, but the maximum effect is achieved only after a week of regular use (if in the first days it reduces gastric secretion by 26%, then after a week - up to 50%), therefore, it is possible to judge the disappearance of symptoms not earlier than after 5-7 days reception. Acidity is restored in 3 - 4 days after the end of the application.

Unlike the rest of the proton pump inhibitors in this section of the best remedies, Controloc can be taken without consulting a doctor for up to 4 weeks.

The most common side effects are indigestion (nausea, bloating, pain, constipation or diarrhea); headache, dizziness.

It is combined with almost any drug (with the exception of azatanovir, in which therapy it is contraindicated to take Controloc).

Possible non-prescription analogues: Panum, Paltaz.

Advantages

• relatively affordable price,

disadvantages

• 14 tablets per package, which is inconvenient for regular use.

Active ingredient: rabeprazole

Formally, the license for the production of this medicine belongs to the Russian branch of Johnson and Johnson, but the substance (active ingredient) is produced in Switzerland, and the tablets themselves are in Japan. So the quality of this proton pump inhibitor is undeniable, but the price is quite high.

Available in dosages of 10 and 20 mg, the first is released without a prescription.

Take 1 tablet per day, without crushing or chewing the tablet. Neither the time of day nor food intake affect the effectiveness of the drug.

The effect begins to appear within an hour after ingestion, and after a day, gastric secretion decreases by 69%.

It is combined with most drugs, but concomitant use with azatonavir is not recommended.

Contraindicated in case of individual intolerance, pregnancy, lactation and children under 18 years of age due to the lack of safety studies in these groups.

Possible non-prescription analogues: Beret, Norflux, Ulcernil, Rabelok.

Advantages

• effectiveness does not depend on food intake,
• combined with most drugs.

disadvantages

• high price.

Best Prescription Proton Pump Inhibitors

In this section, we have collected drugs that should only be sold by prescription.

Active ingredient: esomeprazole.

It is produced in the form of tablets for oral administration of 20 and 40 mg, as well as in the form of a powder for the preparation of suspensions in a dosage of 10 mg.

This is one of the few original modern medicines with an affordable price (except for the powder form, which has no analogues on the Russian market)

At the first dose, the action begins within an hour, the effect “reaches its maximum” by the 5th day of use, reducing the concentration of hydrochloric acid in gastric juice by 90%.

The usual method of application is 1 time per day, but if the medicine was prescribed in combination with antibiotics to destroy Helicobacter pylori - 2 times a day along with antibiotics.

Esomeprazole powder can be used to treat children, but indications are limited to GERD and reflux esophagitis.

Side effects - headache, dyspepsia.

Contraindicated in case of individual intolerance, children under one year old, pregnant women and lactating women due to lack of safety data.

Possible analogues: Esomeprazole, Emaner, Pemozar, Rediomez

Active ingredient: lansoprazole.

Available in capsules of 15 and 30 mg.

The effect increases during the first 4 days of administration, at the maximum, a decrease in the synthesis of hydrochloric acid is achieved up to 97%. Restoration of functions occurs 3-4 days after cessation of use. Eating slows down absorption but does not affect effectiveness.

Use once a day, preferably in the morning. If the medicine is prescribed to destroy Helicobacter pylori, it should be taken 2 times a day. If antacids are prescribed in parallel, it is better to take them separately from Lancid, as they prevent the complete absorption of the drug.

Possible adverse events are typical for the entire group of proton pump inhibitors - abdominal discomfort, stool disorders, bloating, headache.

Contraindicated in case of individual intolerance, in the 1st trimester of pregnancy (but there are no safety studies in other periods), during lactation.

Possible analogues: Lanzabel, Lanzaptol, Epicurus.

Advantages

• affordable price;

disadvantages

• prohibited during pregnancy.

The active substance is dexlansoprazole.

On the one hand, this remedy is based on a relatively new active substance with high biological activity. On the other hand, until the patent has expired and generics have not appeared, the original manufacturer remains a monopolist, and the price of a medicine is quite high.

Available in capsules of 30 and 60 mg.

The peculiarity of this drug is not only in the active substance, but also in the release form. In ordinary, at first glance, capsules, several types of granules are packed, which dissolve in the intestine, depending on the pH of the medium. That is, after taking, not all the active substance is released at once. and different granules dissolve at different times as the food bolus advances. Due to this, the effect comes on more smoothly and lasts longer. If necessary, the capsule can be opened and the contents diluted in a small amount of water or food that does not require chewing.

Possible side effects are flatulence, dyspepsia.

Contraindicated in case of individual intolerance, patients taking HIV protease inhibitors, children under 18 years of age, pregnant and lactating women.

Advantages

• original drug,
• modified release, prolonging the effect.

disadvantages

• high price.

The best combined drugs

As already mentioned, proton pump inhibitors are often prescribed in combination with antibiotics to destroy Helicobacter pylori, eliminating the cause of an ulcer or gastritis. To save the patient from having to remember when and which pills to take, they began to produce drugs that combine these groups of drugs in one remedy. Another possible combination is proton pump inhibitors and agents. normalizing the motility of the gastrointestinal tract. They are prescribed for the treatment of reflux esophagitis.

Strictly speaking. this is not a single drug, but a set of tablets and capsules containing the proton pump inhibitor omeprazole, the antibiotic clarithromycin, and the antibacterial and antiprotozoal agent tinidazole. All this is packed in strips with the inscription "morning" or "evening". It is necessary to take the contents of the corresponding strip during or immediately after a meal, as is clear from the description - in the morning and in the evening. It is impossible to divide, chew or otherwise crush tablets or capsules.

Contraindicated in:

1. component intolerance,
2. alcoholism (cannot be combined with ethyl alcohol),
3. liver or kidney failure,
4. impaired bone marrow hematopoiesis,
5. children, pregnant, lactating.

The course of treatment is from 7 to 14 days, specific recommendations are given by the attending physician. The packaging of the drug is designed for 7 days, so you may need two.

Contraindicated in:

1. the simultaneous use of some antiviral, antifungal and antibacterial agents (for more detailed information, we refer readers to the instructions, since the list is not limited to 1 - 2 items);
2. gastrointestinal bleeding, perforation, intestinal obstruction;
3. insufficiency of liver function of moderate and severe degree,
4. pregnant and lactating,
5. children under 18 years of age.

Advantages

• normalizes the motility of the esophagus, stomach, intestines,

disadvantages

• a wide range of contraindications,
• possible side effects.

Attention! This rating is subjective, is not an advertisement and does not serve as a purchase guide. Before buying, you need to consult with a specialist.

Proton pump inhibitors (synonyms: proton pump inhibitors, proton pump inhibitors, proton pump inhibitors; proton pump blockers, blockers H+/K+-ATPase, hydrogen pump blockers, PPIs, PPIs, etc.) - antisecretory drugs intended for the treatment of acid-dependent diseases of the gastrointestinal tract by reducing the production of hydrochloric acid due to blocking of the proton pump in the parietal cells of the gastric mucosa - H+/K+-ATPase.

According to the modern Anatomical-Therapeutic-Chemical Classification of Medicines (ATC) proton pump inhibitors (IPP) are included in the section A 02B"Antiulcer drugs and drugs for the treatment of gastroesophageal reflux" to the group A 02BC"Proton Pump Inhibitors". It lists international generic names for seven proton pump inhibitors (the first six are approved in the US and the Russian Federation; the seventh, dexrabeprazole, is not currently approved for use):

• A 02BC 01 Omeprazole
• A 02BC 02 Pantoprazole
• A 02BC 03 Lansoprazole
• A 02BC 04 Rabeprazole
• A 02BC 05 Esomeprazole
• A 02BC 06 Dexlansoprazole
• A 02BC 07 Dexrabeprazole

Proton pump inhibitors in combination with various antibiotics are also placed in the group A 02BD Combinations of drugs for eradication Helicobacter pylori».

Data have also been published on a number of new proton pump inhibitors, which are currently at various stages of development and clinical trials (tenatoprazole, D lansoprazole, ilaprazol, etc.).

Proton pump inhibitors are currently recognized as the most effective drugs that suppress the production of hydrochloric acid.

Proton pump inhibitors are widely used in clinical practice in the treatment of acid-dependent diseases of the gastrointestinal tract (including when eradication is necessary). Helicobacter pylori), such as:

- gastroesophageal reflux disease (GERD);

- gastric and / or duodenal ulcer;

- Zollinger-Ellison syndrome;

- damage to the gastric mucosa caused by the use of non-steroidal anti-inflammatory drugs;

- gastrointestinal bleeding of various origins

– functional dyspepsia;

quadruple or triple therapy with antibiotics.

Proton pump inhibitors are also indicated to prevent acidic stomach contents from entering the respiratory tract during general anesthesia (Mendelssohn's syndrome).

Proton pump inhibitors are available in dosage forms such as "coated tablets", "capsules", "enteric capsules" (PPIs, except for esomeprazole, are rather unstable to the effects of acidic stomach contents), as well as "lyophilisate for the preparation of a solution for infusions", "powder for solution for infusions". Parenteral forms for intravenous administration are especially indicated for treatment in cases where oral administration of the drug is difficult.

According to the chemical structure, all PPIs are derivatives of benzimidazole and have a single molecular core.

In fact, they all differ only in chemical radicals on the pyridine and benzimidazole rings, which determine their individual properties regarding the duration of the latent period, the duration of the action of the drug, and the features pH-selectivity, interactions with other drugs taken simultaneously, etc.

Esomeprazole, dexlansoprazole and dexarabeprazole are optical isomers of omeprazole, lansoprazole and rabeprazole, respectively. Due to this modification, they have a higher biological activity.

The mechanism of action of various proton pump inhibitors is the same, and they differ mainly in their pharmacokinetics and pharmacodynamics.

It should be noted that, although all proton pump inhibitors have the same mechanism of action, which ensures the similarity of their clinical effects, however, each of them has pharmacokinetic features (see table), which determines their individual properties and can serve as the basis for choosing when prescribing and conducting therapy, although, depending on the genetically determined type of metabolism, the pharmacokinetics of PPIs and their concentration in the blood can vary significantly in different patients.

Table. PPI pharmacokinetics

Options	Omeprazole 20 mg	Esomeprazole 40 mg	Lansoprazole 30 mg	Pantoprazole 40 mg	Rabeprazole 20 mg
Bioavailability, %
With max, mg/A
AUC, µmol/LhH
T 1/2, h
Tmax, h

For example, the minimum inhibitory concentration for omeprazole is 25-50 mg / l, lansoprazole - 0.78-6.25 mg / l, pantoprazole - 128 mg / l.

According to the results of comparative studies, attention should be paid to the fact that in omeprazole and esomeprazole, the pharmacokinetics increase during the first days of administration, after which they reach a plateau, while in lansoprazole, pantoprazole and rabeprazole they do not change, remaining stable.

Attention should also be paid to the fact that the main indicator that determines the rate of development of the PPI effect is their bioavailability. For example, it has been shown that omeprazole has the lowest bioavailability (after the 1st dose, it is 30-40% and increases to 60-65% by the 7th dose). In contrast, the bioavailability of the initial dose of lansoprazole is 80-90%, which leads to a faster onset of action of this drug.

Thus, as noted by many researchers, in the early stages of therapy, lansoprazole has some advantages in the speed of onset of effect, which potentially increases the patient's adherence to treatment.

However, it should be noted that various PPI preparations currently used in clinical practice differ in the rate of onset of the clinical effect only in the first days of treatment, and by the 2-3rd week of administration, these differences are lost.

An essential moment for the practice of application is, for example, such a moment that the intake of antacids, like food, does not affect the pharmacokinetics of pantoprazole. Sucralfate and food intake may alter the absorption of lansoprazole. The pharmacokinetics of omeprazole may be altered by food intake but not by liquid antacids. Therefore, lansoprazole and omeprazole are taken 30 minutes before meals, and pantoprazole and rabeprazole - regardless of the meal.

It has been established that for all PPIs, the duration of the antisecretory effect does not correlate with the concentration of the drug in the blood plasma, but with the area under the concentration-time pharmacokinetic curve ( AUC), reflecting the amount of drug that reached the proton pump. Comparative studies have found that after the 1st dose of all PPIs, the highest rate AUC was at pantoprazole. In esomeprazole, it was less, but, gradually increasing, by the 7th dose, it was slightly higher than AUC pantoprazole. Indicator AUC omeprazole was the lowest among all compared PPIs.

Therefore, - omeprazole should be prescribed 2 times a day, - and drugs with the highest rate AUC(pantoprazole and esomeprazole) for most patients it is sufficient to take once. It is noted that for a certain number of patients the above can be attributed to lansoprazole and rabeprazole.

However, it should be noted that the clinical significance of this fact is mainly reduced to the frequency of taking various PPIs, and the frequency of taking the drug, in turn, is associated with the problem of patient adherence to treatment.

But, at the same time, it should still be taken into account that there is a significant variation in the duration of the antisecretory effect, both for different proton pump inhibitors, and individually from 1 to 12 days. Therefore, the determination of the individual rhythm of administration and doses of drugs for each patient individually should be carried out under the control of intragastric pH-metrics.

An important difference between the various PPI preparations is their pH- selectivity. It is known that selective accumulation and rapid activation of all PPIs occur only in an acidic environment. The rate of their conversion into the active substance with increasing pH depends on the value R Ka for nitrogen in the structure of pyridine. It was found that for pantoprazole R Ka is 3.0 for omeprazole, esomeprazole and lansoprazole - 4, for rabeprazole - 4.9. This means that at pH 1.0-2.0 in the lumen of the secretory tubules, all PPIs selectively accumulate there, quickly turn into sulfenamide and act equally effectively. With an increase pH PPI transformation slows down: the activation rate of pantoprazole is reduced by 2 times when pH 3.0 omeprazole, esomeprazole and lansoprazole - at pH 4.0 rabeprazole - at pH 4.9. Pantoprazole practically does not turn into an active form when pH 4.0 omeprazole, esomeprazole and lansoprazole - with pH 5.0 when rabeprazole activation is still in progress. Thus, pantoprazole is the most pH-selective, and rabeprazole - the least pH- selective PPI.

In this regard, it is interesting that some authors, the ability of rabeprazole to be activated in a wide range pH is regarded as its advantage, since it is associated with a rapid antisecretory effect. According to others, low pH The selectivity of rabeprazole is its disadvantage. This is due to the fact that reactive forms of PPIs (sulfenamides) are potentially able to interact not only with SH-cysteine ​​groups of the proton pump, but also with any SH-organism groups. Currently, in addition to parietal cells, proton pumps ( H + /To+ - or H + /Na+ -ATPase) were found in cells and other organs and tissues: in the epithelium of the intestine, gallbladder; renal tubules; corneal epithelium; in the muscles; cells of the immune system (neutrophils, macrophages and lymphocytes); osteoclasts, etc. This means that if PPIs are activated outside the secretory tubules of the parietal cell, they can affect all these structures. In the cells of the body there are organelles with an acidic environment (lysosomes, neurosecretory granules and endosomes), where pH 4.5-5.0 - therefore, they can be potential targets for PPIs (in particular, rabeprazole).

From this it was concluded that for selective accumulation in the secretory tubules of the parietal cell R Ka IPP optimally should be below 4.5.

It is the difference pH-selectivity of proton pump inhibitors is also discussed as a pathogenetic mechanism for potential side effects of PPIs during their long-term use. Thus, the possibility of blocking the vacuolar H+ -ATPase of neutrophils, which may increase the patient's susceptibility to infection. So, in particular, against the background of PPI therapy, an increased risk of community-acquired pneumonia has been described, however, it should be noted that such a complication is most likely not with long-term treatment, but only in the initial period of PPI use.

It should also pay attention to the fact that the therapeutic effect of PPIs significantly depends on the rate of excretion of drugs from the body. Metabolism of proton pump inhibitors allowed in Russia occurs mainly in the liver with the participation of CYP 2C 9, CYP 2C 19, CYP 2D 6 and CYP 3A 4, - cytochrome isoenzymes R 450. Polymorphism of the genes of the cytochrome system CYP 2With 19 is a determining factor in the fact that the rate of onset and duration of the antisecretory effect of PPIs in patients differ significantly.

It was found that in the Russian population, the prevalence of gene mutations CYP 2C 19 encoding PPI metabolism (homozygotes, no mutations, - fast PPI metabolism; heterozygotes, one mutation; two mutations, - slow metabolism), for representatives of the Caucasian race they are 50.6%, 40.5% and 3.3%, for Mongoloid race - 34.0%, 47.6% and 18.4%, respectively. Thus, it turns out that from 8.3 to 20.5% of patients are resistant to a single dose of PPI.

The exception is rabeprazole, the metabolism of which takes place without the participation of isoenzymes. CYP 2C 19 and CYP 3A 4, what is apparently the reason for the constant value of its bioavailability after the first application, as well as its least interaction with drugs metabolized through the cytochrome system P 450 and the least dependence on the polymorphism of the gene encoding isoform 2 C 19 compared to other proton pump inhibitors. Rabeprazole less than other drugs affects the metabolism (destruction) of other drugs.

The clearance of omeprazole and esomeprazole is significantly lower than that of other PPIs, which leads to an increase in the bioavailability of omeprazole and its stereoisomer esomeprazole.

Phenomena such as "resistance to proton pump inhibitors", "nocturnal acid breakthrough", etc., observed in a number of patients, may be due not only to genetic factors, but also to other features of the state of the organism.

Speaking about the treatment with proton pump inhibitors, one should, of course, note the problem of the safety of their use. This problem has two aspects: the safety of PPIs as a class and the safety of individual drugs.

Side effects from the use of proton pump inhibitors can be divided into two groups: side effects observed with short courses of therapy, and those that occur with long-term use of these drugs.

The safety profile of proton pump inhibitors in short (up to 3 months) courses of therapy is very high. Most often, with short courses of therapy, side effects from the central nervous system, such as headache, fatigue, dizziness, and from the gastrointestinal tract (diarrhea or constipation) occur. In rare cases, allergic reactions (skin rash, bronchospasm) are noted. With intravenous administration of omeprazole, cases of visual and hearing impairment have been described.

It has been found that with prolonged (especially for several years) continuous use of proton pump blockers, such as omeprazole, lansoprazole and pantoprazole, hyperplasia of enterochromaffin cells of the gastric mucosa or progression of atrophic gastritis occurs. It was noted that the risk of developing nodular hyperplasia ECL-cells becomes especially high when the level of serum gastrin exceeds 500 pg/ml.

These changes are usually pronounced with long-term use of high doses of PPIs (at least 40 mg of omeprazole, 80 mg of pantoprazole, 60 mg of lansoprazole). With prolonged use of large doses, a decrease in the level of absorption of the vitamin was also noted. B 12 .

In fairness, it should be noted that in practice the need for long-term maintenance of such high doses of proton pump inhibitors is usually only in patients with Zollinger-Ellison syndrome and in patients with severe erosive-ulcerative esophagitis. According to the Committee for Medicinal Products in Gastroenterology FDA (Food and Drag Administration, USA), "...there is no significant increase in the risk of developing atrophic gastritis, intestinal metaplasia or gastric adenocarcinoma with long-term use of PPIs." Therefore, we can safely say that, in general, these drugs have a good safety profile.

An important problem of the safety of treatment is the possibility of changing the effects of drugs when taken together with PPIs. Pantoprazole has been found to have the lowest affinity for the cytochrome system among PPIs. P 450, since after the initial metabolism in this system, further biotransformation occurs under the influence of cytosolic sulfatransferase. This explains the lower potential for drug-drug interactions with pantoprazole than with other PPIs. Therefore, it is believed that if it is necessary to take several drugs for the simultaneous treatment of other diseases, the use of pantoprazole is the safest.

A separate point should be noted and undesirable effects upon discontinuation of treatment with proton pump inhibitors. For example, a number of studies have emphasized that after discontinuation of rabeprazole, there is no “rebound” (withdrawal) syndrome, i.e. there is no compensatory sharp increase in the level of acidity in the stomach - the secretion of hydrochloric acid after treatment with this PPI is restored slowly (within 5-7 days). "Withdrawal syndrome", more pronounced with the abolition of esomeprazole, prescribed to patients at a dose of 40 mg.

Taking into account all the above features of various proton pump inhibitors (metabolic features associated with genetics, causes of resistance, the possibility of nighttime "acid breakthroughs", etc.), we can conclude that any one "best" drug for the treatment of acid-related diseases does not exist. Therefore, in order to avoid failures in PPI therapy, the selection and prescription of proton pump inhibitors should be individually and timely adjusted taking into account the response to the treatment being carried out and, if necessary, should be accompanied by an individual selection of drugs and doses of their intake under control. pH-metry (daily pH-metry) or gastroscopy.

Against the background of long-term treatment with various proton pump inhibitors, acquired (secondary) resistance to certain PPIs may appear. Such resistance becomes noticeable after long-term treatment with the same drug, when its effectiveness decreases significantly against the background of continuous use for a year or more, but the transfer of patients to treatment with other PPIs improves their condition.