Proton pump inhibitors: generations of drugs and their features. Proton pump inhibitors: an overview of the group of drugs Are there new drugs that are safer and more effective than PPIs
![Proton pump inhibitors: generations of drugs and their features. Proton pump inhibitors: an overview of the group of drugs Are there new drugs that are safer and more effective than PPIs](https://i2.wp.com/rmj.ru/data/articles/Image/t11/n5/t2882.gif)
WITH secretion of hydrochloric acid by parietal cells of the gastric mucosa is due to transmembrane transfer of protons, which is carried out with the help of a proton pump - H + , K + - dependent ATPase. proton pump inhibitors selectively accumulate in the acidic environment of the secretory tubules parietal cells, where their concentration is 1000 times higher than the concentration in the blood. In the secretory tubules, these drugs - benzimidazole derivatives undergo a number of changes, as a result of which they pass into active form . Then they form strong covalent bonds with certain areas of H + , K + - ATP-ase, excluding the possibility of conformational transitions of the enzyme, and block its work. Proton pump inhibitors are the most potent of all antisecretory agents. This explains the leading position of this class of drugs in the treatment of acid-dependent and H. pylori-associated diseases (Table 1).
Proton pump inhibitors effectively control intragastric pH, which has been proven by numerous studies with 24-hour pH-metry. The effect of these drugs on acid production and pH is dose dependent. The standard dose of omeprazole (20 mg) with daily administration can reduce intragastric acidity by 80%. For comparison, the percentage of intragastric acidity reduction when using ranitidine 300 mg or famotidine 40 mg is 69% and 70%, respectively. The degree and duration of the pH increase are predictive of acid-related diseases. So, the optimal conditions for the healing of a duodenal ulcer is to maintain pH> 3 for 18 hours a day, for the healing of reflux esophagitis -> 4, for the eradication of infection H. pylori-> 5. Histamine H2-receptor blockers are inferior to proton pump inhibitors, due to the more pronounced antisecretory effect of the latter, which makes it possible to achieve optimal pH values in the treatment of acid-dependent diseases.
Proton pump inhibitors and gastroesophageal reflux disease Different classes of drugs are used to treat GERD:
- antacids
- alginates
- prokinetics
- H 2 -blockers of histamine receptors
- proton pump inhibitors.
The choice of therapy is determined by the form of gastroesophageal reflux disease (endoscopically negative or occurring with reflux esophagitis) and the severity of reflux esophagitis. Antacids and alginates are ineffective both in relieving symptoms and in healing esophagitis, therefore they are of secondary importance.
Efficiency in clinical studies has shown antagonists of H 2 receptors of histamine. Cisapride, which does not affect gastric secretion, but improves the barrier function of the lower esophageal sphincter, is as effective as histamine blockers. Optimal results were shown by the most powerful blockers of acid products - PPIs. They are superior to both cisapride and histamine H 2 receptor antagonists in symptom relief and in the treatment of esophagitis. Currently, this class of drugs is recommended for use as initial therapy for any form of gastroesophageal reflux disease, followed by the transfer of the patient to maintenance treatment with half the standard dose of the drug. As an illustration of the effectiveness of this approach in reflux disease of the esophagus, the results of some clinical studies of omeprazole and lansoprazole are presented in tables 2 and 3.
Proton pump inhibitors in accordance with the European guidelines for the diagnosis and treatment of H. pylori infection (Maastricht Consensus - 2, 2000) are mandatory components of first and second line therapy regimens(Table 4). For diseases associated with H. pylori, triple regimens based on a proton pump inhibitor are recommended as first-line therapy. Increasing and fixing the pH at > 5 is sufficient for the synergistic effect of these drugs and two antibiotics in killing H. pylori. The powerful antisecretory effect of these drugs is important for the elimination of a microorganism that occupies a very peculiar "ecological niche". A shift in pH to more neutral values under the influence of a proton pump inhibitor is an absolutely necessary condition for the anti-Helicobacter pylori effect of antibiotics. Benzimidazole derivatives affect the bioavailability of antibiotics, especially clarithromycin and tetracycline. The combination of a proton pump inhibitor and clarithromycin increases the half-life of both components, as well as the concentration of macrolide in the antrum mucosa and gastric mucus. It is not clear whether the concentration of a proton pump inhibitor in the gastroduodenal mucosa reaches a sufficient level for the drug to have a direct antimicrobial effect, but in studies in vitro antihelicobacter activity of benzimidazoles is confirmed.
(Table 4). In diseases associated with, it is recommended to use triple regimens based on a proton pump inhibitor as first-line therapy. Raising and fixing the pH at > 5 is sufficient for the synergistic effect of these drugs and the two antibiotics in killing. The powerful antisecretory effect of these drugs is important for the elimination of a microorganism that occupies a very peculiar "ecological niche". A shift in pH to more neutral values under the influence of a proton pump inhibitor is an absolutely necessary condition for the anti-Helicobacter pylori effect of antibiotics. Benzimidazole derivatives affect the bioavailability of antibiotics, especially clarithromycin and tetracycline. The combination of a proton pump inhibitor and clarithromycin increases the half-life of both components, as well as the concentration of macrolide in the antrum mucosa and gastric mucus. It is not clear whether the concentration of a proton pump inhibitor in the gastroduodenal mucosa reaches a sufficient level for the drug to have a direct antimicrobial effect, but studies have confirmed the anti-Helicobacter activity of benzimidazoles.As a mandatory component of H. pylori eradication therapy regimens, proton pump inhibitors are used to treat a variety of diseases and conditions (Table 1), and with peptic ulcer of the duodenum and stomach anti-helicobacter therapy pushed monotherapy with antisecretory drugs into the background.
Benzimidazole derivatives as monotherapy made it possible to achieve healing of gastric and duodenal ulcers when taking a standard dose once a day for 2-4 weeks. There are results of clinical studies on successful maintenance therapy with proton pump inhibitors (constant intake of 10-20 mg of omeprazole). However, only eradication therapy H. pylori allows you to change the nature of the course of peptic ulcer disease and prevent recurrence of the disease, and therefore triple therapy based on proton pump inhibitors is recognized as the therapy of choice for this disease.
Monotherapy with antisecretory drugs is advisable to use:
- in peptic ulcer disease within the limited time needed to establish the diagnosis and confirm the presence of infection H.pylor i, before starting a course of eradication therapy H. pylori(it should be remembered that all proton pump inhibitors interfere with the diagnosis of bacteria and lead to false-negative results in almost all methods of its detection);
- with exacerbation of gastric ulcer, as well as with severe exacerbation of duodenal ulcer occurring against the background of severe concomitant diseases, after a course of eradication therapy H. pylori within 2-5 weeks to achieve more effective healing of the ulcer; the applicability of an anti-helicobacter course (7 days) without subsequent monotherapy with an antisecretory drug has been proven with uncomplicated course of doudenal ulcer how to destroy H. pylori, and for scarring of the ulcerative defect and the elimination of pain and dyspeptic syndromes;
- in patients with peptic ulcer with proven intolerance to the components of schemes for eradication H. pylori(eg, known severe allergic reactions to amoxicillin and/or clarithromycin); “classic” antisecretory therapy, including proton pump inhibitors, should be used in the treatment of such patients.
With symptomatic ulcers, in the pathogenesis of which H. pylori does not play a decisive role, naturally, antisecretory drugs serve as the basis of treatment.
Proton pump inhibitors and Zollinger-Ellison syndrome Zollinger-Ellison syndrome is a manifestation of a gastrin-secreting neuroendocrine tumor (gastrinoma): overproduction of gastrin causes hypersecretion, resulting in ulceration of the gastroduodenal mucosa. Zollinger-Ellison syndrome is a rare disease: gastrinoma, as the cause of ulceration, is found in less than 1% of patients with gastric or duodenal ulcers of any origin.
Surgical treatment - removal of a localized tumor - is the most favorable method of treatment from a prognostic point of view, but this is not always possible, for example, the presence of multiple gastrinoma metastases in the liver excludes such tactics. Therefore, most patients with Zollinger-Ellison syndrome undergo symptomatic treatment, the purpose of which is to control hypersecretion, scarring of erosive and ulcerative defects and prevent their occurrence. Before the advent of active antisecretory drugs (histamine H 2 receptor blockers and proton pump inhibitors), the only way to suppress gastric secretion was to perform a total gastrectomy.
The goal of drug therapy is to reduce basal acid production to below 10 meq/h . Proton pump inhibitors, compared with histamine H 2 -receptor blockers, achieve this goal in almost all patients, in addition, over time, their daily dose does not need to be increased (the tolerance phenomenon is characteristic of histamine H 2 receptor antagonists, for benzimidazole derivatives due to a different mechanism action, this phenomenon is not typical), sometimes it can even be reduced.
The dose of a proton pump inhibitor is selected individually (“titrated”) to a level of fixation of basal acid production below 10 meq / h. The daily dose of omeprazole, which ensures compliance with this requirement in 90% of patients with Zollinger-Ellison syndrome, ranges from 20 mg to 120 mg. Omeprazole and lansoprazole have approximately the same efficacy. Clinical studies with 24-hour pH monitoring have shown that omeprazole (daily dose 20-160 mg) and lansoprazole (daily dose 30-165 mg) lead to similar pH profiles and an average pH value (1.8-6.4 and 2. 1-6.4, respectively).
Proton pump inhibitors and NSAID gastropathy The attractiveness of the use of proton pump inhibitors in NSAID gastropathy is due to their high efficiency, which is superior to that of histamine H 2 receptor antagonists. A number of clinical studies have been conducted with proton pump inhibitors, however, of particular interest for the problem under consideration are OMNIUM
(comparison of the effectiveness of omeprazole and misoprostol in the treatment of ulcers caused by NSAIDs; C.J. Hawkey et al., 1998) and ASTRONAUT
(comparison of the effectiveness of omeprazole and ranitidine in the treatment of ulcers caused by NSAIDs; N.D. Yeomans et al., 1998). These studies had a similar design and were conducted in two phases: 1) treatment phase - 4, 8 and 16 weeks and 2) secondary prevention phase - 6 months. The studies included patients who constantly take NSAIDs (mainly rheumatoid arthritis or osteoarthritis), with endoscopically confirmed presence of gastric ulcer, duodenal ulcer and/or erosions (at least 10 erosions of the gastroduodenal mucosa).
The results of the effectiveness of omeprazole in the healing of erosive and ulcerative lesions of the stomach and duodenum caused by NSAIDs, compared with misoprostol, are presented in table 5. Omeprazole (especially at a dose of 20 mg) Significantly more potent than misoprostol for scarring stomach ulcers (p=0.004). Omeprazole is especially superior to misoprostol in scarring of duodenal ulcers. (R<0,001). Интересно отметить, что заживление гастродуоденальных эрозий более активно происходит при применении синтетического аналога простагландина (р=0,01). Омепразол и в дозе 20 мг, и в дозе 40 мг оказался более эффективным по сравнению с ранитидином в заживлении язвы желудка, дуоденальной язвы или эрозий, вызванных НПВП (табл. 6).
The second phase of these studies investigated the potential of omeprazole in the secondary prevention of erosive and ulcerative lesions caused by NSAIDs. Patients who managed to heal erosions or ulcers as a result of the first phase were re-randomized and were selected into comparative groups, which were followed up for 6 months. In the OMNIUM trial, omeprazole 20 mg, misoprostol 400 mcg, or placebo were given maintenance therapy. The results presented in table 7 indicate the superiority of omeprazole as a drug for the secondary prevention of NSAID gastropathy. However, when only the occurrence of erosions is considered, misoprostol was more effective than either omeprazole or placebo. Omeprazole was more effective than ranitidine in preventing NSAID gastropathy in the ASTRONAUT study (Table 8).
In 2002, the results of another study were published that substantiate the widespread introduction into clinical practice of once daily proton pump inhibitors for the prevention of NSAID-associated gastroduodenal ulcers (D.Y. Graham et al.). 537 H. pylori-negative patients taking NSAIDs for a long time had a history of endoscopy-proven gastric ulcers. They were divided into three treatment groups: misoprostol (200 mcg 4 times a day), lansoprazole (15 mg or 30 mg per day) and placebo were prescribed for 12 weeks. As a result (per protocol), it was possible to maintain remission (no gastric ulcer) in 93% of patients taking misoprostol, in 80% and 82% taking different doses of lansoprazole. In the placebo group, only 51% of patients did not have NSAID-related gastric ulcers. When taking into account also the duodenal localization of the ulcer, 88% of patients receiving misoprostol, 83% and 79% of patients receiving 30 and 15 mg of lansoprazole, and only 47% of patients in the placebo group were in remission. 10% of patients treated with misoprostol were excluded from the study due to the development of side effects (usually diarrhea), patients who did not comply with the protocol were excluded from all groups. Therefore, in the final analysis (intention-to-treat analysis), successful prevention of ulcer formation during the 12-week course of treatment was achieved: in the placebo group - in 34% of cases, in the misoprostol group - in 67%, in the lanzporazole group - in 68% (30 mg of the drug) and 69% of cases (15 mg of the drug). Thus, lansoprazole was much more effective than placebo and as effective as misoprostol in preventing endoscopy-proven NSAID-associated ulcers.
The unique mechanism of action of proton pump inhibitors provides this class of drugs with a leading place in the treatment of acid-related diseases. Neither in terms of the breadth of indications, nor in terms of a stable level of effectiveness, they have no analogues in antisecretory therapy. Their widespread introduction into clinical practice has made it possible to radically improve the prognosis for many acid-dependent and H. pylori-associated diseases.
Diseases associated with disorders of the acidity of the gastrointestinal tract are observed on average in half of the adult population of the planet. This category of gastrointestinal pathologies includes a number of syndromes described in the International Classification of Diseases of the 10th revision. Particularly common:
- gastroesophageal reflux disease (GERD),
- peptic ulcers of the gastrointestinal tract,
- stomach dyspepsia.
Gastritis is observed in 80 percent of the population, gastric dyspepsia covers 30-35 percent. It is quite clear that with such disappointing statistics, the problem of curing gastrointestinal pathologies is especially topical.
Proton pump inhibitors inhibit the production of acid in the stomach
Pump is a technical term meaning one of the varieties of a pump. And it is a bit strange to see this name in the anatomy of the human body. However, the term proton pump, applied to hydrogen-potassium adenosine triphosphatase, is able to explain the function of this enzyme protein, which transports positive electrons through the intercellular septum.
A proton pump is also called a proton pump. This is a complex polypeptide chain, consisting of amino acid residues, and containing positive hydrogen and potassium ions in its structure. H+/K+-ATPase was isolated forty years ago as an enzymatic hydrolase protein, and at the same time it was called the proton pump. She takes part in the production of hydrochloric acid and, which converts vitamin B12 from a passive form to an active one.
Hydrogen-potassium adenosine triphosphatase is found in parental cells of the gastric mucosa. They also produce hydrochloric acid. It carries positively charged hydrogen protons (H+) from the cytoplasm of the parental (parietal) cell to the stomach cavity through the superior intercellular septum. In this case, the potassium ion (K+) moves into the cell. Simultaneously, chloride anions (CL-) are transported to the region.
H+ protons are released as a result of the decomposition of carbonic acid (H2CO3) by the action of the enzyme carbonic anhydrase. The remaining cations (HCO3-) are transferred into the blood instead of chlorine cations, which, having moved to the stomach, and combined with hydrogen there, form hydrochloric acid molecules. Thus, hydrochloric acid is released into the lumen of the stomach with the participation of H+/K+-ATPase in the form of H+ and Clv€’ ions, and K+ ions move back through the membrane.
What are proton pump inhibitors and what are they for?
Omez: capsules
Inhibition means restraint. In this case, the inhibition of the synthesis of HCl. The task of proton pump inhibitors is to suppress the production of hydrochloric acid in the stomach, which is achieved by blocking the transport of potassium and hydrogen ions from the cell. Inhibition proved to be effective in the treatment of acid-dependent diseases of the gastrointestinal tract, such as
- dyspepsia of the esophagus,
- stomach ulcer,
- duodenal ulcer,
- duodenitis.
Proton pump inhibitors block the production of hydrochloric acid to varying degrees. These drugs do not develop addiction, there are no side effects. Therefore, this category of drugs was adopted by the World Congress in 1988 in Rome, as the main group of acid-regulating drugs.
Each subsequent development of PPI differs from its previous one in higher activity and duration of action. But the actual effectiveness is influenced by certain factors, the first place of which is occupied by the individual susceptibility of the organism.
PPI mechanism of action
Proton pump drugs are taken by mouth as tablets or capsules. From the stomach, the drug enters the small intestine, where it dissolves and is absorbed into the blood, which first transfers the inhibitor molecules to the liver, and only then they enter the parietal cells of the gastric mucosa, where they accumulate in the secretory tubules.
PPIs are converted to tetracyclic sulfenamide, which does not leave the secretory tubules, binds to the ionic residues of the pump and blocks it. Thus, H+/K+-ATPase is excluded from the formation of hydrochloric acid. In order for this process to resume, the production of a new H + / K + -ATPase enzyme is needed, which occurs after 1.5-2 days. This time determines the duration of the therapeutic effect of proton pump inhibitors.
At the first or one-time use of the drug, its effectiveness is not so significant, since not all proton pumps are currently embedded in the secretory membrane, some of them are inside the cell. These microparticles, together with newly synthesized hydrogen-potassium adenosine triphosphatases, appear on the membrane, they interact with subsequent doses of the drug, and its antisecretory effect is fully performed.
Antisecretory therapy allows you to stop diseases that are dependent on the concentration of hydrochloric acid. Thus, a duodenal ulcer heals at a maintained pH above 3 for 18–20 hours a day; for the treatment of GERD, a pH of more than 4 is required, the bacterium is destroyed in a slightly acidic environment at a pH of more than 5.
What is pH?
Here, let me make a small digression, in which you will find an explanation of the pH value (pe-ash). It is needed to further explain the acidic state of the gastrointestinal tract and how PPI drugs work.
The pH scale, which determines the acid-base nature of liquid substances and solutions, can be compared with a mathematical straight line on which positive and negative numbers are located.
The pH value is 14 units. The chemically neutral substance water (comparable to zero on a mathematical scale) is pH7. Substances with a pH less than 7 are acidic. Those above the number 7 are alkaline. Accordingly, the lower the pH number, the higher the acidity of the substance or solution, and vice versa, the higher the pH, the lower, but the level of the alkaline medium increases.
Characterization of proton pump inhibitors
PPIs are recognized as particularly effective drugs in the treatment of peptic ulcers associated with high acidity, and occupy a leading position among antiulcer medications. The antisecretory result in this case is achieved by directly influencing the formation of hydrochloric acid.
This category of drugs surpasses all other antisecretory drugs in terms of effectiveness and harmlessness of exposure. The PPI includes 5 generations of drugs, the first of which, omeprazole, was developed in 1989.
Omeprazole
Today it is one of the most widely used and widely used drugs. Its effectiveness is confirmed by the results of studies in which more than 50,000 patients with various pathologies of the gastrointestinal tract participated. In comparison of omeprazole with H2-blockers, there is an advantage of the proton pump inhibitor in the effectiveness of the relief of inflammatory processes, and at the same time, the ulcerative mucosal abscess was clearly delayed.
Even in patients with gastrinoma (which produces the hormone gastrin, which stimulates the production of HCl), a positive trend was observed. In addition, omeprazole increased the anti-helicobacter effect of the antibiotics taken. Bioavailability, that is, the amount of the drug reaching the area of its effect in the body, ranges from 50%, 95 percent of which binds to plasma proteins.
The highest content of this medication in the blood is concentrated one hour after ingestion and lasts up to 3 hours. The standard therapeutic regimen involves taking the drug 2 times a day, 20 mg per dose. Within a month, ulcerative wounds of the duodenum are healed by 97%, and stomach ulcers by 80%.
Lansoprazole
This drug has the highest bioavailability of 80-90% in the group of drugs that inhibit the production of hydrochloric acid. Lansoprazole differs from its predecessor in the design of radicals that provide an antisecretory effect.
Studies have shown that on the 5th day of use, Lansoprazole provides a pH in the stomach above 4, for 11.5 hours (for comparison, pantoprazole maintained the same acidity for 10 hours). Lansoprazole is recommended to take 15, 30 and 60 mg per day (depending on the severity of the pathology). In 95% of cases, the ulcer heals within 4 weeks.
Pantoprazole
Pantoprazole is attractive in that it allows long-term use in order to consolidate the therapeutic effect. Despite the variability of the result (acid-base level ranged from 2.3 to 4.3), the methods of administration of the drug do not have a significant effect on its pharmacokinetics.
In other words, Pantoprazole is used both intravenously and orally. A ten-year observation of patients treated with pantoprazole showed that there were no relapses after the use of this drug.
Rabeprazole
On the pyridine and imidazole rings, rabeprazole also has distinctive features from omeprazole, which provide more efficient binding of potassium and hydrogen protons of adenosine triphosphate MЃza. Rabeprazole is absorbed by the body and the therapeutic effect is achieved by 51.8%, it binds to blood proteins by 96.3%. With daily use of this drug at 40 mg per day for a month, the ulcer heals by 91%.
Esomeprazole
In the structural formula of Esomeprazole, there is only one S-isomer, and therefore the drug is not as susceptible to hydroxylation by the liver as its predecessors, which have R-isomers, and are not so quickly excreted from the body. These factors increase the amount of inhibitors reaching the proton pumps in the parietal cells. Esomeprazole, taken at 40 mg per day, keeps a pH greater than 4 for 14 hours. This is the highest therapeutic effect that has been achieved to date.
Helicobacter pylori and PPIs
There are 5 generations of proton pump inhibitors in total.
Speaking about acid-dependent diseases and the causes that give rise to them, one cannot help but recall the gram-negative spiral-like bacterium, since scientists have come to the conclusion that this bacterium is a kind of catalyst, a trigger for the occurrence of these diseases.
And it is this bacterium that settles in the stomach that provokes inflammatory relapses of the gastrointestinal tract. Therefore, the therapy of acid-dependent pathologies is carried out in combination with antibiotics of the tetracycline group, and in particular, with Metronidazole.
Conclusion. Work on the API continues
Five generations of proton pump inhibitors are universally approved and successfully used. Six years ago, a new drug, Dexlansoprazole, was launched on the market and approved for use in the treatment of GERD.
A new IPN is currently being developed and tested in Japan. This is tenatoprazole. It is a derivative of imidazopyridine. True, some experts believe that this drug generally repeats previous generations.
A little earlier, Ilaprazole was developed in Korea, which is 2-3 times more effective than Omeprazole. But in the USA, EU countries and Russia there is no permission for its use. Now Japan is trying to promote this drug to the Western market.
About the safety of proton pump inhibitors - in a video lecture:
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-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 prescribe it less often, since new generation drugs differ for the better in both effectiveness and 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. Analogues - "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.
Catad_tema Clinical pharmacology - articles
Proton pump inhibitors: a few questions on theory and practice
T.L. Lapin
Clinic of propaedeutics of internal diseases, gastroenterology and hepatology. V.Kh. Vasilenko MMA them. THEM. Sechenov, Moscow
Based on data from evidence-based gastroenterology and his own experience, the author formulates answers to the most pressing questions regarding the practical use of proton pump inhibitors (PPIs). In particular, we are talking about the risk of a “withdrawal syndrome” after stopping the course of PPIs, the ratio of the value of PPIs and anti-Helicobacter therapy, the possibility of using PPIs in atrophic gastritis, etc.
The indications for prescribing proton pump inhibitors (PPIs) are very wide, and today it is hardly possible to meet a doctor who does not have his own experience with various representatives of this class of drugs. The diverse clinical situations that arise in the management of patients with acid-dependent and Helicobacter pylori-associated diseases often force the doctor to mobilize both his experience and theoretical knowledge. The literature on IPP includes numerous monographs, whole chapters of solid manuals, and thousands of articles of various kinds. On the one hand, such a rich information base should fully satisfy the interest in IPPs and various aspects of their application, on the other hand, it is often difficult to find an answer to a specific question in the ocean of various information. The form of this article is dictated by the desire of the author to give as short and well-reasoned answers as possible to questions that doctors often have regarding both theoretical and practical aspects of the use of PPIs.
Should we expect a “withdrawal syndrome” after stopping a course of PPIs?
“Withdrawal syndrome”, or “acid rebound” (which may manifest itself, for example, as an early exacerbation of peptic ulcer after stopping a course of antisecretory drug use), is characteristic of H2 receptor blockers. After the withdrawal of histamine receptor antagonists, the occurrence of this syndrome is partly explained by the phenomenon of hypersensitivity of H2 receptors. The parietal cell with “excited” H2 receptors becomes more sensitive even to normal levels of histamine released from enterochromaffin-like cells. It is also assumed that against the background of the use of H2 receptor blockers, the lifetime of proton pumps is extended, and as a result, there are more of them per parietal cell. Both causes lead to the fact that when the course of treatment with H2 receptor blockers is stopped, acid hyperproduction occurs.
PPIs have a fundamentally different mechanism of action and have a different effect on the parietal cell. PPIs do not affect either H2 receptors or other structures located on the basolateral membrane of the parietal cell and involved in the regulation of acid secretion. The target of PPIs is directly the proton pump, the enzyme H + / K + -ATPase, with which these drugs form a strong covalent bond. Thus, the operation of the acid pump is blocked. It is believed that the “withdrawal syndrome” is not typical for PPIs. This is due to the mechanism of action of this class of drugs. In addition, the duration of PPI prescribing in different clinical settings is highly detailed and helps to reduce the risk of acid rebound.
Conclusion. For PPIs, unlike H2-receptor blockers, “withdrawal syndrome” is not typical. Compliance with the duration of PPI treatment for various indications for their appointment helps to reduce the risk of “acid rebound”.
Will the healing of a peptic ulcer be achieved during an exacerbation of a peptic ulcer when only a course of eradication therapy against H. pylori is carried out? Is it necessary to prescribe antisecretory therapy at the end of the H. pylori eradication course?
In order to exhaustively answer these questions, it is necessary to consider: 1) the timing and results of the use of PPI as monotherapy in exacerbation of peptic ulcer and 2) the timing and results of PPI treatment in the eradication therapy of H. pylori infection in exacerbation of peptic ulcer.
The generally accepted average duration of treatment with an antisecretory drug for exacerbation of duodenal ulcer is 4 weeks, gastric ulcer - 8 weeks. Ideas about the need for just such a duration of treatment have developed with the introduction of H2-blockers into clinical practice. PPIs significantly faster promote ulcer healing. So, when analyzing the results of several controlled studies, it turned out that when taking omeprazole 20 mg / day, the healing of duodenal ulcer after 2 weeks of treatment occurred in 57-80% of patients against 28-52% when using ranitidine 300 mg / day. Thus, in the first two weeks of treatment, the difference in the rate of ulcer scarring against the background of the use of PPIs and H2-blockers is especially large. After 4 weeks of treatment, the difference is smaller, although it still persists: on the background of PPIs, ulcers healed in 93-95% of patients, and on the background of H2-blockers - in 80-85%. Let me remind you that the duration of the standard course of H. pylori eradication therapy is at least 7 days, and in recent years there has been a tendency to increase it to 10 or 14 days. The basic drug of antihelicobather therapy - PPI - will ensure rapid healing of the ulcer during eradication.
However, ulcer healing should be considered from different angles, since not only the antisecretory effect of PPI is important in this process. The destruction of H. pylori itself and the resulting regression of inflammatory changes in the gastric mucosa probably have a positive effect on ulcer scarring. It has been proven that in case of uncomplicated duodenal ulcer, treatment can be limited only to a course of eradication therapy, without continuing to take antisecretory or other agents after it, which will be enough to repair the mucosal defect. To prove the correctness of this provision, I will cite a domestic study as an example.
Patients with exacerbation of duodenal ulcer (92 people) received standard triple therapy with Omez (omeprazole, Dr. Reddy's Laboratories Ltd.) at a dose of 40 mg / day in combination with amoxicillin (2000 mg / day) and clarithromycin (1000 mg / day) for 7 days.Then randomization was carried out: one group of patients continued therapy with omeprazole 40 mg / day for another 2 weeks, the other group of patients did not receive any more treatment. Eradication of H. pylori was achieved in 82.6% Of fundamental importance is the fact that ulcer healing occurred in 91.5% of patients who received Omez monotherapy after an anti-Helicobacter pylori course, and in 93.3% of patients who received only a weekly course of H. pylori eradication and no further treatment.
Conclusion. Standard eradication therapy for H. pylori infection certainly promotes ulcer healing during exacerbation of peptic ulcer disease. With an uncomplicated duodenal ulcer, it is permissible to conduct only an anti-Helicobacter pylori course for 7-14 days - this will ensure scarring of the ulcer in most patients. In exacerbation of gastric ulcer, as well as in severe exacerbation of duodenal ulcer, with its complicated course, in the presence of concomitant diseases after a course of H. pylori eradication therapy, PPIs are used for another 2–5 weeks to achieve more effective healing of the ulcer.
Can standard H. pylori eradication therapy be started if the patient is already taking a PPI?
There are a few works that demonstrate a positive or, on the contrary, a negative effect of a PPI course immediately preceding H. pylori eradication therapy (PPI-based regimens). According to some authors, such “pretreatment” with PPI reduces, according to others, it increases the percentage of successful eradication of H. pylori. It should be noted that the main international recommendations and publications on evidence-based gastroenterology did not include requirements not to prescribe eradication therapy while taking PPIs or, conversely, to increase the percentage of successful eradication of the microorganism, necessarily preceding it with PPIs.
Let's turn to the Russian study. Standard triple therapy with amoxicillin and clarithromycin based on Omez was received by 80 patients with duodenal ulcer. Patients were randomized into 2 groups: group 1 received omeprazole for 3 days prior to eradication therapy, group 2 received no prior therapy. In the 1st group, it was possible to destroy H. pylori in 88.6% of cases, in the 2nd - in 82.2%.
Conclusion. At present, there is not enough evidence to suggest that taking a PPI prior to standard eradication therapy will have any effect on the success of anti-Helicobacter pylori treatment.
How can PPIs be used in prophylactic (anti-relapse) courses of treatment for patients with peptic ulcer who are under dispensary observation?
Ideas about the need for seasonal treatment of peptic ulcer with various classes of drugs in order to prevent relapse should be considered outdated. Consider the prevention of recurrence of peptic ulcer from the perspective of evidence-based gastroenterology.
The anti-relapse treatment of peptic ulcer is considered to be eradication of H. pylori infection. The main result of successful sanitation of the gastroduodenal mucosa from H. pylori is the cessation of peptic ulcer recurrence in most patients. Let's turn to a systematic review of experts at the Cochrane Library. Fifty-three clinical studies were analyzed on the given topic. There was no statistical difference in the effectiveness of H. pylori eradication therapy and continuous maintenance antisecretory drugs in terms of preventing duodenal ulcer recurrence (4 studies, 319 patients; relative risk of recurrence = 0.73 (95% CI 0.42–1.25). H. pylori eradication was more effective than placebo in preventing a relapse of the disease (27 studies, 2509 patients; relative risk of recurrence = 0.20 (95% CI 0.15–0.26). In terms of preventing recurrence of gastric ulcer, eradication therapy of infection H. pylori was more effective than placebo (10 studies, 1029 patients; relative risk of recurrence = 0.28 (95% CI 0.18-0.43). So, according to the conclusion of one of the most authoritative sources of evidence-based medicine, anti-Helicobacter pylori treatment does prevent relapses duodenal ulcer and gastric ulcer.
Prior to the widespread introduction into clinical practice of eradication therapy for H. pylori infection, a maintenance course of treatment with a constant (daily) intake of an antisecretory agent was used as an anti-relapse treatment for peptic ulcer. Thus, in a multicenter study by H. Festen, 928 patients with remission of peptic ulcer (after exacerbation treatment with a 2–8-week course of omeprazole 20–40 mg/day) received maintenance therapy for a year. It turned out that in terms of ensuring remission, omeprazole 20 mg/day is more effective than ranitidine 150 mg/day: against the background of omeprazole, it was possible to prevent ulcer recurrence in 87% of cases, against the background of ranitidine - in 63% (p = 0.0001). The use of omeprazole at a dose of 10 mg/day was also quite effective - 71% of patients remained in remission.
Conclusion. For the prevention of recurrence of gastric and duodenal ulcers, PPIs are used primarily as the basis of standard therapy for the eradication of H. pylori. The proven destruction of this microorganism reduces the risk of a new exacerbation of the disease. If adequate anti-Helicobacter treatment is not possible, then it is advisable to prescribe long-term maintenance PPI therapy to prevent ulcer recurrence.
Can PPIs be used for atrophic gastritis?
Atrophy is the loss of the glands of the stomach with their replacement with fibrous tissue or metaplastic epithelium. Due to the loss of glands, atrophic gastritis is characterized by a decrease (to some extent) in the acid-forming function of the stomach. A logical question arises: does it make sense to use the most active antisecretory drugs - PPIs - for gastritis with “affected” acid products?
Atrophic gastritis is an indication for H. pylori eradication therapy. This indication was introduced in connection with the formation of an active tactic for the prevention of gastric cancer. Atrophic gastritis with intestinal metaplasia is a precancerous disease. By acting on the etiological factor of gastritis, it is possible to stop the cascade of pathological changes in the gastric mucosa, which can lead to the development of adenocarcinoma. As basic preparations for anti-Helicobacter pylori therapy, PPIs are not only possible, but also advisable to use in atrophic gastritis as part of standard regimens. Successful eradication of H. pylori certainly cures gastritis. Can this measure reduce the risk of atrophy and intestinal metaplasia and reverse the development of precancerous changes in the gastric mucosa? An analysis of the literature allows us to state that after the destruction of the H. pylori infection, atrophic changes and intestinal metaplasia do not worsen. Despite significant limitations in conducting a number of studies, it can still be concluded that in some patients a regression of atrophy and intestinal metaplasia can be observed. There is strong evidence to suggest that early eradication of H. pylori before atrophic changes appear reduces the risk of gastric cancer.
The second side of the problem raised is also extremely interesting and is sometimes reflected in the form of a question: do PPIs provoke cancer? About 10 years ago, data were published on the accelerated development of atrophy (especially in the body of the stomach) with maintenance therapy with histamine H2 receptor blockers and PPIs. Atrophic gastritis is a precancerous disease, which calls into question the safety of PPI use. A more detailed study of the relationship between atrophic gastritis and PPIs showed that PPIs do not have any effect on the morphology of the gastric mucosa. The cause of chronic gastritis is H. pylori infection, and PPIs, having a significant effect on the pH of the stomach, alkalize the microenvironment of the bacteria, making their viability almost impossible. With PPI monotherapy, H. pylori is redistributed throughout the gastric mucosa - from the antrum they pass into the body of the stomach with lower pH values, and inflammation is activated there. Schenk B.E. et al. examined the characteristics of gastritis in gastroesophageal reflux disease during 12 months of treatment with omeprazole 40 mg in three groups:
- H. pylori-positive patients underwent eradication therapy;
- H. pylori-positive patients received placebo instead of eradication therapy;
- initially H. pylori-negative patients.
While maintaining H. pylori, the activity of inflammation increased in the body of the stomach and decreased in the antrum; with successful eradication of H. pylori, inflammation activity decreased both in the body of the stomach and in the antrum; in patients without H. pylori infection, no histological changes were detected. Thus, there is no connection between the progression of atrophic gastritis and the intake of omeprazole. The progression of atrophic gastritis occurs only against the background of H. pylori infection.
Conclusion. The use of PPIs as part of the eradication therapy of H. pylori in atrophic gastritis is considered as an event aimed at reducing the risk of exacerbation of precancerous changes in the mucous membrane. The presence of atrophic gastritis is not a contraindication to the use of PPIs if there are grounds for such an appointment.
Which group of drugs has more severe side effects: H2 blockers or PPIs?
The pharmacological characteristics and features of the short-term and long-term use of PPIs and H2 receptor blockers have been well studied. For various antisecretory agents, there are isolated reports of serious side effects and intolerance. Both classes of drugs rarely cause side effects (from H2-blockers we are talking about ranitidine and famotidine), rather information is recorded on adverse events. How these adverse events are directly related to the intake of antisecretory drugs can not always be judged, especially since often their number does not differ from that in the placebo group. The side effects described are usually mild and reversible. On the part of the gastrointestinal tract, diarrhea, constipation, abdominal pain, nausea, a transient increase in aminotransferases were observed; from the side of the central and peripheral nervous system - headache, dizziness, drowsiness. There are skin reactions in the form of a rash and / or itching.
It is currently believed that the frequency of side effects of PPIs is equal to their frequency in the placebo group and does not exceed 5%. If we turn to Russian clinical practice, then PPIs have been widely studied from the point of view of their safety. So, in the work of O.N. Minushkina et al. when using a standard dose of omeprazole (Omez) in 40 patients with gastroesophageal reflux disease, a side effect (headache) was registered in only one patient.
Conclusion. The frequency of side effects in the use of PPIs and H2 blockers is the same and does not exceed that in the placebo group.
How long can PPI treatment be continued?
For a number of indications, the PPI course can be very long (months and years): this is supportive therapy for peptic ulcer and gastroesophageal reflux disease, and the treatment of Zollinger-Ellison syndrome, and the treatment of NSAID-gastropathy. As a rule, doctors and patients are concerned about the safety of long-term use of PPIs.
From the studies devoted to the analysis of the safety of long-term use of PPIs, let us turn to the results of Klikenberg-Knol E.C. et al. : Omeprazole 20–40 mg/day has been used as maintenance treatment for severe gastroesophageal reflux disease. The average follow-up period was 6.5 years, the maximum - 11.2 years. The average frequency of adverse events per year of treatment was 0.52%, which allowed the authors to conclude that long-term maintenance therapy for reflux esophagitis is safe with a high efficiency of maintaining remission (on average, 1 exacerbation episode per 9.4 years of follow-up). In this study, special attention was paid to the control of gastrin levels. It is known that, due to the pronounced antisecretory effect of PPIs, their administration is accompanied by reversible hypergastrinemia (the reaction of cells regulating gastric acid production to a decrease in acid production). It turned out that while taking PPIs in the group of patients infected with H. pylori, the average value of gastrin compared with the baseline was 200%, in the group of patients without H. pylori infection - only 161%. Separately, we considered 2 cases of high hypergastrinemia (an increase from the initial elevated values of 430 and 173% to 6320 and 9650%, respectively), which was observed in senile people with severe atrophy in the body of the stomach, and both patients were H. pylori-positive. Hypergastrinemia had no negative clinical or morphological significance.
Conclusion. For certain indications, PPIs can be prescribed for a long time. Long-term use of PPIs is not associated with an increased risk of side effects.
LITERATURE
1. Alekseenko S.A. Does prior treatment with proton pump inhibitors affect the eradication of Helicobacter pylori? // Clinical perspectives of gastroenterology, hepatology. 2005. No. 2. S. 37–39.
2. Minushkin O.N., Maslovsky L.V., Shuleshova A.G. Evaluation of the efficacy and safety of omez monotherapy at a dose of 20 mg twice a day in the treatment of gastroesophageal reflux disease. // Clinical perspectives of gastroenterology, hepatology. 2003. No. 2. S. 11–14.
3. Pasechnikov V.D., Minushkin O.N., Alekseenko S.A. et al. Is Helicobacter pylori eradication sufficient to heal duodenal ulcers? // Clinical perspectives of gastroenterology, hepatology. 2004. No. 5. S. 27–31.
4. Festen HPM. Prevention of duodenal ulcer relapse by ling-term treatment with omeprazole. Scand J Gastroenterol 1994;49(suppl. 201):39–41.
5. Ford A, Delaney B, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori positive patients (Cochrane Review). From The Cochrane Library. Chichester, UK: John Wiley & Sons, Ltd 2005, Issue 1.
6. Klikenberg-Knol EC, Nelis F, Dent J, et al. Long-term omeprazole treatment in resistant gastroes-ophageal reflux disease: efficacy, safety and influence on gastric mucosa. Gastroenterology 2000;118:661–69.
7. Kuipers EJ, Lundell L, Klikenberg-Knol EC, et al. Atrophic gastritis and Helicobacter pylori infection in patients with reflux oesophagitis treated with omeprazole or fundoplication. N Engl J Med 1996;334:1018–213.
8. Lambert R, Creutzfeldt W, Struber HG, et al. Long-term omeprazole therapy in peptic ulcer disease: gastrin, endocrine cell growth, and gastritis. Gastroenterology 1993;104:1356–70.
9. Malfertheiner P, Sipponen P, Naumann M, et al. Helicobacter pylori eradication has the potential to prevent gastric cancer: a state-of-the-art critique. Am J Gastroenterol 2005;100:2100–15.
10. Modlin IM, Sachs G. Acid diseases related. biology and treatment. Schnetztor-Verlag Gmbh Konstanz 1998, p. 121–42.
11. Schenk B, Kuipers E, Nelis GF, et al. Effect of Helicobacter pylori eradication in chronic gastritis during omeprazole therapy. Gut 2000; 46:615–21.
12. Vanderhoff BT, Tahboub RM. Proton Pump Inhibitors: An Update. Am Fam Physician 2002;66: 273–80.
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Today, about 21 million people in the United States take prescription drugs for heartburn, pain, and stomach discomfort.
We are talking about drugs from the group of proton pump inhibitors (PPIs) and H2-histamine blockers.
But what do you have to pay for taking these highly effective drugs?
A recent study found that proton pump inhibitors are associated with an increased risk of myocardial infarction. And this is not all that patients taking PPIs may encounter.PPIs include esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Pariet), omeprazole (Omez), and others.
Many drugs in this group are available without a doctor's prescription. They block the so-called proton pump in the cells of the gastric mucosa, thereby reducing the production of hydrochloric acid. Excess hydrochloric acid is the main cause of heartburn and stomach discomfort. PPIs are used in the complex treatment of stomach ulcers, gastritis and to prevent damage to the esophagus in acid reflux.
Due to the emergence of new data on the safety of PPIs and H2-histamine blockers, the medical publication WebMD decided to ask two well-known American experts what they think about these drugs.
What exactly did the researchers find?
The authors of the latest study analyzed the medical records of almost 3 million patients, many of whom were taking proton pump inhibitors and H2-histamine blockers. None of the patients had coronary heart disease.H2-histamine blockers include the somewhat outdated drug cimetidine (Tagamet), as well as the more modern famotidine (Quamatel), ranitidine (Zantac), and nizatidine (Axid).
H2-histamine blockers, or H2-histamine receptor blockers, are classified as antisecretory drugs that reduce the production of hydrochloric acid. Unlike PPIs, these drugs block the H2-histamine receptors of the parietal cells of the stomach. They are used for chronic gastritis, peptic ulcer, Barrett's esophagus and other acid-dependent diseases.
The analysis showed that those patients who take PPIs have an increased risk of myocardial infarction. This does not apply to H2-histamine blockers. However, the design of this work does not allow to prove a causal relationship between PPI use and heart attack.
Scientists are at a loss to answer what could be the reason for such a connection, although previous studies have shown that proton pump inhibitors can damage the endothelium of blood vessels. This may explain why PPI use is associated with an increased risk of myocardial infarction.
“Based on the results of this study, we can say that with regular use of proton pump inhibitors, the risk of myocardial infarction increases by an average of 16%. On the one hand, this is a big number. But if you take into account how many heart attacks do occur, then it turns out that taking PPIs leads to 1 additional heart attack per 4,000 people taking these drugs. When you consider the huge benefits of these drugs, it's not so clear, - says Dr. Brian Lacy (Brian Lacy).
Dr. Lacey is the head of the department of gastroenterology and hepatology at the Dartmouth-Hitchcock Medical Center (Lebanon, New Hampshire, USA). He was not directly involved in the latest study.
Does the risk of heart attack depend on the duration of PPI use?
“Based on the results of this study, we cannot answer this question. We do not know if this risk depends on the duration of proton pump inhibitor use, dose, or other factors. Further work is needed for this,” says Dr Lacey.If PPIs do damage the vascular endothelium over time, as scientists have previously argued, then it can be assumed that the risk of heart attack will increase with prolonged use of these drugs.
Can I take PPIs for a long time?
FDA experts say that proton pump inhibitors, prescribed by a doctor, are usually taken for six months. Without prescription, these drugs are allowed to be used no more than 14 days in a row and no more than 3 times a year. But American doctors say they sometimes take much longer.According to Dr. Lacey, there is no set maximum duration of treatment for prescription PPIs - it is determined by the doctor depending on the situation. Some patients take them for years. But he stipulates that the lower the dose and the shorter the duration of treatment, the better.
“It is true that I have patients who have been taking proton pump inhibitors day after day for more than 10 years and they have no significant side effects,” Lacey said.
Why are proton pump inhibitors dangerous?
In 2012, the FDA warned that prescription PPIs can significantly lower blood magnesium levels, leading to muscle spasms and irregular heartbeats. The same year, the agency stated that PPIs increase the risk of Clostridium difficile infection with severe diarrhea.“We know that PPI use is associated with an increased risk of bone fractures and intestinal infections. Patients are afraid to take these drugs for many reasons, but I think they are generally safe,” says Dr. Paul Buckley III, Chief Surgeon at the Heartburn and Acid Reflux Center at Baylor Scott & White Healthcare (Round Rock, Texas, USA).
What should I look for if I am already taking proton pump inhibitors?
According to Dr. Lacey, your doctor should ideally ask about unusual events at every visit.“It’s hard to say what you need to pay attention to in the first place. One side effect, severe diarrhea, may indicate a Clostridium difficile infection, so you should definitely consult a doctor in this case. Some people who have just started taking PPIs (the first three weeks) may develop watery stools. If it does not go away after 5-7 days, you should contact your doctor. Sometimes switching to another drug helps,” Lacey says.
How to change lifestyle during treatment with proton pump inhibitors?
Dr. Lacey believes that lifestyle changes in this case are really necessary:1. The most important thing is to follow the diet recommended by your doctor.
2. Do not eat at night and reduce the fat content in dinner. Do not eat fried and fast food.
3. Try to normalize body weight: your BMI should be no higher than 27-30.
“I tell my patients that they should eat no later than 4 hours before going to bed. This gives them time to digest properly. Fast food "on the go" can disrupt digestion and trigger heartburn. You should also avoid certain foods that cause heartburn (wine, tomatoes, mint),” adds Dr. Buckley.