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Seminar "NON-STEROID ANTI-INFLAMMATORY GASTROPATHY, ETIOLOGY, PATHOGENESIS, CLASSIFICATION, CLINIC, DIAGNOSIS AND TREATMENT."

Conducts: Republican Medical University

The date of the: from 06/01/2015 to 06/01/2016

TERMINOLOGY AND NOMENCLATURE.

TERMINOLOGY. The term non-steroidal anti-inflammatory gastropathy (NSAID-gastropathy, NSAID-gastropath) was proposed in 1986 by S. H. Roth, which usually refers to erosive and ulcerative lesions of the gastroduodenal zone associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs). According to ICD-10, the diagnosis should be formulated as follows, for example, “NSAID gastropathy: gastric ulcer complicated by bleeding” or other erosive and ulcerative lesions of the gastroduodenal zone (Y 45.8, K 25, K 92).

Definition. NSAID-induced gastropathy is a collective concept that includes ulcers and erosions of the mucous membrane of the gastroduodenal zone and a special form of gastritis - “chemical”, in accordance with the Sydney classification, associated with the use of non-steroidal anti-inflammatory drugs and having a characteristic clinical and endoscopic picture, manifested by damage to the mucous membrane stomach and/or duodenum with the development of erosions, ulcers and life-threatening complications (bleeding, perforation). It has been established that about half of life-threatening gastrointestinal bleeding is caused by taking NSAIDs.

CLASSIFICATION OF NSAID-INDUCED GASTROPATHIES

There is no single generally accepted classification of NSAID-induced gastropathy. Taking NSAIDs affects all parts of the gastrointestinal tract, causing a wide range of disorders. The most well-known pathology associated with NSAID use is NSAID-induced gastropathy. This term describes damage to the mucous membrane of the upper gastrointestinal tract detected during endoscopic examination with the formation of erosions and ulcers of the stomach and/or duodenum, and the development of life-threatening complications for the patient - gastrointestinal bleeding, perforation of ulcers, obstruction of the gastrointestinal tract.

The most well-known classification of erosive and ulcerative changes that occur in patients taking NSAIDs is the Lanza classification (1993), based on the scoring of pathology detected during endoscopic examination - from single hemorrhages to complicated ulcers, and allowing the unification of esogastroduodenoscopy (EGD) data. .

Endoscopic classification according to the Lanza scale for assessing damage to the mucous membrane of the stomach and duodenum

Depending on the characteristics of the lesion and clinical symptoms, the following are also distinguished:

• NSAID-induced dyspepsia
• NSAID-induced esophagitis
• NSAID-induced esophageal ulcer
• NSAID-induced gastropathy
• NSAIDs – induced erosive gastropathy
• NSAID-induced gastric ulcer
• NSAID-induced duodenal ulcer

EPIDEMIOLOGY AND ETIOLOGY OF NSAIDS – GASTROPATHY

The epidemiology and etiology of NSAID-induced gastropathy is closely related to the discovery and frequency of use of NSAIDs. After salicylic acid was isolated from willow bark in 1829, its use began in the treatment of various diseases manifested by pain or inflammation. In 1860, the German chemist A. Kolbe first developed a method for the synthesis of salicylic acid, but it did not find application in medicine due to the presence of pronounced undesirable properties. Acetylsalicylic acid was discovered in 1893 by Felix Hoffman and patented by Bayer in 1899 under the brand name “aspirin.”

Acetylsalicylic acid is the first synthetic medicinal substance, which is still one of the most popular drugs in the world. Along with the beginning of clinical studies of the effectiveness of acetylsalicylic acid, the first mentions of its adverse effects on the digestive organs appeared. Douthwait A., Lintoff J. in 1938 first presented in the Lancet an endoscopic picture of “aspirin” erosions of the gastric mucosa. These data led to the emergence of the concept of NSAID-induced pathology of the gastroduodenal zone, and in the 70-80s of the last century, extensive study of NSAID gastropathy began.

Nonsteroidal anti-inflammatory drugs are the most commonly used drugs in medical practice. Around 30 million people worldwide take these drugs every day. The annual consumption of drugs containing acetylsalicylic acid by the world's population exceeds 40 billion tablets. About 500 million prescriptions for NSAIDs are written per year, and the number of self-administration of NSAIDs is 7 times higher.

Such popularity of NSAIDs and their widespread use in all areas of medicine is due to their combination of unique properties: analgesic, anti-inflammatory, antipyretic and antiplatelet. They are used to treat diseases and pathological conditions associated with the presence of fever, inflammation, acute and chronic pain syndrome in neurology, dentistry, gynecology, migraine, myalgia, neuralgia, headache, toothache, pain during premenstrual syndrome, etc. .d. NSAIDs are most often used in the treatment of diseases of the musculoskeletal system - rheumatoid arthritis, ankylosing spondylitis, osteoarthritis. In rheumatology, NSAIDs are used for a long time and in high doses. According to the American Association of Rheumatology, with regular use of these drugs, the incidence of damage to the upper gastrointestinal tract - erosive and ulcerative lesions, perforation, bleeding - can reach 40%.

According to statistical data, with long-term use of NSAIDs, gastro- and duodenopathy occur in 70% of patients, erosions and ulcers of the gastric mucosa - in 10-30%. A study of patients who have been using NSAIDs for a long time and who have no complaints characteristic of gastric damage; during prophylactic endoscopy, characteristic endoscopic signs of NSAID-induced gastropathy are revealed.

NSAID-induced ulcers and erosions are one of the most common reasons for hospitalization of patients in surgical and gastroenterological hospitals in Europe and the USA. In 1% of patients receiving long-term treatment with NSAIDs, severe gastro-duodenal complications such as gastric bleeding or ulcer perforation develop within a year. These complications are one of the most important causes of death in patients with rheumatic diseases. A new direction for the use of NSAIDs is the prevention of cancer, primarily colon adenomas, colorectal cancer, and their relapses.

Considering the increase in most countries of the world in the number of elderly people suffering from degenerative diseases of the musculoskeletal system, as well as the rejuvenation of this pathology as a result of physical inactivity, an increase in the number of obese people, and also the fact that aspirin, due to its antiplatelet properties, has found widespread use in prevention vascular accidents associated with atherosclerosis, one can assume an increase in the consumption of NSAIDs and, accordingly, erosive and ulcerative lesions of the upper parts of the digestive canal.

PATHOGENESIS

Modern ideas about the pathogenesis of NSAID-induced gastropathy are based on the cyclooxygenase (COX) concept. Currently, two forms of COX have been discovered and studied: structural (COX-1) and induced (COX-2). For the gastrointestinal tract, the most important is the functional activity of cyclic oxygenase type 1 (COX-1), physiological, normally constantly present in the tissues of a living organism and ensuring the regulation of the function of pain mediators, the implementation of tissue inflammation, and the regulation of adequate release of platelets. The COX-2 isoform is not detected in normal tissues and its expression is induced by inflammatory mediators (lipopolysaccharides, interleukin-1, tumor necrosis factor alpha) from cellular substances of the body (macrophages, monocytes, vascular endothelial cells, etc.), which causes clinical manifestations inflammatory processes - pain, increased body temperature, swelling, dysfunction of the organ. Thus, COX-1 protects the gastrointestinal mucosa, and COX-2 is involved in the formation of prostaglandins at the site of inflammation. Inhibition of COX-2 activity determines the anti-inflammatory effect of NSAIDs.

Classification of non-steroidal anti-inflammatory drugs by selectivity towards various forms of cyclooxygenase

Most NSAIDs are non-selective inhibitors of the cyclooxygenase enzyme, suppressing the action of both its isoforms - COX-1 and COX-2. Cyclooxygenase is responsible for the production of prostaglandins from arachidonic acid, which in turn is obtained from phospholipids of the cell membrane due to the enzyme phospholipase A 2. NSAIDs suppress the production of prostaglandins not only in areas of inflammation, but also at the systemic level, therefore the development of gastropathy is a kind of programmed pharmacological effect of these drugs. Inhibition of the formation of eicosanoids - prostacyclin (PG I2), PG E2 and thromboxane A2 leads to undesirable side effects of NSAIDs, such as erosions and ulcerative lesions of the gastrointestinal tract, gastric bleeding and renal dysfunction. Eicosanoids such as PG E2 and prostacyclin in the gastric mucosa perform a protective, gastroprotective function. They stimulate mucus production, inhibit the secretion of hydrochloric acid, increase the secretion of protective bicarbonates and improve tissue nutrition by dilating blood vessels and improving microcirculation. NSAIDs affect all levels of the protective intestinal barrier - preepithelial, epithelial and postepithelial.

In the formation of NSAID gastropathy, significant importance is attached to the imbalance between the factors of aggression and protection of the gastrointestinal mucosa. NSAIDs have the ability to have a negative effect on the metabolism of the mucous membrane of the digestive tract, significantly reducing its protective potential and resistance to the damaging effects of exo- and endogenous factors of aggression. NSAIDs cause an increase in the penetration of hydrogen and sodium ions into the mucous membrane, which leads to acidification of the submucosal layer of the stomach. It is assumed that NSAIDs, through proinflammatory cytokines, can induce apoptosis of epithelial cells. When using these drugs, the hydrophobic layer on the surface of the gastric mucosa is affected, the composition of phospholipids is depleted and the secretion of gastric mucus components is reduced.

NSAIDs also enhance lipid peroxidation. The resulting products of free radical oxidation cause damage to the gastric mucosa and destruction of mucopolysaccharides. A decrease in PG synthesis leads to a decrease in the synthesis of mucus and bicarbonates, which are the main protective barrier of the gastric mucosa from aggressive factors of gastric juice. When taking NSAIDs, the level of prostacyclin and nitric oxide decreases, which adversely affects blood circulation in the submucosal layer and poses an additional risk of damage to the mucous membrane of the stomach and duodenum.

The widespread use of aspirin in cardiological practice, and the peculiarities of its antiplatelet effect, makes it possible to distinguish damage to the gastric mucosa into a separate group - aspirin-induced gastropathy (A-gastropathy). The main mechanism of its action is due to the irreversible inhibition of platelet cyclooxygenase, as a result of which the synthesis of cyclic endoperoxides, which are precursors of a powerful vasoconstrictor and inducer of platelet aggregation - thromboxane A2, is reduced. In addition, aspirin, as well as most other NSAIDs, are weak acids in their molecular structure and have direct toxic effect . Due to diffusion into the cells of the gastric mucosa, they cause a direct damaging effect on intracellular organelles and destroy epithelial cells.

The second mechanism of influence on the stomach is systemic toxic effect. NSAIDs, regardless of the form of administration (oral, injection, rectal, local) enter the systemic circulation and inhibit the production of mucins, impair microcirculation in the mucous membrane, reducing its trophic properties, reducing the protective factors of the mucous membrane of the digestive canal.

Until now, the significance of Helicobacter pylori in the pathogenesis of NSAID-induced gastropathy is not entirely clear. NSAID-induced gastropathy can occur in both patients infected and not infected with H. pylori. There is an opinion that infection with H. pylori increases the likelihood of developing NSAID-induced ulcers and erosions. According to randomized clinical trials, eradication of H. pylori before starting NSAIDs reduces the risk of developing ulcers and erosions, but does not affect the recurrence rate of NSAID-induced ulcers and gastrointestinal bleeding.

CLINICAL AND DIAGNOSTICS OF NSAIDS – GASTROPATHIES

Clinical manifestations of NSAID gastropathy include various symptoms characteristic of damage to the digestive organs that occur while taking NSAIDs. Clinical manifestations range from minor dyspeptic complaints to severe ones, including life-threatening ones. The clinical picture of NSAID gastropathy is characterized by an imbalance between symptoms and the severity of endoscopic changes. Often, in patients who note pain or a feeling of heaviness in the epigastric region, nausea, heartburn and other dyspeptic disorders, endoscopic examination reveals minor changes in the mucous membrane. On the contrary, with an asymptomatic or low-symptomatic course, endoscopy reveals the presence of multiple erosions and ulcers of the stomach and duodenal bulb. The asymptomatic course of NSAID-induced gastropathy in some cases can lead to the development of such serious complications as bleeding and perforation, often leading to death.

For NSAIDs- induced dyspepsia characteristic is a complex of subjective symptoms that arise while taking NSAIDs in the absence of a characteristic endoscopic picture of damage to the gastric mucosa. The clinic of dyspeptic syndrome that occurs while taking NSAIDs is nonspecific and similar to the clinic of non-ulcer dyspepsia. Its peculiarity is the relationship between taking medications and the development of certain symptoms. With NSAID-associated dyspepsia, patients complain of a burning sensation, a feeling of heaviness in the epigastric region, which occurs shortly after taking NSAIDs.

NSAID-induced dyspepsia occurs more often with the use of low doses of NSAIDs or antiplatelet doses of aspirin for coronary heart disease. Although dyspepsia is not a life-threatening complication, its occurrence significantly affects the quality of life and complicates adequate treatment of the underlying disease.

The development of dyspepsia is probably largely due to the local action of NSAIDs, which causes reverse diffusion of hydrogen ions into the gastric mucosa and its acidification. In an alkaline intracellular environment, NSAIDs become ionized, accumulate locally in relatively high concentrations, and have a damaging effect on cells. Confirmation of this mechanism is that derivatives of enolic and indoleacetic acids, which have the highest acidic properties, most often cause side effects from the gastrointestinal tract. Cellular acidosis and subsequent changes in epithelial cell metabolism are characteristic manifestations of peptic injury. A decrease in pH stimulates pain receptors localized in the submucosal layer. The influence of NSAIDs on gastrointestinal motility may play a certain role in the development of dyspepsia symptoms.

The development of NSAID-induced dyspepsia is more common in older people. It is very important that the clinic of dyspepsia develops equally when taking both classical NSAIDs and selective COX-2 inhibitors. The use of NSAIDs in suppositories and injectable forms can in many cases reduce dyspeptic symptoms that occur during oral administration of these drugs. There are significant differences in individual tolerability of non-selective COX-2 inhibitors, which is apparently determined by different rates of absorption and duration of contact with the gastrointestinal mucosa.

NSAIDs – induced gastroesophageal reflux (GER). Clinical manifestations of GER, such as heartburn, regurgitation and dysphagia, are very common in patients taking NSAIDs, especially in elderly patients. However, the question of the participation of NSAIDs in the development of GER remains open. Although some authors consider the use of NSAIDs to be risk factors for GER, there is no reliable evidence of their effect on the tone of the lower esophageal sphincter and esophageal clearance. At the same time, a number of undesirable effects of NSAIDs may potentially play a role in the development of GER. NSAIDs can increase gastric secretion, which may cause a burning sensation in the chest.

Heartburn that appears after taking NSAIDs is obviously due to the local effect of the drugs on the mucous membrane, as well as the traditional recommendation to use NSAIDs after meals with liquid, which can cause GER. Taking NSAIDs after meals, especially enteric-coated drugs, can significantly increase the time they remain in the stomach and thus the time of contact with the mucosa. In addition, if a patient experiences GER, the likelihood of NSAIDs entering the esophagus increases, leading to a significant increase in the time the drug is exposed to the esophageal mucosa. NSAIDs can have a certain effect on gastrointestinal motility, causing stagnation of gastric contents and thereby provoking reflux.

More significant damage to the esophagus when taking NSAIDs may occur in patients suffering from GER or having prerequisites (lower esophageal sphincter insufficiency, hiatal hernia) for reflux. If GER exists, taking NSAIDs can cause the development of erosions and ulcers of the esophageal mucosa and increase the risk of esophageal bleeding. A relationship has been identified between long-term use of NSAIDs (including low doses of acetylsalicylic acid) and the development of peptic stricture of the esophagus.

NSAIDS – INDUCED GASTROPATHIES. One of the most studied forms of damage to the upper gastrointestinal tract caused by the use of NSAIDs. Local and systemic effects of NSAIDs are involved in the development of NSAID-induced gastropathy. One of the key links in the contact action of NSAIDs, in addition to acidification of the mucous membrane, is the blockade of the enzyme systems of epithelial cells, the uncoupling of the processes of oxidative phosphorylation and ATP formation, leading to a decrease in the resistance of cells to the damaging effects of the acid-peptic factor. The uncoupling of oxidative phosphorylation leads to a decrease in ATP synthesis and a deterioration in the energy supply of the gastric mucosa.

Histological examination of biopsy specimens of the gastric mucosa in NSAID-induced gastropathy reveals nonspecific changes similar to the histological picture of “chemical” gastritis. In most patients, this pathology is masked by histological manifestations of chronic antral gastritis associated with H. pylori. A characteristic morphological feature of NSAID-induced gastropathy is that ulcers and multiple erosions can be detected against the background of minimally pronounced changes in the mucosa. The favorite localization of erosive changes in the gastric mucosa in NSAID-induced gastropathy is the antrum of the stomach, while for H. pylori - associated peptic ulcer disease, gastritis, histological changes are characteristic, indicating chronic active gastritis.

NSAID-induced gastropathy is typically characterized by the development of erosions, often multiple or ulcers, often single, small and shallow, localized in the antrum of the stomach. Unlike peptic ulcers, duodenal ulcers are less common. With NSAID-induced ulcers, there are often no or mild symptoms, which can be explained by the analgesic effect of NSAIDs, as well as the patient’s concentration on pain in the affected organ (joints, muscles, etc.).

The absence of subjective symptoms does not allow us to exclude the presence of NSAID-induced gastric or duodenal ulcers, especially since “silent” ulcers caused by taking NSAIDs are more often the cause of gastrointestinal bleeding compared to manifest forms of the disease. Therefore, endoscopic examination is the only reliable method for diagnosing NSAID-induced gastropathy.

The physician should pay special attention to patients who are starting to take NSAIDs for the first time. NSAID gastropathy most often occurs in the first 1-3 months from the start of taking medications. The risk of developing this pathology in patients who successfully survived the first months of taking NSAIDs can be assessed as relatively low. Patients who have responded to NSAIDs by developing gastropathy are prone to frequent recurrence of the disease if the medication is continued.

The phenomenon of adaptation of the gastrointestinal mucosa to the effects of NSAIDs is possible in rare cases with the appearance of isolated erosions and hemorrhages in the first days of starting to take these drugs. The superficial changes that occur in these patients may subsequently disappear on their own. In most cases, changes in the gastrointestinal mucosa tend to worsen and tend to recur with repeated doses of NSAIDs. The recurrent nature of NSAID-induced gastropathy determines the need to prevent this pathology during the entire period of taking NSAIDs, regardless of its duration.

Complications of NSAID-induced gastropathy. Bleeding from the upper gastrointestinal tract is among the most frequent and dangerous. Despite the advances in the treatment of peptic ulcers achieved in recent years and the reduction in the number of surgical interventions for complications of the disease, the number of bleedings and mortality from them in patients with NSAID gastropathy remains quite high. According to statistics, 44% of all hospitalizations for bleeding from the upper gastrointestinal tract occur in patients over 60 years of age. The main cause of severe bleeding is uncontrolled use of aspirin and other NSAIDs by elderly people.

Risk factors for gastrointestinal complications with NSAID use

According to systematic reviews, in 34.6% of patients with acute gastrointestinal bleeding, a connection is found with taking NSAIDs. Moreover, a number of studies indicate even higher figures. According to the General Surgery Clinic of the Sechenov Moscow Medical Academy, the number of gastrointestinal bleedings has increased 2.5 times over 15 years. Moreover, in 59% of cases, a connection with taking NSAIDs was indicated.

A characteristic feature of bleeding from the upper gastrointestinal tract in patients taking NSAIDs is the suddenness of the bleeding in the absence of clinical signs of gastric damage. Typically, bleeding begins with vomiting "coffee grounds" or the appearance of melena. At the same time, the patient’s general condition sharply worsens. In this case, anxiety or lethargy, pallor, decreased blood pressure, and tachycardia are noted. A critical hemodynamic situation occurs when blood loss reaches 40% of the circulating blood volume.

Endoscopic diagnosis of ulcer bleeding is usually not difficult. However, with NSAID-induced gastropathy, there are difficulties in identifying the source of bleeding. Endoscopically, a large number of submucosal hemorrhages, erythema and erosions are detected. Most endoscopists define erosion as an area of ​​hemorrhage or shallow defects in the mucosa with a core of necrosis no more than 3-5 mm in diameter. Often, with NSAID-induced gastropathy, chronic bleeding develops, leading to anemia.

Risk factors play an important role in the development of bleeding in NSAID-induced gastropathy. The most important risk factors for NSAID-induced gastropathy are the presence of a history of ulcers and the elderly age of patients (over 65 years). Additional risk factors are taking NSAIDs in high doses, taking several different drugs from this group at the same time, concomitant use of anticoagulants and glucocorticoids, as well as severe concomitant diseases, primarily of the cardiovascular system.

To reduce the incidence of dangerous gastroduodenal complications, a new class of NSAIDs was created - selective COX-2 inhibitors. Selective COX-2 inhibitors have shown good analgesic and anti-inflammatory effects. These data allowed us to recommend selective COX-2 inhibitors for widespread use in clinical practice. In many countries, these drugs are used as often as classical drugs. It is most advisable to use these drugs when there is a serious risk of developing gastroduodenal complications. According to the recommendations of the UK National Institute for Clinical Research, the indication for the prescription of selective COX-2 inhibitors is the need for long-term analgesic and anti-inflammatory therapy in the presence of risk factors for the development of NSAID-induced gastropathy.

However, the use of selective COX-2 inhibitors only reduces, but does not completely eliminate, the possibility of developing dangerous complications, especially in groups of patients with risk factors for the development of this pathology. The risk of developing complications from the digestive system increases when taking selective COX-2 inhibitors and low, antiplatelet doses of aspirin together. This combination occurs in most patients over 65 years of age who suffer from diseases of the cardiovascular system.

Studies have shown that the incidence of gastrointestinal bleeding and perforation of ulcers in patients taking celecoxib together with antiplatelet doses of aspirin and in patients receiving ibuprofen and diclofenac was practically the same and only thanks to the combination of drugs with omeprazole it was possible to prevent the development of complications. Evaluating these data, it should be concluded that if the risk of developing serious gastroduodenal complications is very high, then the most adequate method of preventing this pathology will be the use of selective COX-2 inhibitors in combination with powerful antisecretory drugs.

TREATMENT OF NSAID-INDUCED GASTROPATHIES.

Treatment of NSAID gastropathy is a complex task, since NSAIDs are the main drugs prescribed to patients with numerous rheumatic, neurological and other diseases. Antisecretory drugs are used in the treatment of NSAID gastropathy. It is believed that antacids as a means of preventing and treating NSAID gastropathy have not proven themselves. Sucralfate has been proposed as an acceptable drug with gastroprotective properties that can accelerate the healing of NSAID-induced ulcers, but in its effectiveness it is inferior to both antisecretory drugs and synthetic analogues of prostaglandin E2.

A synthetic analogue of PGE 1, misoprostol, was created specifically for the prevention and treatment of NSAID gastropathy. Despite the significant effectiveness of this gastroprotector, its use in NSAID-induced gastropathy often causes diarrhea, a burning sensation in the chest and in the epigastric region. Inconvenience of use (4 times a day, 200 mcg), a large number of side effects and high cost limit the use of this drug. Currently, experts rarely prescribe misoprostol for the prevention of NSAID gastropathy, preferring PPIs.

Regarding the prescription of H2 blockers as a means of preventing and treating NSAID-induced gastropathy, the opinions of modern researchers agree that relatively long-term use of drugs of this group inevitably causes hyperplasia of enterochromaffin-like cells (ECL-cells) and after their withdrawal the phenomenon “ ricochet." Moreover, even ultra-high doses of ranitidine (600 mg/day) do not prevent the development of NSAID-induced gastric ulcers.

The drug of choice in the treatment of NSAID-induced gastropathy is omeprazole. Omeprazole is the first and well-studied antisecretory drug from the group of proton pump inhibitors. The main property of omeprazole is the inhibition of the acid-forming function of the stomach through its inhibitory effect on the intracellular enzyme H/K-ATPase (often called the proton pump). Omeprazole reduces both basal and stimulated secretion. The drug is concentrated in the acidic contents of the secretory tubules of the gastric mucosa, gradually moving towards the parietal cells. At the surface of cell membranes, under the influence of hydrochloric acid, omeprazole transforms into the active form - sulfenamide, having tropism for the sulfhydryl groups of the H / K-ATPase enzyme.

Numerous studies conducted on animals and healthy volunteers have demonstrated the high antisecretory activity of omeprazole, superior to that of H2 blockers. The antisecretory effect after taking omeprazole at a dose of 20 mg occurs within the first hour, the maximum effect is after 2 hours, inhibition of 50% maximum secretion lasts 24 hours. Studies have revealed the protective properties of the drug against the gastric mucosa. The effectiveness of omeprazole monotherapy in the treatment of gastric and duodenal ulcers has been the subject of numerous studies, including comparative trials with H2 histamine blockers. In the vast majority of studies, the duration of scarring and the percentage of healed ulcers when using omeprazole exceeded those when using histamine receptor blockers. Clinical manifestations of peptic ulcer disease, including pain in the epigastric zone, were also relieved faster when taking omeprazole than when treated with H2 blockers.

The ability of omeprazole to negatively affect HP infection has also been revealed. Omeprazole at a dose of 40 mg/day, taken for 28 days, can provide almost complete sanitation of the antrum from Helicobacter pylori infection (HP). The disappearance of bacteria was explained not by the direct bactericidal effect of the drug, but by the suppression of the vital activity of microorganisms due to changes in the quality of their habitat. The data obtained served as a rationale for the introduction of omeprazole into HP eradication regimens. Numerous clinical trials studying the effectiveness of various HP eradication regimens have proven (level of evidence A) the feasibility of using omeprazole and were accepted by all conferences in Maastricht.

Studies have also been conducted on omeprazole in the treatment and prevention of erosive and ulcerative lesions of the gastrointestinal tract associated with the use of non-steroidal anti-inflammatory drugs. The ASTRONAUT study (Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID – associated Ulcer Treatment) compared the effectiveness of omeprozole and ranitidine in 541 patients with NSAID gastropathy. Omeprazole was superior to ranitidine in both preventive and therapeutic effectiveness. Research results indicate the effectiveness of omeprazole at a dose of 40 mg/day in scarring of stomach and duodenal ulcers, and at a dose of 20 mg/day a high degree of prevention of relapses of NSAID gastropathy is achieved.

Omeprazole demonstrates therapeutic activity in reflux esophagitis, Zollinger-Ellison syndrome and other hypersecretory conditions. As an additional remedy, it is used in the treatment of acute and chronic pancreatitis. Another important quality of omeprazole is the low incidence of side effects when using it. Due to its therapeutic and pharmacoeconomic properties, omeprazole has gained wide popularity among gastroenterologists.

1. For ulcers or multiple erosions stomach or duodenum: main course of treatment with omeprazole at a dose of 40 mg/day for 2–4 weeks, maintenance treatment with omeprazole at a dose of 40 mg/day for 2–4 weeks, then taken as required;

2. For gastrointestinal bleeding caused by taking NSAIDs, the dose of omeprazole before stopping bleeding is 80 mg/day, after stopping bleeding - 40 mg/day for 4-6 weeks, switching to 20 mg/day for 4 weeks;

3. With GER caused by taking NSAIDs, the dose of omeprazole is 20 mg/day for 2-4 weeks with transition to on-demand administration. In the presence of erosive and ulcerative lesions of the mucous membrane of the esophagus, the dose of omeprazole is 40 mg/day for 4-6 weeks with a transition to a dose of 20 mg/day for 4 weeks with a transition to on-demand administration;

4. For NSAID-induced dyspepsia the dose of omeprazole is 20-40 mg/day for 2 weeks with transition to on-demand administration.

Prevention of NSAID-induced gastropathy

1. Primary prevention carried out when NSAIDs are first prescribed. It is advisable to conduct an endoscopic examination in all patients with risk factors, as well as in patients suffering from diseases of the gastrointestinal tract. Prescription of selective COX-2 inhibitors to patients with risk factors for the development of NSAID-induced gastropathy. If there is a very high risk of developing serious complications, switch to the use of selective COX-2 inhibitors with parallel administration of a prophylactic dose of omeprazole. Carrying out endoscopic monitoring in all patients with risk factors 1-3 months after starting NSAIDs.

2. Secondary prevention (prevention of relapses of NSAID-induced gastropathy while continuing to take NSAIDs). It is recommended to switch to the use of selective COX-2 inhibitors. If you continue to take “classical” drugs or several drugs (NSAIDs against the background of low doses of aspirin or in combination with glucocorticosteroids), preventive use of a PPI (omeprazole 20 mg/day). If there is a very high risk of developing serious complications, switch to the use of selective COX-2 inhibitors with parallel administration of omeprazole at a dose of 40 mg per day.

Prevention of relapses and treatment of NSAID-induced gastropathy should be carried out throughout the entire period of taking NSAIDs (4-6 weeks or more if necessary).

Conclusion:

NSAID-induced gastropathy remains a pressing problem, despite the introduction of selective COX-2 inhibitors into clinical practice. The fact that it is often asymptomatic and can manifest itself as gastrointestinal tract disease dictates the need for prophylactic administration of gastroprotective drugs. The PPI omeprazole is the drug of choice in preventing the development of NSAID-associated gastrointestinal complications.

Do you reach for an aspirin tablet when you have a high fever? Run to the pharmacy for ibuprofen if you have a severe headache? Do you take diclofenac for back pain? Without a doubt, in at least one case you answered “yes”. Nonsteroidal anti-inflammatory drugs (NSAIDs/NSAIDs), which include aspirin, ibuprofen and diclofenac, are one of the most popular classes of drugs worldwide. In the last 10 years alone, their consumption has tripled, and sales are only going up. At the same time, the number of patients with NSAID-induced gastropathy is growing.

Development mechanism

NSAID gastropathy is a lesion of the upper digestive tract that develops as a result of long-term (from 4 weeks) use of non-steroidal anti-inflammatory drugs.

How do NSAIDs work and why does gastropathy develop? Nonsteroidal anti-inflammatory drugs block the enzyme cyclooxygenase (COX). Moreover, both types that are present in the body at once - COX-1 AND COX-2.

The first performs many important functions, including protecting the gastric mucosa. The second is responsible for the production of prostaglandins, triggering the mechanism of pain and inflammation. It is logical that inhibition of COX “collapses” these processes and contributes to damage to the mucous membrane. Therefore, after long-term use of NSAIDs, patients often experience erosions and ulcerations in the stomach.

The most popular non-steroidal anti-inflammatory drugs:

• diclofenac;
• indomethacin;
• ketoprofen;
• ketorolac;
• ibuprofen;
• nimesulide;
• celecoxib;
• tenoxicam;
• dexketoprofen;
• naproxen.

RISK FACTORS

According to statistics, 30% of all patients using NSAIDs experience gastropathy, regardless of the route of administration (oral, parenteral, rectal). At risk:

• Older patients. NSAID-induced gastropathy develops more easily in patients over 65 years of age due to age-related changes in the gastrointestinal tract;
• Women. Statistics show that women more often and not always justifiably resort to NSAIDs for menstrual pain and headaches;
• Patients with Helicobacter pylori And stomach ulcer ;
• Patients taking other medications in parallel. The combined use of NSAIDs with glucocorticosteroids and anticoagulants is especially dangerous;
• People taking multiple NSAIDs at once. The highest risk of developing gastropathy was recorded in the first month of taking anti-inflammatory drugs, when the gastrointestinal tract tries to adapt to these drugs;
• Patients with bad habits. Smoking and alcohol, which cause irritation and inflammation of the gastric mucosa. This is “fertile” soil for the development of erosions and ulcers.

Symptoms

In half of all cases of NSAID gastropathy, patients do not feel any painful symptoms. The other 50% of patients experience:

• pain on an empty stomach, often at night;
• feeling of heaviness in the epigastric region;
• nausea;
• flatulence;
• decreased appetite.

Diagnostics

Based on a survey and examination of the patient, a gastroenterologist may suspect the development of gastropathy while taking non-steroidal anti-inflammatory drugs. But to confirm the diagnosis, the patient is sent for esophagogastroduodenoscopy (EGD). This study shows the condition of the gastric mucosa, the presence and number of ulcerations.

Additional research:

• test for Helicobacter pylori infection;
• stool occult blood test;
• pH-metry of gastric juice;
• Ultrasound of the abdominal cavity.

Treatment

To cure NSAID-induced gastropathy, it is necessary, first of all, to eliminate the source of the problem - Avoid harmful medications. Unfortunately, this is not always possible; many people are forced to take such medications for life. But, if it is possible to cancel NSAIDs, it is better to do so.

To restore the gastric mucosa, an appointment is prescribed gastroprotectors (rebagit) in combination with antisecretory drugs (proton pump inhibitors or H2-blockers of histamine receptors).

Gastroprotectors are needed to increase the synthesis of prostaglandins, increase the production of mucus in the stomach, protect the mucous membrane from the effects of toxic substances and help it regenerate. And antisecretory drugs - to reduce the production of hydrochloric acid.

If tests show Helicobacter pylori infection, eradication therapy with antibiotics in combination with probiotics is also carried out.

Prevention

Uncontrolled use of nonsteroidal drugs and the development of NSAID gastropathy can result in the development of peritonitis and sepsis. To avoid these dangerous health effects, take NSAIDs only as directed by your doctor. And if you cannot do without anti-inflammatory drugs, “cover” the gastric mucosa with gastroprotectors to avoid the formation of erosions and ulcers.

NSAID gastropathy can manifest itself not only with dyspepsia and pain symptoms, but also with secretive, potentially dangerous phenomena - perforations, ulcers, bleeding. Unlike classical peptic ulcer disease, NSAID gastropathy most often affects the upper gastrointestinal tract rather than the duodenum, and usually develops in elderly patients. Gastroscopy reveals erythema, diffuse erosion, microbleeding, and crater-shaped ulcers.

CAUSES OF NSAID GASTROPATHY

Any patient taking nonsteroidal anti-inflammatory drugs (NSAIDs) may develop gastroduodenal complications. The presence of gastrointestinal complaints in a patient does not always allow us to talk about the development of erosive and ulcerative changes in the gastric mucosa. Approximately 30-40% of patients receiving long-term (more than 6 weeks) NSAID therapy experience symptoms of dyspepsia that do not correlate with data obtained during endoscopic examination: up to 40% of patients with erosive and ulcerative changes in the mucous membrane of the upper gastrointestinal tract do not complain and On the contrary, in 50% of patients with dyspepsia, the mucous membrane was in normal condition.

Factors that increase the risk of developing gastric ulcers and complications when prescribing NSAIDs:

• age over 65 years;
• history of peptic ulcer;
• large doses or simultaneous use of several NSAIDs;
• concomitant therapy with glucocorticosteroids (GCS);
• long term of therapy;
• the presence of a disease requiring long-term use of NSAIDs;
• female;
• bad habits: smoking, drinking alcohol;
• Availability H. pylori.

In the course of many years of research, increased sensitivity of women to NSAIDs was established. With the combined use of NSAIDs and glucocorticosteroids (GCS), the risk of developing erosive and ulcerative lesions of the gastrointestinal tract increases 10 times. The increased risk of complications can be explained by systemic effects. GCS, by blocking the enzyme phospholipase A2, inhibit the release of arachidonic acid from phospholipids of cell membranes, which leads to a decrease in the formation of prostaglandins. The dose and duration of NSAID use are among the determining risk factors for the development of gastroduodenal ulcers and their complications. A high risk of ulcers is observed with long-term therapy, maximum in the first month of taking the drugs. The reduction in risk is further explained, apparently, by an adaptation mechanism. Any NSAID can cause mucosal damage, but the relative risk of complications in different groups of drugs varies according to some authors. The greatest risk of complications when taking piroxicam and consistently decreases for indomethacin, naproxen , ibuprofen. When taking different groups of NSAIDs in combination, their side effects are cumulative. The dose of the drug taken also plays an important role. Thus, if the usual total dose is exceeded, the risk of complications increases by 4 times.

Currently, three groups of drugs are used to prevent and treat NSAID-induced gastropathy: second-generation H2 receptor blockers ranitidine And famotidine 3rd generation, 1st group H+K+AT-phase blockers omeprazole, 2nd group synthetic analogues of prostaglandins E1 misoprostol.

The rationale for prescribing drugs that block the production of HCl acid is to target the following results:

• reducing the activity of pepsin or its inactivation when the intergastric pH increases to 4 or higher, especially when approaching 6, is one of the main tasks in the treatment of NSAID-induced gastropathy;
• reduction of reverse diffusion of H+ and their damaging effect on the gastric mucosa.

It has been established that suppression of acid production leads to scarring of ulcers and epithelization of erosions, even with prolonged use of NSAIDs, which is especially important for patients with rheumatic diseases who are forced to take medications for years. The main drug for the prevention of NSAID-induced gastro- and duodenopathy is misoprostol- a synthetic analogue of prostaglandin E1. In addition, the drug reduces the risk of developing severe complications in patients taking NSAIDs and who are at risk. When mucosal infections are detected in patients with NSAID-induced gastro- and duodenopathy H. pylori, it is advisable to supplement the prescription of antibacterial drugs.

An effective way to reduce the risk of NSAID gastropathy is to use drugs with the least side effects: ibuprofen, diclofenac .

Table Risk factors for gastropathy and cardiovascular complications while taking NSAIDs

Management tactics for patients receiving NSAIDs:

• assess risk factors for digestive organs and cardiovascular complications in patients before therapy;
• take into account the presence of chronic diseases;
• do not overlook a history of skin reactions to NSAIDs;
• if the patient has severe chronic diseases, NSAIDs are prescribed in consultation with doctors of the relevant specialties;
• before treatment it is necessary to examine: endoscopy, general blood test, determine the level of alanine aminotransferase (ALT), ASTH, bilirubin, creatinine in the blood;
• treatment should begin with the least toxic drug;
• use the minimum required dose;
• It is advisable to avoid polypharmacy (simultaneous use of multiple drugs);
• Monitoring of patients receiving NSAIDs is necessary.

---------
According to the report of Alexey Olegovich Bueverov, professor of the department of medical and social examination and outpatient therapy of the First Moscow State Medical University named after. THEM. Sechenova, Doctor of Medical Sciences at the symposium within the framework of the XXIV Russian National Congress "Man and Medicine"

Karasyova G.A.

Belarusian Medical Academy of Post-Graduate Education, Minsk

NSAID-gastropathy: from understanding to prevention and treatment strategy development

Summary. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most popular treatment for a range of diseases, but they can cause serious gastrointestinal (GI) complications. Taking risk factors into account and prescribing safer NSAIDs and proton pump inhibitors (PPIs) can reduce the incidence of gastrointestinal complications. The drug of choice among PPIs can be pantoprazole (Nolpaza, KRKA), which is characterized by minimal potential for interaction with other drugs, as well as proven high safety and effectiveness.

Keywords: non-steroidal anti-inflammatory drugs, proton pump inhibitors, gastropathy.

Summary. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most popular medications to relieve the symptoms of a number of diseases. However, NSAIDs can cause serious gastrointestinal complications. To take into account risk factors and to use safer NSAIDs and Proton-pump inhibitors (PPIs) allow to reduce the frequency of gastrointestinal tract (GIT) complications.

Pantoprazole (Nolpaza) is characterized by lowest potential of drug interaction, high safety and efficacy and can be a drug of choice among PPI.

Keywords: nonsteroidal anti-inflammatory drugs, proton-pump inhibitors, gastropathy.

One of the most important problems associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is their damaging effect on the gastrointestinal tract (GIT), which can lead to severe complications.

On Most often, nonsteroidal anti-inflammatory drugs have a damaging effect on the stomach and duodenum; this pathology is referred to as “NSAID-induced gastropathy” or “NSAID-gastroduodenopathy syndrome.” The term “NSAID gastropathy” was proposed in 1986 to distinguish the specific damage to the gastric mucosa that occurs with NSAID use from classic gastroduodenal ulcers.

NSAID gastropathy is erosive and ulcerative lesions of the gastroduodenal region that occur with the use of NSAIDs and have a characteristic clinical and endoscopic picture. Their features: multiple nature, asymptomatic course and high risk of manifestation of gastrointestinal bleeding (GIB), identified connection with the use of NSAIDs, localization in the antrum (less often in the body of the stomach and duodenum), absence of an inflammatory shaft around the ulcer; histological sign - foveal hyperplasia of the mucous membrane; relatively rapid healing after discontinuation of non-steroidal anti-inflammatory drugs. The outcome of upper gastrointestinal exposure to aspirin and NSAIDs can be dramatic, including bleeding and perforation, which determines the surgical aspect of the problem.

Nonsteroidal anti-inflammatory drugs are the most commonly used drugs in medical practice. Around 30 million people worldwide take these drugs every day. About 500 million prescriptions for NSAIDs are written per year. 10-20% of people over 65 years of age take or have taken NSAIDs. Self-administration of NSAIDs is 7 times higher than recommended by a doctor. The expected use of NSAIDs will only increase, which is associated with an increase in the number of over-the-counter drugs, an aging population, and an increase in the frequency of prescription of aspirin as an antiplatelet agent.

Erosion and ulcers of the gastric mucosa occur in 10-30% of people taking NSAIDs for a long time. With long-term (more than 6 weeks) use of NSAIDs, gastro- and duodenopathy develop in 70% of patients. Changes in the mucous membrane of the gastroduodenal zone are often recurrent in nature with minimal subjective sensations or a complete absence of clinical manifestations, which often becomes the reason for late consultation with a doctor.

In 1/3 of patients who take NSAIDs for a long time and do not have any symptoms from the gastroduodenal zone (in 34% of cases), according to E.L. Nasonova and A.E. Karateeva (2000), during preventive esophagogastroduodenoscopy, characteristic endoscopic signs of NSAID gastropathy are revealed.

Range of diseases for which I use NSAIDs are extremely broad. Along with rheumatic diseases (rheumatoid arthritis, ankylosing spondylitis, gout, etc.), the range of indications for prescribing NSAIDs includes pain of various origins (neuralgia, myalgia, headaches and toothaches, pain due to primary dysmenorrhea, etc.), as well as ischemic disease hearts. In addition, NSAIDs are used for chemoprophylaxis of colon adenomas, colorectal cancer, and their recurrences.

Significant increase in NPS consumption P led to an increase in the incidence of systemic toxic effects associated primarily with damage to the gastric mucosa (GMU) and duodenal mucosa. A feature of NSAID gastropathy is that it affects the upper gastrointestinal tract and usually develops in elderly rather than young patients.

The main mechanism of the therapeutic effect of NSAIDs is associated with interruption of the cyclooxygenase (COX) pathway of arachidonic acid metabolism, as a result of which the synthesis of prostaglandins, the most important products of inflammation, is suppressed. Currently, two forms of COX have been discovered and studied: structural (COX-1) and induced (COX-2). COX-1 protects the gastrointestinal mucosa, and COX-2 is involved in the formation of prostaglandins at the site of inflammation. The range of major physiological effects of prostaglandins includes stimulation of the secretion of protective bicarbonates and mucus; increased local blood flow to the mucous membrane; activation of cell proliferation in the processes of normal regeneration. Inhibition of COX-2 activity actually determines the anti-inflammatory effect.

In the formation of both NSAID gastropathy and gastroduodenal peptic ulcers, significant importance is attached to an imbalance between the factors of aggression and protection of the gastrointestinal mucosa, while NSAIDs affect all levels of the protective intestinal barrier - preepithelial, epithelial and postepithelial.

The following factors are considered as etiopathogenetic factors in the development of NSAID gastropathy: local irritation of the coolant and subsequent formation of ulcers; inhibition of the synthesis of prostaglandins (PG) (PGE2, PGI2) and their metabolites prostacyclin and thromboxane A2 in the coolant, which perform the function of cytoprotection; impaired blood flow in the mucous membrane due to previous damage to the vascular endothelium after taking NSAIDs.

The topical damaging effect of nonsteroidal anti-inflammatory drugs is manifested by the fact that some time after the administration of these drugs, an increase in the penetration of hydrogen and sodium ions into the mucous membrane is observed. NSAIDs suppress the production of prostaglandins not only in areas of inflammation, but also at the systemic level, so the development of gastropathy is a kind of programmed pharmacological effect of these drugs.

It is assumed that non-steroidal anti-inflammatory drugs, through pro-inflammatory cytokines, can induce apoptosis of epithelial cells. When using these drugs, the hydrophobic layer on the surface of the gastric mucosa is affected, the composition of phospholipids is depleted and the secretion of gastric mucus components is reduced. In the mechanism of the ulcerogenic effect of NSAIDs, changes in lipid peroxidation play an important role. The resulting products of free radical oxidation cause damage to the gastric mucosa and destruction of mucopolysaccharides. In addition, NSAIDs have a certain effect on the synthesis of leukotrienes, a decrease in the number of which leads to a decrease in the amount of mucus, which has cytoprotective properties. A decrease in PG synthesis leads to a decrease in the synthesis of mucus and bicarbonates, which are the main protective barrier of the coolant against aggressive factors of gastric juice.

When taking NSAIDs, the level of prostacyclin and nitric oxide decreases, which adversely affects blood circulation in the submucosal layer of the gastrointestinal tract and creates an additional risk of damage to the mucous membrane of the stomach and duodenum. Changing the balance of protective and aggressive gastric environments leads to the formation of ulcers and the development of complications: bleeding, perforation, penetration.

The meaning is still not entirely clear Helicobacter pylori in the pathogenesis of NSAID gastropathy. Apparently infection H. pylori increases the likelihood of developing NSAID-induced ulcers, erosions and gastrointestinal tract. However, NSAID gastropathy can also occur in patients not infected H. pylori. According to randomized clinical trials, eradication H. pylori before starting to take NSAIDs significantly reduces the risk of developing ulcers and erosions, but does not affect the frequency of relapses of NSAID-induced ulcers and gastrointestinal tract. At the same time, eradication treatment is less effective in patients with NSAID gastropathy compared to maintenance therapy with proton pump inhibitors (PPIs). As follows from the recommendations of the Maastricht Consensus 3rd revision (2005):

When using NSAIDs, the risk of developing NSAID gastropathy is higher in patients with H. pylori(+) than in patients with H. pylori(-);

If NSAIDs are planned, patients should first be tested for the presence of H. pylori, and if the result is positive, they should be prescribed eradication therapy to prevent the occurrence of ulcers and/or bleeding;

Eradication H. pylori reduces the risk of developing NSAID gastropathy;

If there is an increased risk of ulceration and/or bleeding, eradication alone is not sufficient H. pylori. In such patients, proton pump inhibitors are recommended.

Erosive and ulcerative lesions of the stomach and duodenum (accompanied by dyspepsia or asymptomatic) are detected during endoscopic examination in almost 40% of patients taking NSAIDs for a long time.

However, up to 40% of patients with erosive and ulcerative changes in the mucous membrane of the upper gastrointestinal tract do not complain; on the contrary, up to 50% of patients with dyspepsia have normal mucous membrane.

The symptoms of the pathology in question are well known to clinicians. These are pain (usually in the epigastric region) associated with taking the drug (patients switch to taking it after meals to reduce discomfort), dyspeptic syndrome - a feeling of heaviness after eating, a feeling of rapid satiety, swelling in the epigastric area, less commonly nausea, vomiting. Pain and dyspeptic syndromes are not characterized by seasonality, unlike the “classic” gastroduodenal ulcer.

In approximately 30-40% of examined patients receiving long-term (more e 6 weeks) NSAID therapy, symptoms of dyspepsia are noted that do not correlate with the data obtained from esophago-gastroduodenoscopy. NSAID gastropathy, as a rule, occurs within the first 1-3 months from the start of treatment, which is why patients who first started taking NSAIDs require increased attention from a doctor for timely diagnosis of complications. The greatest likelihood of erosive and ulcerative lesions is observed in the first month of NSAID use, then it decreases slightly and remains stable over the next several years of use.

For NSAID-induced gastropathy, the development of erosions (often multiple) or ulcers localized in the antrum of the stomach is typical. NSAID-induced ulcers are often single, relatively small in size and shallow; multiple ulcers, contrary to popular belief, are relatively rare.

The morphological picture observed during histological examination of biopsies of the gastric mucosa in NSAID-induced gastropathy is nonspecific. Although NSAIDs can cause peculiar changes in the mucous membrane (NSAID-induced gastritis), similar to the histological picture of “chemical” gastritis, in most patients this pathology is masked by the histological manifestations of chronic antral gastritis associated with H. pylori. At the same time, with NSAID-induced gastropathy, ulcers and multiple erosions can be determined against the background of minimally pronounced changes in the mucosa, in contrast to H. pylori- associated peptic ulcer disease, in which the characteristic background of the ulcer is chronic active gastritis.

The individual pharmacodynamic characteristics of NSAIDs also play a role in the development of NSAID gastropathy. Drugs from this group have different effects on the ratio of the activity of COX isoenzymes. I agree About this theory, the lower the concentration of the drug required to block COX-1 (i.e., the less selectivity of the drug for COX-2), the more often it causes the development of gastroduodenal complications. Data from a meta-analysis of population studies show that the risk of developing gastroduodenal complications decreases in the series indomethacin - piroxicam - naproxen - diclofenac - ibuprofen.

Predicting the possible development of NSAID gastropathy allows taking into account risk factors that were identified by epidemiologists when analyzing data obtained from a retrospective study of large groups of patients taking NSAIDs. The presence of such factors is associated with a significantly higher relative risk of developing serious gastroduodenal complications at the population level.

The most important risk factors for NSAID-induced gastropathy are the presence of a history of ulcers and the elderly age of patients (over 65 years). Additional risk factors: concomitant use of anticoagulants and high doses of glucocorticoids, use of NSAIDs in high doses, simultaneous use of several different drugs from this group, severe concomitant diseases, primarily of the cardiovascular system.

According to the recommendations of the American College of Gastroenterology (2009) for the prevention of complications of gastropathy induced by NSAIDs, according to the risk of toxic effects of NSAIDs on the digestive tract, all patients can be divided into the following groups:

1. High risk:

There is a history of a complicated ulcer, especially a recent one;

Multiple (more than 2) risk factors;

2. Moderate risk (1-2 risk factors):

Age over 65 years;

High dose of NSAIDs;

There is a history of an uncomplicated ulcer;

Concomitant use of acetylsalicylic acid (including in low doses), corticosteroids or anticoagulants.

3. Low risk: no risk factors.

For patients at high risk, it is better to avoid taking NSAIDs. In the case of absolute indications for prescribing this group of drugs, it is advisable to use selective COX-2 inhibitors simultaneously with PPIs or misoprostol. For persons at moderate risk, selective COX-2 inhibitors or non-selective NSAIDs are recommended concomitantly with PPIs or misoprostol. In the absence of risk factors, there is no need for prophylactic prescriptions.

The dose of the drug and the duration of treatment also affect the occurrence of NSAID gastropathy. Thus, in patients over the age of 60 years, when prescribed doses exceeding the standard by 1.5 times, the risk of its development increases by 2.8 times, and if the dose is tripled, it increases by 8 times.

At the same time, it was found that erosive and ulcerative lesions of the stomach are possible even with treatment with small doses of acetylsalicylic acid (150-300 mg/day), often prescribed to prevent thrombosis in coronary heart disease. The use of selective COX-2 inhibitors reduces the risk of developing erosive and ulcerative lesions, but does not completely eliminate them.

Based on the pathogenesis, no significant connection was found between the method of administration of NSAIDs (orally, parenterally or rectally) and the incidence of erosive and ulcerative lesions, since the main ulcerogenic effect is due to the systemic toxic effect of NSAIDs.

Treatment of NSAID gastropathy is a difficult task, since complete abolition of NSAIDs without the use of acid-suppressive drugs does not lead to healing of ulcers and erosions in 60% of patients over the next 1-3 months. Goals of therapy: relief of clinical symptoms, epithelization of mucosal defects, prevention of complications, prevention of relapses, improving the quality of life of patients.

Choice of drug for the prevention and treatment of erosive and ulcerative lesions. Based on the results of the clinical trials OMNIUM (comparing the effectiveness of omeprazole and misoprostol in the treatment of ulcers caused by NSAIDs) and ASTRONAUT (comparing the effectiveness of omeprazole and ranitidine), it should be noted that PPIs are the treatment of choice for the healing of ulcers caused by NSAIDs, especially gastric ulcers, in terms of the effectiveness and tolerability of therapy. While using misoprostol, diarrhea was detected in 11% of patients, 8.9% of patients complained of abdominal pain, and 16.9% stopped taking it prematurely. In randomized multicenter studies (SCUR, OPPULENT, ASTRONAUT, OMNIUM), it was clearly demonstrated that PPIs are significantly more effective in healing NSAID-induced erosive and ulcerative lesions of the stomach and duodenum than ranitidine used for these purposes. PPIs are able to maintain intragastric pH above 4.0 for a long time, even with a single dose.

An important issue is the safety of therapy and the possibility of changing the effects of drugs when taken together with PPIs. This couple tram corresponds to pantoprazole (Nolpaza,company "KRKA"), which has a much greater potential for drug interactions than other PPIs. Pantoprazole is the only PPI that binds to cysteine ​​822, which is located deep in the transport domain of the proton pump and becomes inaccessible to glutathione and dithiothreitol, which can reverse the inhibition. It is assumed that cysteine ​​822 ensures the stability of the bond and the duration of inhibition of the proton pump and acid production. Therefore, pantoprazole has a longer-lasting acid suppressive effect than other PPIs. The time to restore inhibited acid secretion is about 15 hours for lansoprazole, about 30 hours for omeprazole and rabeprazole, and about 46 hours for pantoprazole.

Pantoprazole has a lower affinity for the hepatic cytochrome P450 system, does not affect its activity and does not produce clinically significant reactions with many drugs, including antiplatelet agents. In this regard, the scope of its application is significantly expanding, since pantoprazole is more suitable for use in combination with other drugs. The pantoprazole (Nolpaza) molecule has a unique double shell, which protects the active substance from the aggressive acidic environment of the stomach and allows it to be absorbed in the intestines. Nolpaza is the drug of choice for cardiac patients at risk of developing gastrointestinal complications who are forced to take NSAIDs and antiplatelet drugs.

Pantoprazole undergoes little first-pass metabolism. Its absolute bioavailability is about 77%, and its protein binding percentage is about 98%. The drug can be taken regardless of food intake or antacids. It does not accumulate in the body, and repeated doses of the drug during the day do not affect its pharmacokinetics. In elderly people, as well as in patients with renal failure, including those on hemodialysis, no dose adjustment of pantoprazole for oral or intravenous administration is required. In the work of F. Mearin et al. , a placebo-controlled comparison of the effectiveness of lansoprazole, pantoprazole and misoprostol (200 mg 4 times daily) in eliminating the manifestations of NSAID-induced dyspepsia was conducted. The researchers took into account both dyspepsia syndrome, which included abdominal pain, heartburn, bloating, feeling of fullness in the stomach/quick satiety/abdominal distension, and pain and heartburn separately. By the end of the 12th week of treatment with pantoprazole, symptoms of dyspepsia disappeared in 66% of cases, abdominal pain in 77%, heartburn in 87% of cases, regardless of the dose used.

These results were superior to misoprostol and placebo. In addition, misoprostol at the indicated dose contributed to the development of diarrhea and colicky abdominal pain in some patients. You should also be careful when using the drug in women of childbearing age. The researchers conclude that proton pump inhibitors are preferable for the prevention and treatment of dyspepsia and ulcerations, and also emphasize the need for additional studies comparing the effectiveness of proton pump inhibitors.

Doctor's tasks:

1. Assess the risk of complications of cardiovascular diseases.

2. Assess the risk of gastroduodenal ulcers and their complications (bleeding, perforation).

3. Carry out practical activities in accordance with approved methodological recommendations.

Based on clinical and epidemiological studies, experts have approved the following tactics as having the highest degree of certainty.

In the group of patients with a high risk of NSAID gastropathy, preference is given to selective COX-2 inhibitors even if the presence of infection is confirmed H. pylori It is recommended to carry out eradication therapy followed by taking a proton pump blocker - pantoprazole (Nolpaza) for the entire duration of NSAID use.

The treatment algorithm for patients with NSAID gastropathy involves resolving the issue of discontinuing aspirin and other non-selective NSAIDs or replacing them with selective COX-2 inhibitors. If this is possible, then after transferring the patient to selective COX-2 inhibitors, proton pump blockers are prescribed in standard doses for a course of 4 to 8 weeks, and in case of complicated erosions and ulcers, double doses of PPI are prescribed. H2 blockers and the synthetic prostaglandin analogue misoprostol are less effective treatments.

If it is impossible to discontinue aspirin and non-selective NSAIDs, treatment of erosive and ulcerative lesions is carried out against the background of their continued use, but constant maintenance therapy is prescribed with standard or double doses of proton pump blockers, if an infection is detected H. pylori eradication therapy is recommended.

With the development of gastrointestinal tract ulcers, according to a meta-analysis, antisecretory therapy is the most important component of conservative therapy, since its use reduces mortality from ulcerative bleeding.

In the first three days, intensive antisecretory PPI therapy is carried out. Administration begins with a bolus intravenous infusion of a standard or double dose of PPI, followed by an intravenous drip of the drug (for pantoprazole - 8 mg/h). To achieve adequate hemostasis in the first three days of PPI therapy, the intraluminal pH should be 6.0 or higher, which will ensure platelet aggregation, thrombus formation and prevent its proteolysis under the influence of gastric juice. From the fourth day, they switch to prescribing PPIs orally in a standard dose. The indicated value of intragastric pH can be achieved only with intravenous administration of sufficiently large doses of proton pump inhibitors. The daily dose of pantoprazole is up to 240 mg.

Secondary prevention of NSAID gastropathy includes: patient education; taking NSAIDs with meals; prescribing an effective and safe PPI; FEGDS after 1-3 months. from the start of taking NSAIDs; FEGDS before starting treatment in patients with a history of ulcers or complications in the history; diagnosis and treatment of infection H. pylori before starting NSAID treatment; after a course of eradication - constant use of PPIs in a therapeutic or prophylactic dosage.

Features of pantoprazole (Nolpaza) are presented in table. 2.

table 2 . Features of pantoprazole (Nolpaza)

At the present stage of development of gastroenterology, it is especially important to emphasize the relevance of studying NSAID-induced gastropathy, which by the beginning of the new century is gaining increasing medical and social significance. At the same time, the number of hospitalizations and deaths associated with taking NSAIDs, as well as the economic costs of treating NSAID-induced diseases, are steadily growing every year, which dictates the need to introduce standards of prevention taking into account existing risk factors for gastrointestinal complications.

The effectiveness of PPIs used in the treatment and prevention of gastropathy induced by NSAIDs and aspirin has been convincingly confirmed in randomized clinical trials.

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