Current approaches to the treatment of patients with stomach ulcers and duodenal ulcers

Gastric ulcer (Hx) and 12 ulcers of the duodenum (YADPK) are common diseases of the digestive system. In Europe and North America decreased frequency of this pathology, but in Russia and Belarus, this trend has been observed. The Russian Federation has about 3 million people suffer from Hx and YADPK that ranges from 2 to 5% of the adult population. Of this amount, operated every 10th patient. In Minsk in 2006 reported an increased incidence of diseases of the digestive system in adolescents is 6.4%, and the primary disease they increased by 15.2%, with a decrease of this index in adults is 3.8%. The growth rate of morbidity in adolescents is mainly associated with the identification of ulcers duodenum.

Ulcer usually develops in the young, able-bodied and most creative age, significantly more often in men. At a young age dominated by duodenal localization (15-20 times more frequently than gastric) [15].

In most cases, ulcers recur from one to two times per year, resulting in temporary disability, and the accession of complications - and to counter. According to statistics, every 10th patient with an ulcer complications with different localization is the most frequent and formidable of which was bleeding from the ulcer. In 50-70% of cases, the cause of bleeding from the upper nevarikoznyh gastrointestinal tract (GIT) - ulcers. Despite ongoing therapy and surgery, and mortality in bleeding remains the same - 6-8% [12]. No less important is the indicator of quality of life of patients and Hx YADPK. Decreased social, physical, sexual activity, intellectual activity and psycho-social activities in these individuals [5].

Ulcer - a disease multivariate genesis. It is based on the onset and progression is based on different factors: genetic predisposition, the role of helikobaktera, the balance between protection and aggression factors. At the present time, especially in the duodenal form, attach great importance to the infectious agent - Helicobacter pylori (HP) [9,10].

Epidemiological data from various countries indicate that approximately 100% of ulcers, which are localized in the duodenum, and about 80% of gastric ulcers associated with persistence of HP. HP considered the most important etiopathogenetic factor not only ulcers but chronic gastritis (type B), duodenitis, MALT-lymphoma of stomach. In 1994, WHO experts assigned to the HP group I carcinogen risk for gastric cancer.

Currently, HP is the most studied organism. Deciphered its genetic code to clarify the meaning of NO in the genesis and gastroenteologicheskih negastroenterologicheskih diseases.

The study begins with the HP 1983, when Robin Warren and Barry Marshall discovered and studied this microorganism. In 2005, for the discovery and study the role of NO in the pathogenesis of ulcers and chronic gastritis it was awarded the Nobel Prize in Physiology or Medicine. This discovery has stimulated the development of new approaches to the treatment of ulcers, significantly improved the prognosis and quality of life of patients [3]. But the best proof of the validity of the theory of infectious disease is a significant reduction in HF associated with ulcers and a tendency to reduce the incidence of gastric cancer [6]. This was achieved after the development and implementation in Europe, North America, Australia, the so-called eradication therapy whose aim was to eradicate parasitic HP [9].

The main principle of treatment of ulcers associated with HP, as HP and other related diseases - eradicated. Eradication means the complete destruction of the vegetative (active) and coccoid (inactive) forms of bacteria in the stomach and the HP APP and promotes long-term remission of ulcers.

Without eradication therapy for most patients relapse occurs within the first year. According to a systematic review of Cochrane Library experts an anti ulcer treatment is also considered to eradication of HP. The main result of the successful renovation of the gastroduodenal zone from HP - the termination of relapses in most patients with ulcers.

H. pylori (eradication) therapy has been gradually developed the Maastricht consensus. Indications for eradication therapy was taken at the Maastricht Consensus 2 (2000) and include:

1) Hx and YADPK in the acute phase, and (most importantly) in remission, including complicated by an ulcer;

2) chronic antral gastritis;

3) MALTomu stomach;

4) atrophic gastritis;

5) the state after gastrectomy for cancer of the stomach;

6) HP eradication can be done at the request of the patients in the absence of clinical disease.

H. pylori therapy is divided into 2 stages: 1st line and 2nd line (table).

Schemes of eradication therapy by the Maastricht Treaty-2 (2000)

Note: * at least 7 days, ** at least 10 days

Given the pent-up since 2000, a huge amount of material on the results of therapy of H. pylori identified by the growth of resistance to the standards of the pyloric helikobaktera therapy of H. pylori in 2005 in Florence, recommendations were developed for the treatment of HP-associated ulcers, which are called Maastricht-3. Emphasis was placed on the following points:

1) increase the duration of eradication schemes up to 14 days (14-day scheme of 12% more efficient than the 7-day);

2) 7-day scheme may also apply if the "local" studies demonstrated its efficiency and profitability;

3) the indications for eradication therapy extend to patients with long-term aspirin and other nonsteroidal anti-inflammatory drugs (but remember that only the eradication therapy is not enough to prevent the occurrence of symptomatic ulcers);

4) atrophic gastritis: HP eradication suspend distribution of atrophic gastritis and leads to regression, but the effect on intestinal metaplasia is not established;

5) Triple therapy in the age aspect: in the elderly may be somewhat reduced dose of antibiotics;

6) in the diagnostic plan: rapid urease test provides an opportunity to diagnose and prescribe HP therapy of H. pylori;

7) treatment of the 1st line: proton pump inhibitor (PPI), 2 times per day + clarithromycin 500 mg 2 times a day plus amoxicillin (or metronidazole) 1000 mg 2 times a day;

8) treatment of the 2nd line (kvadroterapiya): IPP 2 times a day plus tetracycline 500 mg four times a day plus ranitidine bismuth citrate 120 mg 4 times a day (or 240 mg 2 times a day) + metronidazole 1500 mg per day.

The second regimen is recommended if resistance to clarithromycin HP in the region exceeds 10% and / or a hypersensitivity to amoxicillin or clarithromycin.

The leading factor in helikobaktornoy infection from the mucous membrane of stomach and duodenum is the level of secretion of hydrochloric acid, and this, in turn, is determined by the host's genetic features [1]. If a person has the level of secretion of hydrochloric acid is low, HP begins colonize any part of the stomach. When stored or acidity HP infests the antrum and modified (metaplazirovannyh) regions of the mucous membrane of the KDP [9].

The impact of HP on gastric mucosa and duodenal multifaceted. HP is the cause of the secondary hypersecretion of hydrochloric acid in the stomach, as This microorganism alkalify antrum products of hydrolysis of urea with urease (an enzyme produced by bacteria present). The consequence of excessive alkalinity antrum is hypergastrinemia, which, in turn, affecting the gastric parietal cells, stimulates production of hydrochloric acid. In addition, HP will help the specific inflammation with the formation of its mediators (cytokines, epidermal growth factor, etc.). This is especially characteristic of cytotoxic strains of HP. It is cytotoxic strains of HF can cause inflammation in the mucous membrane of the stomach and duodenum, as well as promote the development of destructive and ulcerative processes in the stomach and duodenum. In this regard, we can conclude that it was his persistence in HP in the gastric mucosa and duodenal creates conditions for the perpetuation of the inflammatory process, the formation of destructive processes in the duodenal mucosa and can lead to cancer. Hence the only right direction in therapy - eradication of HP.

The goals of treatment associated ulcers HP:

1) elimination of symptoms as soon as possible;

2) destruction of bacteria in the HP gastroduodenal mucosa;

3) the relief of inflammation in the lining of the stomach and duodenum;

4) The healing of ulcers and erosions;

5) prevention of exacerbations and complications, including lymphoma and cancer of the stomach.

It is established that ulcerative defect healed within 4 weeks in 100% if it is possible to maintain the stomach pH above 4.0 for 18-20 hours during the day. In patients with Hx usually detected more moderate rates of gastric secretion, but is required antisecretory therapy for all patients. To achieve such control treatment by using STI.

"Gold" standard antiulcer treatment is omeprazole. Omeprazole - the first and most widely used ulcer drug. It is now widely used PPIs following: omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole [3,4,7].

PPIs are substituted benzimidazole derivatives. STI at baseline have biological activity. But, being inherently weak bases, they accumulate in the secretory canaliculi of parietal cells, where under the influence of hydrochloric acid are converted into sulfenamidnye derivatives, which form covalent disulfide bonds, sulfhydryl groups inactivate the H + K + ATPase, resulting in a decrease in both basal and stimulated secretion of hydrochloric acid. The mechanism of action of drugs by blocking the final stage of secretion of hydrochloric acid. Antisecretory effect occurs within 1.5-2 hours after dosing. Prinimat PPI appropriately on an empty stomach or before meals, as the peak concentration of drug in blood achieved when the largest number of proton pump will be activated (just 1.5-2 hours). The high therapeutic activity of PPI is due to their pronounced antisecretory activity 2-10 times higher than that of H _2-blockers. Particularly important role to play in the eradication therapy of PPI, as antibiotics (amoxicillin and clarithromycin) are inactivated in an acidic environment. Therefore, the stronger inhibited gastric secretion, the longer and more effective antibiotics act on Helicobacter. The duration of block of hydrochloric acid caused an update rate of proton pumps. Typically, half of pumps updated in person for 30-48 hours [7,11,13,14]. Necessary to note the absence of the phenomenon of "rebound" in this group of drugs. A very important point in the treatment of ulcers associated HP is the fact that in patients with severe suppression of the secretion, the population of HP, based in the stomach, passes from the resting state of reproduction, namely dividing microbial cells antibiotics act more actively. Another important point - a feature of metabolism of clarithromycin and PPIs: drugs relatively slow metabolism of each other in the liver, which allows them to provide a stronger and more prolonged antimicrobial and antisecretory action [9,10,13].

Clarithromycin and amoxicillin for HP provide the maximum among all the schemes used in the bactericidal effect of antibiotics. In clarithromycin and amoxicillin less contraindications and side effects, a higher eradication rate than tetracycline. Only 3-10% of patients during therapy of H. pylori experience side effects that cause drug withdrawal.

At present, medical science is increasingly considered the question of adherence to treatment. Good adherence to therapy in patients with various diseases characterized by a reduction in mortality from these diseases, a decrease in frequency of relapses and complications. Hx, YADPK and threatening complications, and continues to be important public health problem. In our opinion, improve adherence to treatment of patients with Hx and YADPK can help:

1) providing access to specialist gastroenterology care to the population;

2) training of patients with ulcer (an explanation of the value of HP and its role in the formation of ulcers and the need for treatment);

3) simplification of dosing regimens and medication (treatment 1 st and 2 nd line).

In this connection it should be emphasized convenience of the dosage form "Peptipak" (company ╚Pharmacare Int.Co╩), which has in its composition stripes package, designed for a day of admission, which include all 3 drugs a first-line therapy: omeprazole 20 mg (2 capsules), clarithromycin 500 mg (2 tablets) and amoxicillin 500 mg (4 capsules), designed for two-time reception at night. This allows you to quickly begin treatment, the patient saves time searching for drugs alone in the pharmacy chain, it is convenient to use. Regimen is simple and well painted.

Therapy and Hx YADPK is integrated in the treatment regimen inputs 3-4 of the drug. To improve patients' adherence to the treatment of a vigorous search for new dosage forms, improved dosing schedules of drugs, which include, above all, reducing the multiplicity of reception, and very importantly - how to simplify their application. A striking example is the form of "Peptipak" (Pharmacare Int.Co). According to the IG Bereznyakova [2], is also important transition from the authoritarian model of the behavior of the doctor toward the patient to cooperate with him.

References:

1. Aruin LI The quality of healing of gastroduodenal ulcers: functional morphology, the role of pathogenetic therapy meodov / / Exper. and clinical. Gasroenterologiya, 2006. - № 5. S. 1-5.

2. Birch IG Ways to improve adherence to treatment in hypertension / / Ukrainian honey. Newspaper, 2007. - Vol. № 10.

3. Burkov SG Current approaches to treatment of diseases kislotozavisimyh / / BC, 2007. - № 7.

4. Isakov, VA The theory of disease kislotozavisimyh proton pump inhibitor in Questions and Answers / / Consilium medicum, 2006. - T. 8. - № 7.

5. NN Krylov Factors affecting the quality of life of patients with peptic ulcer of the duodenum 12 / / RZHGGK, 1996. - № 4. - App. 1. - C 318.

6. Lazebnik LB, Vasiliev J., Grigoriev PY, Grinevich VB Therapy and other diseases kislotozavisimyh / / Exper. and clinical. Gastroenterology, 2003. - № 4. - S. 3-18.

7. Lapina TL Proton pump inhibitors: a few questions on the theory and practice / / Farmateka, 2006. - № 1.

8. Loginov, AF "Maastricht-3" - the modern tactics of diagnosis and treatment of infection Helicobacter pylori / / Farmateka, 2006. - № 12.

9. Maev IV, Samsonov AA Current standards of treatment kislotozavisimyh diseases associated with H. pylori (Maastricht consensus Materials-3) / / Consilium medicum, application, 2006. - T. 8. - № 1.

10. Maev IV, Samsonov AA Duodenal ulcer: different approaches to the modern conservative therapy / / Consilium medicum, 2004. - T. 6. - № 1.

11. Maev IV, Trukhmanov AS, Kucheryavyy Y. Pharmacoeconomics kislotozavisimyh diseases / / RZHGGN, 2006. - № 3. - S. 68-76.

12. International guidelines for the management of patients with bleeding nevarikoznym of the upper gastrointestinal tract / / Rus. honey. magazine, 2005. - № 14. - S. 3-10.

13. Minushkin ON Complex issues of therapy proton pump inhibitors / / attending physician, 2007. - № 6.

14. Samsonov AA Proton pump inhibitors - drugs of choice in the treatment of diseases kislotozavisimyh / / Farmateka, 2007. - № 6 ..

15. Zimmermann JS Chronic gastritis and peptic ulcer disease / Essays clinical gastroenterology. - Vol. 1. - Perm, 2000. - 256.