do with
increased frequency of gastroesophageal reflux disease, there is a marked reduction in the incidence
ulcer. So, if in the 70's and 80's of the last century
is general consensus that every tenth person in your life can get
ulcer disease [2], but now the prevalence of peptic ulcer disease
dropped several times and is, for example, is currently in the U.S.
2,5% [7]. At the same time, while maintaining the same level of frequency of perforation of ulcers
significantly increased the frequency of ulcer bleeding (with due
ulcers gastric localization), which is due to the increasing use of nonsteroidal anti-inflammatory dasgs
( NSAIDs) [8]. Still remain significant
costs associated with treating patients with peptic ulcer disease, which in the U.S.,
example, totals $ 3.1 billion, ranking 4 th place after the costs associated with
treatment of gastroesophageal reflux disease, gallstones,
colorectal cancer [7].

This positive trend is largely due to the change of our
views on the pathogenesis of peptic ulcer disease (first of all, with the discovery of the role
Helicobacter pylori (HP) in the development of peptic ulcer and its recurrence) and
review of approaches to its treatment. If earlier treatment of this disease
to recommend all kinds, including "Exotic" means (for example,
quail eggs, "live" and "dead" water, etc.) that served as VH Vasilenko
[1] the basis for the formulation of his famous aphorism ("
gastroduodenal ulcers heal with medication, without treatment and even in spite of treatment), then in 90gody
last century was created by the protocol of treatment of peptic ulcer,
based on current approaches and principles of pharmacotherapy of this disease.

Principles of pharmacotherapy of peptic ulcer:

the same approach to the treatment of gastric ulcers and duodenal ulcers;

mandatory basic antisecretory therapy;

choice of antisecretory product that supports the intragastric pH> 3
about 18 hours a day;

appointment antisecretory dasgs in a strictly defined dose;

endoscopic control with a 2- weekly intervals;

duration of antisecretory therapy, depending on the time of ulcer healing
;

H. pylori eradication therapy for HP-positive patients;

mandatory monitoring the effectiveness of therapy through antihelikobakterinoy 4-6
weeks;

repeated courses of therapy for Helicobacter its inefficiency;

supporting preventive treatment antisecretory dasg in HP-negative patients
;

influence on risk factors for poor response to therapy (replacement of NSAIDs
paracetamol, selective COX-2 inhibitor, a combination of NSAID with misoprostol ,
software complains of patients, etc.).

ulcer treatment protocol involves primarily holding
basal antisecretory therapy , which aims at arresting
pain syndrome and dyspeptic disorders, as well as achieving
scarring of the ulcer as quickly as possible.

In 1990, W. Burget et al. [6] published data meta-analysis of 300 papers,
under which concluded that the gastric ulcer and duodenal ulcer
scarring in almost all cases, if during the day can support
level of intragastric pH> 3, about 18 hours. Neither H ₂ blockers or
selective anticholinergics, antacids, and even less to fulfill this condition can not.
only proton pump blockers satisfy this requirement, which
explains why the latter group of dasgs are currently under
treatment of peptic ulcer are most effective.

pharmacotherapy protocol provides for the appointment of the base
antisecretory medication in a strict dose. Duration of treatment depends on the results
endoscopic control, which is performed with a two-week
intervals (ie at 4, 6, 8 weeks). To evaluate the effectiveness of a
antiulcer dasg use is not counted in the average time of scarring, and
frequency healed ulcers at 4, 6, 8, etc. weeks of treatment.

Although the mechanism of action of different proton pump inhibitors is the same (
blocking the activity of H +, K + ATPase of parietal cells), their effectiveness may be
uneven. Time of onset of action of these dasgs depends on how quickly they turn
from its inactive form into an active (sulfenamidnuyu).
For example, rabeprazole is transformed into its active form faster than
omeprazole, lansoprazole and pantoprazole, which causes amorerapid onset of its
the inhibitory effect compared to other proton pump blockers [5].
This makes the appointment of rabeprazole during basal
antisecretory therapy ismorepreferable. In addition, rabeprazole is less than
other proton pump blockers (eg, omeprazole), interacts with
system cytochrome P450 enzymes in the liver, resulting in, firstly, it
antisecretory effect appears to bemorestable and secondly, the metabolism of other dasgs
at his reception is not disturbed.

important principle of modern pharmacotherapy of peptic ulcer is
there are no fundamental differences in approaches to the treatment of gastric and duodenal ulcers
. Long been thought that duodenal ulcer
require use of antisecretory dasgs and ulcers of the stomach
dasgs that stimulate regeneration. It is now considered
acknowledged that after the confirmation of a benign nature of gastric ulcers
treatment of such patients is exactly the same as the treatment of patients with duodenal ulcers
(but only for a longer time, given the somewhat slow
Scarring of stomach ulcers).

"Achilles heel" of conservative treatment of peptic ulcer disease is as
known high recurrence rate of ulcers after the cessation of a course of treatment
exacerbation, which in the first year is 70%. This
served as the basis for appointment after course of treatment
maintenance pharmacotherapy . Most often, this purpose is practiced
daily intake of half-dose proton pump inhibitors, which reduces the frequency of
recurrence of ulcers during the year to 15%. Effectiveness of other ways to keep
antisecretory therapy "supporting self-medication"
(yourself treatment) or therapy "on demand" (on demand), when the patients themselves
determine the need for dasgs based on their well-being,
is less than high: the frequency of exacerbations of peptic ulcer disease during the year
of this treatment 3035%. Currently, when a pivotal role in the treatment of anti-
began to occupy antigelikobakterna therapy, indications for supportive therapy
antisecretory dasgs significantly narrowed. It is considered necessary in
HRotritsatelnyh patients with peptic ulcer (1520% of patients
with stomach ulcers, and about 5% of patients with duodenal ulcers), as well as patients,
which several attempts antigelikobakterna treatment with different
eradication schemes have been unsuccessful.

every patient with peptic ulcer, which in the gastric mucosa revealed
HP, one or another method (rapid urease test,
morphological method, with the help of DNA polymerase HP
chain reaction, etc.) is carried out eradication therapy .

This therapy includes a combination of several antibiotics.
In most schemes antigelikobakterna therapy include blockers of proton pump
that increasing the pH of gastric contents, creating unfavorable conditions for life
HP and, moreover, increase the efficiency of
antibiotics. In this case, the use of rabeprazole in the schemes of eradication therapy
should be considered preferable to other proton pump blockers
, given themorerapid onset of its antisecretory action
and over-explicit antigelikobakterna activity (in the conditions in
vitro ), which is conducive to and potentiates the effect of antibiotics. This allows us to avoid
prior appointment antisecretory dasgs (such as,
in cases of omeprazole) before the eradication.

decision of the Maastricht consensus conference of the European Group for the study of pyloric
gelikobaktera (1996) for the eradication therapy was
recommended the use of three possible schemes for 1st line, each of which is necessarily included in
designation of one of the proton pump inhibitors in standard doses
2 times a day and two antibacterial agents in various combinations and doses
.

HP eradication rate when applying these schemes exceeded 90%.

the ineffectiveness of schemes 1st line recommended scheme
eradication therapy 2nd line, the so-called Course quadrotherapy.

eradication therapy 2 lines

Blockers proton pump 2 times a day

colloidal bismuth subcitrate 120 mg x 4 times

Tetracycline 500 mg x 4 times

Metronidazole 250 mg x 4 times

duration of treatment in 7 days

As an alternative scheme proposed combination pilorida (ranitidine bismuth citrate
) 400 mg 2 times a day with one of the antibiotics
clarithromycin (250 mg, 4 times or 500 mg 2 times daily) or amoxicillin
(500 mg 4 times a day).

In recent years, during eradication therapy revealed
serious problems associated with growing resistance to antibiotics of strains of HP
dasgs in the first place, metronidazole (more than 30% of cases)
and clarithromycin (more than 10% of cases). In practical terms, this meant
significant reduction in the rate of eradication in the application of schemes whose composition
were given antibiotics. For example, in cases of resistance
HP to metronidazole and clarithromycin efficiency schemes,
containing these dasgs, decreased from 9,193% to 4,469%. Among the methods
overcome the resistance of HP strains to antibiotics
recommended:

increasing the duration of eradication therapy to 10-14 days (data
meta-analysis confirm the higher efficiency of this scheme compared with
7-day);

increase daily dose of clarithromycin (in combination with metronidazole and proton pump blockers
) from 500 to 1000 mg;

possibility of replacing metronidazole furazolidone.

most effective way to improve the effectiveness of eradication therapy
was considered the correct approach to the selection of one or another of its scheme, which was reflected in the recommendations
conference held in Maastricht in 2000 to
initiative of the European Study Group on Helicobacter pylori [4]. In
outcome document of this conference for the first time contained a proposal to plan
results of eradication therapy, allowing for its failures. Furthermore
, it was reduced the number of possible schemes antigelikobakterna therapy.

currently stored triple scheme of 1st line , containing
proton pump inhibitors (or ranitidine bismuth citrate) in a standard dose of 2
times a day in combination with antibacterial dasgs (Fig. 1). In this
combination of clarithromycin with metronidazole considered preferable,
because it can contribute to achieving the best result for
need subsequent appointment quadrotherapy.

Fig. 1. Algorithm for managing patients with peptic ulcer

protocol eradication therapy involves mandatory controls its
efficiency, which is held 4-6 weeks after its completion (in
this period the patient did not take antibiotics) using
breath test or polymerase chain reaction for detection of DNA HP
feces. When you save the HP in the gastric mucosa is carried re
course of eradication therapy with the use of therapy 2-nd line with subsequent
control of its effectiveness as 4-6 weeks (Fig. 1) that allows
to complete sanitation of the gastric mucosa and prevent the risk of
recurrence of peptic ulcer [3].

as 2nd line therapy has retained its value scheme quadrotherapy
(Fig. 1). In the absence of effect during the second year of follow-up treatment in
solved individually in each case.

ineffectiveness of conservative treatment of patients with peptic ulcer may
manifested in two ways: chastoretsidiviasyuschem during peptic ulcer disease (ie
with the frequency of exacerbations, 2 times a year and above) and the formation of refractory
gastroduodenal ulcers (ulcers, scarring is not within 12 weeks of continuous treatment
).

factors determining chastoretsidiviasyuschee for peptic ulcer disease,
are:

colonization of the gastric mucosa HP;

taking NSAIDs;

a history of peptic ulcer bleeding and perforation;

low "Compliance» (compliance ), ie lack of willingness of the patient to
cooperate with the doctor, which is manifested in the refusal of patients to stop smoking and
alcohol, irregular medication [8].

to activities that enhance the effectiveness of treatment of patients with
chastoretsidiviasyuschim course of peptic ulcer may include the following:

HP eradication, decreasing in its successful completion rate of recurrent ulcers
during the year from 70% to 4-5% and also reduces the risk of recurrent bleeding,

appointment of long-term maintenance therapy of antisecretory dasgs
patients with HP-negative peptic ulcer disease,

replacement of NSAIDs or paracetamol selective inhibitors of cyclooxygenase-2,

appointment with the need to continue taking NSAIDs appropriate
«cover" (proton pump inhibitors or misoprostol),

rise Compliance patients.

factors contributing to the formation of refractory gastroduodenal ulcers,
may make HP infection, intake of NSAIDs, low "Compliance" of patients, large and giant size
ulcer, latent syndrome ZollingeraEllisona [8].
Conduct mepropriyaty above, as well as increasing the dose of proton pump inhibitors
23 times, a careful examination of the patients in order to avoid
gastrinoma (primarily determine the level of seasm gastrin)
allow in many cases to solve successfully the problem of treating refractory ulcers.

Thus, the improvement of the results of conservative treatment of peptic ulcer
led to a radical change in approaches to treating patients, which resulted in a significant reduction
indications for operations for peptic ulcer disease (in
including ulcer bleeding) and was first put on the agenda
question of principle, curability of the disease.

Literature:

1. Vasilenko, WH What we do not know about peptic ulcer disease: Current issues
Gastroenterology. M., 1970. Vol.3. S.317

2. VH Vasilenko, comb, AL, Sheptulin AA Peptic ulcer disease. M., 1987.

3. Recommendations for the diagnosis and treatment of Helicobacter pylori infection in adults
gastric ulcer and duodenal ulcer / / Ross. Journ.
gastroenterol. gepatol. koloproktol. 1998. № 1. S.105107.

4. Diagnosis and treatment of infection Helicobacter pylori, modern
presentation (Report of the Second Conference on the adoption of the Maastricht consensus
2122 September 2000) / / Ross. Journ. gastroenterol. gepatol. kolproktol. 2000.
№ 6. P.79.

5. Besancon M., Simon A., Sachs A., Shin J.M. Sites of reaction of the
gastric H, KATPase with extracytoplasmic thiol reagents / / J.Biol.Chem. 1997.
Vol.272. P.2243822446.

6. Burget D.W., Chiverton K.D., Hunt R.H. Is there an optimal degree of acid
supression for healing of duodenal ulcers? A model of the relationship between
ulcer healing and acid supression / / Gastroenterology. 1990. Vol.99. P.345351.

7. Laine L. Peptic ulcer disease: where are we and where do we go from here?
AGA Postgraduate Course. May, 1819, 2002. Course syllabus. San Francisco, 2000.
P.2025.

8. Soll A.H. Peptic ulcer and its complications / / Sleisenger Fordtrans
Gastrointestinal and Liver Disease.
PhiladelphiaLondodnTorontoMonytrealSydneyTokyo. 1998. Vol.1. P.620678.

Published with permission from Russian
Medical Journal.