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ILMIY METODIK JURNAL
Normal va Pathologist of Physiology Department , Pathologist of Physiology Assistant :
Xaqqulova Marta Alisherovna
Students :
Nusratova Elsevar, Kulmatov Husniddin
Institution: Tashkent State Medical University
NSAID-PATHOLOGICAL PHYSIOLOGY OF GASTROPATHY IN PATIENTS WITH
RHEUMATOLOGICAL DISEASES
One of the most important issues in modern rheumatology is the gastroduodenal side effects
associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), which can lead to
severe complications. NSAIDs most commonly have a damaging effect on the stomach and
duodenum, a condition termed "NSAID-induced gastropathy" or "NSAID-gastroduodenopathy
syndrome." The term "NSAID-gastropathy" was introduced in 1986 to distinguish specific
gastric mucosal lesions associated with NSAID use from classic gastroduodenal ulcers.
NSAID-Gastropathy refers to erosive-ulcerative lesions in the gastro-duodenal area that arise
from NSAID use, showing a characteristic clinical and endoscopic pattern. These lesions have
distinct features: they are often multiple, show mild symptoms, and carry a high risk of
gastrointestinal bleeding (GIB); there is a documented association with NSAID intake, with
localization primarily in the antral part (less frequently in the div of the stomach and
duodenum), absence of an inflammatory border around the ulcer; histological features include
foveolar hyperplasia of the mucosa; and relatively rapid healing after NSAID discontinuation.
The effects of aspirin and NSAIDs on the upper GI tract can lead to severe consequences,
including bleeding and perforation, underscoring the surgical implications of this issue.
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly used medications in
medical practice. Approximately 30 million people worldwide take these medications daily.
Each year, around 500 million prescriptions for NSAIDs are issued. About 10-20% of
individuals over 65 years old take or have taken NSAIDs. Self-administration of NSAIDs is
seven times higher than what is recommended by physicians. The expected use of NSAIDs is
likely to increase, associated with the rise of over-the-counter medications, an aging population,
and the growing frequency of aspirin being prescribed as an antiplatelet agent. Erosions and
ulcers of the gastric mucosa occur in 10-30% of individuals who take NSAIDs for an extended
period. With prolonged (more than 6 weeks) use of NSAIDs, gastro- and duodenopathies
develop in 70% of cases. Changes in the mucous membrane of the gastro-duodenal zone often
have a recurrent nature, with minimal subjective sensations or a complete absence of clinical
manifestations, which often leads to delayed consultations with a physician. In one-third of
patients who take NSAIDs for a prolonged period and have no symptoms related to the gastro-
duodenal zone (in 34% of cases), according to E.L. Nasonov and A.E. Karateev (2000),
characteristic endoscopic signs of NSAID gastropathy are revealed during preventive
esophagogastroduodenoscopy.
The significant increase in the consumption of NSAIDs has led to a rise in the frequency of
systemic toxic effects, primarily associated with damage to the gastric mucosa and the mucosa of
the duodenum. A distinctive feature of NSAID gastropathy is the involvement of the upper
gastrointestinal tract and its development typically in elderly patients rather than in younger ones.
The main mechanism of the therapeutic action of NSAIDs is associated with the interruption of
the cyclooxygenase (COX) pathway in the metabolism of arachidonic acid, which leads to the
JOURNAL OF IQRO – ЖУРНАЛ ИҚРО – IQRO JURNALI – volume 15, issue 02, 2025
ISSN: 2181-4341, IMPACT FACTOR ( RESEARCH BIB ) – 7,245, SJIF – 5,431
ILMIY METODIK JURNAL
suppression of prostaglandin synthesis—key products of inflammation. Currently, two forms of
COX have been discovered and studied: constitutive (COX-1) and inducible (COX-2). COX-1
protects the gastrointestinal mucosa, while COX-2 is involved in the production of
prostaglandins at the site of inflammation. The spectrum of primary physiological effects of
prostaglandins includes the stimulation of protective bicarbonate and mucus secretion;
enhancement of local blood flow in the mucosa; and activation of cell proliferation in the
processes of normal regeneration [1]. The inhibition of COX-2 activity is what determines the
anti-inflammatory effect. In the formation of both NSAID gastropathy and gastro-duodenal
peptic ulcers, significant importance is attributed to the disruption of the balance between
aggressive factors and the protective mechanisms of the gastrointestinal mucosa, with NSAIDs
affecting all levels of the intestinal barrier—pre-epithelial, epithelial, and post-epithelial [17, 18].
As etiopathogenetic factors in the development of NSAID gastropathy, the following factors are
considered: local irritation of the gastric mucosa and subsequent ulcer formation; inhibition of
the synthesis of prostaglandins (PG) (PGE2, PGI2) and their metabolites, prostacyclin and
thromboxane A2, in the gastric mucosa, which perform a cytoprotective function; and disruption
of blood flow in the mucosa against the background of prior endothelial damage to blood vessels
after taking NSAIDs [14]. The topical damaging effect of non-steroidal anti-inflammatory drugs
manifests in that after some time following the administration of these drugs, an increase in the
permeability of hydrogen and sodium ions into the mucosa is observed. NSAIDs suppress the
production of prostaglandins not only at the sites of inflammation but also at the systemic level,
so the development of gastropathy is a kind of programmed pharmacological effect of these
medications [11, 18].
It is suggested that non-steroidal anti-inflammatory drugs (NSAIDs) can induce apoptosis of
epithelial cells through pro-inflammatory cytokines. The use of these drugs damages the
hydrophobic layer on the surface of the gastric mucosa, depletes the composition of
phospholipids, and reduces the secretion of components of gastric mucus. In the mechanism of
the ulcerogenic action of NSAIDs, an important role is played by the alteration of lipid
peroxidation. The products formed from free radical oxidation lead to damage to the gastric
mucosa and the breakdown of mucopolysaccharides. Additionally, NSAIDs have a certain effect
on the synthesis of leukotrienes, and a decrease in their number results in a reduction of mucus
that possesses cytoprotective properties. A decrease in the synthesis of prostaglandins leads to a
reduction in the synthesis of mucus and bicarbonates, which are the primary protective barrier of
the gastric mucosa against the aggressive factors of gastric juice [2, 6, 8].
When taking NSAIDs, the levels of prostacyclin and nitric oxide decrease, which
adversely affects circulation in the submucosal layer of the gastrointestinal tract and creates an
additional risk of damage to the gastric mucosa and the duodenum. Changes in the balance
between protective and aggressive factors in the stomach lead to the formation of ulcers and the
development of complications such as bleeding, perforation, and penetration [15, 16]. To date,
the significance of Helicobacter pylori in the pathogenesis of NSAID gastropathy is not entirely
clear. Apparently, infection with H. pylori increases the likelihood of developing NSAID-
induced ulcers, erosions, and gastrointestinal bleeding [3].
The symptoms of the discussed pathology are well known to clinicians. These include pain
(more often in the epigastric region) associated with the intake of the medication (patients switch
to taking it after meals to reduce discomfort), dyspeptic syndrome—feelings of heaviness after
eating, a sense of rapid satiety, bloating in the epigastric area, and less frequently nausea and
vomiting. The pain and dyspeptic syndromes are not characterized by seasonality, unlike
"classical" gastro-duodenal ulcers [7]. Approximately 30-40% of examined patients undergoing
prolonged (more than 6 weeks) NSAID therapy report symptoms of dyspepsia that do not
JOURNAL OF IQRO – ЖУРНАЛ ИҚРО – IQRO JURNALI – volume 15, issue 02, 2025
ISSN: 2181-4341, IMPACT FACTOR ( RESEARCH BIB ) – 7,245, SJIF – 5,431
ILMIY METODIK JURNAL
correlate with the findings obtained during esophagogastroduodenoscopy. NSAID gastropathy
typically develops within the first 1-3 months of starting treatment; therefore, patients who have
just begun taking NSAIDs require increased attention from physicians for timely diagnosis of
complications. The highest likelihood of developing erosive and ulcerative lesions is observed in
the first month of NSAID use; thereafter, it decreases somewhat and remains stable over the
following years of treatment.
In NSAID-induced gastropathies, the development of erosions (often multiple) or ulcers
localized in the antral part of the stomach is typical. NSAID-induced ulcers are more often single,
relatively small, and shallow; multiple ulcers, contrary to popular belief, are relatively rare.
Individual pharmacodynamic characteristics of NSAIDs also play a role in the development of
NSAID gastropathies. Drugs in this group exert different effects on the activity ratio of COX
isoenzymes. According to this theory, the lower the concentration of the drug required to block
COX-1 (i.e., the lower the selectivity of the drug for COX-2), the more frequently it causes the
development of gastro-duodenal complications. Data from meta-analyses of population studies
show that the risk of developing gastro-duodenal complications decreases in the following order:
indomethacin – piroxicam – naproxen – diclofenac – ibuprofen.
The potential development of NSAID gastropathy can be predicted by considering risk factors
that have been identified by epidemiologists in the analysis of data obtained from retrospective
studies of large groups of patients taking NSAIDs. The presence of such factors is associated
with a significantly higher relative risk of developing serious gastro-duodenal complications at
the population level. Among the most important risk factors for NSAID-induced gastropathies
are a history of ulcers and older age (over 65 years) of patients. Additional risk factors include
concomitant use of anticoagulants and high doses of glucocorticoids, use of NSAIDs in high
doses, simultaneous use of multiple different medications from this group, and severe
comorbidities, primarily of the cardiovascular system [11].
The dose of the medication and the duration of treatment also affect the occurrence of NSAID
gastropathy. For instance, in patients over 60 years old, the risk of developing gastropathy
increases 2.8 times when doses exceeding standard levels by 1.5 times are prescribed, and it
increases 8 times when the doses are tripled. At the same time, it has been established that
erosive and ulcerative lesions of the stomach can occur even with treatment using low doses of
acetylsalicylic acid (150–300 mg/day), which is often prescribed for the prevention of
thrombosis in ischemic heart disease [19]. 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 correlation has been found between the route of
administration of NSAIDs (oral, parenteral, or rectal) and the frequency of developing erosive
and ulcerative lesions, as the primary ulcerogenic effect is due to the systemic toxic action of
NSAIDs. Treating NSAID gastropathy presents a challenging task, as complete cessation of
NSAIDs without prescribing acid-suppressive medications does not lead to healing of ulcers and
erosions in 60% of patients within the next 1-3 months. The goals of therapy include alleviating
clinical symptoms, epithelialization of mucosal defects, prevention of complications, prevention
of recurrences, and improving the quality of life for patients.
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JOURNAL OF IQRO – ЖУРНАЛ ИҚРО – IQRO JURNALI – volume 15, issue 02, 2025
ISSN: 2181-4341, IMPACT FACTOR ( RESEARCH BIB ) – 7,245, SJIF – 5,431
ILMIY METODIK JURNAL
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