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NSAIDs induced gastropathy

Patophysiology, Prevention and Treatment

Chudahman Manan
Gastroenterology Division, Dept. of Internal Medicine
Medical Faculty Univ. Indonesia, Ciptomangunkusumo Hospital
Nsaids is the most etiology of acute gastric mucosal lesion. Patomechanism of NSAIDs
gastropathy due to 2 independent mechanisms: topical injury to the mucosa and systemic
depletion of cytoprotective prostaglandins.
Topical injury may occur because NSAIDs are weak acids, with pKas in the 3-5 range.
Thus, they are nonionized in the acidic environment of the stomach lumen, allowing them
to diffuse freely across cell membranes and accumulate in the neutral environment of the
mucosal cells.
Indirect topical injury can also occur due to the fact that some NSAIDs are prodrugs that
undergo enterohepatic circulation and can thereby damage the gastrointestinal mucosa
after conversion to the active metabolite.
However, it is the systemic effect of NSAIDs that appears to play the major role in the
pathogenesis of NSAID-induced injury. NSAIDs block the action of the COX enzyme,
which catalyzes the conversion of arachidonic acid to prostaglandins. The 2 COX
isoforms, COX-1 and COX-2, have contrasting functions. COX-1 is responsible for the
maintenance of normal cellular function in many types of tissue, including
gastrointestinal mucosa. By contrast, COX-2 is induced in inflammatory cells, and
inhibition of COX-2 activity appears to limit the inflammatory response.
The role inbalanced of acid as aggressive factor and some defensive factors mainly
prostaglandin make the condition of mucosa sensitive to influence of luminal contents,
and this condition appear after failure of mucosal adaptive process. The adaptive process
of mucosa is the natural condition of the body to counteract some action come from
luminal content of stomach. After 2 to 4 weeks the result of adaptive process success or
failure. If the adaptive process failure will make mucosal lesion, The most clinically
important aspect of NSAID-induced gastrointestinal injury is the occurrence of serious
complications such as gastrointestinal perforation, gastric obstruction due to peptic ulcer,
or hemodynamically significant GI bleeding.
According to patophysiology of NSAIDs induced gastropathy, the role of acid and mucus
barrier have predominat aspects for acute gastric mucosal lesions.
Management of NSAIDs gastropathy.
The clinical aspect for medical services, how to prevent or treatment however NSAIDs
still consumed by the patients. Prevention of NSAIDs gastropathy especially for the

patients with high risk group and treatment of mucosal lesion for the group patients must
be consumed the NSAIDs continuously.
The management of Nsaids gastropathy divided for 2 aspects according to
1. Direct effect of Nsaids to gastric mucosal, this condition strongly related to acid
concentration (pH) in the gastric lumen. PPI will be use for prevention in high risk group
and the treatment for patients with gastric mucosal lesion that Nsaids still consumed
continuously. PPI that control or decrease acid in the stomach are considered a valuable
palliative; if taken regularly while NSAIDs are used, they offer some protection to those
who must take NSAIDs.
All five PPIs appear to have similar efficacy in the treatment of various acid-peptic
disorders. The newer agents, rabeprazole, seem to have fewer drug interactions. This is
a particularly important consideration in older patients who are already taking several
other medications. While the average wholesale prices of all agents in this class are
Differences in the onset of action and the relative potencies of the various PPIs are
largely due to differences in the acid instability of the parent compounds. A PPI such as
rabeprazole, for example, is more acid unstable (ie, has a higher pKa) than the firstgeneration PPIs -- thus, in the parietal cell canaliculus, it is protonated earlier and at a
higher pH compared with omeprazole or lansoprazole.
Additionally, these investigators determined that rabeprazole achieved 88% of maximal
acid suppression after the first dose, versus 42% with omeprazole.
2. Systemic effect of Nsaids togastric mucosal, this condition strongly related to
defensive factors especially to thickness and quality of mucus. Human gastric mucins
play a major role in gastroprotection against acid and pepsin. Thus, the primary
function of MUC6 could be the protection of epithelial cells from endogenous agents
such as proteases, Mucus as the first mucosal barrier to prevent noxious agent in the
lumen to influence the epithel of gastric mucosa. Cytoprotector drugs will be use for
prevention and aggravation of mucosal lesion, although the patient consumed Nsaids
continuously. Teprenone have systemic effects for cytoprotection, to prevent and
treatment acute gastric mucosal lesion.
The double blind study of teprenone in Gastroenterology Division, Department of
Internal Medicine, co-operation with The Center of Clinical Drugs Study (PUKO),
Department of Pharmacology, Medical Faculty, University of Indonesia, for prevention
and treatment acute gastric mucosal lesions due to NSAIDs, clinical symptoms and
endoscopic appearance for the patients with teprenone consumed, have improved of
clinical symptoms (79.5%) and endoscopic appearance in the first week (p<0.0001)
and the second week (p<0.001). The result of study the teprenone group compared
with placebo group have significantly difference. (p<0.05)


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Dept of Internal Medicine, Medical Faculty University of Indonesia,
Ciptomangunkusumo Hospital