Sucralfate in the Treatment of Gastritis
A Review
COLIN L. SMITH, M.D. Southampton, England
astritis remains one of the most problematic dis-
G orders of the upper gastrointestinal tract etiolog-
ically, pathologically, and therapeutically. There are
many causes of gastritis, from acute toxins (alcohol)
and drugs (e.g., nonsteroidal anti-inflammatory
drugs) to the acute and chronic inflammatory gastritis
of CampyZobacter pyZori Cl] and the more complex
nonspecific acute and chronic inflammatory
gastritides of as yet unknown origin. In many pa-
tients, gastritis results from a combination of these
various origins. The result is that for investigations
and experimental studies it is increasingly difficult to
define gastritis with specificity. Animal studies at-
tempt to create individual types of gastritis, but many
forms of human gastritis cannot be found or created in
animals. Thus, experimental studies in animals have
the limitations of both etiologic and structural differ-
ences from humans, but conversely have the benefit of
allowing the study of specific-origin gastritis. None-
theless, in humans the most increasingly frequent
form of gastritis is that associated with nonsteroidal
anti-inflammatory drugs (NSAIDs), the prescription
rate for which is rising [S].
Whereas C. pylori-associated gastritis, although
not fully understood, can be improved by a variety of
agents including colloidal bismuth subcitrate [3], the
management of NSAID- or alcohol-induced gastritis
and ulceration has been, until recently, less clear. In
part, the damage is a consequence of the inhibition of
prostaglandin synthetase with secondary effects on
mucus and bicarbonate secretion, epithelial regenera-
tion, and intracellular biochemical integrity. These
changes alone do not explain all the injurious effects of
NSAIDs. NSAID toxicity does not necessarily corre-
late with the degree of cyclo-oxygenase inhibition
when? for example, aspirin is more injurious to the
gastric mucosa than other more prostaglandin-inhibit-
ing NSAIDs [4]. It may also be related to alterations
in the lipoxygenaseicyclo-oxygenase relationship [51.
It is established that NSAID-associated gastric and
duodenal ulceration will heal with any of the com-
monly used ulcer-healing therapies, both anti-acid
(histamine antagonists) [6,7] and “mucosal enhancers”
(e.g., sucralfate, [7,8]), but perhaps the most impor-
tant role is in the prophylaxis and treatment of gastri-
tis, nonspecific, alcohol-, aspirin:, or NSAID-induced.
This latter point is of particular importance, since the
continuance of NSAID therapy is often essential to
those with severe joint disease. Until now the per-
~ Medical Unit, Southampton General Hospital, Southampton,
From the Professorial
England. Requests for reprints should be addressed to Dr. Colin L. Smith, Professorial
Medical Unit, Southampton General Hospital, Southampton, SO9 4XY England.
70 June 9, 1989 The American Journal of Medicine
ceived wisdom has been to stop the NSAIDs until the
lesions have healed, despite some evidence that heal-
ing occurs while NSAID therapy is continued [?‘I. The
rationale for treatment would therefore be restoration
of those mucosal activities interrupted by the
NSAIDs or prevention of their interruption.
Sucralfate, an aluminium salt of sucrose octasul-
phate, is highly effective in healing acute peptic ulcers
E;L-:kuid protects the gastric mucosa against injury
USING LABORATORY ANIMALS
As indicated earlier, studies using laboratory ani-
mals are confined almost exclusively to those investi-
gating acute erosive or hemorrhagic necrotic gastritis
produced by a variety of noxious agents, including
ethanol, aspirin, sodium hydroxide, and thermal in-
jury. Sucralfate successfully protects gastric mucosa
against all of these agents [13-171 when given prior to
the damaging agent but is less effective if given after
the event. The mechanisms of action of sucralfate are
dealt with in great detail elsewhere in this supple-
ment, but in the context of gastritis sucralfate binds to
the ulcerated surface to provide a protective layer
[18,19] and increases gastric mucosal prostaglandin
production [14] in a dose-dependent manner [20,21], a
protective action similar to that afforded by exoge-
nous prostaglandins [22,231 or prostaglandin precur-
sors [24]. This protective effect of sucralfate on muco-
sal prostaglandins can be diminished by a dose of indo-
methacin [14] sufficient to inhibit prostaglandin syn-
thetase.
Although prostaglandin enhancement may be part
of the protective action of sucralfate, this action is not
the sole mechanism by which sucralfate acts. Some
studies would suggest that the protection is indepen-
dent of prostaglandin enhancement [25,26]. Sucralfate
increases mucosal bicarbonate and mucus secretion
[21,25,26] and although many of these increases are
consequent to prostaglandin activity and may be
blocked by indomethacin, in a number of studies they
have been shown to be independent of such a relation-
ship [25,26].
Whereas animal studies in general have studied the
protective effect of pretreatment with sucralfate, the
majority of cases of human acute gastritis, particu-
larly those related to NSAIDs, are to date treated
after the occurrence of damage and further differ from
those of animals in the time over which the damage
occurs and by the coexistence of other inflammatory
gastritis, infective or autoimmune.
STUDIES WITH HUMANS
As with the studies employing laboratory animals,
there is no doubt that sucralfate can protect against
Volume 86 (suppl 6A)