Gastropathies due to drugs toxins and other agents

Acetylsalicylic acid and other non-steroidal anti-inflammatory drugs

It is well known that acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs) can cause gastric injury including gastritis, gastric ulcers and gastrointestinal hemorrhage. Gastroduodenal damage can be seen at endoscopy in 20-40% of adults taking NSAIDs, and the overall risk for peptic complications (hemorrhage and perforation) in these patients is about three times greater than in controls.15 There are no data on the frequency of upper gastrointestinal injury in children related to NSAID use. Because of the risk of Reye syndrome and the availability of different types of antipyretic drugs, the use of acetylsalicylic acid and NSAIDs in children has significantly diminished.

The routine use of these drugs in different clinical conditions is associated with severe complications such as mucosal erosions and ulceration, and gastrointestinal bleeding. Endoscopic features include hemorrhagic gastric erosions (most often in the corpus) and gastric ulcers (mainly in the antrum). Histology shows foveolar hyperplasia, edema, vascular dilatation and congestion, increased smooth muscle fibers in the lamina propria and, characteristically, a relative paucity of inflammation. The term 'chemical gastritis' is usually employed for this condition.

Several mechanisms are thought to play a role in the pathogenesis of NSAID-induced injury, including inhibition of prostaglandin (PG) synthesis, increased platelet-activating factor, platelet dysfunction, increased oxygen free radicals, increased neutrophil adherence, decreased mucosal blood flow and topical irritant effects.16 Endogenous PGs are well-known mucosal defense factors, protecting the gastric mucosa against injury caused by a variety of toxic stimuli. PGs are synthesized through cyclo-oxygenase (COX), which is the target of NSAIDs. Two isoforms of COX molecules (COX-1 and COX-2) have been recognized. COX-1 is a constitutively expressed enzyme in many tissues, including the gastrointestinal tract, and is usually active, while COX-2 is an inducible enzyme predominantly expressed at the site of inflammation. It has been shown that the side-effects of NSAIDs are related to COX-1 affinity, while their therapeutic effects are dependent on activity against COX-2.17


The association between peptic ulcer disease and corticosteroids has never been accepted unequivocally. Ng et al described two cases of gastric perforation in preterm babies treated with dexametha-sone for bronchopulmonary dysplasia.18 A meta-analysis of 71 controlled studies performed by Messer et al demonstrated an increased risk for gastrointestinal ulceration and hemorrhage among adult patients who had received corticosteroids, and the risk was correlated with the dosage employed.19 Although to date there are no similar studies in childhood it is commonly agreed that, when steroids are administered to children for long periods, prophylactic therapy for gastric mucosal damage should be started concomitantly (see p.109).

Other agents

Gastropathies can be caused by a variety of drugs including potassium chloride, calcium, valproic acid, chemotherapeutic agents and antibiotics, such as penicillin, chloramphenicol, sulphon-amides, tetracyclines and cephalosporins. In neonates the administration of PGE1 can induce gastric outlet obstruction due to antral hyper-


In experimental animals, exposure to a high concentration of ethanol rapidly produces grossly evident focal hemorrhagic erosions. Chronic ingestion of alcohol may also result in human gastric pathology. Endoscopic findings include subepithelial hemorrhages ('blood under plastic wrap'), usually in the fundus and corpus, and small white-based erosions.21 Histology reveals areas of subep-ithelial hemorrhage, associated with superficial and deep epithelial damage, and marked edema of the surrounding mucosa. Inflammatory cell infiltrate is usually minimal. Experimental studies in animals have shown that alteration of the mucosal microcirculation might be an early event in the evolution of ethanol-induced gastric injury, as suggested by the occurrence of focal damage of mucosal capillaries and increased permeability within 1 or 2 min after intragastric instillation of a high concentration of ethanol.22

Gastric ulcerations have been reported in association with cocaine and methamphetamine abuse. In children requiring enteral nutrition, ulcers and small multiple erosions, usually localized in the proximal stomach, have been described after placement of gastrostomy feeding tubes. Subepithelial hemorrhages and focal erosions are commonly detected after ingestion of a foreign body or endoscopic procedures.

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