Modern approaches to primary prevention of NSAIDs-gastropathy and enteropathy
In the article the underlying mechanisms of NSAIDs-induced injuries of upper (stomach and proximal duodenum) and lower (small intestine) gastrointestinal tract are discussed. The distinct mechanisms of NSAID-induced injury in the stomach/proximal duodenum versus the more distal small intestine likely dictate distinct strategies for prevention, such as use of PPI, COX-2-inhibitors, prostaglandins, antibiotics and probiotics, new combination of NSAIDs with phosphatidylcholine, NO or H2S. Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed medications in the world. Unfortunately, extensive usage of NSAIDs to relieve pain and inflammation is limited because of its considerable gastrointestinal toxicity. Previous clinical and experimental studies having been focused mostly on NSAID-induced injuries of the gastroduodenal area, now researchers'' interest has shifted to NSAID-induced injuries of the small intestine, the so-called NSAID enteropathy, which have proved to occur much more often than it was suggested earlier. Since video capsule endoscopy (VCE) and new types of enteroscopy were introduced into practice, it has turned out that occurrence of intestinal injuries in healthy volunteers taking aspirin or NSAIDs can reach 75% of all the cases. Unfortunately, NSAID enteropathy is either not diagnosed or simply ignored in overwhelming majority of cases before VCE is performed. A pathognomic sign of NSAID-induced injury is development of concentric ''diaphragmlike'' strictures on the small intestine which develop because of scarring after healing of ulcerous intestinal lesions and cause nonspecific symptoms or intestinal obstruction. Histologically, these strictures are characterised by the development of fibrosis in the submucous layer and thickened muscular layer of the mucosa. As the muscular layer of the small intestine itself is usually intact, the risk of perforation of the intestine in its balloon dilation is low. That is why this method of stricture treatment is preferable to a surgical intervention. The relative risk for developing diverticulitis or diverticular bleeding in individuals taking NSAIDs or aspirin ranges from 1.8 to 16.7. However, though COX-2 selective inhibitors provide better tolerance and safety, they cannot prevent all gastrointestinal side effects of NSAIDs; besides, they possess certain cardiovascular toxicity. That is why at present it is highly desirable to develop and introduce into clinical practice effective anti-inflammatory drugs whose safety profile should be better than that in the NSAIDs used now.