Non-steroidal anti-inflammatory drugs (NSAIDs) and gastro-intestinal toxicity: current issues.
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs and their widespread use is associated with increased gastro-intestinal toxic effects such as ulceration, haemorrhage, perforation and death. They result in these complications mainly by reducing cytoprotective prostaglandins (PGE2 and PGI2) in the stomach, through the inhibition of cyclo-oxygenase (COX) enzyme. The increased morbidity and mortality, in addition to enormous cost, associated with NSAID-associated side effects, necessitates a need for safer GI-friendly NSAID. Various approaches have been used to counteract NSAID associated side effects with varying degrees of success and acceptance. These include the use of alternative analgesia, anti-acid secretory agents like proton pump inhibitors, sucralfate and prostaglandin analogues. In addition, new types of NSAIDs are being developed, based on new understanding of their mechanism of action and the pathogenesis of inflammation. These include a new class of NSAIDs called "selective Cox-2 inhibitors". These agents preserve the COX-1 that is responsible for the production of cytoprotective prostaglandins in the stomach and selectively inhibit COX-2 induced at the sites of inflammation. Selective COX-2 inhibitors exert the same analgesic and anti-inflammatory effects as the existing NSAIDs but may be less toxic to the stomach. In this review the background development and well-structured clinical trials on this new generation NSAIDs are discussed.
Shah
A A
AA
Department of Medicine/Gastroenterology, Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Republic of Ireland.
Fitzgerald
D J
DJ
Murray
F E
FE
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000517:prevention & control; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D010437:Peptic Ulcer / Q000139:chemically induced / Q000517:prevention & control
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes