title: New insight into the mechanisms of gastroduodenal injury induced by nonsteroidal anti-inflammatory drugs: practical implications.
abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs), especially acetylsalicylic acid (ASA), are commonly used in the therapy of various diseases. However, the serious side effects of these drugs, such as bleedings, acute lesions, gastric ulcers, and even intestinal perforations, are widely recognized. NSAIDs inhibit cyclooxygenase (COX) activity resulting in the suppression of mucosal generation of gastroprotective prostaglandins (PGs) derived from a constitutive isoform, COX-1, as well as an inducible isoform, COX-2. COX-1-derived PGs are responsible for gastroprotection, while PGs generated via COX-2 activity also play an important role in gastroprotection and ulcer healing. Recently, a new class of NSAIDs has been developed by adding NO moiety to conventional NSAIDs. In contrast to native NSAIDs, their NO-releasing derivatives such as NO-ASA were found to exhibit lower gastric toxicity despite inhibiting both COX-1 and COX-2 activity in the gastric mucosa. Similar limited gastrointestinal toxicity and protective actions were observed with a new class of hydrogen sulfide (H₂S)-releasing NSAIDs, such as H₂S-releasing naproxen (ATB-346). Dual antiplatelet therapy with ASA and clopidogrel increases the risk of gastrointestinal bleeding in patients with acute coronary syndrome in whom concomitant treatment with a proton-pump inhibitor (PPI) was less effective owing to the interaction of clopidogrel and PPI with the same hepatic cytochrome P-450. In conclusion, new derivatives of NSAIDs releasing vasoactive gaseous mediators NO or H₂S are associated with fewer gastrointestinal adverse effects, suggesting that, in the future, they may be used as a safer alternative in everyday clinical practice and antithrombotic therapy.
authors: Sławomir
authors: S
authors: Kwiecień
authors: Katarzyna
authors: K
authors: Magierowska
authors: Zbigniew
authors: Z
authors: Śliwowski
authors: Dagmara
authors: D
authors: Wójcik
authors: Marcin
authors: M
authors: Magierowski
authors: Tomasz
authors: T
authors: Brzozowski
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004381:Duodenal Ulcer / Q000139:chemically induced* / Q000517:prevention & control; D005753:Gastric Mucosa / Q000187:drug effects; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000517:prevention & control; D006801:Humans; D012307:Risk Factors; D013270:Stomach / Q000187:drug effects*; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000517:prevention & control
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D001241:Aspirin