title: Exacerbation of inflammatory bowel diseases associated with the use of nonsteroidal anti-inflammatory drugs: myth or reality?
abstract: BACKGROUND
  Nonsteroidal anti-inflammatory drugs (NSAIDs), conventional and selective cyclooxygenase-2 (COX-2) inhibitors, are among the most widely used medications for the treatment of various inflammatory conditions. There is strong evidence of a possible association between the use of these drugs and the relapse of inflammatory bowel diseases (IBD).
  
  
  OBJECTIVE
  Our objective was to examine the literature regarding the exacerbation of IBD associated with the use of conventional NSAIDs and selective COX-2 inhibitors and the underlying pathogenetic mechanisms.
  
  
  METHODS
  We reviewed articles, including original papers, controlled trials, case reports, reviews, and editorials published in English at the PubMed, Scopus Database, and Science Direct database, searching with the following keywords: nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, Coxibs, inflammatory bowel diseases (IBD), ulcerative colitis (UC), Crohn's disease (CD).
  
  
  RESULTS
  There is substantial evidence that exacerbation of IBD happens after treatment with NSAIDs, but the available data remain conflicting, and it is not clear whether selective COX-2 inhibitors are safer than traditional NSAIDs. However, there is some evidence that selective COX-2 inhibition and COX-1 inhibition (with low-dose aspirin) appear to be well-tolerated in the short term. Regarding the mechanisms of relapse, the reduction of prostaglandins appears to be the hallmark of the NSAIDs adverse effects.
  
  
  CONCLUSIONS
  Further randomized, double-blind, controlled trials should be performed to address this issue, and more in vitro studies to identify the pathways involved are required.
authors.affiliation: Clinical Pharmacology, Faculty of Medicine, University of Crete, Crete, Greece.
authors.forename: Helenie
authors.initials: H
authors.lastname: Kefalakes
authors.forename: Theodoros J
authors.initials: TJ
authors.lastname: Stylianides
authors.forename: George
authors.initials: G
authors.lastname: Amanakis
authors.forename: George
authors.initials: G
authors.lastname: Kolios
mesh_terms: D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects* / Q000494:pharmacology; D003093:Colitis, Ulcerative / Q000139:chemically induced; D003424:Crohn Disease / Q000139:chemically induced; D051545:Cyclooxygenase 1 / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects* / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects; D004359:Drug Therapy, Combination; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced*; D012008:Recurrence
chemical_list: D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human