title: Cyclooxygenase-2 inhibitor celecoxib: a possible cause of gastropathy and hypoprothrombinemia.
abstract: Gastrointestinal side effects from nonsteroidal anti-inflammatory drugs (NSAIDs) result mainly from inhibition of the enzyme cyclooxygenase (COX)-1; it is responsible for the synthesis of prostaglandin E2, which leads to increased mucosal blood flow, increased bicarbonate secretion, and mucus production, thus protecting the gastrointestinal mucosa. In inflammation, COX-2 is induced, causing synthesis of the prostaglandins in conditions such as osteoarthritis and rheumatoid arthritis. Two NSAIDs (celecoxib and rofecoxib) with very high specificity for COX-2 and virtually no activity against COX-1 at therapeutic doses have been approved for clinical use. In trials of celecoxib and rofecoxib, only 0.02% of patients had clinically significant gastrointestinal bleeding, compared to a 1% to 2% yearly incidence of severe gastrointestinal side effects with NSAIDs. Our patient had arthritis of the hips and chronic atrial fibrillation and was on warfarin therapy for stroke prevention; less than a week after starting celecoxib therapy, gastrointestinal bleeding and hypoprothrombinemia occurred.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, 35294, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Linder
authors.forename: K E
authors.initials: KE
authors.lastname: Mönkemüller
authors.forename: J V
authors.initials: JV
authors.lastname: Davis
authors.forename: C M
authors.initials: CM
authors.lastname: Wilcox
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000925:Anticoagulants / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy; D001281:Atrial Fibrillation / Q000188:drug therapy; D001639:Bicarbonates / Q000378:metabolism; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced*; D006621:Hip Joint; D006801:Humans; D007020:Hypoprothrombinemias / Q000139:chemically induced*; D015994:Incidence; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007783:Lactones / Q000009:adverse effects; D008297:Male; D008565:Membrane Proteins; D009093:Mucus / Q000187:drug effects; D010544:Peroxidases / Q000037:antagonists & inhibitors*; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013449:Sulfonamides / Q000009:adverse effects*; D013450:Sulfones; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D001639:Bicarbonates; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D014859:Warfarin; D010544:Peroxidases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D015232:Dinoprostone