title: Drug insight: cyclo-oxygenase-2 inhibitors--a critical appraisal.
abstract: Following the withdrawal of rofecoxib and valdecoxib, the discussion concerning selective cyclo-oxygenase (COX)-2 inhibitors was often characterized more by emotions than scientific evidence. In fact, the original rationale of these substances is still valid, in that selective COX2 inhibitors cause significantly fewer severe side effects in the gastrointestinal tract than traditional NSAIDs. Off-label long-term use of COX2 inhibitors in patients with a history of colorectal adenomas in well-designed, placebo-controlled trials showed that treatment with these agents is associated with an increased rate of cardiovascular adverse effects. Other studies have shown that both COX2 inhibitors and NSAIDs are associated with a similar cardiovascular risk, suggesting that there is presently no rationale for a further differentiation of these groups of drugs in terms of cardiovascular toxicity. Referring to the current debate, potential mechanisms underlying cardiovascular adverse effects associated with the long-term use of COX2 inhibitors and NSAIDs are discussed. Moreover, this Review summarizes the pharmacology of COX2 inhibitors with emphasis on their different pharmacokinetic characteristics.
authors: Institute of Toxicology and Pharmacology, University of Rostock, Germany. burkhard.hinz@med.uni-rostock.de
authors: Burkhard
authors: B
authors: Hinz
authors: Bertold
authors: B
authors: Renner
authors: Kay
authors: K
authors: Brune
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000517:prevention & control; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D006801:Humans; D010146:Pain / Q000188:drug therapy; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D018570:Risk Assessment
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin