title: [Pharmacology of cyclooxygenase 2 inhibition].
abstract: Prostaglandins are important modulators of pain and inflammation. Both, pain and inflammation can be inhibited either at the level of the phospholipase A2 by corticosteroids or at the level of the cyclooxygenase (COX) by non steroidal anti-inflammatory drugs (NSAIDs). Formally, "cyclooxygenase" in general was thought to be responsible for the synthesis of prostaglandins involved in pain, inflammation and fever as well as cytoprotection in the stomach, hemostasis and blood flow in the kidneys. Later, two isoenzymes, cyclooxygenase-1 and cyclooxygenase-2 were discovered. It was postulated cyclooxygenase-1 to exist constitutively and to be responsible for cytoprotection and hemostasis whereas cyclooxygenase-2 is inducible and involved in pain, inflammation and fever. In the meanwhile also constitutive cyclooxygenase-2 was discovered in various tissues. Cyclooxygenase-inhibitors may be divided into four groups: non selective ones (ibuprofen, diclofenac etc.), cyclooxygenase-1 selective inhibitors (SC-560), cyclooxygenase-2 preferential ones (meloxicam) and cyclooxygenase-2 selective inhibitors (celecoxib, rofecoxib, parecoxib). Selective cyclooxygenase-2-inhibitors in opposite to classic non steroidal anti-inflammatory drugs are without effect on bleeding time in therapeutic doses. The most important side effects of non steroidal anti-inflammatory drugs are bleeding, ulceration and perforation in the upper gastrointestinal tract and damage in the kidneys. Selective cyclooxygenase-2-inhibitors show less gastroduodenal ulcerations. Risk patients, however, still need gastroprotection during therapy with cyclooxygenase-2-inhibitors. In patients with low dose aspirin prophylaxis cyclooxygenase-2-inhibitors do not show any benefit compared to classic non steroidal anti-inflammatory drugs (CLASS-study). Less gastrointestinal side effects do not mean a higher overall safety benefit. Cardiovascular and thrombotic side effects of rofecoxib are higher than those of naproxen (VIGOR-study). Concerning valdecoxib, hypersensibilities are reported, probably due to its sulfonamidstructure. The same side effects are to be expected with its prodrug, parecoxib. Drug-drug interactions with cyclooxygenase-2-inhibitors and anticoagulant drugs are to be expected as well as other interactions with drugs, metabolised by the cytochrom P450 system.
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie, Universitätsplatz 4, A-8010 Graz. eckhard.beubler@uni-graz.at
authors.forename: Eckhard
authors.initials: E
authors.lastname: Beubler
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D004347:Drug Interactions; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases
vernacular_title: Pharmakologie der Cyclooxygenase-2-Inhibition.