Cyclooxygenase inhibitors: any reservations?
The discovery of two cyclooxygenase isozymes, constitutive COX-1 and inducible COX-2, has resulted in the rapid development of selective inhibitors of COX-2, such as celecoxib and rofecoxib. Compared with traditional non-steroidal anti-inflammatory drug agents, use of COX-2 selective inhibitors is associated with decreased incidence of adverse gastric events as a result of minimal inhibition of gastroprotective COX-1, but with equivalent anti-inflammatory benefit through inhibition of COX-2. However, there is evidence to suggest that the 'COX-1 = constitutive, COX-2 = inflammatory' paradigm is less distinct than originally proposed. Futhermore, selective COX-2 inhibitors may have other consequences as a result of the change in the eicosanoid profile. Thus, despite the relatively safe gastrointestinal profile, vigilant post-marketing surveillance for other adverse effects is required.
Penglis
P S
PS
Rheumatology Unit, Royal Adelaide Hospital, South Australia. peter.penglis@student.adelaide.edu.au
James
M J
MJ
Cleland
L G
LG
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D015777:Eicosanoids / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D015777:Eicosanoids; D007527:Isoenzymes; D014409:Tumor Necrosis Factor-alpha; D011451:Prostaglandin-Endoperoxide Synthases