Authors: Graham, G.G.; Graham, R.I.; Day, R.O.

Source: Current Pharmaceutical Design, Volume 8, Number 12, 1 June 2002 , pp. 1063-1075(13)

Publisher: Bentham Science Publishers

Abstract:

Comparisons are made between the specific COX-2 inhibitors, celecoxib and rofecoxib, and acetaminophen. The specific COX-2 inhibitors are a significant advance in therapy because their antiinflammatory, analgesic and antipyretic activities are associated with a high degree of gastrointestinal safety. Acetaminophen is often not considered to be a potent inhibitor of COX-2 but it is a potent inhibitor of prostaglandin synthesis in intact cells after stimulation by cytokines. Its weak activity on the pathway of prostanoid synthesis involving COX-1 is shown by its weak anti-platelet activity and good gastrointestinal safety. The specific COX-2 inhibitors and acetaminophen are analgesic after dental surgery, orthopedic surgery and in osteoarthritis although acetaminophen appears to be a slightly weaker agent. The apparent analgesic activity of both the COX-2 inhibitors and acetaminophen may, in part, be due to their anti-inflammatory properties. Both groups of drugs also decrease the urinary excretion of prostacyclin metabolites consistent with inhibition of the systemic and renal activity of the COX-2 system. During repeated dosage with the specific COX-2 inhibitors, the 24 hour urinary excretion of sodium is only inhibited for the first day of treatment while the excretion of sodium is still decreased over the first 3 hours after the individual doses. Therapeutic doses of the COX-2 inhibitors and overdoses of acetaminophen have been associated with the development of occasional cases of acute renal failure. Acetaminophen also may decrease the excretion of sodium and the reason for its greater renal safety at therapeutic doses is unclear. Myocardial infarction has also been attributed to the specific COX-2 inhibitors from metaanalysis of large scale clinical trials and examination of reports of adverse drug reactions although this is still a topic of considerable discussion. No such associations have been made with acetaminophen, possibly because it is a weak inhibitor of COX-1 in platelets.

Keywords: analgesia; paaracetamol; rofecoxib; acetaminophen; celecoxib; gastrointestinal safety; osteoarthritis

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1381612023394917

Publication date: 2002-06-01

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• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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