Page 108 - Athletic Health Handbook
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Mechanism of Action first of these new agents and quickly research design and lack of random-
and Usage of NSAIDs became the most widely prescribed ized, double-blind placebo control
and COX-2 Inhibitors NSAIDs in the United States. studies as major limitations to identi-
fying the benefits of NSAID use after
Conventional NSAIDs decrease Effects of NSAIDs on injury. Comparison among studies
inflammation by blocking both Musculoskeletal Injuries has yielded conflicting results related
cyclooxygenase (COX) enzyme to differences in the drug, dosage,
isoforms, COX-1 and COX-2, Clinical trials have demonstrated and severity of injury being investi-
and reduce pain by inhibiting that COX-1 NSAIDs can diminish gated. Given this cited disparity, it
prostaglandin (PG) production.2–4 symptoms after acute musculoskeletal is difficult to advocate or condemn
Prostaglandins stimulate local nocicep- injury, reduce inflammation, and aid the use of NSAIDs in the treatment
tors and enhance edema formation in the return to full function. The of acute soft tissue injuries.
by increasing vascular permeability. use of NSAIDs appears indicated
By limiting PG production through in the treatment of acute ligament Early Warnings with Celebrex™
the alteration of arachidonic acid sprains, muscle strains, tendonitis, and Vioxx™
metabolism, NSAIDs may affect and eccentric muscle injury.8 Non-
other physiologic functions such as COX-2 selective NSAIDs such as Amidst the attention surrounding
platelet aggregation, gastric function, diclofenac, piroxicam, nimesulide, these drugs was a concern that selective
and various effects in the kidney. naproxen, and ibuprofen are COX-2 inhibition might suppress
commonly used as adjunctive ther- prostacyclin, leaving platelet throm-
COX-1 inhibition by conventional apy in the treatment of acute joint boxane A2 relatively unopposed,
NSAIDs is known to cause gastroin- injury. COX-2 NSAIDs have also favoring thrombosis.15,16 Although
testinal (GI) effects, as well as exert demonstrated similar efficacy. selective COX-2 anti-inflammatory
adverse renal effects through its inhi- drugs were hypothesized to avoid the
bition of prostaglandin synthesis Clinical data have demonstrated renal and GI effects seen in COX-1
(Table 1).5-7 Because of these effects, the efficacy of NSAIDs for alleviating NSAIDs, data supporting this claim
exclusively blocking COX-2 mediated short-term mild to moderate pain is inconsistent at best. By October
inflammation and pain while main- and acute inflammation, but a less 2000, the FDA had received 233
taining COX-1 prostaglandin-medi- consistent association with long-term reports of renal failure associated with
ated GI and platelet function was healing of injured tissue.9–13 In a the administration of rofecoxib and
appealing. Celecoxib (Celebrex™) review of NSAID use in acute soft celecoxib.17 Annually, an estimated
and rofecoxib (Vioxx™) were the tissue injuries, Hertel14 cited poor

Table 1: Mechanism by which traditional and COX-2 selective NSAIDs inhibit COX enzymes
ARACHIDONIC ACID

Cyclooxygenase 1 [COX-1] Cyclooxygenase 2 [COX-2]
(constitutive) (induced by inflammatory stimuli)

COX-2-selective NSAIDs X

X Non-selective NSAIDs X

Prostaglandins Prostaglandins

Gastrointestinal cytoprotection Inflammation
Platelet activity Pain
Fever

COX-2 INHIBITORS AND NON-SELECTIVE NSAIDS 108
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