- NSAIDs: Non-selective cyclo-oxygenase inhibitors
a. Arylanthranilic acids (mefenamic acid, meclofenamate)
b. Arylbutyric acids (nabumetone)
c. Arylpropionic acids (ibuprofen, ketoprofen, fenoprofen, naproxen, ketorolac)
d. Indene derivatives (sulindac)
e. Indole derivatives (indomethacin)
f. Naphthylacetic acid derivatives (nabumetone)
g. Oxicams (piroxicam, meloxicam, tenoxicam)
h. Phenylacetic acid derivatives (diclofenac)
i. Phenylalkanoic acid derivatives (flurbiprofen)
j. Pyrazolone derivatives (phenylbutazone, azapropazone)
k. Pyrrolealkanoic acid derivatives (tolmetin)
l. Salicylate derivatives (aspirin, diflunisal) - NSAID: Selective COX-2 inhibitors
a. Coxibs (celecoxib, rofecoxib)
This list provides examples for each category. There are other analogs as well, reflecting
the widespread use of these agents.
The nonsteroidal anti-inflammatory agents block the cyclooxygenase enzyme that
catalyzes the conversion of arachidonic acid to the prostaglandins PGG 2 and PGH 2.
Since these two cyclic endoperoxides are the precursors of all other prostaglandins, the
implications of cyclooxygenase inhibition are significant. Prostaglandin E 1 is known to
be a potent pyrogen (fever-causing agent), and PGE 2 causes pain, edema, erythema
(reddening of the skin), and fever. The prostaglandin endoperoxides (PGG 2 and PGH 2 )
can also produce pain, and inhibition of their synthesis can thus account for the action
of the nonsteroidal anti-inflammatory agents.
Most of the nonsteroidal anti-inflammatory drugs (NSAIDs) are carboxylic acids.
Aspirin (8.69) (acetylsalicylic acid, ASA) has been used since the turn of the last
century to reduce pain and fever, but the parent compound, salicylic acid, has been
known and used since antiquity, owing to its common occurrence as a glycoside in wil-
low bark. Acetylation merely decreases its irritating effect. Among the numerous other
salicylates known and used, flufenisal (8.70) has a longer duration of activity and fewer
side effects than aspirin. Mefenamic acid (8.71) and flufenamic acid (8.72) are deriva-
tives of anthranilic acid, while ibuprofen (8.73) and naproxen (8.74) are derivatives of
phenylacetic and naphthylacetic acids, respectively.
Among indole derivatives, indomethacin (8.75) is very widely used despite side
effects. Its indene analog sulindac (8.76) is a pro-drug, the active form being its —SH
derivative. Piroxicam (8.77) is a long-lasting anti-rheumatoid agent but can have seri-
ous gastrointestinal side effects. The once widely used phenylbutazone (8.78) deriva-
tives have too many side effects and have fallen into disrepute.
Among the nonselective cyclooxygenase (COX) inhibitors, there is no clear-cut
statistical evidence for the superiority of one or another of these useful drugs. Individual
patients may do better with some than with others, and there are differences in side
effects, primarily gastric bleeding and renal toxicity, which can be especially serious
with the prolonged administration of high doses—necessary in chronic diseases such as
ENDOGENOUS MACROMOLECULES 525