Chemical Properties
Celecoxib (Celebrex) and rofecoxib (Vioxx) are the two
available COX-2 inhibitors. Both lack a carboxylic
group present in most NSAIDs and therefore are able to
orient into the COX-2 enzyme in a selective manner that
differs from that of other NSAIDs.They have low aqueous
solubility that prevents parenteral administration.
Mechanism of action
As previously discussed, the COX-2 inhibitors have selectivity
for inhibition of the COX-2 enzyme, which has
low constitutive activity but is highly inducible at sites
of tissue injury. In addition to the peripheral role of
COX-2 in inflammation, COX-2 may play an important
role in the CNS. COX-2 is expressed constitutively in
some excitatory neurons in the brain and spinal cord
and is induced in traumatic brain injury such as that induced
by ischemia and seizures. It has been hypothesized
that COX-2 may also be involved in neurodegenerative
diseases, since COX-2 inhibitors have shown
some positive effects in Alzheimer’s disease. Thus, the
mechanism of action of COX-2 inhibitors may involve
brain and spinal cord sites as well as local sites of injury.
Clinical Use
Celecoxib has been approved for the treatment of osteoarthritis
and rheumatoid arthritis, and rofecoxib has
been approved for the treatment of osteoarthritis, acute
pain and primary dysmenorrhea. Celecoxib and rofecoxib
do not appear to differ in efficacy for the treatment
of osteoarthritis. However, neither drug has efficacy
greater than that of the non-selective NSAIDs.
Since the COX-2 enzyme appears to play an important
role in colon cancer the COX-2 inhibitors may find future
uses in the treatment or prevention of colorectal
cancer.
Side effects
The major advantage of the COX-2 inhibitors is their
decreased GI effects and formation of gastric ulcerations
compared with the COX nonselective agents.
However, once an ulcer is present, COX-2 is induced in
response, and the COX-2 enzyme is essential for wound
healing.Therefore, celecoxib and rofecoxib can delay in
wound healing and increase the time for ulcer repair
and tissue regeneration. Patients with gastric ulcers should be switched if possible to another antiinflammatory
to allow ulcers to heal.
Celecoxib is contraindicated during pregnancy, since
COX-2 levels must be maintained for ovulation and onset
of labor. COX-2 seems to be involved into the regulation
of the renin–angiotensin system, and both celecoxib
and rofecoxib use are associated with transient
sodium retention.
