C H A P T E R 1 6
Anti-inflammatory, antiarthritis and related agents
249
stomach lining, regulation of blood clotting and water
and salt balance in the kidney. The COX-2 inhibitors are
thought to act only at sites of trauma and injury to more
specifically block the inflammatory reaction.
The adverse effects associated with most NSAIDs
are related to blocking of both of these enzymes and
changes in the functions that they influence—GI integ-
rity, blood clotting and sodium and water balance. The
COX-2 inhibitors are designed to affect only the activity
of COX-2, the enzyme that becomes active in response
to trauma and injury. They do not interfere with
COX-1, which is needed for normal functioning of these
systems. Consequently, these drugs should not have the
associated adverse effects seen when both COX-1 and
COX-2 are inhibited. Experience has shown that the
COX-2 inhibitors still have some effect on these other
functions, and people should still be evaluated for GI
effects, changes in bleeding time and water retention.
Recent studies suggest that they may block some pro-
tective responses in the body, such as vasodilation and
inhibited platelet clumping, which is protective if vessel
narrowing or blockage occurs; blocking this effect could
lead to cardiovascular problems. Box 16.5 summarises
the actions and adverse effects of the COX-1 and COX-2
receptors.
The NSAIDs are indicated for relief of the signs and
symptoms of rheumatoid arthritis and osteoarthritis, for
relief of mild to moderate pain, for treatment of primary
dysmenorrhoea and for fever reduction.
Pharmacokinetics
The NSAIDs are rapidly absorbed from the GI tract,
reaching peak levels in 1 to 3 hours. They are metabo-
lised in the liver and excreted in the urine. NSAIDs cross
the placenta and enters into breast milk. Therefore, they
are not recommended during pregnancy and breastfeed-
ing because of the potential adverse effects on the fetus
or neonate.
Contraindications and cautions
• The NSAIDs are contraindicated in the presence of
allergy to any NSAID or salicylate, and celecoxib
is also contraindicated in the presence of allergy
to sulfonamides. Additional contraindications are
cardiovascular dysfunction or hypertension
because
of the varying effects of the prostaglandins
; peptic
ulcer or known GI bleeding
because of the potential
to exacerbate the GI bleeding
; and pregnancy or
breastfeeding
because of potential adverse effects on
Specialists treating people with chronic pain have
petitioned to have the FDA return rofecoxib and valdecoxib
to the market, citing people who could only obtain relief
using those drugs. Some people only respond to these
particular NSAIDs, and these specialists feel that people
should have a choice, being informed of the risks, to
continue their use to relieve pain. Clearly, more long-term
studies are needed.The nurse may be asked about this
controversy and what recommendations are in place
by people who want relief from pain but really want to
understand the risks to their health.To get a complete
summary of the research, the report to the FDA, and current
recommendations and research, go to
and
click on NSAIDs under HotTopics on the right side of the
page.This site is updated regularly and offers information
geared to people and to healthcare professionals.
The evidence (continued)
BOX 16.4
COX-1
Site of action
Found in many tissues, important for homeostasis
Effects
• Converts arachidonic acid to inflammatory
prostaglandins
• Maintains renal function
• Provides for gastric mucosa integrity
• Promotes vascular haemostasis, increases bleeding
• Autocrine effects causing fever
Effects of blocking
• Decreases swelling, pain, inflammation
• Sodium retention, oedema, increased blood pressure
• Gastrointestinal erosion, bleeding
• Decreases fever
COX-2
Site of action
Induced by inflammatory stimuli at the site of
inflammation
Effects
• Increases pain, inflammation
• Vasodilates
• Blocks platelet clumping
Effects of blocking
• Decreases pain, inflammation
• Prevents protective vasodilation, allows platelet
clumping, which can lead to myocardial infarction and
cerebrovascular accident
• Myriad of skin reactions, including Stevens–Johnson
syndrome
■■
BOX 16.5
Comparison of cyclooxygenase (COX) receptors
