242
P A R T 3
Drugs acting on the immune system
Salicylates are some of the oldest anti-inflammatory
drugs used. They were extracted from willow bark,
poplar trees and other plants by ancient peoples to
treat fever, pain and what we now call inflammation.
They are generally available without prescription and
are relatively non-toxic when used as directed. Aspirin
(
Aspro
,
Astrix
,
Cartia
,
Cardiprin
and others), which is
available OTC, is one of the most widely used drugs for
treating inflammatory conditions. Additional synthetic
salicylates include balsalazide (
Colazide
), mesalazine
(
Pentasa, Mesasal
) and olsalazine (
Dipentum
) which are
mostly used to reduce inflammation in ulcerative colitis
and other inflammatory bowel diseases. A person who
does not respond to one salicylate may respond to a dif-
ferent one.
Therapeutic actions and indications
Salicylates inhibit the synthesis of prostaglandin, an
important mediator of the inflammatory reaction
(Figure 16.1). The antipyretic effect of salicylates may
be related to blocking of a prostaglandin mediator of
pyrogens (chemicals that cause an increase in body tem-
perature and that are released by active white blood cells)
at the thermoregulatory centre of the hypothalamus. At
low levels, aspirin also affects platelet aggregation by
inhibiting the synthesis of thromboxane A
2
, a potent
vasoconstrictor that normally increases platelet aggrega-
tion and blood clot formation. At higher levels, aspirin
inhibits the synthesis of prostacyclin, a vasodilator that
inhibits platelet aggregation.
Salicylates are indicated for the treatment of mild to
moderate pain, fever and numerous inflammatory condi-
tions, including rheumatoid arthritis and osteoarthritis.
(See Box 16.3 and the Critical thinking scenario for
more on rheumatoid arthritis.) See Table 16.1 for usual
indications for each type of salicylate.
Pharmacokinetics
Salicylates are readily absorbed directly from the
stomach, reaching peak levels within 5 to 30 minutes.
They are metabolised in the liver to salicylic acid, an
active metabolite and excreted in the urine, with a
half-life of 15 minutes to 12 hours, depending on the
salicylate. Salicylates cross the placenta and enter breast
milk; they are not indicated for use during pregnancy or
breastfeeding because of the potential adverse effects on
the neonate and associated bleeding risks for the mother.
Contraindications and cautions
Salicylates are contraindicated in the presence of known
allergy to salicylates, other NSAIDs (more common with
a history of nasal polyps, asthma or chronic urticaria) or
tartrazine (a dye that has a cross-sensitivity with aspirin)
because of the risk of allergic reaction
; allergic reaction
to aspirin can induce bronchospasm and, in rare cases,
TABLE 16.1
DRUGS IN FOCUS Salicylates
Drug name
Dosage/route
Usual indications
aspirin (Aspro, Astrix)
Adult: 325–650 mg PO or PR q 4 hours
Myocardial infarction (MI): 300–325 mg PO
Paediatric: 65–100 mg/kg per day PO or PR in
four to six divided doses; if <2 years of age,
consult with prescriber
Treatment of fever, pain, inflammatory
conditions; at low dose to prevent the
risk of death and MI in people with
history of MI, prevention of transient
ischaemic attacks
balsalazide (Colazide)
Three 750-mg capsules PO t.d.s. for 8 weeks
Treatment of mildly to moderately acute
ulcerative colitis in adults
mesalazine (Pentasa,
Mesasal)
500 mg PO t.d.s.; one enema at bedtime, or
one suppository once daily
Treatment of ulcerative colitis and other
inflammatory bowel diseases in adults
olsalazine (Dipentum)
1 g/day PO in two divided doses
Treatment of ulcerative colitis and other
inflammatory bowel diseases in adults
Sensitivity to anti-inflammatory drugs
African Americans have a documented decreased
sensitivity to the pain-relieving effects of many of the
anti-inflammatory drugs.They do, however, have an
increased risk of developing GI adverse effects to these
drugs, including paracetamol.This should be taken into
consideration when using these drugs as analgesics.
Increased doses may be needed to achieve a pain-
blocking effect, but the increased dose will put these
people at an even greater risk for development of the
adverse GI effects associated with these drugs. Monitor
these people closely, and use non-drug measures to
decrease pain, such as positioning, environmental
control, physiotherapy, warm soaks and so on. If African
American people are prescribed anti-inflammatory
drugs, provide teaching about the signs and symptoms
of GI bleeding and what to report, and monitor regularly
for any adverse reactions to these drugs. Sensitivity
to anti-inflammatory drugs has been reported in other
ethnic groups such as Japanese, Koreans and Chinese.
However, evidence is still inconclusive and more
multicentre research in the future is needed to establish
pharmacogenetic considerations in prescribing NSAIDs
in some ethnic populations.
Cultural considerations
BOX 16.2
