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P A R T 3
Drugs acting on the immune system
the neonate or mother
. The risk for cardiovascular
dysfunction is increased with high doses, increasing
duration of use and in people with other CV risk
factors. The lowest effective NSAID dose should be
used for the shortest possible duration; caution should
be used with renal or hepatic dysfunction,
which
could alter the metabolism and excretion of these
drugs
,
and with any other known allergies,
which
indicate increased sensitivity.
• All NSAIDs (including COX-2 inhibitors) have been
associated with the development of acute kidney
injury. Acute kidney injury is more likely to occur
in individuals with other risk factors—particularly
hypovolaemic states. Renal function should be
monitored in at risk individuals. If acute kidney
injury occurs, the NSAID should be stopped.
NSAIDs should be avoided in people who develop
or have a history of interstitial nephritis.
• Colonic ulceration, perforation and haemorrhage
have been associated with NSAIDs. NSAID-induced
diaphragm strictures are usually found in the
ascending colon. Symptoms suggestive of ulceration
and diaphragm strictures in the large intestine are
chronic diarrhoea, iron deficiency anaemia and weight
loss, rather than pain and sub-acute obstruction.
Adverse effects
People receiving NSAIDs often experience nausea, dys-
pepsia, GI pain, constipation, diarrhoea or flatulence
caused by direct GI effects of the drug. The potential
for GI bleeding is often a cause of discontinuation of the
drug. Headache, dizziness, somnolence and fatigue also
occur frequently and could be related to prostaglandin
activity in the CNS. Bleeding, platelet inhibition and
even bone marrow depression have been reported with
chronic use and probably are related to the blocking
of prostaglandin activity. Rash and mouth sores may
occur, and anaphylactoid reactions ranging up to fatal
anaphylactic shock have been reported in cases of severe
hypersensitivity.
Severe cutaneous adverse reactions (SCARs) have
been reported with NSAIDs. These include bullous erup-
tions, erythema multiforme, epidermal necrolysis, toxic
epidermal necrolysis and Stevens–Johnson syndrome.
SCARs may cause permanent sequelae such as disfigure-
ment, blindness and death. Importantly, these reactions
may occur without warning.
Clinically important drug–drug interactions
There is often a decreased diuretic effect when these
drugs are taken with loop diuretics; there is a potential
for decreased antihypertensive effect of beta-blockers if
these drugs are combined; and there have been reports
of lithium toxicity, especially when combined with ibu-
profen. People who receive these combinations should
be monitored closely, and appropriate dose adjustments
should be made by the prescriber. Avoid the concomitant
use of more than one NSAID, or a NSAID with a COX-2
inhibitor and/or an anticoagulant where possible. If such
a combination is necessary, a gastro-protective agent
such as a proton pump inhibitor should be considered.
Prototype summary: Ibuprofen
Indications:
Relief of the signs and symptoms of
rheumatoid arthritis and osteoarthritis; relief
of mild to moderate pain; treatment of primary
dysmenorrhoea; fever reduction.
Actions:
Inhibits prostaglandin synthesis by blocking
cyclooxygenase-1 and -2 receptor sites, leading
to an anti-inflammatory effect, analgesia and
antipyretic effects.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
30 mins
1–2 hours
4–6 hours
T
1/2
:
1.8 to 2.5 hours; metabolised in the liver and
excreted in the urine.
Adverse effects:
Headache, dizziness, somnolence,
fatigue, rash, nausea, dyspepsia, bleeding,
constipation.
P
aracetamol
Paracetamol (
Dymadon, Panadol
) is used to treat
moderate to mild pain and fever and is often used in place
of the NSAIDs or salicylates. It is the most frequently
used drug for managing pain and fever in children.
It is widely available over the counter and is found in
many combination products. It can be extremely toxic.
It causes severe liver toxicity that can lead to death when
taken in high doses. Every year children die from inad-
vertent paracetamol overdose when parents give their
child more than one OTC drug containing paracetamol
or administer a high dose of paracetamol. The US FDA
and drug manufacturers have joined forces to produce
mass media ads warning parents about this possibility.
Therapeutic actions and indications
Paracetamol acts directly on the thermoregulatory cells
in the hypothalamus to cause sweating and vasodilation;
this in turn causes the release of heat and lowers fever.
The mechanism of action related to the analgesic effects
of paracetamol has not been identified.
Paracetamol is indicated for the treatment of pain
and fever associated with a variety of conditions, includ-
ing influenza; for the prophylaxis of children receiving
diphtheria–pertussis–tetanus (DPT) immunisations
