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9 Analgesics(PGI 2 )invascular endothelium. As a result, COX-2 inhibitors may alter the delicate
thromboxane/prostacyclin balance in favour of platelet aggregation, vasoconstric-
tion and thromboembolism.Other effects
Gastric irritation – intestinal erosions not limited to the stomach are commonly
encountered during prolonged administration of NSAIDs. These lesions result in
aspectrum of adverse effects from mild pain to iron deficiency anaemia and fatal
haemorrhage. Many elements (mucous layer, bicarbonate secretion, rapid cell
turnover and an abundant blood supply) are involved in the protection of the
intestinal mucosa against acid and enzyme attack. Prostaglandins are involved in
many of these elements so that when their synthesis is inhibited, protection is
reduced. During aspirin therapy acetylsalicylate and salicylate ions are trapped in
the alkaline environment of the mucosal cells thereby increasing their potential for
side-effects. The potential for haemorrhage is increased due to its effect on platelet
function. Meloxicam is more selective towards COX-2 and has been associated with
reduced gastric ulceration although a similar renal toxicity profile when compared
with other NSAIDs. Diclofenac blocks both forms equally while indomethacin and
aspirin have a much higher affinity for COX-1.
NSAID sensitive asthma – acute severe asthma may be precipitated in up to 20%
of asthmatics when given NSAIDs and is associated with chronic rhinitis or nasal
polyps. Those affected are usually middle-aged – children are relatively spared. By
inhibiting cyclo-oxygenase, more arachidonic acid is converted to leukotrienes
which are known to cause bronchospasm. Aspirin also causes an abnormal
reaction to the platelets of susceptible patients causing the release of cytotoxic
mediators.
Renal function – renally produced prostaglandins (PGE 2 and PGI 2 )areessential in
maintaining adequate renal perfusion when the level of circulating vasoconstric-
tors (renin, angiotensin, noradrenaline) is high. Aspirin and other NSAIDs may alter
this delicate balance by inhibiting their production, reducing renal perfusion and
potentially leading to acute renal failure. At low doses of aspirin (<2 g.day−^1 ), urate
is retained as its tubular secretion is inhibited. At higher doses (>5 g.day−^1 ), aspirin
becomes uricosuric as re-absorption of urates is inhibited to a greater degree. It is
rarely used for this purpose as the side effects at higher doses are unacceptable.
Analgesic nephropathy may develop after prolonged use of aspirin. The features
are papillary necrosis and interstitial fibrosis. NSAIDs may precipitate fluid reten-
tion and this may become significant in those with heart failure. COX-2 inhibitors
appear to lead to a greater degree of fluid retention and hypertension.
Platelet function – while altered platelet function may be advantageous in certain
circumstances (acute myocardial infarction and prevention of stroke), during the
peri-operative period it may cause increased blood loss. The reduced production