Pharmacology for Anaesthesia and Intensive Care

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9 Analgesics

Non-specific COX inhibitors

Salicylates

Aspirin

Uses

Aspirin (acetylsalicylic acid) is widely used for its analgesic and anti-inflammatory

effects. It is also used for its effects on platelet function in acute myocardial infarction

and the prevention of stroke.

Mechanism of action

Atlow dose, aspirin selectively inhibits platelet cyclo-oxygenase while preserving

vessel wall cyclo-oxygenase. This has the effect of reducing TXA 2 -induced vaso-

constriction and platelet aggregation while leaving vessel wall synthesis of prostag-

landins unaltered and, therefore, dilated.

Other effects


Metabolic – aspirin also has effects on the metabolic state, which are usually of

little significance, but in overdose these become significant. It uncouples oxida-

tive phosphorylation, thereby increasing oxygen consumption and carbon dioxide

production. Initially minute ventilation is increased to keep PaCO 2 static. However,

when aspirin levels are increased significantly the respiratory centre is stimulated

directly causing a respiratory alkalosis. The picture is complicated in the premor-

bid state by a metabolic acidosis. However, in children the respiratory centre is

depressed by rising aspirin levels, and a metabolic acidosis occurs earlier so that a

mixed respiratory and metabolic acidosis is more common.

Features of aspirin overdose

Common


Usually conscious – only unconscious in massive overdose


Sweaty


Tinnitus


Blurred vision


Tachycardia


Pyrexia


Hyperventilation


Respiratory alkalosis (subsequently complicated by metabolic acidosis)

Rare


Nausea and vomiting, epigastric pain


Oliguria


Gastrointestinal bleed