How they work

The mechanisms for each of the three drugs mentioned previously are slightly different, however they all involve the cyclo-oxygenase (COX) cycle. COX is responsible for catalysing the transformation of unsaturated fatty acids into prostaglandins.

Cyclo-oxygenase exists in two forms – in the tissues it is in the constitutive isoform (COX 1), but at the sites of inflammation it is present as another isoform (COX 2). Cytokines are responsible for the conversion between the two forms. The inhibition of the COX 2 isoform is responsible for the anti-inflammatory action, while the inhibition of the COX 1 isoform may be responsible for the adverse effect on the gastrointestinal tract, caused by gastrointestinal toxicity.

Aspirin irreversibly inhibits the constitutive form of the enzyme (COX 1). This results from steric hindrance of the enzyme’s active site to the substrate. While other NSAIDs are only reversible competitive inhibitors of the enzyme.

Paracetamol acts through a different mechanism again. It acts by reducing the cytoplasmic peroxide tone, peroxide is necessary to activate the haem enzyme (COX 1) to the ferryl form (COX 2). Paracetamol is relatively ineffective in areas of acute inflammation, because neutrophils and monocytes produce hydrogen peroxide and lipid peroxide in such high levels that the effects of the drug are overcome. Paracetamol is, however, effective in areas of inflammation where leukocyte infiltration is low.

The exact mechanism for ibuprofen is not entirely known. It is believed, however, that the anti-inflammatory effects are secondary to the inhibition of the release of prostaglandins. It is believed that the mechanism by which ibuprofen acts is closely related to that of aspirin and paracetamol.

Although it has not yet been proved, it is believed that ibuprofen’s analgesic, anti-inflammatory and antipyretic actions are linked to the inhibition of prostaglandin synthesis in the hypothalamus.