- Their main role is with the decreased formation of cytokines. Particularly, Th2 cytokines as these recruit and activate eosinophils, and are also released by eosinophils.
- They also reduce the production of the vasodilators PGE2 and PGE1, by inhibiting the production of COX-2.
- Ultimately, these two effects reduce the influx of eosinophils to the lung. Long term use of steroids will also ultimately reduce the responsiveness of the lung to bronchoconstrictors.
- There is also decreased production of IL-3 – which regulates mast cell production – and thus long term there are fewer mast cells residing in the lungs, and the early phase reaction is also inhibited (particularly useful in allergen and exercise activated disease).
- There is also upregulation of β2 receptors – which helps enhance the effect of β2 agonists.
- Beclomethasone – this is one of the most widely used inhaled corticosteroids. It is poorly absorbed by the gut (so reduces systemic availability when drug is swallowed). It is also inactivated very slowly once it enters the systemic circulation, and thus this is a draw back.
- Budesonide –undergoes massive fist pass metabolism if it gets into the systemic circulation, and is preffered to beclomethasone when large doses of drug are needed.
- Fluticasone – is very poorly absorbed from the gut, and is used in similar situations to budesonide.
- 5% will get oral candidasis (the risk can be reduced if you rinse out your mouth after each use – teeth cleaning can also reduce the risk, as can using a spacer)
- Hoarseness of the voice – as the drugs can affect the laryngeal muscles.
- Bone degredataion can occur in doses of beclomethasone over 800μg
- In children, doses over 400μg can cause short term growth retardation
- use of the drugs should be stepped down once the asthma is under control