Inhaled Corticosteroids
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Introduction

Inhaled corticosteroids (ICS) are used for their anti-inflammatory effects in asthma and COPD.
They are available as single agents, or in combination with other inhaled medications, such as beta-agonists (e.g. salbutamol or formoterol) and anti-muscarinic agents (such as tiotropium).
Inhaler technique is an important part of appropriate use, including the use of a spacer with metered-dose inhalers (MDI – aerosol type), and it is important to warn patients about the risk of oral thrush, and to wash their mouth out with water after use to reduce this risk.

Mechanism

  • 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.
For further information on the systemic effects of steroids see the Cushing’s disease notes.

Pharmacokinetics

The full effect of these drugs is only seen 1-2 weeks of daily inhalation, however, the initial effects occur just 6-12 hours after first use.
Generally the drugs only ever exhibit systemic effects when inhaled in very high doses.

Unwanted effects

The side effects of inhaled corticosteroids are much less than those seen with prolonged or frequent use of oral corticosteroids. The systemic effect is much less when compared to the oral drugs. However, risks – albeit small – are still present and many patients or parents can be understandably anxious about ICS use.

  • 5% will get oral candidiasis – thrush –  (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)
  • Dysphonia – hoarseness of the voice – as the drugs can affect the laryngeal muscles.
  • Bone degradation and osteoporosis can occur in doses of beclomethasone over 800μg
  • In children, doses over 400μg can cause short term growth retardation
    • Reassure parents that the effect is thought to be small
    • Use the smallest effective dose
    • Advise parents that poorly controlled asthma can also result in reduced growth
  • Increased risk of cataracts
  • Use of the drugs should be stepped down once the asthma is under control

Drugs

  • 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.
  • Fluticasoneis very poorly absorbed from the gut and hence not used orally, but is useful for respiratory indications and is used in similar situations to budesonide
    • Be aware there are two preparations. The commonly use fluticasone propionate and the much stronger, but less frequently use fluticasone furoate. Be careful when prescribing as the doses are different, and fluticasone furoate should not be used in children
  • Mometasone
  • Ciclesonide
  • Hydrocortisone

Clinical use

In asthma, if a patient is using an inhaled β2 agonists more than once per week, then they should also consider using an oral steroid as a preventative. – they are first introduced on step 2 of the asthma management scale.
In COPD, a similar step-wise approach to management is used, but steroids are typically introduced later in this step-wise process:
  • Step one – short acting broncodilators, including beta-agonists and anit-muscarinic agents
  • Step two – long acting bronchodilators (+ short acting bronchodilators)
  • Step three – Add inhaled corticosteroids to step two

References

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Dr Tom Leach

Dr Tom Leach MBChB DCH EMCert(ACEM) currently works as a GP Registrar and an Emergency Department CMO in Australia. He is also a Clinical Associate Lecturer at the Australian National University. After graduating from his medical degree at the University of Manchester in 2011, Tom completed his Foundation Training at Bolton Royal Hospital, before moving to Australia in 2013. He started almostadoctor whilst a third year medical student in 2009. Read full bio

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