Inhaled Corticosteroids

Mechanism of Action

When asthmatic patients are exposed to allergens, there is activation of Th2 cells (T helper cells), cytokine generation leading to differentiation and activation of eosinophils and IgE binding to receptors on mast cells and eosinophils.

Inhaled corticosteroids, or glucocorticoids, exert anti-inflammatory effects by regulating gene transcription via intracellular glucocorticoid receptors.

After entering cells, they bind to cytoplasmic glucocorticoid receptors, and the complex translocates to the nucleus. In simple terms, they suppress cytokine production, decrease microvascular permeability and inhibit eosinophil recruitment and survival. 

Actions of Glucocorticoids

• Induce biosynthesis of specific proteins like lipocortin 
• Inhibit transcription factors such as NF-κB and AP-1 leading to a reduction in pro-inflammatory cytokine gene expression
• Reduce cytokine production, including IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-13, IFN-gamma and TNF-α
• Decrease activation and proliferation of T lymphocytes, particularly Th2 cells
• Reduce eosinophil recruitment and survival (via inhibition of IL-5 and GM-CSF)
• Decrease IgE-mediated responses and mast cell activation
• Upregulate β2-adrenoceptors, enhancing responsiveness to β2-agonists
• Suppress cytokine-induced COX-2 expression.

Overall, this leads to reduced airway inflammation, decreased mucus production, and reduced airway hyperresponsiveness.

By TeachMeSeries Ltd (2026)

Fig 1: Main mechanisms of action of glucocorticoids. After entering the cell, they bind to cytoplasmic glucocorticoid receptors, and the complex translocates to the nucleus. The complex then modulates gene transcription either by inducing activation and repression of genes.

Pharmacokinetics

ICS are absorbed into the systemic circulation from the lungs and have a local anti-inflammatory effect on the bronchial mucosa. They are mainly metabolised by CYP3A4 after absorption via the lung. Specific pharmacokinetics for each ICS is outlined in the table below. 

Steroid Potency

Differing doses of inhaled corticosteroids can be categorised into low, moderate and high. Key points to note: 

• Fluticasone propionate is approximately double the potency of beclometasone dipropionate and budesonide. 
• Extra fine particle MDIs such as QVAR® are double the potency of regular MDI and DPIs for beclometasone such as Clenil®. 
• Fluticasone furoate (Revlar Ellipta®) is more potent than fluticasone propionate (Flixotide®/Seretide®). 

The table below provides specific examples of low, moderate and high dosing in people aged 12 years and over.

By TeachMeSeries Ltd (2026)

Fig 2: Table describing inhaled corticosteroid potency

Formulations

ICS are also available in combination therapies alongside LABA, and as triple therapy inhalers with LABA and LAMA. The table below describes ICS formulations available in the UK (without LABA/LAMA):

Cautions and Adverse Effects

Common side effects such as oral thrush, sore throat and a croaky voice can be prevented via the use of a spacer and rinsing the mouth after inhalation. 

Furthermore, visual disturbance from central serous chorioretinopathy (CSCR), cataract and glaucoma has been reported with topical corticosteroid use, therefore any blurred vision or visual disturbances should be referred to an ophthalmologist. 

In children, height should be monitored due to the risk of growth suppression. In addition to this, care should be taken in people with active/quiescent tuberculosis, and untreated infections. 

With inhalation therapies, there is a very rare risk of paradoxical bronchospasm, often attributed to non-active components in the formulation such as preservatives or propellants. Signs include immediate wheeze and shortness of breath after dosing, which can be treated with a fast-acting inhaled bronchodilator such as salbutamol. If this reaction occurs, therapy should be discontinued and an alternative sought. 

Adrenal Suppression

In patients on regular high dose ICS, adrenal suppression can occur, due to suppression of the patient’s ability to synthesise corticosteroids; this is less likely with fluticasone, mometasone and ciclesonide which all have a low systemic bioavailability. 

In severe hepatic dysfunction, glucocorticoid excretion may be reduced leading to increased systemic exposure, increasing the risk. Furthermore, there is an increased risk of systemic side effects when inhaled glucocorticoids are co-administered with CYP3A4 inhibitors such as ritonavir and ketoconazole, however the risk is less with beclometasone which is less dependent on CYP3A4 metabolism. 

Patients should be issued with steroid emergency cards if they have adrenal insufficiency and steroid dependence, as they are at risk of adrenal crises during illness and surgery. With inhaled therapies, this includes patients taking beclometasone >1000mcg daily or fluticasone >500mcg daily, furthermore patients on lower doses of ICS in combination with other glucocorticoids or with CYP3A4 inhibitors. 

Patients should be counselled to use a spacer with pMDIs, not stop ICS suddenly, carry their steroid emergency card, follow sick day rules (where applicable) and identify the signs and symptoms of adrenal suppression. 

Many patients requiring high doses of inhaled ICS may have also received oral steroids such as prednisolone to manage their symptoms (further increasing the risk of adrenal suppression) and some patients may have “rescue packs” prescribed for use in exacerbations. Patients may also require re-introduction of systemic steroid therapy during periods of stress or significant compromisation of the inhaled route of administration. 

Alongside adrenal suppression, systemic effects of inhaled corticosteroids may occur with high dose inhaled ICS therapy. These adverse effects include cushings syndrome, cushingoid features, reduced bone density, growth retardation in children, cataract, glaucoma, blurred vision and psychological effects such as insomnia, anxiety and depression.

References

1. Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan DJ. Rang & Dale’s Pharmacology. 9th ed. London: Elsevier; 2019. 
2. BNF Accessed 21/03/26
3. EMC Qvar Autohaler 100 micrograms – Summary of Product Characteristics (SmPC) – (emc) | 582 Accessed 21/3/26 
4. EMC Flixotide 50 micrograms Evohaler – Summary of Product Characteristics (SmPC) – (emc) | 3824 Accessed 21/3/26
5. NG245 asthma: Inhaled corticosteroid doses 12/11/2025 Accessed 21/3/26
6. Flixotide 50 micrograms Evohaler – Summary of Product Characteristics (SmPC) – (emc) | 3824 Accessed 22/3/26
7. Alvesco 160 mcg Inhaler – Summary of Product Characteristics (SmPC) – (emc) | 13890 Accessed 22/3/26