How inhaled corticosteroids work in asthma
Inhaled corticosteroids are steroids that bind receptors inside cells and change gene transcription (how genes are read), which calms airway inflammation in asthma.
Remember
Inhaled corticosteroids calm the inflammation rather than open the airway, so their benefit builds over days to weeks and, used on their own, they are preventers (taken every day, even when there are no symptoms), not relievers (which open the airway).
Memory aid
bronchodilators open the airway now, steroids calm the inflammation that keeps narrowing it
It contrasts the quick opening effect of bronchodilators with the slower calming effect of steroids on the inflammation.
Inhaled corticosteroids such as beclometasone, budesonide, fluticasone and mometasone form the cornerstone of asthma maintenance, the regular treatment used to keep asthma controlled. Their target is the inflammation that lies behind the symptoms, not the tight muscle.
The drug crosses the cell membrane and binds a glucocorticoid receptor, a protein that the steroid attaches to, found in the cytoplasm (the fluid inside the cell). The steroid-receptor complex travels into the nucleus, where it alters gene transcription, the process in which a gene is read so that a protein can be made.
The cell then makes fewer cytokines, which are signalling proteins that act between immune cells, and fewer other inflammatory mediators (chemical signals that call in immune cells and cause swelling). With less inflammation the airway lining is calmer, so there are fewer symptoms and the risk of asthma attacks is lower.
One recognised route is that the activated receptor switches on the gene for lipocortin, a protein that is also called annexin A1 and inhibits phospholipase A2. The enzyme frees arachidonic acid, a fatty acid that the cell membrane stores, and cells convert it into prostaglandins and leukotrienes (inflammatory signals that cause swelling and airway narrowing). With less arachidonic acid freed, less of both is made.
Because the drug changes the proteins that cells make, the effect builds over days to weeks and does not relieve sudden breathlessness. Inhaled corticosteroids on their own are therefore preventers, not relievers: a reliever such as salbutamol opens the airway within minutes.
Key facts
- Where it acts
- inside the cell, where the steroid binds a glucocorticoid receptor in the cytoplasm before the complex moves into the nucleus.
- Main effect
- gene transcription changes, so the cell makes fewer cytokines and other inflammatory mediators.
- Lipocortin route
- receptor activation switches on the gene for lipocortin (annexin A1), a protein that inhibits phospholipase A2, so less arachidonic acid is available and fewer prostaglandins and leukotrienes are made.
- Onset
- the effect builds up over days to weeks, so inhaled corticosteroids on their own are preventers and not relievers.
- Secondary change
- inhaled corticosteroids also increase the number of beta-2 receptors on airway cells (the receptors that salbutamol stimulates to relax airway smooth muscle), a slower change that helps beta-2 agonists work.
Exam traps
- Inhaled corticosteroids do not work like aspirin by blocking cyclooxygenase (the enzyme aspirin blocks), because they act earlier in the pathway, where they cut off the supply of arachidonic acid.
- Salbutamol, a reliever, gives rapid bronchodilation (quick opening of the airway) within minutes; beclometasone does not, because it is a preventer.
- Blocking leukotriene receptors, as montelukast does, is not the mechanism of inhaled corticosteroids, because montelukast blocks one inflammatory mediator at its receptor, whereas inhaled corticosteroids act through receptors inside the cell.
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