Inhaled Corticosteroids

1. Introduction:

• Inhaled corticosteroids (ICS, also known as glucocorticosteroids, glucocorticoids, steroids) are by far the most effective controllers used in the treatment of asthma and the only drugs that can effectively suppress the characteristic inflammation in asthmatic airways, even in very low doses.

•  By contrast, ICS are largely ineffective in suppressing pulmonary inflammation in COPD and have a poor clinical effect. In both asthma and COPD ICS are commonly given as combination inhalers with long-acting β2-agonists (LABA).

2. Mechanism of action: 

Inhaled corticosteroids (ICS) have two main mechanisms of action in treating asthma:

• Non-genomic mechanism: ICS molecules intercalate into the phospholipid bilayers of cell membranes, altering membrane fluidity and rapidly changing cellular functions

This includes inhibiting the uptake of norepinephrine in airway smooth muscle cells, which increases the vasoconstrictor signal and decreases airway blood flow.

• Genomic mechanism: ICS molecules cross the cell membrane and bind to intracellular glucocorticoid receptors (GRs)

 The ICS-GR complex then translocates to the nucleus, where it binds to DNA and alters transcription of inflammatory genes

 This switches off multiple activated inflammatory genes that encode cytokines, chemokines, and adhesion molecules

3. Uses:

Inhaled corticosteroids (ICS) are primarily used to treat asthma and chronic obstructive pulmonary disease (COPD) 

. They are the most effective controllers of asthma symptoms and are recommended as first-line therapy for all patients with persistent asthma 

Key uses of inhaled corticosteroids include: 

• Reducing asthma symptoms and exacerbations 

• Improving lung function and quality of life in asthma patients 

• Allowing many asthma patients to lead normal lives 

• Reducing the need for oral corticosteroids in severe asthma 

• Decreasing the number Of COPD exacerbations and potentially slowing disease progression

4. contraindication: 

1. Hypersensitivity: Individuals who have a known hypersensitivity or allergic reaction to corticosteroids or any of the components present in the inhaled corticosteroid medication should not use it.

2. Active respiratory infections: such as severe bacterial or viral infections, as they may suppress the immune response and hinder the body's ability to fight the infection. 

3. Untreated fungal infections: Inhaled corticosteroids may worsen fungal infections in the mouth and throat.

4. Tuberculosis (TB): They should be used only in conjunction with appropriate anti-tuberculosis therapy and under the guidance of a healthcare professional.

5. Uncontrolled systemic infections: Inhaled corticosteroids may suppress the immune system and mask the signs of systemic infections. 

6. Pregnancy and breastfeeding: The use of inhaled corticosteroids during pregnancy and breastfeeding should be carefully evaluated by a healthcare professional. 

5. Side effects:

The side effects of inhaled corticosteroids can include:

1. Oral and throat irritation: Some people may experience mouth and throat irritation,. This side effect can be minimized by rinsing the mouth with water after each use.

2. Fungal infections: The use of corticosteroids may increase the risk of developing fungal infections in the mouth and throat (oral candidiasis). 

3. Difficulty speaking

5. Rare side effects: Rare side effects may include increased eye pressure (glaucoma), adrenal gland suppression, and decreased bone calcium.

6. Pharmacokinetics:

1. Absorption: Inhaled corticosteroids (ICS) are absorbed through the airway mucosa and alveolar surface, with some also swallowed and absorbed from the gut.

2. Distribution: Once absorbed, they reach systemic circulation, where they may undergo metabolism in the liver, particularly through first-pass metabolism.

3. Metabolism: ICS such as budesonide and fluticasone propionate undergo greater first-pass metabolism than beclomethasone dipropionate (BDP), impacting systemic effects.

4. Excretion: Metabolized corticosteroids are cleared from the body, with factors like lung bioavailability, oral bioavailability, systemic absorption, and protein binding influencing their excretion rates.

7. Examples of drug-drug interactions:  

1. CYP3A4 Inhibitors: Medications such as ketoconazole, ritonavir, and certain calcium channel blockers can inhibit the activity of the liver enzyme CYP3A4. This can lead to increased systemic exposure to the corticosteroid, potentially increasing the risk of systemic side effects.

2. CYP3A4 Inducers: Drugs like rifampin, phenytoin, and carbamazepine induce CYP3A4 activity, which may result in decreased systemic exposure to corticosteroids, reducing their efficacy.

3. Other Corticosteroids: Concurrent use of systemic corticosteroids with ICS may increase the risk of systemic corticosteroid effects, such as adrenal suppression.

4. Beta-blockers: Non-selective beta-blockers, when used concomitantly with ICS, may exacerbate bronchospasm in patients with asthma due to their antagonistic effect on beta-2 receptors.

5. Diuretics: Some diuretics, particularly loop diuretics like furosemide, may cause hypokalemia, which can increase the risk of cardiac arrhythmias when combined with corticosteroids.

8. Drug-Food interaction:

• • Grapefruit: can inhibit the activity of enzymes in the liver, including CYP3A4, which may affect the metabolism of certain medications. 

  • High-Fat Meals: can increase the systemic absorption of certain inhaled corticosteroids, potentially leading to higher blood levels and increased risk of systemic side effects. 

  •  Calcium-Rich Foods: may interfere with the absorption of corticosteroids when taken orally. However, since ICS are typically inhaled directly into the lungs, this interaction is less relevant.

  • Alcohol: alcohol intake can impair lung function and may exacerbate respiratory conditions such as asthma or chronic obstructive pulmonary disease (COPD). 

9. Doses: 

10.Monographs