Pharmacology Focus: Asthma Medications – Part 2

 Preventers & Add-On Therapies

In Part 1, we explored bronchodilators – which treat bronchoconstriction, one part of the asthma puzzle. But asthma is fundamentally a chronic inflammatory disease, and ongoing airway inflammation needs long-term control to prevent symptoms, reduce exacerbations, and preserve lung function.

This is where preventers and add-on anti-inflammatory therapies come in.

🔥 What drives inflammation in asthma?

Asthma involves chronic inflammation of the airways, characterised by:

✅ Infiltration of eosinophils, mast cells, and T helper 2 (Th2) lymphocytes

✅ Release of pro-inflammatory cytokines (IL-4, IL-5, IL-13)

✅ Increased airway oedema, mucus hypersecretion, and airway hyperresponsiveness

This inflammation persists even when patients feel well — which is why preventers are used every day, not just during flare-ups.

🛡️ Inhaled Corticosteroids (ICS) – e.g. Budesonide, Fluticasone, Beclometasone

Mechanism of Action:

Bind to intracellular glucocorticoid receptors, modifying gene transcription → ↓ production of pro-inflammatory cytokines, ↓ eosinophil activation, ↓ mast cell numbers → reduced airway inflammation and hyperresponsiveness

📌 ICS are the first-line preventer in asthma, used daily for long-term control.

They improve symptoms, reduce exacerbation frequency, and may slow disease progression.

🧠 Link to pathophys: ICS target the core inflammatory processes in asthma — unlike bronchodilators, they modify disease activity, not just symptoms.

⚠️ Adverse effects:

Oral candidiasis (thrush) – due to local immunosuppression; reduced by using a spacer and rinsing the mouth after inhalation

Dysphonia (hoarse voice) – due to laryngeal muscle effects

At higher doses or long-term: systemic corticosteroid effects (rare when inhaled properly), e.g. adrenal suppression, bone density loss, bruising

💊 Leukotriene Receptor Antagonists (LTRAs) – e.g. Montelukast

Mechanism of Action:

Block cysteinyl leukotriene receptors (CysLT1) on airway smooth muscle and immune cells → ↓ leukotriene-mediated bronchoconstriction, mucus secretion, and inflammation

📌 Taken orally, once daily

Often used as an add-on in mild-to-moderate asthma, especially when there’s an allergic or exercise-induced component

Also used in children where inhaled therapies are challenging

🧠 Leukotrienes are key mediators released by mast cells and eosinophils — so this therapy helps dampen allergic-type inflammation.

⚠️ Adverse effects:

Generally well tolerated

Headache, gastrointestinal upset

Rare reports of neuropsychiatric symptoms (e.g. mood changes, vivid dreams, agitation, suicidal ideation rarely) – explain to patients and monitor - mechanism largely  unknown but several theories exist

💉 Monoclonal Antibodies (Biologics) – e.g. Omalizumab, Mepolizumab, Dupilumab

Used in severe asthma with poor control despite high-dose ICS + LABA.

🔹 Omalizumab – Anti-IgE

📌 Binds to circulating IgE, preventing it from activating mast cells and basophils → ↓ allergic inflammation

Used in allergic asthma with high IgE levels

🔹 Mepolizumab, Benralizumab – Anti-IL-5 pathway

📌 Target eosinophilic asthma by blocking IL-5 signalling → ↓ eosinophil survival and recruitment

🔹 Dupilumab – Anti-IL-4 receptor

📌 Blocks IL-4 and IL-13 signalling → broader anti-Th2 inflammation effects

💉 Given via subcutaneous injection every 2–8 weeks

Accessed via specialist referral and asthma biologic access criteria

⚠️ Adverse effects:

Injection site reactions

Hypersensitivity (rare)

Long-term safety still being studied, but well tolerated in trials

🧠 Key take-home points:

📌 Asthma is fundamentally inflammatory, not just bronchospastic

📌Inhaled corticosteroids are the cornerstone of preventer therapy

📌Add-ons like montelukast or biologics are selected based on phenotype (e.g. allergic, eosinophilic) and response

📌Preventers should be used daily, even when asymptomatic — asthma control is about preventing inflammation, not just reacting to symptoms

🧪Between bronchodilators and preventers, you now have a solid grasp of how we tailor treatment to the underlying disease process — not just the symptoms.