Pharmacology Focus: Asthma Medications – Part 1

Bronchodilator therapies in Asthma

Asthma management isn't just about relieving symptoms — it's about understanding the underlying pathophysiology and targeting different mechanisms. Bronchodilators play a key role in managing airway narrowing, a hallmark of asthma, but they don't all work the same way.

Let’s look at the major bronchodilator classes used in asthma: short-acting β2 agonists (SABAs), long-acting β2 agonists (LABAs), and muscarinic antagonists (SAMAs and LAMAs) — and link them to the science behind the symptoms. 

🔬 A quick pathophysiology refresher

Asthma is a chronic inflammatory disorder of the airways. It involves: 

• ✅ Airway hyperresponsiveness
• ✅ Reversible airway obstruction (mainly due to bronchial smooth muscle contraction)
• ✅ Airway inflammation with oedema and mucus hypersecretion

Triggers (e.g. allergens, infection, exercise) can provoke bronchoconstriction, narrowing the airways and producing symptoms like wheeze, cough, chest tightness, and breathlessness. 

💊 So how do bronchodilators help?

They directly relax bronchial smooth muscle, targeting bronchoconstriction (but not inflammation).

🚑 Short-Acting Beta2 Agonists (SABAs) – e.g. Salbutamol (Ventolin)

Mechanism of Action:

SABAs stimulate β2-adrenoceptors on airway smooth muscle. This activates adenylate cyclase, increases cyclic AMP (cAMP), and activates protein kinase A, which inhibits myosin light chain kinase → leading to smooth muscle relaxation and bronchodilation.

🕒 Onset: 5–15 minutes | Duration: ~4–6 hours

📌 Used as needed for rapid relief of acute bronchoconstriction or prior to exercise

🧠 Link to pathophys: SABAs directly counteract bronchial smooth muscle constriction, a key driver of acute asthma symptoms. However, they don’t treat the underlying inflammation, which is why they are not suitable as long-term monotherapy. 

🛡️ Long-Acting Beta2 Agonists (LABAs) – e.g. Salmeterol, Formoterol

Same mechanism as SABAs, but with a longer duration of action (12–24 hours).

🧭 Formoterol has a fast onset and can be used for both symptom relief and maintenance.

Salmeterol has a slower onset and is generally maintenance.

📌 Used regularly, always in combination with an inhaled corticosteroid (ICS) for moderate-to-severe asthma. 

📌 Important safety note: LABAs must always be combined with an ICS in asthma treatment. Why?

LABAs treat the symptom of bronchoconstriction, not the cause — inflammation.

While patients may feel better due to the bronchodilation, the underlying airway inflammation continues unchecked, potentially worsening over time. 

• ❗ LABAs can mask worsening inflammation, giving a false sense of control and delay care-seeking
• ❗ Ongoing unchecked inflammation increases the risk of severe exacerbations
• ❗ Clinical studies have shown increased risk of asthma-related death when LABAs are used as monotherapy 

The combination of LABA + ICS ensures both symptoms and the disease process are addressed. This risk is why LABA monotherapy is contraindicated in asthma 

💨 Muscarinic Receptor Antagonists (Anticholinergics)

e.g. Ipratropium (SAMA), Tiotropium (LAMA)

These bronchodilators work via a completely different mechanism: they block the parasympathetic nervous system’s cholinergic input to the airways.

🔹 Short-acting muscarinic antagonist (SAMA) – Ipratropium

Mechanism of Action:

Blocks muscarinic M3 receptors on airway smooth muscle, preventing acetylcholine-induced bronchoconstriction and mucus secretion.

🕒 Onset: 15–30 minutes | Duration: ~4–6 hours

📌 Mainly used in acute severe asthma, often in emergency settings alongside salbutamol (dual bronchodilator nebulisers)

It is less potent and slower-acting than SABAs but may be beneficial in certain patients, especially where vagal tone contributes to bronchospasm.

🔹 Long-acting muscarinic antagonist (LAMA) – Tiotropium

📌 Used as a maintenance add-on in patients with persistent symptoms despite ICS + LABA, particularly older adults or those with asthma-COPD overlap

🧠 Especially useful when there's evidence of fixed airway obstruction or frequent exacerbations 

⚠️ Adverse Effects of Bronchodilators – Mechanism Matters

Although these drugs are inhaled to target the lungs, systemic absorption can still occur — particularly at high doses or with frequent use.

β2 Agonists (SABA and LABA):

• Tremor – due to β2 stimulation of skeletal muscle receptors, enhancing neuromuscular transmission
• Tachycardia / palpitations – either from β1 spillover at high doses or reflex tachycardia from peripheral β2-mediated vasodilation
• Hypokalaemia – β2 activation increases intracellular potassium uptake, lowering serum potassium
• Hyperglycaemia – β2 stimulation in liver promotes glycogenolysis and gluconeogenesis
• Headache, restlessness – possibly due to β2 stimulation in CNS or vasodilation

Antimuscarinics:

• Dry mouth – due to M3 receptor blockade reducing salivary gland secretion
• Blurred vision - from muscarinic blockade in the ciliary muscle of the eye, which impairs accommodation (focusing on near objects)
• Urinary retention – caused by inhibition of detrusor muscle contraction in the bladder (also mediated by muscarinic receptors), reducing the ability to void

These effects are rare and more likely with nebulised anticholinergics or in elderly patients, who may have reduced cholinergic reserve or comorbid conditions

Systemic effects are generally mild due to low absorption from the lungs

🧪 Addendum: What about theophylline?

Theophylline is an older bronchodilator in the methylxanthine class. You can see it in one of the diagrams below. Theophylline works by inhibiting phosphodiesterase (PDE) → leading to increased intracellular cAMP, promoting bronchodilation. It may also have mild anti-inflammatory effects via adenosine receptor antagonism.

So why don’t we use it much anymore?

•  Narrow therapeutic index – small margin between therapeutic and toxic plasma levels
•  High risk of side effects – including nausea, tremor, insomnia, and at high levels: seizures, arrhythmias
•  Numerous drug interactions – especially through the CYP450 enzyme system
•  Unpredictable pharmacokinetics – variable absorption and metabolism, requiring serum level monitoring

📌 Today, theophylline is rarely used in asthma management and generally reserved for specialist-directed care or settings where inhaled therapies are not feasible.

📍Next in Part 2: Preventer medications and anti-inflammatory therapies – we’ll unpack how inhaled corticosteroids, leukotriene antagonists, and biologics like anti-IgE target the inflammatory cascade driving long-term asthma.