Bronchodilators and Lung Anatomy

• In obstructive lung diseases like asthma, bronchodilators help keep airways open due to reversible narrowing.
• Bronchodilators are divided into four groups based on their mechanism: β2-agonists, muscarinic antagonists, leukotrienes antagonist, and methylxanthines.
• β2-agonists and muscarinic antagonists mimic or inhibit the autonomic nervous system's effects on bronchial smooth muscle.

Lung Anatomy and Autonomic Nervous System

• The trachea branches into bronchi, then bronchioles.
• Bronchioles contain the lumen, mucosa (epithelial cells and lamina propria with immune cells), smooth muscles, and submucosa.
• Smooth muscles are controlled by the autonomic nervous system: sympathetic ("fight or flight") and parasympathetic ("rest and digest").
• Sympathetic nerves release norepinephrine, which binds to β2 adrenergic receptors, relaxing smooth muscles and increasing airway diameter.
• Parasympathetic nerves release acetylcholine, which binds to muscarinic M3 receptors, contracting smooth muscles and narrowing airways.

Asthma and COPD

• Asthma and COPD narrow respiratory airways, obstructing airflow and causing wheezing, shortness of breath, and chest tightness.
• Asthma's airway narrowing results from reversible muscle spasms.
• COPD's airway narrowing results from irreversible chronic inflammatory damage.
• β2-agonists relax smooth muscles in asthma, while muscarinic antagonists prevent muscle contraction.
• Bronchodilators in COPD can prevent complete airway closure during expiration for symptomatic relief, despite the irreversibility.

β2-Agonists

• β2-agonists, administered via inhalers, bind to β2 adrenergic receptors on bronchial smooth muscle cells.
• Binding activates adenylyl cyclase, increasing cAMP production and relaxing smooth muscle.
• They are fast-acting and localized; thus, the preferred treatment for quick symptom relief with minimal side effects.
• β2-agonists stimulate β2 receptors on immune cells, decreasing inflammatory mediator release and inflammation.
• These events dilate narrowed airways and improve airflow.
• Inhaled β2-agonists are divided into short-acting (SABA) and long-acting (LABA) groups.

Short-Acting β2-Agonists (SABA)

• SABAs include albuterol, metaproterenol, and terbutaline.
• Inhaled albuterol produces bronchodilation within 5 minutes, lasting 2-4 hours.
• SABAs are best for acute asthma attacks and exercise-induced bronchospasm, but less useful for prophylaxis.
• Side effects of SABAs: tachycardia, palpitation, muscle tremors, restlessness, and insomnia (due to sympathetic stimulation).

Long-Acting β2-Agonists (LABA)

• LABAs include salmeterol and formoterol.
• LABAs have a slow onset, unsuitable for acute asthma attacks.
• LABAs' long duration (over 12 hours) makes them effective as twice-a-day prophylactic or maintenance therapy for asthma and COPD.
• Side effects of LABAs: similar to SABAs, but potentially exaggerated due to longer action, including arrhythmias that can lead to heart failure and death.
• LABAs are rarely used as monotherapy and are added to inhaled corticosteroids when symptoms are not well controlled.
• This combination reduces the dosage and systemic side effects of both medications.

Muscarinic Antagonists

• Muscarinic antagonists, administered via inhalers, bind to M3 muscarinic receptors on tracheal and bronchial smooth muscles.
• Binding blocks acetylcholine, reducing smooth muscle constriction.
• Ipratropium bromide (short-acting, 4-6 hours) and tiotropium bromide (long-acting, 24 hours) are commonly used.
• Muscarinic antagonists are less effective for asthma but more effective for COPD.
• For severe asthma and COPD, combining muscarinic antagonists with LABAs leads to stronger and longer-lasting effects.
• Side effects of muscarinic antagonists: tachycardia, dry mouth, restlessness, pupil dilation.
• Contraindications: narrow-angle glaucoma, as they relax ciliary muscles, worsening aqueous humor drainage obstruction.

Mnemonic Summary

• 2 headed bee for β2-agonists
• A 3 armed musketeer carrying a shield in each arm to represent the muscarinic antagonists that block the M3 receptors
• The bee relaxing with a tall friend(LABA) and a short friend(SABA)
• Albert Einstein represents albuterol. He's wearing a turban on his head for terbutaline, and on top of that is a metal helmet for metaproterenol.
• A wheezing jogger to help you remember SABAs are used for symptomatic relief during acute asthma attacks and exercise induced asthma.
• A very long salmon for salmeterol, wearing formal wear for formoterol.
• A cop for COPD and a no smoking sign for asthma prophylaxis.
• The angry racoon to represent sympathetic response. He’s sitting up in bed because he’s too angry to sleep, and his little heart is about to pop out of his chest represents side effects of β2-agonists
• Two tropical palm trees by the musketeer since they have “tropium” in their name.
• The shorter tree has a rat in it for the shorter acting ipratropium while the longer tree has ties hanging off of it for the long acting tiotropium
• Since they are more effective for COPD and less effective for asthma, let’s have a very buff cop holding a tiny no smoking sign.
• A girl who’s in love with the musketeer. Her hearts beating faster, she’s got dry mouth, and her pupils are dilated represents side effects
• Her eyes are almost popping out of her head, which represents the contraindication for people with glaucoma!

Quick Recap

• Obstructive lung diseases (asthma/COPD) are treated with bronchodilators that cause smooth muscle relaxation and bronchi dilation.
• This is achieved by stimulating β2 receptors with β2-agonists or inhibiting muscarinic M3 receptors with muscarinic antagonists.
• Short-acting β2-agonists (e.g., albuterol) treat acute asthma attacks and exercise-induced asthma.
• Long-acting β2-agonists and muscarinic antagonists are effective for prophylactic therapy for severe asthma and COPD.