How are respiratory medications classified?

Classification of Respiratory Medications

Respiratory medications are classified into distinct pharmacological categories based on their mechanism of action and therapeutic purpose: bronchodilators (subdivided into β2-agonists, anticholinergics, and methylxanthines), anti-inflammatory agents (corticosteroids), mucolytics, antibiotics, and other specialized agents.

Primary Classification System

Bronchodilators

Bronchodilators work through direct relaxation of airway smooth muscle cells and represent the cornerstone of symptomatic treatment for obstructive airway diseases 1, 2.

β2-Adrenoceptor Agonists

• Short-acting β2-agonists (SABAs): Salbutamol (albuterol) and terbutaline, used for acute symptom relief 3, 4
• Long-acting β2-agonists (LABAs): Available as once-daily formulations (indacaterol, olodaterol, vilanterol) or twice-daily formulations (salmeterol, formoterol) 1, 2
• LABAs demonstrate efficacy in preventing COPD exacerbations, though with less effectiveness than long-acting antimuscarinics 5

Anticholinergic Agents (Muscarinic Receptor Antagonists)

• Short-acting antimuscarinics: Ipratropium bromide, used for acute exacerbations 3, 4
• Long-acting muscarinic antagonists (LAMAs): Available as once-daily (tiotropium, glycopyrronium, umeclidinium, aclidinium) or twice-daily formulations 1, 2
• LAMAs show superior efficacy versus LABAs in preventing COPD exacerbations and are recommended as first-line monotherapy 3, 5

Methylxanthines

• Theophylline: Oral bronchodilator requiring dose adjustment to achieve peak serum levels of 5-15 μg/L 3, 6
• The American College of Chest Physicians recommends avoiding intravenous methylxanthines during acute exacerbations due to increased side effects without added benefit 4

Anti-Inflammatory Agents

Inhaled Corticosteroids (ICS)

• Examples: Budesonide (Pulmicort respules), fluticasone propionate 3, 7
• Guidelines explicitly state that inhaled corticosteroid monotherapy is not recommended for stable COPD 3
• ICS should be combined with LABAs in fixed-dose combinations for maintenance therapy 3, 7

Systemic Corticosteroids

• Oral prednisone: 40 mg daily for exactly 5 days during acute exacerbations—no longer than 5-7 days total 4
• Oral administration is equally effective to intravenous and should be the default route 4

Combination Therapies

Fixed-dose combinations demonstrate superior efficacy to monotherapies:

• LAMA/LABA combinations: Show superior symptom control and exacerbation prevention versus monotherapies 3, 5, 2
• ICS/LABA combinations: Effective for preventing acute exacerbations, though with relatively higher pneumonia risk 3
• Triple therapy (LAMA/LABA/ICS): Recommended for patients with frequent exacerbations despite dual bronchodilation 3, 4

Antibiotics

Macrolides

• Azithromycin, erythromycin: Possess antimicrobial, anti-inflammatory, and immunomodulating effects 3
• Reduce exacerbation frequency by approximately 35-45% when used for chronic suppression 3

Acute Treatment Antibiotics

• First-line choices: Amoxicillin-clavulanate, macrolides, or tetracyclines for 5-7 days 4
• Indicated when increased sputum purulence occurs with either increased dyspnea or increased sputum volume 4

Nebulized Antibiotics

• Colistin, gentamicin, tobramycin: Used specifically for cystic fibrosis patients with established Pseudomonas aeruginosa infection 3
• Tobramycin demonstrates 7.8-12% improvement in FEV1 for moderate to severe CF lung disease 3

Mucolytics and Mucokinetic Agents

• N-acetylcysteine (NAC), erdosteine, carbocysteine: Oral agents evaluated for preventing COPD exacerbations 3
• rhDNase (dornase alfa): Nebulized agent specifically for cystic fibrosis 3
• 0.9% sodium chloride: Sometimes nebulized to assist physiotherapy; water should never be used as it causes bronchoconstriction 3

Phosphodiesterase Inhibitors

• Roflumilast: Oral selective phosphodiesterase-4 inhibitor for severe COPD with chronic bronchitis and history of exacerbations 3, 4
• Critical caveat: Roflumilast is only for prevention, never for acute exacerbations 4

Specialized Agents

For Cystic Fibrosis

• Pentamidine: Nebulized for HIV-positive patients as treatment or prophylaxis for Pneumocystis carinii pneumonia 3

For Palliative Care

• Lignocaine (lidocaine) 2%: Nebulized 2-5 mL to relieve severe non-productive cough in terminal care, preceded by β-agonist via hand-held inhaler 3
• Patient must remain nil by mouth for one hour afterwards 3

Route of Administration Classification

Inhaled Medications

• Preferred route to enable drugs to act directly on airways with better tolerability and safety profile than oral medications 3, 1, 2
• Delivered via metered-dose inhalers with spacers or nebulizers (equally effective, though nebulizers preferred for severely ill patients) 4

Oral Medications

• Categories: Antibiotics, corticosteroids, phosphodiesterase inhibitors (roflumilast, theophylline), mucolytic agents, and statins 3
• Selection depends on drug type, patient factors, and access to inhaled medications 3

Nebulized Medications

• Indications: Large drug doses needed, coordinated breathing difficult, hand-held inhalers ineffective, or drugs unavailable in inhaler form 3
• Gas flow rate of 6-8 L/min typically used to nebulize 50% of particles to 2-5 μm diameter for small airway deposition 3

Critical Clinical Distinctions

Oxygen versus air for nebulization:

• In acute severe asthma, oxygen is used to nebulize bronchodilators because patients are hypoxic 3
• In COPD, air should be used unless oxygen is prescribed, due to risk of carbon dioxide retention 3

Mouthpiece versus mask selection:

• Mouthpieces are mandatory for nebulized steroids (prevent facial deposition), antibiotics (allow filter use), and sometimes anticholinergics (prevent glaucoma exacerbation) 3
• Masks are better for acutely ill patients and young children 3