Respiratory agents

Respiratory agents are a diverse group of pharmacological products used to prevent, relieve, or treat a wide range of respiratory tract diseases and pulmonary pathologies. These conditions include asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, pulmonary arterial hypertension, interstitial lung diseases, acute respiratory infections, and chronic bronchitis, among others. Respiratory agents work by modulating airway tone, reducing inflammation, diluting mucus, treating infections, or improving oxygenation and ventilation.

The spectrum of respiratory agents includes bronchodilators, inhaled corticosteroids, antileukotrienes, mucolytics, anti-infectives, oxygen therapy, monoclonal antibodies, and systemic agents affecting pulmonary physiology. Their routes of administration vary and include inhalation, oral, intravenous, subcutaneous, and intramuscular.

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1. Classification of Respiratory Agents

Respiratory agents can be classified into the following main categories:

A. Bronchodilators

Used to relax smooth muscles of the bronchial tree and widen the airways, improving airflow.

i. Beta-2 Adrenergic Agonists

• Short-acting (SABA):

  • Albuterol (Salbutamol) – Ventolin, ProAir

  • Levalbuterol – Xopenex

• Long-acting (LABA):

  • Salmeterol – Serevent

  • Formoterol – Foradil

  • Indacaterol, Vilanterol, Olodaterol

Mechanism: Activate β₂-adrenergic receptors → ↑ cAMP → bronchial smooth muscle relaxation.

ii. Anticholinergics (Muscarinic Antagonists)

• Short-acting (SAMA): Ipratropium bromide

• Long-acting (LAMA):

  • Tiotropium – Spiriva

  • Aclidinium, Glycopyrrolate, Umeclidinium

Mechanism: Block muscarinic M3 receptors → inhibit bronchoconstriction.

iii. Combination Bronchodilators

• SABA + SAMA: Albuterol + Ipratropium (Combivent)

• LABA + LAMA: Vilanterol + Umeclidinium (Anoro Ellipta)

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B. Anti-Inflammatory Agents

i. Inhaled Corticosteroids (ICS)

• Beclomethasone, Budesonide, Fluticasone, Ciclesonide, Mometasone

Mechanism: Inhibit phospholipase A2 → reduce prostaglandins, cytokines, and chemokines.

ii. Systemic Corticosteroids

• Prednisone, Methylprednisolone, Dexamethasone

• Used in acute exacerbations, ARDS, or severe asthma

iii. Leukotriene Modifiers

• Montelukast, Zafirlukast, Zileuton

• Oral agents used in asthma, allergic rhinitis

Mechanism: Inhibit leukotriene synthesis or block leukotriene receptors → reduce bronchoconstriction and inflammation.

iv. Mast Cell Stabilizers

• Cromolyn sodium, Nedocromil sodium

• Rarely used now due to low efficacy and short duration

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C. Monoclonal Antibodies and Biologics

Used in severe eosinophilic or allergic asthma, chronic urticaria, or other rare pulmonary conditions.

Agent	Target	Indications
Omalizumab	IgE	Allergic asthma
Mepolizumab	IL-5	Eosinophilic asthma
Benralizumab	IL-5 receptor α	Severe eosinophilic asthma
Dupilumab	IL-4/IL-13	Asthma, chronic rhinosinusitis
Tezepelumab	TSLP	Severe asthma (non-eosinophilic inclusive)

D. Mucolytics and Expectorants

Used to thin or liquefy thick respiratory secretions.

• Dornase alfa (Pulmozyme) – Used in cystic fibrosis

• N-acetylcysteine (NAC) – Mucolytic and antioxidant

• Hypertonic saline (3–7%) – Induces mucosal hydration

• Guaifenesin – OTC expectorant

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E. Antitussives

Suppress cough via central or peripheral mechanisms.

• Dextromethorphan – NMDA receptor antagonist

• Codeine, Hydrocodone – Opioid antitussives

• Benzonatate – Anesthetizes stretch receptors in airways

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F. Respiratory Anti-Infectives

i. Inhaled Antibiotics

• Tobramycin, Aztreonam, Amikacin – Cystic fibrosis, bronchiectasis

ii. Systemic Antibiotics for Pulmonary Infections

• Macrolides: Azithromycin, Clarithromycin

• Fluoroquinolones: Levofloxacin, Moxifloxacin

• Beta-lactams: Amoxicillin-clavulanate, Ceftriaxone

• Antitubercular agents: Isoniazid, Rifampin, Pyrazinamide, Ethambutol

iii. Antifungals

• Itraconazole, Voriconazole – Invasive aspergillosis, ABPA

iv. Antivirals

• Oseltamivir, Zanamivir – Influenza

• Remdesivir – COVID-19 pneumonia

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G. Pulmonary Vasodilators

Used in pulmonary arterial hypertension (PAH) and associated conditions.

• Inhaled Nitric Oxide

• Treprostinil (Tyvaso)

• Iloprost

• Sildenafil, Tadalafil – PDE-5 inhibitors

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H. Oxygen Therapy

• Administered via nasal cannula, face mask, or high-flow systems

• Indicated in hypoxemic respiratory failure, ARDS, and COPD exacerbations

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I. Other Supportive Agents

• Caffeine citrate – Neonatal apnea

• Theophylline – Rarely used bronchodilator with narrow therapeutic index

• Magnesium sulfate (IV) – Acute severe asthma exacerbations

• Surfactants (e.g., beractant) – Neonatal respiratory distress syndrome

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2. Routes of Administration

Route	Example Agents	Indications
Inhalation	SABAs, LABAs, ICS, antibiotics	Asthma, COPD, CF
Oral	Montelukast, guaifenesin, macrolides	Asthma, chronic bronchitis, infections
Intravenous (IV)	Methylprednisolone, remdesivir, antibiotics	Severe exacerbations, pneumonia
Subcutaneous/IM	Omalizumab, mepolizumab, dupilumab	Biologic therapy in asthma, eosinophilia
Intratracheal	Surfactants, selective drug delivery	Neonatal care, experimental settings

3. Common Respiratory Agent Combinations

• Fluticasone + Salmeterol – Advair (ICS + LABA)

• Budesonide + Formoterol – Symbicort

• Ipratropium + Albuterol – Combivent (SAMA + SABA)

• Umeclidinium + Vilanterol – Anoro Ellipta (LAMA + LABA)

• Fluticasone + Vilanterol + Umeclidinium – Trelegy Ellipta (Triple therapy)

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4. Clinical Applications by Condition

Condition	Primary Agents Used
Asthma	ICS, LABAs, SABAs, leukotriene modifiers, biologics
COPD	LABAs, LAMAs, ICS (in selected), PDE-4 inhibitors
Cystic Fibrosis	Dornase alfa, inhaled antibiotics, hypertonic saline
Pulmonary Arterial Hypertension	Inhaled prostanoids, PDE-5 inhibitors, endothelin receptor antagonists
Acute Pneumonia	Beta-lactams, macrolides, fluoroquinolones
Tuberculosis	Rifampin, Isoniazid, Pyrazinamide, Ethambutol
Influenza	Oseltamivir, Zanamivir
Neonatal RDS	Surfactants (beractant, calfactant)
COVID-19 (Severe)	Remdesivir, dexamethasone, tocilizumab, oxygen, ventilation

5. Adverse Effects and Monitoring

Drug Class	Common Adverse Effects	Monitoring Required
SABAs/LABAs	Tremor, tachycardia, hypokalemia	Electrolytes (K⁺), heart rate
ICS	Oral candidiasis, hoarseness	Mouth rinsing, growth (children)
Anticholinergics	Dry mouth, urinary retention	BPH symptoms
Antibiotics (inhaled)	Bronchospasm, cough	Sputum culture, FEV₁
Biologics	Injection reactions, eosinophilia	Blood eosinophil count
Theophylline	Arrhythmia, seizures	Serum drug levels
Systemic steroids	Hyperglycemia, osteoporosis	Blood glucose, bone mineral density

6. Contraindications and Precautions

Agent Type	Major Contraindications
LABAs (monotherapy)	Should not be used without ICS in asthma
ICS	Caution in TB, untreated infections
Opioid antitussives	Respiratory depression, children <12
Theophylline	Seizure disorder, cardiac arrhythmias
PDE-5 inhibitors	Nitrates use, hypotension
Leukotriene inhibitors	Neuropsychiatric symptoms (rare but caution advised)

7. Summary of Generic and Brand Names

Generic Name	Brand Name	Class/Use
Albuterol (Salbutamol)	Ventolin, ProAir	SABA
Salmeterol	Serevent	LABA
Budesonide	Pulmicort	ICS
Tiotropium	Spiriva	LAMA
Montelukast	Singulair	Leukotriene receptor antagonist
Mepolizumab	Nucala	IL-5 monoclonal antibody
Dornase alfa	Pulmozyme	Mucolytic (CF)
Tobramycin (inhaled)	TOBI	Inhaled antibiotic
Sildenafil	Revatio	PDE-5 inhibitor for PAH
Remdesivir	Veklury	Antiviral (COVID-19)
Omalizumab	Xolair	IgE antibody (allergic asthma)