Ashma drugs
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"asthma"[MeSH Terms] AND "drug therapy"[MeSH Terms]
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Here is a thorough overview of asthma drugs, drawn from Katzung's Basic and Clinical Pharmacology (16th Ed.) and Harrison's Principles of Internal Medicine (22nd Ed., 2025):
Drugs Used in the Treatment of Asthma
Asthma therapy is divided into two broad categories: relievers (rescue therapy for acute symptoms) and controllers (long-term anti-inflammatory therapy). Treatment is guided by a step-up/step-down approach based on severity and symptom control.
1. Short-Acting Beta-2 Agonists (SABA) - Relievers
The cornerstone of acute symptom relief.
| Drug | Brand | Notes |
|---|---|---|
| Albuterol (salbutamol) | Proventil, ProAir, Ventolin | Most widely used |
| Levalbuterol | Xopenex | R-enantiomer of albuterol |
| Terbutaline | Brethine | Also used SC in emergency |
| Metaproterenol | Alupent | Less selective |
| Epinephrine | Primatene Mist | Non-selective, emergency use |
Mechanism: Stimulate beta-2 receptors on bronchial smooth muscle → increase cAMP → bronchodilation.
Use: As-needed rescue therapy. If needed more than twice a week, a controller is indicated.
Safety note: Using 2+ canisters/month is a marker of increased fatality risk - Katzung's, p. 563.
2. Long-Acting Beta-2 Agonists (LABA) - Controllers
| Drug | Brand |
|---|---|
| Salmeterol | Serevent |
| Formoterol | Foradil |
| Vilanterol | Combination inhalers only |
| Indacaterol | Arcapta |
Key point: LABAs must never be used as monotherapy in asthma - they are always combined with an ICS. The former FDA "black box" warning about fatal asthma risk with ICS/LABA has been removed after studies confirmed safety of the combination. Monotherapy remains contraindicated.
Formoterol is unique among LABAs for its rapid onset, enabling its use as both a controller AND reliever (the SMART/AIR strategy: budesonide/formoterol as-needed at all steps).
3. Inhaled Corticosteroids (ICS) - First-Line Controller
The cornerstone of asthma therapy for all levels of persistent asthma.
| Drug | Notes |
|---|---|
| Beclomethasone | Solution formulation, small-particle |
| Budesonide | Available as nebulizer solution (age 0-11) |
| Fluticasone propionate | Most widely studied |
| Fluticasone furoate | Once-daily dosing available |
| Mometasone | Also once-daily |
| Ciclesonide | Solution formulation, small-particle |
Mechanism: Bind cytoplasmic glucocorticoid receptor → nucleus → inhibit T-cell activation, eosinophil function, NF-kB pathways → reduce airway inflammation and hyperresponsiveness.
Effects: Reduce exacerbations, improve FEV1, decrease asthma mortality.
Side effects (ICS): Local - thrush, hoarseness (use a spacer, gargle). Systemic at high doses: bruising, osteoporosis acceleration, glaucoma, cataracts, growth suppression in children.
4. ICS/LABA Combination Inhalers
The most effective step-up for patients not controlled on ICS alone - more effective than doubling ICS dose.
| Combination | Brand |
|---|---|
| Fluticasone propionate + salmeterol | Advair |
| Budesonide + formoterol | Symbicort |
| Mometasone + formoterol | Dulera |
| Fluticasone furoate + vilanterol | Breo Ellipta |
GINA/AIR strategy: ICS/formoterol (low dose) can be used as both regular controller AND as-needed reliever at all steps of therapy (Steps 1-5), replacing SABA-only rescue.
5. Muscarinic Antagonists (Anticholinergics)
Short-Acting (SAMA)
- Ipratropium (Atrovent, Combivent) - Used as alternative/add-on in acute severe asthma in the ER; additive to SABAs in reducing hospitalization rates.
Long-Acting (LAMA)
- Tiotropium (Spiriva) - As effective as adding a LABA on top of ICS; reduces exacerbations in patients with persistent airflow obstruction.
- Others: Aclidinium (Tudorza)
6. Leukotriene Modifiers
Two sub-classes:
Leukotriene Receptor Antagonists (LTRA)
- Montelukast (Singulair) - Oral, once daily; first-line alternative to ICS for mild persistent asthma; effective in allergic rhinitis, aspirin-exacerbated disease, and exercise-induced bronchoconstriction; widely used in children. Safety note: Associated with neuropsychiatric events including suicidal ideation (FDA black box).
- Zafirlukast (Accolate) - Oral, twice daily.
5-Lipoxygenase Inhibitor
- Zileuton (Zyflo CR) - Oral, twice daily (extended release). Raises liver transaminases in ~3%; inhibits CYP1A2.
7. Theophylline
An oral phosphodiesterase inhibitor (increases cAMP). Rarely used today due to narrow therapeutic window, multiple drug interactions, and inferior bronchodilation compared to modern agents. Occasionally used as adjunctive therapy at Steps 3-5.
8. Cromolyn Sodium
Inhaled mast cell stabilizer. Only available by nebulizer, requires 2-4x/day dosing. Mildly effective; primarily used in pediatrics when ICS side effects are a concern. Also useful for exercise-induced bronchospasm.
9. Biologic (Targeted) Therapies - Severe Asthma (Step 5)
Reserved for moderate-to-severe asthma uncontrolled on high-dose ICS/LABA.
| Biologic | Target | Indication | Notes |
|---|---|---|---|
| Omalizumab (Xolair) | Anti-IgE | Allergic asthma (IgE ≥30 IU/mL + perennial allergen sensitization) | SC every 2-4 weeks; reduces exacerbations 25-50% |
| Mepolizumab (Nucala) | Anti-IL-5 | Eosinophilic asthma | SC every 4 weeks |
| Reslizumab (Cinqair) | Anti-IL-5 | Eosinophilic asthma (blood eos ≥400) | IV every 4 weeks |
| Benralizumab (Fasenra) | Anti-IL-5 receptor alpha | Eosinophilic asthma | SC every 4-8 weeks |
| Dupilumab (Dupixent) | Anti-IL-4/IL-13 receptor | Moderate-severe eosinophilic or OCS-dependent asthma | SC every 2 weeks |
| Tezepelumab (Tezspire) | Anti-TSLP | Severe asthma (age 12+); no biomarker required | SC every 4 weeks |
All require parenteral administration and are expensive. Some can cause anaphylaxis (monitor after injection).
10. Step-Up Therapy Framework (GINA, Harrison's 2025)
| Step | Regular Therapy | As-Needed Reliever |
|---|---|---|
| 1 | None | Low-dose ICS/formoterol or SABA |
| 2 | None or low-dose ICS | Low-dose ICS/formoterol or SABA (+ PRN ICS) |
| 3 | Low-dose ICS/formoterol | ICS/formoterol (low-medium dose) |
| 4 | Medium-dose ICS/formoterol | ICS/formoterol |
| 5 | High-dose ICS/LABA + LAMA | Add biologic (anti-IgE/anti-IL-5/anti-IL4R/anti-TSLP), LTM, or OCS |
Recent Evidence (2024-2025)
- A 2025 JAMA network meta-analysis (PMID 39465893) evaluated inhaled reliever therapies for asthma, providing updated comparative data on SABA vs. ICS/formoterol strategies.
- A 2024 systematic review and meta-analysis (PMID 38395640) confirmed benefit of IV magnesium sulfate for acute severe asthma exacerbations in children.
Sources: Katzung's Basic and Clinical Pharmacology, 16th Ed. | Harrison's Principles of Internal Medicine, 22nd Ed. (2025)
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