Drugs for asthma
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"asthma" AND "pharmacotherapy"
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Drugs for Asthma
Asthma pharmacotherapy is organized around two principles: relievers (for acute symptoms) and controllers (for long-term prevention). Treatment is stepped up or down based on symptom frequency, FEV1, and exacerbation history.
1. Beta-2 Adrenoceptor Agonists (β2-Agonists)
Short-Acting (SABA) - "Relievers"
| Drug | Notes |
|---|---|
| Albuterol (salbutamol) | Drug of choice for acute bronchospasm; inhaled aerosol; onset within minutes |
| Levalbuterol | R-isomer of albuterol |
| Terbutaline | Also used as a tocolytic |
- Mechanism: Activate β2 receptors → ↑ cAMP → smooth muscle relaxation → bronchodilation
- Use: On-demand rescue therapy; also first-line in acute severe attacks (4 puffs every 20 min × 3 over 1 hour)
- Toxicity: Tachycardia, tremor, hypokalemia; overuse (>2 canisters/month) is a marker of increased asthma fatality risk
Long-Acting (LABA) - "Controllers"
| Drug | Notes |
|---|---|
| Salmeterol | Slow onset, 12-hour duration; never use as monotherapy |
| Formoterol | Rapid onset (can also serve as reliever); 12-hour duration |
| Vilanterol | Once-daily; used in fixed combinations |
- Key rule: LABAs must always be combined with an ICS - never used as monotherapy due to risk of severe/fatal attacks
- Combinations: Fluticasone/salmeterol (Advair), Budesonide/formoterol (Symbicort), Fluticasone furoate/vilanterol (Breo), Mometasone/formoterol (Dulera)
2. Inhaled Corticosteroids (ICS) - Cornerstone Controllers
| Drug | Examples |
|---|---|
| Beclomethasone | First ICS widely used |
| Budesonide | Also available as nebulizer solution |
| Fluticasone propionate/furoate | High potency |
| Mometasone | |
| Ciclesonide | Prodrug, activated in airways |
- Mechanism: Suppress airway inflammation; ↓ mucosal edema, ↓ mucus secretion, ↓ eosinophilic infiltration
- Indication: Any persistent asthma (symptoms >2×/week or nocturnal >2×/month, or FEV1 <80% predicted)
- Toxicity (local): Oral candidiasis, dysphonia - use spacer + rinse mouth after
- Toxicity (systemic at high doses): Adrenal suppression, growth retardation in children, osteoporosis
Per Katzung's Basic and Clinical Pharmacology, 16th Ed, if a standard ICS dose does not control asthma, the best strategy is adding a LABA rather than doubling the ICS dose.
3. Muscarinic Antagonists (Anticholinergics)
| Drug | Class | Notes |
|---|---|---|
| Ipratropium bromide | Short-acting (SAMA) | Additive with β2-agonists in severe acute asthma (reduces hospitalization); alternative for β2-agonist-intolerant patients |
| Tiotropium | Long-acting (LAMA) | Approved add-on for asthma ≥6 yrs uncontrolled on ICS + LABA; improves lung function and increases time to exacerbation |
- Mechanism: Block M3 muscarinic receptors on airway smooth muscle → bronchodilation
- Effects nearly equal to but not greater than sympathomimetics for baseline airway resistance
4. Methylxanthines
| Drug | Notes |
|---|---|
| Theophylline | Oral/IV; narrow therapeutic index; monitoring required |
| Aminophylline | IV theophylline salt used in acute severe asthma |
- Mechanism: Nonselective phosphodiesterase inhibition → ↑ cAMP → bronchodilation; also adenosine receptor antagonism; anti-inflammatory effects
- Therapeutic range: 5-15 mcg/mL (above 20 mcg/mL = toxicity)
- Toxicity: Nausea, arrhythmias, seizures; many drug interactions (cimetidine, fluoroquinolones, erythromycin reduce clearance)
- Current role: Modest add-on when ICS + LABA are insufficient; less favored due to side effects and drug interactions
5. Leukotriene Modifiers
Leukotriene Receptor Antagonists (LTRAs)
| Drug | Notes |
|---|---|
| Montelukast | Most widely used; oral, once daily; especially useful in children and aspirin-induced asthma; also treats allergic rhinitis |
| Zafirlukast | Oral, twice daily; CYP interactions |
- Mechanism: Block CysLT1 receptors → ↓ bronchoconstriction, ↓ airway inflammation
- Indication: Alternative to low-dose ICS for mild persistent asthma; add-on therapy
- Special note: FDA added a boxed warning for neuropsychiatric events (behavior changes, depression, suicidality) with montelukast
5-Lipoxygenase Inhibitor
| Drug | Notes |
|---|---|
| Zileuton | Blocks leukotriene synthesis; hepatotoxicity risk; liver monitoring required |
6. Biologic / Targeted Therapies (Severe Asthma)
Reserved for moderate-to-severe asthma inadequately controlled on ICS/LABA:
| Drug | Target | Indication |
|---|---|---|
| Omalizumab (Xolair) | Anti-IgE | Allergic asthma with elevated IgE + positive perennial allergen skin test |
| Mepolizumab (Nucala) | Anti-IL-5 | Severe eosinophilic asthma (↓ eosinophil production) |
| Reslizumab (Cinqair) | Anti-IL-5 | Severe eosinophilic asthma (IV infusion) |
| Benralizumab (Fasenra) | Anti-IL-5Rα | Severe eosinophilic asthma (depletes eosinophils rapidly) |
| Dupilumab (Dupixent) | Anti-IL-4/IL-13 receptor | Moderate-to-severe eosinophilic or oral steroid-dependent asthma |
| Tezepelumab (Tezspire) | Anti-TSLP | Severe asthma - no biomarker requirement (broadest indication) |
- All are given parenterally (SC or IV) every 2-8 weeks
- Risk of anaphylaxis (< 0.5%); mepolizumab → risk of herpes zoster (vaccinate before starting)
- High cost limits use; blood eosinophil count guides selection
7. Other Agents
| Drug | Use |
|---|---|
| Systemic corticosteroids (prednisone, methylprednisolone) | Acute severe attacks: 0.5 mg/kg every 6-12 hours; short courses for exacerbations |
| Magnesium sulfate (IV) | Severe acute asthma not responding to standard therapy (bronchodilation via Ca2+ antagonism) |
| Epinephrine (SC) | Acute severe attack if inhaled β2-agonist unavailable |
| Heliox | Helium-oxygen mixture; reduces airway resistance in severe obstruction |
| Cromolyn sodium | Mast cell stabilizer; largely obsolete; used prophylactically (exercise-induced asthma) |
Stepwise Approach (GINA Framework)
| Step | Treatment |
|---|---|
| Step 1 (intermittent) | SABA as needed (± low-dose ICS as needed per GINA) |
| Step 2 (mild persistent) | Low-dose ICS daily OR LTRA |
| Step 3 (moderate persistent) | Low-dose ICS + LABA (preferred) OR medium-dose ICS |
| Step 4 (severe persistent) | Medium/high-dose ICS + LABA ± LAMA |
| Step 5 (uncontrolled on Step 4) | Add biologic (omalizumab, anti-IL-5, dupilumab, tezepelumab) or low-dose OCS |
Acute Severe Attack - Management Summary
- Oxygen to maintain SpO2 > 93%
- Inhaled albuterol - continuous or every 20 min × 3
- Ipratropium - add to albuterol in moderate-severe attacks
- Systemic corticosteroids - IV methylprednisolone or oral prednisone
- IV magnesium sulfate - single dose in life-threatening attack
- ICU/intubation if respiratory failure (CO2 retention, exhaustion, altered consciousness)
Sources: Katzung's Basic and Clinical Pharmacology, 16th Ed. | Harrison's Principles of Internal Medicine, 22nd Ed. | Murray & Nadel's Textbook of Respiratory Medicine | Lippincott Illustrated Reviews: Pharmacology
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