What are the main pharmacological classes used in asthma and COPD?

Asthma and COPD are treated with overlapping but distinct pharmacological classes. Short-acting beta-2 agonists (SABAs, e.g., salbutamol/albuterol) are rapid bronchodilators acting within minutes — used for acute symptom relief in both conditions. Long-acting beta-2 agonists (LABAs, e.g., salmeterol, formoterol, indacaterol) provide sustained bronchodilation over 12–24 hours. Inhaled corticosteroids (ICS, e.g., budesonide, fluticasone, beclomethasone) are the cornerstone of asthma controller therapy — reducing airway inflammation, eosinophil infiltration, and cytokine release. Long-acting muscarinic antagonists (LAMAs, e.g., tiotropium, umeclidinium) block M3 receptors in airway smooth muscle to provide bronchodilation — more effective in COPD than asthma. For severe asthma, biologics (dupilumab, mepolizumab, benralizumab, tezepelumab) target specific inflammatory pathways.

How do inhaled corticosteroids differ from systemic corticosteroids in pharmacokinetics?

Inhaled corticosteroids (ICS) are designed to maximise local anti-inflammatory activity in the airways while minimising systemic exposure — achieved through three mechanisms. First, ICS are administered directly to the target organ, requiring much lower doses than systemic equivalents. Second, ICS have high first-pass hepatic metabolism — oral bioavailability is low (budesonide ~10%, fluticasone propionate ~1%) which means the swallowed fraction is largely inactivated. Third, they have high local tissue affinity (lipophilicity) but rapid systemic clearance when absorbed. Fluticasone furoate (Breo, Relvar) and fluticasone propionate have the highest topical potency and lowest oral bioavailability but also the longest half-life (fluticasone furoate ~20h) — necessitating once-daily dosing. Ciclesonide is activated by airway esterases to des-ciclesonide (active) — minimising oropharyngeal candidiasis.

What is SMART therapy in asthma and what is the pharmacological basis?

SMART (Single Maintenance and Reliever Therapy) uses a combination ICS/fast-acting LABA inhaler (budesonide/formoterol) for both daily maintenance dosing and on-demand symptom relief. The pharmacological basis is formoterol's unique dual profile: unlike salmeterol (onset ~10–15 min, full effect at 30 min), formoterol has a rapid onset (2–3 minutes) comparable to salbutamol but with a sustained 12-hour duration. This makes formoterol suitable as both maintenance therapy and reliever — whereas salmeterol is too slow for acute relief. GINA 2022–2026 guidelines now recommend low-dose budesonide/formoterol as the preferred reliever (Track 1) for mild asthma in adults and adolescents, replacing SABA monotherapy for Step 1–2 asthma, after the SYGMA 1 and 2 trials demonstrated superior exacerbation prevention with as-needed ICS/formoterol vs as-needed SABA alone.

What are the biologic therapies for severe asthma and how do they target eosinophilic inflammation?

Biologics for severe asthma target specific inflammatory mediators in type 2 (eosinophilic/allergic) airway inflammation. Mepolizumab (Nucala) and reslizumab (Cinqair) are anti-IL-5 monoclonal antibodies — IL-5 is the key cytokine driving eosinophil production and survival; both reduce exacerbations by ~50% in high eosinophil count patients. Benralizumab (Fasenra) targets the IL-5 receptor (IL-5Rα) on eosinophils and basophils, inducing apoptosis via ADCC — achieves near-complete eosinophil depletion. Dupilumab (Dupixent) blocks IL-4Rα, the shared receptor subunit for IL-4 and IL-13 — broader anti-type 2 inflammation including reduction of IgE, FeNO, and eosinophilia; approved for type 2 asthma with ≥300 eos/µL or FeNO ≥25 ppb. Tezepelumab (Tezspire) targets TSLP (thymic stromal lymphopoietin) — an epithelial alarmin upstream of all type 2 and type 3 pathways, making it effective even in non-eosinophilic severe asthma.

What are the key drug interactions and monitoring requirements for theophylline and roflumilast?

Theophylline (a methylxanthine/phosphodiesterase inhibitor) has a narrow therapeutic index (10–20 mg/L) and is metabolised by CYP1A2 — making it susceptible to multiple drug interactions. CYP1A2 inducers (rifampicin, carbamazepine, smoking cessation) reduce theophylline levels; CYP1A2 inhibitors (ciprofloxacin, fluvoxamine, enoxacin, erythromycin) increase levels, risking toxicity. Toxicity at levels >20 mg/L: nausea, vomiting, tachyarrhythmias, seizures. Roflumilast (Daxas), a selective PDE4 inhibitor for severe COPD with chronic bronchitis, causes dose-dependent adverse effects: nausea, diarrhoea, weight loss, and rare neuropsychiatric effects (suicidal ideation, anxiety) — requiring dose up-titration (250 µg daily × 4 weeks, then 500 µg). Roflumilast is a CYP3A4/1A2 substrate; rifampicin and oral contraceptive failure interactions have been reported. Both theophylline and roflumilast require careful patient selection and monitoring.

Clinical pharmacology

Respiratory pharmacology guide

A clinical pharmacology reference for asthma and COPD medicines — covering SABA, LABA, ICS, and LAMA mechanisms, inhaled corticosteroid PK and adverse effects, SMART therapy, severe asthma biologic selection by biomarker, and narrow-TI drug monitoring (theophylline, roflumilast).

Inhaled therapy classes: mechanisms and key agents

Class	Mechanism	Key agents	Duration	Primary use
SABA	β2 agonism → ↑ cAMP → airway smooth muscle relaxation	Salbutamol, levalbuterol, terbutaline	4–6 hours	Acute symptom relief (asthma + COPD)
LABA	β2 agonism (sustained)	Salmeterol (12h), formoterol (12h), indacaterol (24h), vilanterol (24h)	12–24 hours	Maintenance; NEVER monotherapy in asthma
ICS	Glucocorticoid receptor → ↓ NF-κB → ↓ inflammatory cytokines	Budesonide, fluticasone propionate/furoate, beclomethasone, ciclesonide	12–24 hours	Cornerstone asthma controller; add-on in COPD with eosinophilia
LAMA	M3 muscarinic receptor blockade → ↓ bronchoconstriction, ↓ mucus	Tiotropium, umeclidinium, glycopyrronium, aclidinium	12–24 hours	COPD first-line; add-on in uncontrolled asthma
SAMA	M3 blockade (short-acting)	Ipratropium	4–6 hours	Acute COPD exacerbation; acute severe asthma (adjunct)
ICS/LABA combo	ICS + LABA synergy (steroid primes β2 receptors; LABA improves corticosteroid sensitivity)	Budesonide/formoterol, fluticasone/salmeterol, fluticasone furoate/vilanterol	12–24 hours	Moderate–severe asthma; COPD step-up
Triple therapy (ICS/LABA/LAMA)	All three mechanisms combined	FF/VI/UMEC (Trelegy), BUD/FORM/GLYCO (Breztri)	24 hours (OD)	Severe COPD; uncontrolled asthma with LAMA add-on

GINA 2026 asthma step therapy

The Global Initiative for Asthma (GINA) 2026 guidelines structure treatment as a 5-step ladder, with the key paradigm shift being the removal of SABA monotherapy as preferred Step 1–2 reliever in adults and adolescents.

Steps 1–2 (mild)

Track 1 (preferred): As-needed low-dose ICS/formoterol (budesonide/formoterol) — reliever only. Track 2: Low-dose ICS maintenance + SABA reliever, or as-needed ICS + SABA. The ICS component of the reliever prevents the post-exertional inflammation missed by SABA monotherapy.

Steps 3–4 (moderate–severe)

Low/medium-dose ICS/LABA maintenance + as-needed low-dose ICS/formoterol reliever (SMART). Step 4 adds medium/high-dose ICS/LABA + LAMA add-on. Referral for biologic consideration at Step 4–5 if inadequate control.

Step 5 (severe refractory)

Add-on biologic therapy guided by inflammatory biomarkers: blood eosinophils, FeNO, total IgE, and periostin. High-dose ICS/LABA/LAMA + biologic. Tiotropium add-on reduces severe exacerbations by ~21%. OCS-sparing with biologics preferred over chronic oral corticosteroids.

GOLD COPD vs GINA asthma

COPD (GOLD): LAMA ± LABA first-line (no ICS monotherapy); ICS added only if blood eos ≥300/µL or ≥2 exacerbations/year. Asthma-COPD overlap (ACO): treat as asthma (ICS essential). Triple therapy (TRELOGY study): ↓ moderate/severe COPD exacerbations vs dual therapy.

Severe asthma biologics: selection by biomarker

Biologic	Target	Key eligibility biomarker	Route/Frequency	Main effect
Omalizumab (Xolair)	Anti-IgE (free IgE)	Total IgE 30–700 IU/mL + sensitisation confirmed	SC Q2–4W (weight/IgE-based)	↓ exacerbations ~50%; ↓ IgE-driven mast cell activation
Mepolizumab (Nucala)	Anti-IL-5	Blood eos ≥300/µL (≥150 if OCS-dependent)	SC 100 mg Q4W	↓ exacerbations ~53%; ↓ blood + sputum eosinophils
Benralizumab (Fasenra)	Anti-IL-5Rα	Blood eos ≥300/µL	SC 30 mg Q4W×3 then Q8W	Near-complete eosinophil depletion via ADCC; ↓ exacerbations ~51%
Dupilumab (Dupixent)	Anti-IL-4Rα (blocks IL-4 + IL-13)	Eos ≥300/µL OR FeNO ≥25 ppb	SC 200–300 mg Q2W	↓ exacerbations ~68%; ↓ FeNO, ↓ IgE, ↓ eosinophilia; useful in atopic comorbidities
Tezepelumab (Tezspire)	Anti-TSLP (epithelial alarmin)	No specific eosinophil threshold required	SC 210 mg Q4W	↓ exacerbations ~70% (NAVIGATOR trial); effective regardless of eos count or atopic status

Frequently asked questions

What are the main pharmacological classes used in asthma and COPD?: Asthma/COPD pharmacology: SABA (salbutamol, levalbuterol): β2 agonism → ↑ cAMP → smooth muscle relaxation — onset 3–5 min, duration 4–6h; PRN reliever. LABA (salmeterol 12h, formoterol 12h, indacaterol 24h, vilanterol 24h): sustained β2 agonism — controller/maintenance; NEVER monotherapy in asthma (fatal SMART trial data — requires ICS co-prescription). ICS (budesonide, fluticasone, beclomethasone, ciclesonide): glucocorticoid receptor → ↓ NF-κB → ↓ inflammatory cytokines, ↓ eosinophilia; local activation in airways (ciclesonide = prodrug activated by esterases). LAMA (tiotropium, umeclidinium, glycopyrronium): M3 receptor blockade → ↓ bronchoconstriction and mucus secretion; superior to LABA in COPD; additive with ICS/LABA. Reference: GINA 2026 guidelines ↗ and GOLD COPD report ↗.
How do inhaled corticosteroids differ from systemic corticosteroids in pharmacokinetics?: ICS pharmacokinetics: Lung deposition depends on device (pMDI: ~10–30%; DPI: ~20–40%; nebuliser: ~10%) and particle size (MMAD 1–5 µm optimal for lower airway deposition). Oral bioavailability: swallowed fraction absorbed from GI tract but undergoes hepatic first-pass — fluticasone propionate ~1% (minimal systemic from swallowed dose); budesonide ~10%; beclomethasone ~26% (though prodrug, activated in lungs). Systemic AEs at high ICS doses: hypothalamic-pituitary-adrenal (HPA) suppression (rare at guideline doses), growth retardation in children (height loss ~0.5–1 cm/year), adrenal crisis on abrupt withdrawal after prolonged high doses, skin thinning. Local AEs: oropharyngeal candidiasis (use spacer + rinse mouth) and dysphonia. GINA recommendation: lowest effective ICS dose once controlled. See our pharmacokinetics basics guide.
What is SMART therapy in asthma and what is the pharmacological basis?: SMART therapy basis: formoterol's dual profile — rapid onset (2–3 min, vs salmeterol 10–15 min) + long duration (12h) — enables a single inhaler to serve both maintenance and reliever roles. Used with budesonide (ICS) in Symbicort/Duoresp. GINA Track 1 (preferred 2022–2026): as-needed low-dose budesonide/formoterol for mild asthma (Steps 1–2); maintenance + reliever at Steps 3–4. Evidence: SYGMA 1 (NEJM 2018) ↗: as-needed budesonide/formoterol non-inferior to twice-daily budesonide for exacerbation prevention; Novel START (NEJM 2019) ↗: confirmed superiority over as-needed SABA for exacerbation prevention. SMART NOT appropriate for: salmeterol/fluticasone combinations (salmeterol too slow for relief). See GINA 2026 ↗.
What are the biologic therapies for severe asthma and how do they target eosinophilic inflammation?: Severe asthma biologics: Anti-IL-5: mepolizumab (monthly SC), reslizumab (monthly IV) → ↓ eosinophil production; blood eos ≥300/µL at treatment threshold. Anti-IL-5Rα: benralizumab (Q4W×3 then Q8W SC) → ADCC-mediated eosinophil depletion; faster eosinophil reduction than anti-IL-5. Anti-IL-4Rα: dupilumab (Q2W SC) → blocks IL-4 + IL-13 signalling → ↓ IgE, FeNO, eosinophilia; approved for atopic comorbidities (atopic dermatitis, CRS with NP, EoE); see dupilumab paediatric news. Anti-TSLP: tezepelumab (monthly SC) → ↓ ILC2, Th2, mast cells, eosinophils; effective in low eosinophil count severe asthma (eos <300/µL). Anti-IgE: omalizumab (Q2–4W SC) → blocks IgE binding to FcεRI; requires baseline IgE 30–700 IU/mL; oldest biologic — see omalizumab food allergy approval. Biomarker selection: FeNO, blood eosinophils, total IgE.
What are the key drug interactions and monitoring requirements for theophylline and roflumilast?: Theophylline: narrow TI (10–20 mg/L — trough 12h post-dose); CYP1A2 substrate. Interactions: ↑ levels — ciprofloxacin (↑ 2–4×), fluvoxamine (↑ 3×), erythromycin/clarithromycin, cimetidine, allopurinol; ↓ levels — rifampicin, phenytoin, carbamazepine, phenobarbital, smoking (CYP1A2 induction). Smoking cessation ↑ levels by ~40% — adjust dose. Toxicity: GI (N&V >15 mg/L), arrhythmias, seizures (>30 mg/L). See our TDM guide and narrow TI glossary. Roflumilast (PDE4 inhibitor): CYP3A4/1A2 substrate; rifampicin reduces levels ~80% (avoid co-administration); roflumilast + theophylline: ↑ PDE inhibition → ↑ adverse effects; psych contraindications (suicidal ideation history). GOLD COPD guideline ↗: roflumilast reserved for FEV1 <50%, chronic bronchitis, ≥2 exacerbations/year on LABA+ICS+LAMA.