Bronchodilators & Xanthines – Quick Review

Adrenergic (Sympathomimetic) Bronchodilators

• Clinical use: relaxation of airway smooth muscle in reversible obstruction (asthma, COPD, bronchitis, bronchiectasis)
• Classification by duration of action
  • Ultra-short: not emphasized
  • Short-acting (SABA / “rescue”)
  • Salbutamol & Terbutaline • onset $\approx15\,\text{min}$ • duration $4!\text{–}!6\,\text{h}$
  • Long-acting (LABA / “controller”)
  • Salmeterol, Formoterol, Indacaterol, Olodaterol, Vilanterol • duration $12!\text{–}!24\,\text{h}$
• Key points per agent (inhaled forms only)
  • Salbutamol: MDI or DPI $100!–!200\,\mu\text{g}$ per puff, Neb $2.5!–!5.0\,\text{mg}$; continuous neb $10!–!15\,\text{mg/h}$ for severe asthma
  • Terbutaline DPI: $500\,\mu\text{g}$; onset $5!–!15\,\text{min}$, duration $4!–!6\,\text{h}$
  • Salmeterol DPI: $50\,\mu\text{g}$ BID; onset $20\,\text{min}$, duration $12\,\text{h}$
  • Formoterol DPI: $6!\text{–}!12\,\mu\text{g}$ BID; onset $3\,\text{min}$, duration $12\,\text{h}$
  • Indacaterol DPI: $75\,\mu\text{g}$ OD; Olodaterol SMI $2.5\,\mu\text{g}$ OD; Vilanterol only in fixed combinations, OD
• Safety
  • LABA must be combined with inhaled corticosteroid (ICS) in asthma; avoid as monotherapy
• Adverse effects: tremor, tachycardia, tolerance, ↓ bronchoprotection, CNS & metabolic changes
• Monitoring
  • Pre/post peak flow & auscultation
  • Hold if HR ↑ >20\% or >20 beats·min$^{-1}$ above baseline
  • Check glucose, $K^{+}$, ABG/PFT for long-term use

Anticholinergic (Parasympatholytic) Bronchodilators

• Mechanism: block parasympathetic (muscarinic) bronchomotor tone ⇒ bronchodilation proportional to baseline vagal tone
• Main use: COPD maintenance; adjunct/alternative in asthma (e.g., nocturnal symptoms, β-blocker patients, severe attacks)
• Classification
  • SAMA: Ipratropium (MDI $20\,\mu\text{g}$ × $2$ puffs QID; SVN $0.5\,\text{mg}$)
  • LAMA: Aclidinium $400\,\mu\text{g}$ BID; Glycopyrronium $50\,\mu\text{g}$ OD; Tiotropium $18\,\mu\text{g}$ (DPI) or $2.5\,\mu\text{g}$ × $2$ (SMI) OD; Umeclidinium $62.5\,\mu\text{g}$ OD
• Side effects (mostly local): dry mouth (most common), cough, occasional mydriasis
• Combination inhalers (additive bronchodilation)
  • SAMA/SABA: Ipratropium $+$ Salbutamol (Combivent) SMI $20/100\,\mu\text{g}$ Q$4!–!6\,\text{h}$
  • LAMA/LABA OD or BID options: Aclidinium/Formoterol, Indacaterol/Glycopyrronium, Tiotropium/Olodaterol, Umeclidinium/Vilanterol
• Monitoring: same as β-agonists plus ABG/SpO$_{2}$; verify device technique; track exacerbations & nocturnal symptoms

Xanthines (Methylxanthines)

• Agents: Theophylline, Caffeine, Theobromine
• Indications
  • Asthma: sustained-release theophylline as alternative maintenance for mild persistent asthma >5\,\text{y} when other controllers fail
  • COPD: alternative if β$_2$-agonist & anticholinergic inadequate; not for acute exacerbations
  • Apnea of prematurity: caffeine citrate preferred (wider therapeutic index)
• Pharmacology
  • CNS & cardiac stimulation, diuresis, bronchodilation, improved respiratory muscle function, increased ventilatory drive, mild anti-inflammatory action
  • Mechanism uncertain (PDE inhibition, adenosine antagonism, catecholamine release)
• Therapeutic serum levels (theophylline)
  • Target: asthma 5!–!15\,\mu\text{g·mL}^{-1}; COPD $5!–!10$
  • General therapeutic range $10!–!20$; toxicity: nausea >20; arrhythmias >30; seizures $40!–!45$
• Toxicity & side effects: narrow margin; gastric upset, headache, anxiety, diuresis; avoid in peptic ulcer/gastritis
• Factors altering levels: ↑ with viral hepatitis or LV failure; ↓ with smoking; numerous drug interactions; additive effects with β-agonists
• Monitoring
  • Baseline & periodic serum levels, peak flows, PFTs
  • Assess subjective response & ABG/SpO$_{2}$ during therapy
  • Educate: xanthines do NOT treat airway inflammation or disease progression