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Respiratory Medications - Vocabulary Flashcards

Asthma

  • Definition: Chronic inflammatory disorder of the airways with airway obstruction and increased airway hyperresponsiveness to various stimuli, leading to bronchoconstriction.
  • Primary symptoms: dyspnea, coughing, chest tightness, wheezing.
  • Triggers: allergens, cold air, exercise, emotional stress, viral infections, pollutants, and irritants.
  • Pathophysiology overview:
    • Exposure to a stimulus in susceptible individuals → release of mediators from mast cells, eosinophils, basophils, neutrophils, and macrophages.
    • Mediators include histamine, leukotrienes, prostaglandins, adenosine, bradykinin, etc., leading to inflammation of the airway, edema of the bronchial epithelium, and hypertrophy of airway smooth muscle.
    • ↑ Mucus production → mucus plugging of airways; ↑ airway permeability and smooth muscle responsivity → further narrowing.
    • Result: ↑ airway wall thickness, mucus, bronchial smooth muscle contraction, and airflow limitation.
  • Airway changes during asthma:
    • Normal airway: open lumen, normal muscle tone, thin airway wall, minimal mucus.
    • During an attack: narrowed airway, tightened airway muscles, inflamed/thickened airway wall, mucus plugging, reduced airflow.
  • Nighttime phenomena:
    • Some patients experience up to 8\times increase in airway hyperresponsiveness at night due to circadian variation; nocturnal symptoms contribute to asthma-related morbidity and mortality.

COPD

  • Composition: COPD includes chronic bronchitis and emphysema.
    • Chronic bronchitis: productive cough associated with inflammation of bronchioles.
    • Emphysema: permanent destruction and enlargement of distal airways.
  • Clinical features: chronic dyspnea, reduced exercise tolerance, sputum production; obstruction is often irreversible.
  • Pulmonary function testing (PFT): ↓$FEV_1$; obstructive pattern; smoking cessation slows disease progression.
  • Reversible component: some obstruction due to smooth muscle spasm and bronchiolar inflammation can be reversed with bronchodilators.
  • Management considerations: many patients require long-term oxygen therapy during exacerbations; bacterial infections common as COPD progresses.

Rhinitis

  • Inflammation of nasal mucosa; common triggers include pollens, mold spores, dust mites, and viral infections (e.g., rhinovirus).
  • Allergic rhinitis: sneezing, rhinorrhea, itching; can be seasonal or perennial.
  • Viral rhinitis (common cold): self-limiting; symptomatic care.

Drug classes overview

  • Anti-inflammatory drugs
  • Bronchodilators
  • Other drug classes

Anti-inflammatory (respiratory) drugs

Corticosteroids

  • Role: cornerstone anti-inflammatory therapy for asthma and allergic rhinitis; reduce airway inflammation and hyperresponsiveness.
  • Forms: inhaled corticosteroids (ICS) such as Beclomethasone, Budesonide, Fluticasone, Triamcinolone (MDIs and/or inhalers); sometimes systemic steroids for acute exacerbations.
  • Usage rationale: long-term prevention of attacks; most effective anti-inflammatory therapy for asthma and allergic rhinitis; systemic steroids for severe cases or exacerbations.
  • Administration considerations: proper inhaler technique and spacer use improve delivery; maximal benefit typically requires weeks of therapy; adverse effects reduced with inhaled delivery.
  • Adverse events: oropharyngeal candidiasis from local deposition; potential growth suppression or systemic effects with high-dose systemic exposure.
  • Combination products: corticosteroids combined with long-acting beta-2 agonists (LABA) such as Fluticasone/Salmeterol, Budesonide/Formoterol, Mometasone/Formoterol.
  • Pharmacokinetics and practical notes: systemic exposure minimized with inhalation; effects on symptoms and exacerbations observed over weeks.

Mast cell stabilizers

  • Examples: Cromolyn sodium (Intal), Lodoxamide, Nedocromil.
  • Mechanism: stabilize membranes of mast cells and eosinophils to prevent degranulation and release of pro-inflammatory mediators (histamine, leukotrienes).
  • Indications: prophylaxis for mild-to-moderate asthma, allergic rhinitis, and some forms of conjunctivitis; exercise-induced bronchospasm prophylaxis.
  • Administration: inhalation for asthma; ophthalmic solutions for conjunctivitis; nasal formulations for rhinitis.
  • Pharmacokinetics: poor systemic absorption; mostly local if inhaled; oral bioavailability ~1%.
  • Adverse events: generally mild; throat irritation or cough; rare nasal/ocular irritation; rarely systemic effects.
  • Clinical notes: useful for perennial control and exercise-induced asthma; slower onset; do not treat acute bronchospasm.

Leukotriene inhibitors (anti-leukotriene agents)

  • Mechanism: block leukotriene receptors or synthesis, reducing bronchoconstriction, inflammation, and mucus production.
  • Agents: Montelukast (Singulair), Zafirlukast (Accolate).
  • Indications: allergic asthma, exercise-induced asthma prevention, ASA-sensitive asthma; often used as adjuncts or alternatives to ICS in patients unable to take steroids.
  • Pharmacokinetics: oral administration; Montelukast qHS; Zafirlukast bid; both extensively metabolized by CYP450 enzymes.
  • Adverse events: relatively favorable safety profile but potential hypersensitivity; rare liver injury; boxed warning for neuropsychiatric events with Montelukast (as of 2020) including mood changes, agitation, depression, sleep disturbances, and rare suicidality.
  • Drug interactions: Montelukast and Zafirlukast interact via CYP enzymes; Montelukast has fewer interactions; important to consider concurrent drug therapy (phenytoin, warfarin, theophylline) with leukotriene inhibitors (note: interactions vary by agent; refer to current labeling).
  • Clinical notes: can improve lung function and symptoms; oral administration offers convenience; effects may require weeks to reach maximum benefit; children may derive greater benefit.

Phosphodiesterase-4 (PDE4) inhibitors

  • Mechanism: inhibit PDE4 to raise cAMP levels in inflammatory cells, producing anti-inflammatory effects.
  • Example: Roflumilast (Daliresp).
  • Indications: COPD (severe cases) to reduce exacerbations; not a bronchodilator.
  • Efficacy: 4-week treatment can reduce sputum neutrophils/eosinophils and improve FEV1 on average by about 50\ text{ mL}.
  • Adverse events: diarrhea, nausea, weight loss; psychiatric effects such as anxiety, insomnia, depression; caution with CYP1A2 and CYP3A4 interactions; avoid strong inducers or inhibitors that alter metabolism (e.g., rifampin, erythromycin).
  • Important notes: metabolic pathways involve CYP3A4 and CYP1A2; monitor for drug interactions.

Bronchodilators

  • Purpose: relax bronchial smooth muscle to prevent or relieve bronchospasm; mainstay for acute asthma attacks and COPD management.
  • General note: bronchodilators are the only agents that acutely relieve bronchospasm; anti-inflammatory agents prevent or reduce inflammation.

β2-agonists (adrenoceptors)

  • Receptors and mechanism: Beta-2 adrenergic receptor activation increases intracellular cAMP in smooth muscle, causing relaxation and bronchodilation.
  • Receptor selectivity and safety:
    • Selective β2 agonists preferentially relax bronchial smooth muscle with less cardiac stimulation, but high doses can still stimulate β1 receptors and increase heart rate.
    • Human heart contains β2 receptors (approximately 10–50% of total cardiac β receptors), so some cardiac stimulation can occur even with selective agents.
  • Short-acting β2 agonists (SABA): used for rapid relief of acute bronchospasm; inhaled forms preferred.
    • Examples: Albuterol (ProAir, Proventil, Ventolin), Levalbuterol (Xopenex).
  • Long-acting β2 agonists (LABA): used for long-term prevention in asthma and COPD; not for acute relief.
    • Examples: Salmeterol, Formoterol, Arformoterol, Indacaterol (ultra-LABA).
    • Combination products: often combined with ICS (e.g., fluticasone/salmeterol, budesonide/formoterol).
    • Special notes: Salmeterol and Formoterol are used bid (every 12 hours) for chronic prevention; not indicated for treatment of acute bronchospasm; LABA monotherapy in asthma is associated with increased risk of asthma-related death and is contraindicated without inhaled corticosteroid (ICS) background in many guidelines; fixed-dose LABA with ICS reduces risk compared to LABA alone.
  • Notable product safety: boxed warning historically existed for LABA monotherapy to reduce asthma-related death risk; after further study, warning remained specifically for LABA monotherapy and was removed for LABA+ICS combos in 2017 for some products.

Muscarinic receptor antagonists (anticholinergics)

  • Role: bronchodilators used in COPD; also used in combination with β2 agonists.
  • Short-acting: Ipratropium (SAMA) – slower onset than SABA but longer duration; inhaled; improves quality of life in COPD; nasal spray available for rhinorrhea.
  • Long-acting: Tiotropium (LAMA) – once-daily inhaled, first-line for mild-to-severe COPD; long-lasting bronchodilation (24 h).
  • Other muscarinic antagonists: Umeclidinium (LAMA) – inhaled; can be used alone or with vilanterol (ultra-LABA) and/or fluticasone (Trelegy Ellipta).
  • Combinations: Albuterol/ipratropium (Combivent) shows greater bronchodilation than either alone; beneficial in some COPD cases.
  • Adverse events: xerostomia, upper respiratory tract infections; similar adverse profile for ipratropium and tiotropium.
  • Newer agents: Aclidinium (Tudorza Pressair) approved for long-term maintenance COPD; often used in combination therapy.
  • Dosing and delivery: inhaled forms preferred to minimize systemic effects; device technique important for efficacy.

Theophylline

  • Class: Methylxanthine with bronchodilatory, CNS stimulatory, and diuretic effects; similar to caffeine.
  • Mechanisms (multipath): inhibition of phosphodiesterase (PDE) isozymes, adenosine receptor blockade, inhibition of calcium influx, and enhancement of catecholamine release.
  • Pharmacokinetics: well absorbed from the gut with minimal first-pass metabolism; crosses the blood-brain barrier; half-life around 8\ \text{hours} in adults; smoking increases metabolism reducing half-life; children metabolize faster.
  • Therapeutic window: therapeutic serum levels typically 5-15\ \text{mg/L}; higher levels increase toxicity risk.
  • Indications: COPD, asthma, and neonatal apnea when other agents do not adequately control symptoms; can improve FEV1 by roughly 20\% in COPD; reduces dyspnea, increases diaphragmatic contractility, improves exercise tolerance, and reduces fatigue.
  • Monitoring and management: serum levels must be monitored; drug interactions common due to CYP1A2 metabolism; smoking, certain antibiotics (e.g., erythromycin) can raise levels dramatically.
  • Adverse effects: GI distress, CNS stimulation (insomnia, anxiety, tremor, seizures at high levels), cardiac stimulation (tachycardia, arrhythmias); toxic effects correlate with levels >25\ \text{mg/L}.
  • Interactions: CYP1A2 inhibitors (e.g., cimetidine, erythromycin) increase theophylline levels; other drugs (fluoroquinolones, INH, verapamil) can raise levels; monitoring essential.

Immunoglobulin antagonists (monoclonal antibodies, mAbs)

  • Omalizumab (Xolair): for patients ≥12 years with moderate-to-severe allergic asthma; anti-IgE antibody given subcutaneously every 2–4 weeks; used with inhaled corticosteroids (ICS).
  • Mepolizumab (Nucala): add-on for severe eosinophilic asthma in patients ≥12 years; IL-5 antagonist; subcutaneous every 4 weeks.
  • Reslizumab (Cinqair): add-on for severe eosinophilic asthma in adults ≥18 years; IL-5 antagonist; IV every 4 weeks; boxed warning for anaphylaxis and rare association with malignancy.
  • Adverse effects: risk of allergic reactions to the mAb; infusion reactions; potential immunologic effects.

Managing asthma (clinical management concepts)

  • Severity and frequency-based management focuses on days and nights with symptoms; FEV1 as % of predicted value informs classification.
  • Stepwise classifications (per NHLBI 2020 guidelines) include:
    • Intermittent asthma: minimal daily symptoms; no daily controller therapy; rescue SABA as needed.
    • Mild persistent: symptoms > twice weekly but not daily; nighttime symptoms up to once per month; low-dose ICS or cromolyn or LTRA as alternatives.
    • Moderate persistent: daily symptoms; nighttime symptoms > once per week; medium-dose ICS; add LABA if needed; alternatives include theophylline or LTRA.
    • Severe persistent: symptoms throughout the day; frequent nighttime symptoms; often require medium-dose ICS-LABA or high-dose ICS-LABA plus long-term systemic corticosteroids.
  • Stepwise treatment goals: reduce symptoms, minimize rescue inhaler use, prevent exacerbations, optimize lung function.
  • Exacerbations:
    • Mild: one or two SABA treatments q4–6h; reassess; may require additional therapies (ipratropium, oxygen, fluids).
    • Moderate to severe: systemic corticosteroids, oxygen; continuous or back-to-back SABA; consider IV therapies in life-threatening cases.
  • Guidelines evolution (GINA 2024): two management tracks for asthma
    • Track 1 (preferred): ICS-formoterol as maintenance and reliever therapy (MART).
    • Track 2 (alternate): no ICS-formoterol MART; requires separate ICS and SABA regimens; not all ICS-formoterol combinations approved for MART in the US; guidelines emphasize risk of severe exacerbations even in mild asthma.

Antitussives (cough suppressants)

  • Rationale: cough can be beneficial to clear secretions, but non-productive coughs may disrupt sleep, cause rib injury, or worsen wounds.
  • Local-acting: Menthol.
  • Centrally-acting: Dextromethorphan (opioid-like but does not cause analgesia or euphoria at typical doses); Codeine and Hydrocodone are opioid agonists with antitussive effects but limited CNS depression at proper dosing.
  • Dextromethorphan notes: D-isomer of an opioid agonist; widely used OTC antitussive; generally non-sedating at standard doses.
  • Combination products: codeine or hydrocodone-containing preparations often combine with guaifenesin, antihistamines, and decongestants.

Expectorants

  • Guaifenesin: facilitates coughing up mucus by reducing mucus adhesiveness; mechanism not fully understood; widely used OTC.

Management of rhinitis and ocular involvement

Allergic rhinitis management

  • Environmental control of allergens; pharmacologic control with anti-inflammatory medications and symptomatic agents; antihistamines and decongestants for symptom relief.
  • Anti-inflammatory therapy is often required for moderate-to-severe symptoms.

Antihistamines

  • First-line for seasonal allergic symptoms; long-acting agents preferred for convenience: cetirizine, loratadine, fexofenadine.
  • Diphenhydramine: potent antihistamine but with sedative and anticholinergic effects; reserved for nocturnal symptoms unresponsive to other agents.

Corticosteroids for allergic rhinitis

  • Nasal corticosteroids (budesonide, fluticasone, ciclesonide, etc.) are highly effective with minimal systemic adverse effects; preferred anti-inflammatory therapy for AR.

Decongestants

  • Pseudoephedrine and phenylephrine used to treat nasal congestion when anti-inflammatory or antihistamine therapy is insufficient.
  • Pseudoephedrine requires behind-the-counter access in many locations; phenylephrine availability varies by jurisdiction.

Ocular management of allergic conjunctivitis

  • Topical cromolyn and lodoxamide for prevention of conjunctival symptoms; topical decongestants (azelastine, olopatadine) for mild ocular symptoms; NSAIDs (ketorolac) for more severe ocular symptoms; topical corticosteroids generally avoided for long-term ocular use due to adverse effects.

Viral rhinitis (common cold)

  • Self-limiting; management is supportive (APAP/NSAIDs for pain; decongestants; ipratropium for rhinorrhea).

Practical notes on inhaler technique and therapy optimization

  • MDIs (metered-dose inhalers) require proper technique; spacers can improve delivery to lungs and reduce oropharyngeal deposition.
  • Inhaled corticosteroids are used chronically to prevent asthma attacks; peak benefit may take weeks; reduce reliance on rescue inhalers.
  • Combo inhalers (ICS-LABA) provide both anti-inflammatory and bronchodilatory effects; important to follow stepwise therapy and monitor for adverse effects, including systemic steroid exposure in high-dose regimens.
  • Monitoring for adverse effects: oral candidiasis with inhaled steroids; watch for neuropsychiatric effects with montelukast; monitor theophylline levels due to narrow therapeutic index; assess for tachycardia or tremor with β2 agonists; monitor liver function and mild GI symptoms with PDE4 inhibitors.

Summary of key takeaways

  • Respiratory pharmacotherapy is broadly divided into anti-inflammatory agents (corticosteroids, mast cell stabilizers, leukotriene inhibitors, mAbs) and bronchodilators (β2-agonists, muscarinic antagonists, theophylline).
  • The most effective long-term control for asthma and allergic rhinitis typically centers on inhaled corticosteroids; leukotriene inhibitors offer convenient oral options but have boxed warnings for neuropsychiatric events (montelukast).
  • SABAs provide rapid relief of acute bronchospasm; LABAs prevent exercise- or chronic-induced bronchospasm but require ICS when used in asthma due to safety concerns with monotherapy.
  • Muscarinic antagonists (SAMA/LAMA) are particularly important in COPD management, with combinations enhancing bronchodilation.
  • Theophylline remains a secondary option due to narrow therapeutic index and drug interactions, but can improve FEV1 and exercise tolerance in certain patients.
  • Monoclonal antibodies offer targeted therapy for severe allergic or eosinophilic asthma but carry risks of allergic reactions and other rare adverse effects.
  • Management guidelines (NHLBI 2020, GINA 2024) emphasize a stepwise approach and individualized treatment plans to reduce symptoms, prevent exacerbations, and maintain lung function.