L08 - Drugs influencing airway resistance (flipped) Flashcards
What are the different physiological controls of airway diameter?
- NANC innvervation
- Parasympathetic innervation
- Mechanical receptors
- No sympathetic innervation but beta2 adrenoceptors (another flashcard discuss)
- CO2
- Mast cells
Describe how NANC innervation can control airway diameter
BronchoDILATION
- Transmitters: VIP and NO
- In asthma, substance P may cause bronchoconstriction
Describe how parasympathetic innervation can control airway diameter
BronchoCONSTRICTION
- ACh stimulates M3 receptors
Describe how sympathetic innervation can control airway diameter
NO sympathetic innervation but:
- Beta 2 adrenoceptors present on airway smooth muscle
- Circulating adrenaline causes bronchoDILATION
- Beta 2 receptors on mast cells –> inhibit activity
- Beta 2 stimulation promotes muco-ciliary escalator activity
Describe how CO2 can control airway diameter
BronchoDILATION
- Important for ventilation-perfusion matching
Describe how mast cells can control airway diameter
- Present in airway walls
- Mediators released on degranulation cause bronchoCONSTRICTION
- Histamine, leukotrienes, platelet activating factor
- Contribute to asthma pathology
Describe how mechanical receptors can control airway diameter
- Rapidly adapting receptors (RAR) cause bronchoCONSTRICTION
- Slowly adapting pulmonary stretch receptors (PSR) cause bronchoDILATION
What is radial traction?
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- Airways embedded into lung parenchyma
- Parenchyma splints airways open
- Inflation increases radial traction and REDUCES airway resistance
What is alveolar interdependence?
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- Neighbouring alveoli share walls
- Mechanical tethering keeps conducting airways open
- Loss of radial traction and alveolar interdependence INCREASES airway resistance in COPD
What are the different possible pharmacological controls of airway DIAMETER in asthma?
With bronchodilators
- Anti-cholinergic/ muscarini antagonists
- Beta 2 agonists
- Methylxanthines
What is asthma?
- Bronchial hypersensitivity –> airway mucosa inflammation: infiltration of immune cells and thickening
- Increased airway secretions (mucus)
- Pharmacological treatment can target bronchoconstrictor or inflammatory components
- Episodes of bronchoconstriction
Describe the action of anti-cholinergic/ muscarinic antagonists in the treatment of airway diameter (asthma) and give examples
- Block the bronchoconstricting action of ACh
- IPRATROPIUM (inhaled) - quarternary nitrogen in structure prevents systemic abs and reduces side effects (dry mouth/ cough)
Describe the action of beta 2 agonists in the treatment of airway diameter (asthma) and give examples
- Stimulate the AC/ cAMP/ PKA pathway to cause bronchodilation and red inflammation =
- SALBUTAMOL (inhaled); short acting
- SALMETEROL/ TURBUTALINE; slow onset/ long acting
Describe the action of methylxanthines in the treatment of airway diameter (asthma) and give examples
- PDE inhibitors: inc cAMP and cause bronchodilation and reduce inflammation
- THEOPHYLLINE/ AMINOPHYLLINE (oral); they have a NARROW THERAPEUTIC WINDOW
What are the possible side effects of theophylline/ aminophylline
- Headache
- Restlessness
- Abdominal symptoms
- Arrhythmias
What are the possible side effects of salbutamol?
- Tachycardia
- Tremor
- Airway hyper-responsiveness
What are the different possible pharmacological controls of airway INFLAMMATION in asthma?
- Monoclonal anti-IgE antibodies
- Sodium cromoglicate cromolyn
- Histamine receptor antagonists
- Targeting the leukotriene pathway
- Corticosteroids
Describe the action of monoclonal anti-IgE antibodies in the treatment of airway inflammation (asthma) and give examples
- OMALIZUMAB - requires subcutaneous injection every 2-4 weeks
- Reduces circulating IgE antibodies and therefore reduces mast cell degranulation and inflammation
- Used in severe allergic asthma
- In rare instance, can cause anaphylaxis
Describe the action of histamine receptor antagonists in the treatment of airway inflammation (asthma) and give examples
- KETOTIFEN (oral) - H1 receptor antagonist, anti-inflammatory after 6-12 weeks of treatment
- Reduced reliance on steroids and bronchodilators
- Few side effects; 10-15% patients experience drowsiness
Describe the action of targeting the leukotriene pathway in the treatment of airway inflammation (asthma) and give examples
- Leukotriene formation antagonists
- ZILEUTON (oral); inhibits 5-lipoxygenase, short half life
- Leukotriene receptor antagonist (oral)
- Single daily dose, used in severe chronic and exercise-induced asthma. bronchodilates, decreases mucus secretion and reduces inflammation
Describe the action corticosteroids in the treatment of airway inflammation (asthma) and give examples
- Reduce airway inflammation and hyper-responsiveness
- Prevents rather than relieves
- BECLAMETHASONE (inhaled)
- Metabolised to active form in lung, reducing systemic side effects
Describe the action of sodium cromoglicate/ cromolyn in the treatment of airway inflammation (asthma) and give examples
- CROMOLYN (inhaled): a mast cell stabiliser
- Prophylactic treatment
- Mechanism of action not fully understood
- Inhibits release of inflammatory mediators from mast cells and RAR axon reflexes
- Takes 4 weeks to become effective
- Mild side effects such as coughing, wheezing, dry throat
What is aspirin induced asthma?
- Development of asthma following ingestion of aspirin
- Sensitivity develops in adulthood; women> men
- Prevalence approx 21%
- Symptoms include rinhorrhea, nasal congestion, sinusitis
- 5-lipoxygenase upregulated
- MONTELUKAST used as a treatment adjust
