Asthma and Bronchodilators

• • Outside of the bronchus = smooth muscle
  • Within the lumen of the bronchus is mucous and epithelial cells
  • 2 of the main features of the pathophysiology of asthma is that there are abnormalities in the smooth muscle and inflammation within the airway epithelial cells

  
• Asthma = variable narrowing of the airways
• Asthma pathophysiology:

  • Smooth muscle abnormalities
  • Hyperresponsiveness
  • Hypertrophy
  • Airway inflammation
  • Lymphocytes, eosinophils, and mast cells cause mucosal oedema
  • They also cause epithelial disruption
  • Basement membrane thickens too
  • All of this results in the lumen of the airway narrowing
  • Airway obstruction is what results
• Asthma pathophysiology - hyperresponsiveness of smooth muscle:

  • As a result of long-standing asthma, the smooth muscle walls of the bronchi become hyperresponsive
  • This means that when you breathe in a stimulant that can cause bronchoconstriction, the smooth muscle cells are more likely to contract and narrow the airways
• Asthma pathophysiology - hypertrophy of the smooth muscle:

  • Over time the smooth muscle also become hypertrophic, as with any muscle that's continually contracting
  • It can become thicker as a result of this
• Airway inflammation is driven by inhaling an allergen to which you may have a specific IgE antibody present in your bloodstream/at the mucosal lining - this interacts with the allergen to form an antibody complex, which causes mediator release - the kind of mediators you would expect to trigger an asthma attack are the fast-acting ones, like histamine, prostaglandins and leukotrienes - can treat asthma by inhibiting leukotrienes.
• Airflow obstruction = FEV1/FVC <70%

  FEV1 = the most important measurement for looking at airway obstruction

  
• Asthma physiology:

  • Airflow obstruction
  • Variable airflow obstruction - sometimes normal, sometimes abnormal
  • Response to exercise, cold air, irritants (such as strong vapours, smells, solvents, cigarette smoke, pollution, etc)
  • Spontaneous: diurnal variation - difference between morning and night
  • Response to treatment = if you treat someone with asthma, generally the variability will diminish, and you may actually resolve the airflow obstruction
  • Exposure to allergens
• Asthma symptoms:

  • Airflow obstruction
  • Wheeze, breathlessness, chest tightness
  • Variable
  • Variable symptoms
  • Usually worse at night/early morning
  • Worse with exercise, irritant exposures, cold air, etc
  • Airway inflammation
  • Cough, sputum
• Asthma treatment:

  • Non-pharmacological = stop smoking, avoid triggers, lose weight
  • Pharmacological = drugs, devices for administration, protocols/guidelines
  • Bronchodilators = "relievers" - work on smooth muscles to relax them and open up the airway lumen
  • Anti-inflammatory agents = "preventers" - treat the inflammation within the airway epithelial cells
• Airway smooth muscle has vagus nerve acting on it, which in the airway is stimulatory and causes constriction.

  • Sympathetic - wants airway to be open so you can breathe and get oxygen to your muscles.

  Adrenergic response - circulating hormones, like adrenaline, will cause airway smooth muscle relaxation and dilation of the airways.

  Constriction works through cAMP and changes in intracellular calcium. Beta-2 adrenergic receptor waits for adrenaline to act on it.

  
• If you block off the vagus nerve then the beta-2 receptor takes over - causes airway dilation. Therefore anti-cholinergics block off the vagus nerve.

  
• Beta-2 agonists work on the beta-2 receptor through cAMP causing bronchodilation.

  
• Theophylline blocks the breakdown of cAMP and causes increased levels of that intracellularly, which causes smooth muscle relaxation.

  
• Magnesium seems to displace intracellular calcium, but the mechanism is not fully understood. Causes quite potent and rapid smooth muscle relaxation and bronchodilation. Only reserved for acute, severe, life-threatening asthma.

  
• Asthma treatment:

  • Bronchodilators - "relievers"
  • Anti-inflammatory agents - "preventers"
• Asthma treatment - bronchodilators ("relievers"):

  • Beta-adrenergic agonists
  • Anti-cholinergics
  • Theophylline
  • Magnesium
• Asthma treatment - bronchodilators ("relievers"):

  • Beta-adrenergic agonists
  • Short acting "relievers"
  • Onset = 1 min
  • Duration 2-4 hours
  • Salbutamol/ventolin
  • Terbutaline
  • Long acting
  • Duration 12 hours - therefore usually taken twice a day
  • Salmeterol
  • Formoterol
  • Oral/intravenous
  • Oral tablets are a bit old-fashioned now
  • Intravenous beta-adrenergic agonist treatment is occasionally used on pt in intensive care with severe bronchospasm
• Asthma treatment - bronchodilators ("relievers"):

  • Beta-adrenergic agonists
  • Effects of beta-agonists:
  • Bronchodilation
  • Tachycardia
  • Hypokalaemia (drops potassium levels)
  • Hyperglycaemia
  • Tachyphylaxis
• Asthma treatment - bronchodilators ("relievers"):

  • Anti-cholinergics
  • Ipratropium/Tioptropium
  • Inhibit vagal tone and cause bronchodilation
  • Side effects:
  • Dry mouth
  • Glaucoma
  • Urinary retention
• Asthma treatment - bronchodilators ("relievers"):

  • Theophylline
  • Caffeine derivative
  • Oral/IV preparations
  • Narrow therapeutic window - therefore have to check levels if given IV
  • Drug interactions = erythromycin
  • Dangerous in overdose - side efects = tachyarrhythmias, VF (ventricular fibrillation) & convulsions
  • Magnesium
  • Intravenous in acute, severe asthma
• Asthma treatment - anti-inflammatory agents ("preventers"):

  • Corticosteroids
  • Leukotriene antagonists
  • Anti-IgE antibodies
• Asthma treatment - anti-inflammatory agents ("preventers"):

  • Corticosteroids
  • Inhaled: beclomethasone, budesonide, fluticasone
  • Oral prednisolone
  • Intravenous
  • Side effects:
  • Inhaled = oropharyngeal candidiasis, dysphonia, bruising, cataracts
  • Oral = osteoporosis, skin thinning, hypertension, adrenal suppression, diabetes
• Asthma treatment - combined inhalers:

  • Inhaled corticosteroid + long-acting beta agonist
  • Seretide = Salmeterol + fluticasone
  • Symbicort = Eformoterol + budesonide
  • Others
• Asthma treatment - pressurised metered-dose inhalers:

  • Convenient
  • Require co-ordination/breath-actuated devices
  • Require high inspiratory flow
  • Oropharyngeal deposition

  
• Asthma treatment - spacer devices:

  • Decrease need for co-ordination
  • Decrease oropharyngeal deposition
  • Increase airway deposition

  
• Asthma treatment - dry powder inhalers:

  • Usually lower inspiratory flow rate
  • Less coordination needed
  • No propellant

  
• Asthma treatment - nebulisers:

  • Can administer very high doses
  • Inefficient
  • May delay hospital admission

  
• Managing acute severe asthma:

  • Assess the severity
  • Summon help
  • Sit up, support
  • High dose bronchodilator
  • Salbutamol inhaler 100ug/puff
  • Use/improvise spaced device
  • Use nebuliser if available
  • Corticosteroids/oxygen
• Assessing asthma severity - moderate asthma exacerbation:

  • Increasing symptoms
  • PEF >50-75% best or predicted
  • No features of acute severe asthma
• Assessing asthma severity - acute severe asthma:

  • Any one of:
  • PEF 33-50% best or predicted
  • Respiratory rate >=25/min
  • Heart rate >=110/min
  • Inability to complete sentences in one breath
• Assessing asthma severity - life-threatening asthma:

  • Any one of the following in a pt with severe asthma:
  • Clinical signs:
  • Altered consciousness level
  • Exhaustion
  • Arrhythmia
  • Hypotension
  • Cyanosis
  • Silent chest
  • Poor respiratory effort
  • Measurements:
  • PEF <33% best or predicted
  • SpO2 <92%
  • PaO2 <8 kPa
  • "normal" PaCO2 (4.6-6.0 kPa)
• Assessing asthma severity - near-fatal asthma:

  • Raised PaCO2 and/or requiring mechanical ventilation with raised inflation pressures