Asthma and COPD Flashcards
What is asthma?
recurrent reversible obstruction of the conducting airways in response to a stimuli that are not themselves noxious and which do not affect non-asthmatic subjects
What are the main characteristic features of asthma?
- airway obstruction
- airways inflammation
- increased bronchial hyper-responsiveness to wide variety of stimuli
- bronchoconstriction
- mucus secretion
- oedema
What happens when an asthmatic inhales an antigen?
- release of histamines prostaglandins, leukotrienes and cytokines
- causes oedema, bronchoconstriction, increased mucus secretion, inflammatory cell recruitment
What do asthmatic lungs look like using a bronchoscope?
- bifurcations have become obscured
- conduction airways full of mucus
- red inflamed airway walls
- oedema and vascular leakage further compressing the airway
How do house dust mites cause an allergic response?
HDM’s faeces are small enough to end up in the airways and generates an allergic response through cross linking of IgE antibodies and antigen expressed in HDM faeces
How is cilia function altered?
- epithelium is continuously disrupted by exposure to allergen
- constant disruption of cilia results in thickening of the mucus triggered by materials secreted from degranulated eosinophils
- damaged epithelium exposes sensory nerves below which responds to temperature, humidity and irritants in the air
- exposure and stimulation of nerves triggers mucus secretion and muscle contraction- hyperresponsiveness
How does histamine cause bronchoconstriction?
- histamine released from allergen stimulated mast cells stimulate H1 histamine receptors
- activation of these receptors mobilises calcium from the SR increasing intracellular calcium
- calcium binds to calmodulin
- calcium bound CaM activates myosin light chain kinase
- MLCK phosphorylates light chains in the myosin heads and increase activation of myosin ATPase
- active myosin crossbridges slide along actin filaments creating muscle tension- increasing muscle contraction
- histamine signalling also inactivates myosin light chain phosphatase which increases contraction
How do beta2 adrenergic agonists affect G protein coupled receptors?
- agonist activation induces a conformational change causing GTP/GDP exchange and dissociation of the alpha subunits from the beta/gamma subunits
- mediate slower synaptic transmission- coupled to 2nd messenger cascades
- B2 adrenergic receptor is coupled to Gs
How do B2 adrenergic agonists function as bronchodilators?
- B2 receptors found in airway smooth muscle
- stimulation of receptors cause adenyl cyclase activity increasing the production of cAMP from ATP
- increased cAMP increases the activity of protein kinase A, inducing relaxation through 3 mechanisms:
1. inhibiting Ca release
2. inhibition of MLCK
3. increasing activity of myosin light chain phosphatase
What are the different routes of administration of Beta agonists and their pros and cons?
Oral vs inhalation:
- metered dose inhaler produces more bronchodilation at lower doses
- oral route requires larger doses to be effective
- less systemic effects associated with inhaled route
- faster onset of action with inhaled route
Compressor-driven nebuliser:
- expensive, no portability, bacterial contamination
- delivers constant doses
Parental route:
- terbutaline can be injected subcutaneously without the need for patient corporation (i.e. severe asthma)
How do muscarinic antagonists function as bronchodilators?
- they inhibit the parasympathetic innervation of the airway smooth muscle
- under normal conditions, ACh is released at the junction between the post ganglionic parasympathetic nerves and the airway smooth muscle
- ACh stimulates M3 muscarinic ACh receptors on the airway smooth muscle triggering bronchoconstriction
- blockade of M3 muscarinic receptor antagonists block parasympathetic innervation, inhibiting bronchoconstriction
How do xanthines function in airway diseases?
- Xanthines are structurally related to caffeine and can induce bronchodilation
- have to be taken as tablets and therefore associated with system side effects similar to high caffeine usage
What are the cellular actions of glucocorticoids?
- inhibit leukotriene and cytokine synthesis/release
- inhibit lymphocyte proliferation and pulmonary recruitment
- inhibit activation, chemotaxis, adhesion of eosinophils and promotes eosinophil apoptosis
- inhibits mast cell proliferation
- anti-oedema
- increases B2-adrenoceptor function
What are the roles of glucocorticoids in asthma?
- prevents infiltration and activation of inflammatory cells
- reduces mucosal oedema
- improves airflow and lung function
- decreases airway hyperresponsiveness
- decreases frequency and severity of exacerbations
- improves quality of life
Why are cromones used to treat asthma?
- when mast cells are activated by cross-linking with allergens, they degranulate, releasing many different pro-inflammatory mediators including IL-5, histamine etc.
- cromones inhibit mast cell degranulation preventing the release of these mediators from mast cells in response to allergen exposure
