Asthma Flashcards
What is asthma?
Inflammatory condition in which there is recurrent reversible airways obstruction in response to irritant stimuli. Chemical mediators are released by mast cells in airways; bronchoconstriction, mucosal oedema, hypersecretion of mucus
What are the symptoms of asthma?
wheezing, tight chest, cough - especially at night
What is asthma cause by?
genetics
animal allergens
pollen
infections
chemicals
drugs - NSAIDs
smoking
emotions stress
exercise
cold weather
Describe the onset of asthma?
- Cases begin in childhood and can develop later in life
- Late onset: non-T2-type (absence of allergy) - such as NAIDs intolerance, rhino-sinusitis
What are the two onset sub-types?
T2 - allergy, exercise - induced, aspirin exacerbation.
Non-T2 - obesity associated, smoking related
What are the two phases of asthma?
Immediate
Late
What are the 3 features of airway hyper-responsiveness?
- Airway wall inflammation involving neutrophils, T cells (CD8+) alveolar dendritic cells and macrophages. Dendritic cell recruit T cells (CD4+) in the alveolar air spaces and eosinophils in bronchioles
- Luminal obstruction of the airways by mucus caused by hyper-secretion of bronchial mucous glands and infiltration by inflammatory cells.
- Vasodilation of bronchial microvasculature with increases vascular permeability and oedema.
What is hypersensitivity?
Bronchial hyper reactivity is abnormal sensitivity to a stumli - bronchoconstriction.
What is the 1st phase of Th2 response?
Attract inflammatory granulocytes (eosinophils) to the mucosal surface.
What is the 2nd phase of Th2 response?
IL-5 and granulocyte -macrophage colony stimulating factor prime eosinophils to produce cysteinyl leukotrienes to release granule proteins that damage the epithelium.
- This damage is a cause of bronchial hyper - responsiveness
What is the 3rd phase of Th2 response?
Promote IgE synthesis and responsiveness in some asthmatics.
- IL-4 and 13 switch B cells to IgE synthesis and cause expression of IgE receptors on mast cells and eosinophils - enhance adhesion of eosinophils to endothelium.
List the bronchodilators used in the treatment of asthma.
SABA
LABA
Anticholinergics
Methylxanthines
List the anti-inflammatories used in the treatment of asthma
- ICS
- LTRA
Describe the adrenergic receptors
All are typical G protein-coupled receptors
What are the 2 categories of adrenergic receptors?
- alpha - adrenergic receptors - 2 sub types
- beta - adrenergic receptors - 3 sub types
Where are beta1 receptors found?
mainly in the heart and responsible for effects of catecholamines
Where are beta2 receptors found?
mainly in the lungs and responsible for causing smooth muscle relaxation in many other tissues
Describe SABAs MOA and give examples.
MOA - activates B2-R which relaxes smooth muscle and widens airway to relieve symptoms.
- Patients with symptomatic asthma should be given SABA2A
- Well absorbed and does not cross BBB
Examples: Salbutamol, Terbutaline
Describe LABAs MOA
MOA: bind to 2 sites (exo & active) on R - longer duration of effect (12hours) - use x2 a day
- Patients with uncontrolled asthma by SABA alone
- Improve lung function and decreases asthma symptoms
- Must be used in combo with ICS
State examples of LABAs
Fostair - formoterol/ beclometasone
Duoresp - formoterol/ budesonide
Seretide - salmeterol/ fluticasone
Relvar - vilanterol/ fluticasone
Describe anticholinergics MOA and give examples.
MOA: block effects of acetylcholine and inhibit muscarinic GPCR leading to muscle relaxation.
- used in addition to SABA and LABA - rarely used in asthma
Examples:
SAMA - ipatropium
LAMA - tiotropium
Describe Methylxanthines MOA and give examples.
MOA:
- Relaxes smooth muscle of bronchial airways and pulmonary blood vessels which leads to low responsiveness to histamines, metchacholine, adenosine and allergens.
- Competitively inhibits PDE which is the enzyme responsible for breakdown of cAMP in smooth muscle resulting in bronchodilation.
Examples; theophylline
Describe the MOA of ICS and give an example
- Restrain clonal proliferation of the Th cell by decreasing transcription of the IL-2 gene and decreases cytokine formation. Th2 cytokines recruit and activate eosinophils. They are responsible for promoting production of IgE and expression of IgE-R.
- Glucocorticoids inhibit the generation of vasodilators PGE2 and PGI2 by inhibiting COX-2.
- Activate GR & inhibit inflammatory stimuli to decrease inflammation.
Example: beclometasone diproprionate by brand - QVAR or Clenil
Describe the MOA of LTRA and give and examples
- CysLT (LTC4,LTD4,LTE4) are eicosanoids released by mast cells and eosinophils.
- CysLT bind to CysLT type 1 receptor on respiratory airway smooth muscle cells, airway macrophages & pro-inflammatory cells e.g. eosinophils
- Decreases sputum eosinophilia
Examples: montelukast, zafirlukast
