Asthma/Allergy Flashcards
Where are mast cell located?
Generally everywhere in the body however they are most concentrated at sites where there is exposure to pathogens - GIT, resp tract, skin
They are commonly found close to vessels, nerves and glands
What is red man syndrome?
Non-specific mast cell degranulation due to vancomycin treatment.
What are some stimuli for mast cell activation
External
- UV light/ heat
- mechanical activation
- polybasic drugs
- morphine
- vancomycin
- allergen (IgE)
- Stings
Internal
- Hypertonic saline
- Neuropeptide
- Complement
What are the three downstream consequences of mast cell activation?
Degranulation
Arachidonic acid metabolite synthesis
Cytokine synthesis
What are the factors released in mast cell granules?
Histamine Chymase Tryptase Heparin TNF-alpha
What are the factors released in the intermediate stage of mast cell activation
Cysteinyl leukotrienes
Prostaglandin E2
(10-30mins)
What cytokines do mast cells produce in the late phase?
IL-4, IL-5 and granulocyte macrophage colony stimulating factor (GM-CSF). This is dependent on T cells and eosinophils
What effects does histamine acting on H1 receptors have?
Pain and itch (sensory nerve activation) Bronchospasm (smooth muscle contraction) Mucus production Vasodilation Increased vascular leak (via endothelials retracting from each other) CNS activation wakefulness
What effects does histamine acting on H2 receptors have?
Gastric acid secretion
Positive inotropic and chronotrophic effects
What effects do the cysteinyl leukotrienes have?
Vasodilation in skeletal muscle
Hypotension (important in anaphylaxis)
Decreased CO
Asthma: Increase mucus, oedema, Airway SM shortening
Hay fever: Increase mucus, oedema
What are the names of the cysteinyl leukotrienes produced in the intermediate phase?
LTC4, LTA4, LTD4 and LTE4
What receptor do the cysteinyl leukotrienes act on?
CysLT1 receptor
Some mast cell cytokines are regulated by glucocorticosteroids, which are they?
IL-1 and TNF
What are some endogenous inhibitors of mast cell activation?
PGE2, Cortisol, adrenaline
What are some exogenous inhibitors of mast cell activation?
Disodium cromoglycate, nedocromil sodium - applied topically
What is the action of disodium cromoglycate and nedocromil sodium?
Inhibit mast cell degranulation and eosinophil activation and C-fibre activation
Also, activates annexin-1 which is anti-inflammatory
What is Omalizumab?
Murine monoclonal antibody that sterically hinders IgE from binding to FceR1.
Do non-steroidal anti-inflammatory drugs or COX-1 inhibitors have a beneficial effect in asthma?
No net beneficial effect.
Prostaglandins are a mixed beneficial and negative effectss
What role to glucocorticosteroids play in asthma?
They suppress mast cell reactiveness in response to allergen via regulating cytokine and leukotriene action
Are H1 receptor antagonists useful in treating asthma?
NO
When are H1 receptor antagonists used?
Urticaria Hayfever Anaphylaxis and angioedema atopic dermatitis bites and stings motion sickness
What are the three generations of H1 receptor antagonists?
Sedative
Non-sedative
Newer even less sedative
In what conditions are leukotriene receptor antagonists used?
Hay fever and exercise/aspirin induced asthma
What effects for leukotriene receptor antagonists have?
Modest bronchdilation
Are leukotriene receptor antagonists used by themselves?
Nay, they are used with GCS and B2 agonists
Define the clinical features of asthma
Chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing
What host factors are related to the development of asthma?
Genetics - atopy and airway hyperresponsiveness
Weight - increased cytokine production
Gender - more in males before puberty, more in females after puberty
What environmental factors effect asthma development?
Indoor/outdoor smoke Diet Pollution Occupational sensitisers Tobacco Smoke Respiratory infection - rhinovirus associated with dev. and exacerbating asthma
What causes bronchospasm in asthma?
Histamines and leukotrienes
What are the short terms events in an acute asthma attack?
Vasodilation Bronchospasm Increase mucus production Plasma fluid leak Irritation Cholinergic reflex Sensory nerve activation
What are long term effects of asthma
Hypertrophy and hyperplasia of airway SM
Hyperplasia of mucus secreting cells and glands
Fibrosis of subepithelium
Angiogenesis
What drugs are used to remove mucus plugs during acute asthma episodes?
None! Only coughing works and preventative drugs to reduce build up.
What is the difference between controllers and preventers?
Controllers (LABA) provide constant bronchodilation
Preventers reduce mast cell activation and mast cell cytokine production
