L 12,13,14 Allergic Rhinitis Flashcards
What is atopy?
A genetic predisposition to hypersensitivity or allergy.
What is Oedema?
Swelling of soft tissue
What is pruritus?
Itching
Rhinitis means?
Inflammation
Rhinorrhoea means?
Runny Nose
What is an allergy?
immune response to a foreign substance or allergen.
for some people it is not harmful as it makes an immune response but for some people it overreact and cause problems.
Allergic rhinitis can be split into 3 categories:
Seasonal allergic rhinitis
Perennial allergic rhinitis
Non-allergic rhinitis
Is hayfever well diagnosed by health professionals?
No, usually it is overlooked and diagnosed as a cold or asthma.
What are the 2 stages of asthma? + brief explanation
Sensitisation - antigen binds and mounts an immune response with IgE antibodies. Bind to the immune and mast cells to prime them for re-exposure.
Re-exposure - being exposed to the antigen again, and a full immune response occurring due to IgE antigen-antibody complex activating mast cell degranulation
Early phase symptoms of allergic rhinitis
Sneezing
Nasal itching
Rhinorrhoea
Nasal congestion
What are the Early phase symptoms of allergic rhinitis
Early phase symptoms occur within minutes.
Histamine released by mast cells binds to receptors all over body, causing vasodilation and leaky blood vessels.
Interstitial fluid then leaks in = nasal congestion.
Histamine binding also causes increased mucus production (runny nose) and also binds to sensory nerve receptors for sneezing and itching to occur.
Late phase symptoms occur within…. due to
Late phase symptoms occur within 6-12 hours.
Antigen stimulates T&B cells which stimulate mast cells to release cytokines, causing stimulatory cascade to release other mediators.
These other mediators increase dilation and decrease emptying = nasal congestion/obstruction and nasal hyperactivity
What are the 4 strategies to address symptoms of allergic rhinitis?
- Avoid triggers
- Block histamine action via antihistamines and anticholinergics
- Prevent mast cell release via mast cell stabilisers
- Prevent inflammation via corticosteroids.
Which histamine receptor are we most concerned with? What type of receptor is it?
H1 histamine receptor, GPCR
What are the strategies of treating allergic rhinitis?
Symptoms relief
Avoid triggers
With medicine
What type of drug are antihistamines?
Histamine antagonist.
Antihistamines are a class of drugs commonly used to treat symptoms of allergies.
These drugs help treat conditions caused by too much histamine, a chemical created by your body’s immune system.
Antihistamines are most commonly used by people who have allergic reactions to pollen and other allergens
Brief rundown of how antihistamines work
They stabilise the inactive form of the receptor, causing stimulation by histamine to be less possible. Therefore they produce a smaller response.
In other words: Antihistamines block the effects of a substance called histamine in your body. Histamine is normally released when your body detects something harmful, such as an infection. It causes blood vessels to expand and the skin to swell, which helps protect the body.
Effects produced by antihistamines
They decrease vascular permeability
Cause vasodilation
Decrease interstitial fluids
Types of Histamine receptors and they are?
H1,H2,H3,H4
H1 receptor heavily expressed in?
Smooth Muscle, Mast cell, Endothelium and brain
H1 receptors are ?
H1 receptors are INVERSE agonists, because they are not receptor antagonists. They stabilise inactive histamine.so for example if they start showing symptoms in september they start taking medicine in August.
First generation antihistamines have … selectivity and … BBB permeability
First-generation antihistamines have low H1 selectivity and high BBB permeability.
H2 receptors heavily expressed in the areas?
Gastric mucosa, Cardiac muscle, and neutrophils
Second generation antihistamines have … selectivity and … BBB permeability
high H1 selectivity and low BBB permeability.
H3 are heavily expressed in ?
CNS and PNS
Do first gen or 2nd gen antihistamines have a shorter duration of action (in general)?
First generation have a shorter duration of action.
Issues with 1st gen antihistamines
High BBB permeability and low H1 selectivity = more side effects
Examples of 2nd gen antihistamines (x4)
Cetirizine, loratadine, Desloratadine, fexofenadine
Intranasal corticosteroids act primarily during which phase? …. What is their MoA?
Intranasal corticosteroids act primarily during the late phase.
They down regulate recruitment and influx of inflammatory cells. They inhibit the secretion of pro-inflammatory mediators
Corticostiroids activity is mediated by activation of the …. receptor
by activation of the glucocorticoid receptor
Intranasal corticosteroids are ….. for long term use. Which spray would you recommend?
For allergic rhinitis, there is ….. association between glucocorticoid potency and clinical response
They are effective for long term use. Would recommend fluticasone propionate (Flixonase)
For allergic rhinitis, there is no linear association between glucocorticoid potency and clinical response.
Meaning that there is little/no difference between CC spray options.
Does the compound with the highest receptor affinity have superior clinical efficacy?
Not always. As research has shown that there are no linear association between glucocorticoid potency and its clinical response.as the response depends on the drug disposition on the site or systemic circulation and retention of the drug and or availability.
What are the Intranasal side effects of Corticosteroids?
Dryness, stinging, burning, nosebleed (epistaxis), nasal mucosal atrophy (reduction of cells)
How do mast cell stabilisers work? Are they more effective for prophylaxis or post-exposure treatment?
They block mast cell degranulation by prevention of histamine release and other mediators.
Are more effective for prophylaxis.
What are the sympathomimetic drugs for the treatment of decongestants?
Xylometazoline and oxymetazoline (Otrivin) activate adrenergic receptor.They bind with Alpha 1 receptor and constrict the blood vessel which was swollen with inflammation earlier.
Intranasal decongestant examples, onset, use duration, complications.
Examples: xylometazoline and oxymetazoline (e.g otrivin)
Rapid onset
Short duration of use (<5 days) due to risk of rhinitis medicamentosa (aka tolerance develops causing nasal congestion without rhinorrhoea or sneezing)
What are the disadvantages of Atrovent?
Very strong so Use only for 4-5 days and must stop as it may lead to rebound congestion for longer use.
Other allergic rhinitis therapy options (x4) - less common
Saline spray/drops
Intranasal anticholinergics (Ipratropium bromide)
Oral anti-leukotriene receptor antagonists
Immunotherapy
First line treatments for allergic rhinitis:
- 2nd generation oral antihistamines (help with all/majority of symptoms)
- Intranasal steroids (help with majority of symptoms)
- Decongestants for short term use (but only help with congestion)
Eye related symptom treatment
H1 antagonists (e.g levocabastine HCL = livostin), mast cell stabilisers, sympathomimetics
