Asthma Pharmacological, Therapeutic Treatment

Question 1

Extrinsic asthma

Answer 1

Allergic- usually in children

Question 2

Intrinsic asthma

Answer 2

Non-allergic
Later on set
No fam history
No detectable IgE

Question 3

What is the first exposure immunological mechanism of asthma?

Answer 3

1) First exposure- sensitisation occurs
2) Allergen seen as pathogen
3) Macrophage engulf allergen and as an APC go to lymph nodes
4) T cells recruited
5) Present via mHC class 2 molecule to naive T cell presented to naive T cell which activate T helper 2 cells
6) Produce IL-4 and IL-13 which act upon naive B cells
7) B cells naturally produce IgM however IL-4 and IL-13 cause class switching to produce Ig
7) Go on to produce memory B cells and clonal expansion
8) B cells also active T cells to produce more B cells to the particular antigen

Question 4

Spasmogenesis of mast cells leads to what?

Answer 4

Airway narrowing, smooth muscle in airway go into spasm
Lining of lung becomes inflamed, further narrowing
Mucus production increased, further blockage

Question 5

Airway narrowing can go on for how long?

Answer 5

Can go on for up to 3 hours

Question 6

What happens at the early phase of an asthma attack?

Answer 6

• Allergen binds to mast cell
• Mast cell degranulation
• Leads to release of spasmogens
• Leads to bronchospasm
• Release of chemotaxins and chemokines (ie interleukins)

Question 7

What happens at the late phase of an asthma attach?

Answer 7

1) Interleukins leads to activation of inflammatory cells
2) TH2 cells which release other spasmogens
3) Lead to airway inflammation and airway hyper-reactivity leading to bronchospasm and wheezing
4) Toxic products can be produced from eosinophils (inflammatory cell) e.g. EMBP
5) Leads to epithelial cell damage
6) Leads to airway hyper-reactivity hence bronchospasm, wheezing

Question 8

what is FEV1?

Answer 8

how much air you expel in first second

Question 9

What is a good ratio to have for FEV1/FVC

Answer 9

Greater than 0.7

Question 10

What is peak expiratory flow rate?

Answer 10

Initial slope in spirometry

Question 11

Features of moderate asthma (PEF, SpO2, speech, respiration, pulse)

Answer 11

PEF > 50-75%
SpO2> or equal 92%
Speech normal
Respiration > 25/m
Pulse < 110bpm

Question 12

Features of acute asthma?

Answer 12

PEF 33-50%
SpO2> or equal to 92%
Cant complete sentences
Respiration > or equal to 25/m
Pulse > or equal to 110bpm

Question 13

Features of life-threatening asthma

Answer 13

PEF<33%
SpO2<92%
Silent chest, cyanosis, or poor respiratory effort
Arrhythmia or hypotension
Exhaustion, altered consciousness

Question 14

Non-pharmacological asthma measures (some)

Answer 14

Avoidance of triggers
Weight reduction
Smoking cessation

Question 15

What are the pharmacological treatment for asthma?

Answer 15

Relievers- B3 agonist, antimuscarinics, methylxanthines

Preventors- corticosteriods, leukotriene receptor antagonists, cromones

Question 16

Short acting beta agonist example

Answer 16

Salbutamol

Question 17

How do short acting B agonist work?

Answer 17

stimulation of B2 adrenoreceptors on airway smooth muscle
Activating cyclic AMP. They inhibit myosin light chain kinase, start to uncouple actin myosin interactions and lead to bronchodilation

Question 18

How do methylxanthines work?

Answer 18

Phosphodiesterase inhibitors

Phosphodiesterase break down cyclic AMP, so inhibiting elevate cyclic AMP and promote airway relaxation

Question 19

How do antimuscarinics work?

Answer 19

Target M3 subtype- inhibit bronchoconstriction, promote relaxation

Question 20

How do corticosteroids work?

Answer 20

Reduce bronchial inflammatory reactions

Question 21

How does leukotriene work?

Answer 21

Anti inflammatory action

Question 22

How do monoclonal antibodies work?

Answer 22

Selectively bind to IgE antibodies. Reduce action of mast cells. Reduces inflammatory mediated responses

Question 23

What is the re exposure immunological mechanism of asthma?

Answer 23

1) allergen comes along
2) IgE already all over mast cells and basophils
3) Dimerisation cross-linking of these IgE and Fc receptors
4) Leads to calcium channels being opened on mast cell surface
5) Calcium entry, drives degranulation= spasmogen release (release vasoactive amines)