Outline the sensitisation (1st degree exposure) process in asthma
APC to T helper (IL-4) --> b cell --> IgE --> binds to Mast cells.
Salbutamol vs salmeterol on how it enters/affects the cell
- salbutamol directly goes and affects beta adrenoceptor - we think salmeterol hangs around lipid membrane and 'leeches' out to the beta receptor adjacent
Salbutamol vs salmeterol on length of duration
Salbutamol is known as a short acting beta agonist
Which nerve innervates the bronchial smooth muscle?
How does anticholinergics work at the Smooth Muscle receptors?
- Ach is released from the vagus efferent nerve. - Anticholinergics dinds to the Ach receptors on the smooth muscle.
Salmeterol (LABA) vs Ipratropium (Anticholingeric) over time for FEV1
Pathway of Ach pathway to cause constriction (diagram)
(i) = inactive , (a) = active form - Note B2 receptors that activates cAMP pathway - Phosphorylated Myosin and Actin causes contraction.
Diagram of how anticholinergenics work on the synapse on ASM
Tiotropium vs ipratropium
- 10x more potent - long acting version of anticholinergenic - half life of 34.7h, while ipratropium has 0.25h. - tiotropium has a prolonged blockade of M3 receptors
Phosphodiesterase (PDE) inhibitors - most common?
Theophylline - how does it work on relaxing smooth muscle?
Downsides of PDE inhibitors?
- narrow therapeutic range (small difference between effective dose and dose causing side effects) - side effects are nausea and vomiting
How do PDE inhibitors work intracellularly to relax muscle?
- cAMP is broken down by PDE to AMP. - If we inhibit breakdown, we hav emore cAMP and hence more relaxation of muscle
List the isozymes of PDE in different tissues (airway, vascular, endothelium, neutrophil, T cell) (phosphodiesterase)
PDE I - V - theophylline is non selective
Distribution in smooth muscle Airway: II, IV, V Vascular: III, IV
Endothelium III, IV
Neutrophil : IV T Cell: IV
IV is the most common.
What is a good isozyme of PDE to inhibit?
PDE4 inhibitors that are likely to be released in the market
Releationship of BA's on cAMP
cAMP is increased
which drug targets M3 receptors on smooth muscle? (anticholinergenic)
Asthma treatment: When should we take SABA's
- wheezing - before exercise
Asthma treatment: When should we take ICS?
For all but the mildest of asthma
Asthma treatment: When should we take LABA's
We take it with ICS usually - LABA + ICS for moderate to severe asthma
Chronic obstructive pulmonary disease (COPD
COPD vs Asthma (pathogenesis)
COPD: - Destruction of alveoli - CD8+ cell (Th1)
Asthma - CD4+
How is lung function (FEV1) affected at COPD and Asthma?
Clinical differences (symptoms) of Asthma and COPD?
If bronchodilators don't work so well on people with COPD, how do we treat them?
- we still give them bronchodilators > Beta adrenoceptor agonists > Anticholinergics > theophylline (if they are already taking it) - Long acting agents > Tiotropium (once/day) > Salmeterol, Formoterol - ICS for advanced disease > No decline in lung function > decrease in exacerbation rate