L21- Asthma and COPD Flashcards
What’s the difference between asthma and COPD?
Asthma is primarily irreversible. Asthma is reversible, though if left untreated can lead to iirreversible changes in lung function.
What’s FEV1?
The volume of air that can be exhaled from the lungs in one second, after max inspiration
What’s PEFR?
Max. flow rate developed by the lungs after a maximal inspiration.
What is asthma?
A chronic disease of the lungs, involving paroxysmal obstruction of the airways. Predominantly inflammatory
What is chronic obstructive pulmonary disease? COPD
Chronic disease with narrowing of peripheral airways in the lung. Poorly reversiblle. Combined bronchitis and emphysema. Predominantly inflammatory
What is asthma caused by?
Genetic factors
Early environmental influences eg maternal smoking
too-clean environment
What is status asthmaticus?
Severe acute asthma attack that isn’t readily reversed. Medical emergency, can be fatal.
What has changed in an asmathic airway?
- More submucosal glands
- More muscle
- Lots of immunal cells in the submucosal layer
- Basement membrane is thicker
- Loss of ciliated epithelium
So more mucus clogging, and more muscle so muscle contractions block airways more, and less cilia to remove the mucus
Asthma attacks are usually biphasic. What are the 2 phases?
Early phase- bronchospasm
Late phase- Inflammatory phase which usually compromises airways more.
How do immune cells acquire the antibody to be ready to interact with the allergen in allergic asthma?
- Antigen presenting cell interacts with a T helper cell.
- Activated T cell releases cytokines (interleukins)
- These activate other immune cells- eosinophils and mast cells.
- The mast cells then have the antibody and can interact with the allergen.
How do mast cells cause bronchospasm?
When antibodies on the mast cells link to antigens, the mast cell degranulates and releases histamine and other mediators.
Later, leukotriene B4 and prostaglandin D2 are made from membrane lipids. These factors cause bronchospasm.
What’s attracted to the histamine and other signals released by mast cells?
Cells including eosinophils which release toxic proteins that damage the respiratory epithelium (desquamation).
They also release various growth factors that cause sensitizing of the epithelium to further allergens. BAD.
What does histamine cause?
Contraction of smooth muscle, increased bronchial secretions
What do chemotactic factors cause?
Infiltration of lung tissues by neutrophils and eosinophils
What do later mediators- leukotrienes and prostaglandin cause?
Contraction of smooth muscle, increased vascular permeability, increased bronchial secretions
What do major basic proteins from oesinophils cause?
Epithelial desquamation, cell death
Which drugs are important in treating early phase of asthma?
B-2 AGONISTS.
Non-selective B antagonists are BAD for asthma
How do you make adrenaline more selective for B2 receptors?
Increase the length of carbon chain on the N. Also reduces neuronal uptake.
Modifying adrenline by removing the OH groups makes which drugs?
Salbutamol
Terbutaline
Which drugs are long lasting to treat asthma because of their lipid solubility?
Formoterol
Salmeterol
How does salmeterol work?
The catechol-like end of the molecule interacts with the agonist binding site.
The other end anchors the molecule to the exosite.
What are the 2 causes of longevity for salmeterol?
- It’s lipophilicty. so stays in the membrane and slowly leaks out.
- anchoring at the exosite
What do B” adrenoceptors stimulate and via which G protein?
Adenylyl cyclase via the Gs G protein
How do B2 adrenoceptors lead to muscle relaxation?
Activate Adenylyl cyclase
Increases cAMP
cAMP activates protein kinase A
PKA does 2 things-
- negatively modulates myosin light chain kinase
- cellular calcium falls
What are the unwanted affects of B agonist bronchodilators?
Tremor
Tachycardia
Nervous tension
Hypokalaemia
(like in labs with salbutamol)
