Asthma: diagnosis, monitoring, pathophysiology, and management Flashcards
What is asthma defined by
Reversible increases in airway resistance, involving bronco constriction and inflammation
What is asthma characterized by
Reversible decreases in the FEV1:FVC (less than 70-80% suggests increases airway resistance)
What is FEV1
Amount of air a person can force out of their lungs in 1 second
What is FVC
Forced vital capacity (total amount of air exhaled)
How can you also see if a person has asthma (another diagnostic test)
Measure their PEF (peak expiratory flow)
What is the PEF like in an asthma patient
Variable- which is improved with a Beta2 agonist
What is PEF
Maximum velocity of a person’s expired air (peak expiratory flow)
What is COPD
Chronic obstructive pulmonary disease
-chronic bronchitis+ emphysema
What is chronic bronchitis
Increased mucus, airway obstruction, intercurrent infections
What is emphysema
Destruction alveoli
What is the FEv1 like in a person with COPD
Reduced
What is the PEF like in a person with COPD
Little variation
What is chronic bronchitis and emphysema mostly caused by
90% caused by smoking
Which nervous system is used to relax airways
Sympathetic
How does the sympathetic nervous system relax the airways
Release of circulating adrenaline acting on beta2-adrenoreceptors on bronchial smooth muscle and activates them to cause relaxation (bronchodilation)
How does parasympathetic nervous system cause the constriction of airways
- vagus nerve releases acetylcholine at the ganglia
- Binds to muscarinic receptors which activates it and causes constriction
How else is acetylcholine released to cause muscle constriction
End organ of tissue
How else does sympathetic nervous system control bronchial calibre
Sympathetic fibers release NA which acts on adrenoreceptots on parasympathetic ganglia to inhibit transmission
-Beta2 adrenoceptors also are on mucus glands to inhibit secretion
What nerves do airways have
sensory nerves
What happens if dust gets in airway
Stimulates sensory nerve, which then causes bronchoconstriction (reflex response locally) (cough reflex)
What are asthmatic attacks genetically provoked by
- allergens
- cold air
- viral infections
- smoking
- exercise
What are the phases of an asthma attack
-May be characterized by Early phase followed by Late phase (which is more inflammatory)
Clinical features of asthma
-wheezing
-breathlessness
-tight chest
-cough (worse at night/exercise)
(nocturnal in children)
-Decreases in FEV1, reversed by a Beta2 agonist
Once a stimulus is detected, what happens in lungs
-mast cells, mononuclear cells, release mediators
What are the mediators that the mast cells and mononuclear cells release
Spasmogens (immediate response) which constrict the airways and cause bronchospasm
Chemotaxins (signals to white blood cells which tell them to go to the lungs and cause the Late phase (inflammation)
Examples of spasmogens
Histimine
Prostaglandin D2
Leukotrienes C4 and D4
Platelet activating factor (PAF)
How are prostaglandins Made
In the cell membranes, we all have arachidonic acid. Via the COX pathway, it is metabolized to prostaglandin
What is the role of prostaglandin
Bronchoconstrictor
How are leukotrienes made
Arachidonic acid goes down the LOX pathway to form leukotrienes
What are leukotrienes used for
Spasmogens, and are also inflammatory
What is histamine released by
Mast cells
Examples of chemotaxins and their role
- Leukotriene B4, PAF
- leads to Late Phase
- Attract leukocytes, especially eosinophils and mononuclear cells
- Leads to inflammation and airway hyper-reactivity
What do bronchodilator reverse and what phase is this
Bronchospasm (early phase)
What kind of relief do bronchodilators provide
Rapid relief
What other drugs can be used and what is this used for
-preventers used to prevent an attack
What is the drug used as a Beta2 adrenoceptor agonist
Salbutamol
When is salbutamol used
Agent of first choice
What does salbutamol do
Increases FEV1
- Binds to Beta 2 adrenoceptors on smooth muscle
- Produced G protein
- This G proteins activates Adenylylcyclase which is an enzyme which leads to the production of cAMP (second messenger) which causes muscle relaxation
What is cAMP broken down into
PDE into AMP
-stops action of cAMP
Long term effect of beta2 agonist
Leads to the lessened responsiveness of the beta2 adrenoceptors which makes the drug less effective
What drugs are used as a preventative measure and for long term control
Long acting beta agonists (LABA)
Example of a LABA
Salmetarol
What does salmetarol do
Dilate the airways for 12 hours so is used for long term control overnight
What are the two theories of action of xanthines
- Adenosine receptor antagonists
- Phosphodiesterase inhibitors
The are xanthines used
In an emergency (intravenous insertion in an emergency)
What do xanthines do when inhabiting phosphodiesterase inhibitors
Xanthines PDE which means that the breakdown of cAMP is inhibited and so the action of cAMP is prolonged and so theres more muscle relaxation by the action of salbutamol
What are muscarinic M-receptor antagonists mostly used in
COPD (limited value in asthma)
What do muscarinic M-receptor antagonists do
Block parasympathetic bronchoconstriction
Example of muscarinic M-antgonists
Tiotropium
Side effects of muscarinic M-antagonists
- Dry mouth
- constipation
- Blurred vision
because you’re blocking parasympathetic nervousb system
How to reduce musarinicM- antagonist side effects
Inhale the drug
What are anti-inflammatory agents used as
Preventative measure
THEY DO NOT REVERSE AN ATTACK
Drug name used as an anti-inflammatory agent
Corticosteroids
-eg beclometasone (brown inhaler)
What do corticosteroids do
1) Go into the cell because its lipid soluble
2) Activate intracellular receptors
3) Intracellular-drug complex goes to nucleus
4) Tells nucleus which bits of DNA to produce mRNA for
5) mRNA comes out of the nucleus and codes for protein Lipocortin/Annexin A1
6) Lipocortin/annexin A1 inhibits phospholipase A2 which is used to synthesize arachidonic acid (which produces leukotrienes and prostaglandins which inflame the airways)
What are steroids given with and why
Beta 2 agonists to reduce the receptor down-regulation
Side effects of steroids taken
- orally
- Inhaled (and how to prevent this)
Orally- Adrenal suppression
Inhalation- Throat infections, hoarseness (so wash mouth out afterwards)
What is salmetarol
Beta 2 agonist
What are leukotriene receptor agonists (LTRAs) used for
Block the action of leukotrienes
-preventative and bronchodilators
Example of a leukotriene receptor antagonist drug
Montelukast
Initial line of treatment for an asthma patient
Short acting Beta2 agonist (salbutamol) plus a regular inhaled steroid (beclametasone)
If patient’s asthma is not sufficiently controlled by first line of treatment, what do you use next
-and if this fails?
Trial of LABA (or LTRA or xanthine if this fails)
-Increase dose of inhaled steroid
If the patients asthma is not controlled by increasing dose of inhaled steroid?
Add oral steroid
How to know whether to go to next line of treatment
If salbutamol is used >2 times a week
When is a spacer device used (the bottle)
- In patients with poor technique
- Reduce steroid impaction
What should you use before a steroid and what to do after steroids
Bronchodilator
-wash mouth out
