Asthma Flashcards
Asthma
Reversible increases in airway resistance, involving bronchoconstriction and inflammation
What ratio can be used to characterise asthma; what values
reversible decreases in FEV1:FVC
forced expiratory volume in one second : Forced vital capacity
Can Asthma be Lethal
Yes
What variations can be used to diagnose asthma
Variations in PEF (peak expiratory flow) which improve with a B2 agonist indicate asthma
Symptoms of Chronic Bronchitis
Increased mucous, airway obstruction, intercurrent infection
COPD, most common cause, quantitative value used to indicate it
Chronic Obstructive Pulmonary Disease
Some combination of chronic bronchitis and emphysema
> 90% smoking related
FEV1 reduced
Sympathetic control of bronchial calibre
Circulating adrenaline acts on β2 adrenoceptors on bronchial smooth muscles to cause relaxation
(top most important)
sympathetic respose reduces parasympathetic involvement by releasing noradrenaline, inhibitng their transmission
additionally act on β2 adrenoceptors on mucous glands to inhibit secretion
Parasympathetic control of bronchial calibre
Acetyl choline acts on the muscarinic M3-receptors to cause bronchoconstriction and increasing mucous productoin
Factors that predispose asthma attacks
Allergens Cold air Viral infections Smoking Exercise
Clinical features of asthma
Wheezing
Acute onset of Breathlessness
Tight Chest
Cough (worse at night/exercise) (Nocturnal in kids)
Decreases in FEV1 reversed by a B2 agonist
Lung Function Test results (FEV1 vs FVC) graph for normal vs asthamtic patient
Biological response during asthmatic attack
How does PEF Change during an asthmatic attack (Early and late phase)
**This can vary a lot in clinical presentation with both phases simultaenously or only one occurring
What are the 3 Spasmogens
Histamine
Prostaglantin D2
Leukotrienes
How are spasmogens made
Arachidonic acid is present in cell membranes and is chopped out by phosphospholipase A2 (PLA2)
A. Acid is released which is the substrate for the lipooxygenase (LOX) pathway which produces leukotrienes or is the substrate for the cyclooxygenase (COX) pathway which produces prostaglandins
(Also platelets releasing platelet activating factor PAF)
Chemotaxins
Leukotriene B4, PAF (Platelet Activating Factors)
Attract leukocytes to airways and exacerbate asthamtic attack and inflammation
Spasmogens
Chemicals that cause the airways to go into spasm or constriction
Why are anti-histamines not that effective for asthma
Because there are more mediators than just histamine
Pharmacological basis of Asthmatic therapy
Bronchodilators
Reverse bronchospasm and causing rapid relief
(relievers)
Preventors
Used to prevent an attack; may be anti-inflammatory
B2-adrenoceptor agonists
Salbutamol (blue inhaler)
Selective for B2 receptors
Trade name is ventolin
Asthma drug of first choice
Causes brochodilation by acting on b2-adrenoceptors on smooth muscle to increase cAMP; increases FEV1
Mechanism of Salbutamol
Salbutamol (blue inhaler)
Selective for B2 receptors
Trade name is ventolin
Asthma drug of first choice
Causes brochodilation by acting on b2-adrenoceptors on smooth muscle to activate adenylyl cyclase to increase cAMP which increases FEV1 and relaxes lungs
How do B2-Agonists work in terms of para-/sympathetic activity and what is the effect of its overuse
Reduces parasympathetic activity
Prolonged use may lead to receptor down-regulation (desensitisation)
Long Acting Beta Agonists (LABA)
Anti asthma medication used twice a day (e.g. salmeterol) given for long-term control and prevention
Xanthines
e.g. Theophylline
Bronchodilators; not as good as salbutamol (2nd line use); used orally or iv in emergency
Adenosine receptor antagonists Phosphodiesterase inhibitors (thus increasing cAMP)
This is good in emergencies because youre using everything but the kitchen sink to try open the airways
Inhalers and Climate Change
Metered Dose Inhalers (most inhalers) release excessive amounts of hydrofluorocarbons (GHGs) into the atmosphere (equivalent to a drive from london to sheffield per inhaler)
Instead dry powder inhalers are much more sustainable
Inhalers are 4% of NHS GHG emmissions
What is the equivalent lifestyle change of shifting from MDIs to Dry Powder Inhalers on the planet
Equivalent lifestyle change as becoming a vegetarian
PDE IV Inhibitor
Roflumilast - Selective PDE IV inhibitor licensed for COPD
Muscarinic M-receptor antagonists and how is it taken (and why)
Iptratropium/Tiotropium
Blocks parasympathetic bronchoconstriction; little use in asthma but used in COPD
It is inhaled because inhalation prevents antimuscarinic side effects as opposed to tablets that have more undesired systemic effects
Anti-inflammatory Agents (Corticosteroids) for asthma
Preventative - Do not reverse an attack
(use inhaled to avoid systemic effect from pills)
Cotricosteroid binds to intracellular receptor, affects nucleus gene expression, cell is told to produce mRNA that codes for a protein with two names Lipocrortin/Annexin A1; also reduces cytokine production
Function of Lipocortin/Annexin A1
Inhibits synthesis of PGs and LTs by antagonising the magic protein PLA2
PLA2 is responsible for taking the A. Acid out of membranes to produce PGs and LTs
Steroids
Given with B2-agonists to reduce receptor down-regulation (enhances effect of the agonist)
Side effects - throat infections/hoarseness due to myopathy in throat muscles (inhalation)
Tell patient to rinse mouth out after inhalation
Adrenal suppression (oral) (Used for very short period of time)
Leukotriene Receptor Antagonists (LTRA)
Montelukast
Increased role as add on therapy when initial treatment is insufficient
Preventative and a little Bronchodilators
Antagonise actions of LTs by antagonising their receptors
Omalizumab
Used in difficult to treat asthma
Monoclonal antibody (MAB) against free IgE but not bound IgE
Prevents IgE from binding to immune cells which leads to allergen induced mediator release in allergic asthma
Steps of drugs given to asthmatics
Start with short acting B2-agonist plus regular inhaled steroid
–>
Trial of LABA (or LTRA/Xanthine if this fails)
–>
Increase dose of inhaled steroid
–>
Add oral steroid
Guidlines for asthma medication
If salbutamol is used >2 times a week, step up
Spacer device used when technique is poor/reducing steroid impactation
Bronchodilator before steroid
Rinse mouth out after steroid
COPD Treatment
STOP SMOKING FFS
Receiving appropriate vaccinations against stuff like the flu
Bronchodilators (B2-agonist/salbutamol + ipratropium)
Inhaled steroids?
Antibiotics for intercurrent infections
Oxygen therapy
**Ipratropium blocks PS broconstriction
NSAIDs and asthma
Non-steroidal anti-inflammatory drugs
15% of asthmatics are sensitive to such drugs
e.g. aspirin, ibuprofen
They stop PG production (which is good) but increases leukotriene productions
Beta-blockers and asthma
Contraindicated in those with asthma
Think of it like a reverse beta2 agonist
