Asthma and COPD Flashcards
Define asthma
Reversible increases in airway resistance, involving bronchoconstriction and inflammation. FEV1:FVC is less than 70-80% - shows airway resistance. Variations in PEF which improves w beta2 agonist (morning dipping). Managed pharmacology but poor compliance = failure
What is COPD
Chronic bronchitis + emphysema.
>90% smoking related
FEV1 reduces
Little variation in PEF, little reversibility w beta 2 agonist
How does the parasympathetic nervous system control bronchial calibre?
ACh acts on M3 receptors
Bronchoconstriction
Increase mucus
How does the sympathetic nervous system control bronchial calibre?
Vagus nerves stimulates airways.
Circulating adrenaline acting on beta2-adrenoceptors on smooth muscle causing relaxation and inhibiting mucus secretion
Releasing NA acting on adrenoceptors on parasympathetic ganglia to inhibit transmission
What can provoke an asthma attack?
Genetic predisposition is provoked by allergens, cold air, viral infections, smoking, exercise. Characterised by EARLY and LATE phase
List the clinical features of an asthma attack
Wheezing Breathlessness Tight chest Cough - worse at night/exercise Decreases in FEV1, reversed by beta2 agonist
Describe the mechanism for asthma after a stimulus
–> Causes mast cells in lungs to become unstable to release mediators: spasmogens (–>bronchospasm) and chemotaxins (–>WBCs to arrive and inflammation)
TRUE or FALSE? Early phase shows a recovery in an asthma attack and then minutes later a late phase shows much smaller response
False! Late phase comes hours later and is much more prominent response
List examples of spasmogens
Histamine
Prostaglandin (bronchoconstrictors))
Leukotrienes (bronchoconstrictors and chemotaxins)
Platelet activating factor
After arachidonic acid is chopped out of membranes by phospholipase A2 enzyme they produce what two mediators and by what pathway?
Prostaglandin through cyclooxygenase enzyme (COX pathway) and leukotrienes through lipoxygenase enzyme (LOX pathway)
How do bronchodilators work?
Reverse bronchospasm (early phase). Rapid relief - RELIEVERS (before an attack)
What are preventers?
Taken continuously, used to prevent an attack
Prevents but no relief
What is the 1st choice reliever for asthma patients and what is the mechanism?
BETA2-ADRENOCEPTOR AGONISTS (salbutamol). Increases FEV1. Acts on beta2 adrenoceptors in smooth muscle which is coupled w adenylyl cyclase to increase cAMP -> relaxation.
Why is a non-selective (affecting beta1&2) agonist no longer 1st choice reliever?
Had an affect on the heart due to beta-1 receptors on the heart
Why are beta2 agonists given by inhalation
To reduce side effects
What happens with prolonged use of beta2 agonists and what is given to patients to reduce this?
Receptor down-regulation - it will become less responses. Given steroid to reduce this
When are long acting beta agonists (e.g. salmeterol) given and why?
For long term prevention and control (overnight). Binds to receptor and is retained. Has to use with steroids and associated w incr mortality. It isn’t a reliever
What are Xanthines?
Bronchodilators - 2nd line use. Oral. Phosphodiesterase inhibitors (enzymes that break down cAMP)
How do M-receptor antagonists work and how/when are they used?
Block parasympathetic bronchoconstriction (specific for M3).
Inhalation - to reduce muscarinic side effects (dry mouth, constipation)
Little use in asthma, used in COPD
Anti-inflammatory agents - CORTICOSTEROIDS are preventative, what is their mechanism and what are they mainly used for?
(e.g. beclomethasone - inhalation, or prednisolone - oral)
Effects the AA pathway - activate intracellular receptors leading to gene transcription (decr cytokine production) and production of LIPOCORTIN -(inhibits synthesis of PGs and LTs. They are more focused on the anti-inflammatory response
Give the side effects of giving steroids with beta2 agonists and say how you can reduce these
Throat infections (thrush), hoarseness - reduce this by washing mouth out after use or use a space device. Adrenal suppression - it will produce less natural steroids - improve by limiting time scale of use.
They block leukotrienes. They are preventative and bronchodilators. They antagonise actions of LTs. They are a good choice for atopic patients bc it helps with the anti-inflammatory response - what am I?
Leukotriene receptor antagonists (LTRAs)
Omalizumab - for difficult to treat asthma as a last choice drug - what is it and how does it work?
MAB - monoclonal antibody. Directed against IgE but not bound. Prevents them from binding to immune cells and which leads allergen-induced mediator release in allergic asthma.
What is the stepped care approach in BTS guidelines for asthma?
Short acting beta2 agonist plus steroid.
+trial of LABA or LTRA or xanthine.
+increase dose of inhaled steroid.
+oral steroid.
What is considered a failure of treatment in asthma according to BTS guidelines?
Identified as attacks or is they need to use salbutamol for relief more than twice a week
When are spacer devices given?
For young and old patients
Patients w poor technique
To reduce steroid impaction
How are bronchodilators, inhaled steroid, antibiotics and oxygen therapy used in COPD
Bronchodilators - beta2-agonist +tiotropium (longer acting M antagonist)
Inhaled steroids are less effective in COPD.
Antibiotics are used for infections as lungs are susceptible
Describe (roughly) the summary of guidelines to manage COPD
Look at yellow diagram in presentation by randall
Why are NSAIDs (aspirin, ibuprofen) not used in patients w asthma
They may provoke asthma by increasing LT production. They are COX inhibitors - means more AA goes down the LOX pathway - more leukotrienes for an asthma attack.
Why are beta-blockers contraindicated in asthma patients.
Act upon adrenoceptors in the heart (for heart failure) but can still affect the lungs (even if it is selective) - therefore can induce an attack as it blocks the effect of a drug (salbutamol) and natural adrenaline to produce cAMP.
(note: they are used in caution w COPD - you need to weigh consequences).
