Physiology and Pharmacology: (Challis) 11 Asthma Flashcards
What is asthma and what does it result in
Chronic inflammatory disease of the airways
- results in airways hyperresponsiveness
- further resulting in ‘reversible’ airway obstruction
- though hypertrophy/hyperplasia
How can difficulty breathing be quantified?
Measured through FEV1 (Forced expiratory volume in 1 second)
What effect does an allergen have on response with regards to time?
Initial response in attack termed ‘early phase’
- around %60 FEV1 capacity
Some sufferers experience late phase hours later
- more severe broncho-constriction than early phase
Mechanism of early phase attack
Eliciting agent
-> stimulates mast cells
- > release of spasmogens, chemotaxins and chemokines
- > spasmogens cause bronchospasm
Mechanism of late phase attack
Infiltration of cytokine releasing TH2 cells + inflammatory cells e.g. eosinophils
- > mediators, EMBP, ECP released
- >
Define prophylaxis
- example of agents used
Prevent/reduce inflammation using anti-inflammatory agents e.g. using corticosteroids
- beclomethasone
- fluticasone
Problems associated with chronic corticosteroid dosing
- newer corticosteroids minimize risks how? example of one?
- Cushing’s syndrome
- Thinning of skin / easy bruising
- Increased risk of infection
- Increased abdominal fat
- Negative Ca2+ balance -> osteoporosis
New steroid Fluticazone minimises side effects by
- direct delivery to lungs
- favourable pharmacokinetics (poor systemic absorbance, hangs around in airways, any in blood quickly metabolised by liver)
Treatments for symptomatic relief? Examples + why they are effective
Rapid reversal of bronchoconstriction -> Beta2-selective adrenoceptor agonists
e.g. salbutamol, terbutaline, salmeterol
Effective because they relax bronchoconstriction irrespective of cause
- stimulates muscle relaxation
- inhibit mucus secretion
- decrease tissue oedema
- may possess some anti-inflammatory activity
Why choose a B2 selective agonist when treating asthma over a non-selective B adrenoceptor agonist?
Minimise side effects -> non-selective agonist will relieve symptoms but also stimulate heart beat speed, contractile strength
Explain the long-acting nature of salmeterol
Due to the long hydrophobic tail of the molecule that acts like a leash, tethering the molecule to the receptor
this means that the agonist can later re-assert agonist action when the site is free, regardless if a molecule was bound to the site beforehand