Bronchodilators Flashcards
Asthma is divided into
Atopic and non atopic
How does asthma occur
First exposure to antigen/ allergen causes production of IgE antibodies
Subsequent exposure to antigen results in binding to IgE and stimulation of mast cells to release chemical mediators e.g. histamine, leukotrienes
Triggers asthma attack
Non atopic asthma is most likely to occur in adults due to
sensitisation to chemicals or biological products at work
Aspirin sensitivity in some people
Viral infection
Predisposition to rhinitis and nasal polyps in some people
They act by stimulating sensory receptors and nerves in air passage
Immediate phase vs delayed phase of asthma
Immediate phase-
Bronchospasm due to release of spasmogens (histamine, prostaglandins) and chemotaxins
Delayed phase-
Influx and activation of inflammatory cells causes mediators such leukotrienes and interleukins (IL-5 - which activates eosinophils) leads to airway constriction
What is the arachadonic acid pathway
When the phospholipids in in plasma membrane is broken, phospholipase A2 breaks it into arachodonic acid (inflammatory mediator)
Arachodonic acid is then broken by cyclooxygenase (produces prostaglandins - inflammatory mediator) and 5-lipogynase (produces leukotrienes - inflammatory mediators, promote mucus secretion and recruit immune cells to area)
Management of asthma pneumonic
A - Adrenergic β2 agonists - salbutamol
S - Steroids - beclomethasone
T - Theophyline
H - Hydration
M - Mask O2
A - Anticholinergics - ipratropium
Bromide
Types Innervation of bronchial smooth muscles
Sensory receptors
Parasympathetic
Sympathetic
Sensory receptors - irritant receptors and c - fibres which respond to both extrinsic and intrinsic agents by causing bronchoconstriction
Parasympathetic innervation - Via M3 receptors causes bronchoconstriction
NO sympathetic innervation - so circulating adrenaline in bloodstream and on β2 receptors for bronchodilation
Mechanism of action of beta agonists
All beta receptors are Gs
Salbutamol (shortest acting), salmeterol and formoterol
The drug binds to Gs receptor which activates Adenyl cyclase which increases cAMP which increases PKA ( protein kinase A)
This causes smooth muscle relaxation
Long acting B2 agonists (LABA) are…
Salmeterol and formoterol they mimic structure of salbutamol but have a long lipophilic side chain which anchors the drug in the lipid membrane - allows the active portion of the molecule to remain at the receptor site for longer, continually binding and releasing
Used in combination of inhaled corticosteroids
They’re slow onset so should not be used for relief of an acute asthma attack
Side effects can include tachycardia, hyperglycaemia, skeletal muscle tremors
Muscarinic antagonists for asthma
Work via the Gq receptor
E.g ipratropium, tiotropium
Relax bronchial smooth muscles by competitively antogonising the effects of acetylcholine and decreases mucus secretion
Used when patient is already on beta blockers (e.g heart condition)
Come with more side effects as lots of muscarinic receptors in body
Mechanism of action for muscarinic receptor antagonists
Ipratropium bromide, tiotropium work via Gq receptor
Phosholipase C is activated which causes PIP2 to dissolve into DAG and IP3
DAG is bound to membrane and IP3 moves into smooth muscle and finds sarcoplasmic reticulum to release lots of calcium. Ipratropium and tiotropium block this receptor.
Aminophyline use
Type of theophyline
Second line drug
Narrow therapeutic window
Acute bronchodilation
Administered orally
Mechanism of action of aminopyline
Works via Gs excitatory
Inhibits conversion of cAMP to AMP which so there is more cAMP to act on PKA for smooth muscle relaxation
Leukotriene receptor antagonist mechanism of action
Montelukast
Bind to leukotriene receptors so leukotrienes cannot bind
Aspirin is used as an anti inflammatory agent however it causes side effects such as…
Erosion of gut lining - bleed
Dries mucus membranes - wheeze due to coarseness of breathing
