L13 Drugs Used To Treat Asthma Flashcards
How is respiration regulated?
- spontaneous rhythmic discharge via the respiratory centre in the medulla oblongata (we don’t need to think about breathing)
- voluntary control so we can control our breathing ourselves
Autonomic regulation
- respiratory centre modulation by a variety of factors (Pco2, Po2, afferents from lungs)
- regulation of bronchial smooth muscle (efferent pathways to lungs)
What is the parasympathetic innervation in autonomic regulation of the lungs?
Bronchial and vascular smooth muscle and glands
- acetylcholine
- M3 cholinergic receptors
- stimulation results in bronchoconstriction and increased mucus secretions
What is the sympathetic innervation in autonomic regulation of the lungs?
Bronchial smooth muscle
- circulating adrenaline from the adrenal medulla acts on b2 receptors on bronchial smooth muscle
- smooth muscle relaxation and bronchodilation
What is NANC innervation?
Non-adrenergic non-cholinergic
- variety of peptides and other mediators
Inhibitory : NO on bronchial smooth tissue
- smooth muscle relaxation and bronchodilation
Excitatory : substance P, neurokinin A
- smooth muscle contraction and bronchoconstriction
What factors can regulate respiration?
Sensory receptors in airways regulate afferent pathways
- exogenous chemical such as ammonia and sulfur dioxide
- endogenous stimuli such as inflammatory mediators
- physical stimuli such as cold air
How is the smooth muscle in airways regulated?
1) acetylcholine - bronchoconstriction and mucus secretion
2) circulating adrenaline - bronchodilation
3) NANC - inhibitory and stimulatory peptide regulation
4) sensory receptor - sensitive to chemical and physical stimuli
What is asthma?
Recurrent reversible obstruction of the airways
in response to stimuli which are not themselves noxious and do not cause the syndrome in non- asthmatic
What are the symptoms of asthma?
Shortness of breath
Wheezing
Coughing
What causes asthma?
Acute airway obstruction cased by contraction of thr airway smooth muscle
Mucus hypersecretion and thickening/plugging
Airway inflammation
What are the two phases in asthma?
1) immediate phase - bronchoconstriction on exposure to allergen
2) late phase - inflammation in response to inflammatory mediators
What causes the bronchospasm in the immediate phase?
Bronchospasm due to interaction with mast cells
- release of spasmogens-histamine, leukotrienes
-bronchospasm and mucus secretion
- release chemotaxins, LTB4 attraction of leucocytes
What causes the inflammation in the delayed phase?
The influx of cytokine releasing lymphocytes and eosinophils
- long lasting damage to the epithelium of bronchial tissue
- hyper-reactivity of bronchial tissue
What can be used to target and treat the bronchospasms in the immediate phase?
Bronchodilators
- beta2 agonists
- muscarinic antagonists
- xanthines
How do b2 adrenergic agonists dilate the bronchi?
Direct action on the b2 receptors on the bronchial smooth muscle - mimics the circulation of adrenaline
Also inhibits mediator release from mast cells
How are beta2 adrenergic agonists given to patients and what are there side affects?
Given by inhalation
- short acting salbutamol 4-6hr
- long acting salbutamol 12hr
Side effects
- tolerance
- tremor
What is the action of salbutamol and salmeterol on b2 adrenoreceptors?
Smooth muscle relaxation via G-protein coupled receptor
- stimulation of b2 receptor results in activation of Adenylyl cyclase
- increases second messenger cAMP
How do muscarinic antagonists treat asthma?
Dilate bronchi
- block the M3 mediated bromchoconstriction
Decrease mucus secretions
- blocks M3 mediated smooth muscle contraction
Example: ipratropium
- given by inhalation
- non selective but not well absorbed so doesn’t get into circulation and causes many side effects
How do xanthines treat asthma?
Bronchodilation
- blocking phosphodiesterase III and IV increases cAMP leading to bronchodilation
Anti-inflammatory properties
- phosphodiesterases associated with inflammatory processes
Example : theophylline
- well absorbed orally
- narrow therapeutic window
- side effects include CNS stimulation and GI disturbances
What is the role of glucocorticoids?
Suppress the inflammatory response and bronchospasm
- induce synthesis of polypeptide lipocortin which inhibits phospholipaseA2 so decrease production of inflammatory mediators
Examples
- beclomethasone by inhalation
- prednisolone orally
What are the side effects of glucocorticoids?
Opportunistic infections
Cushing like syndrome when taken orally
What is the role of sodium cromolyn?
Originally proposed to be a mast cell stabiliser
- prevents the release of histamine and inflammatory mediators
Inhibits hyper-responsivity
- by depressing neuronal reflexes triggered by irritant receptors
What is cough?
A reflex triggered by mechanical or chemical stimulation of upper respiratory tract
Serves to expel foreign bodies and unwanted material from airways
How is a cough regulated?
Due to sensory components in airways - sensitive to irritants
Central components such as the cough centre in the brain stem
Intercostal and phrenic nerves regulating respiratory muscles
Which drugs reduce the sensory receptor sensitivity in a cough?
- menthol vapour
- eucalyptus oil
- topical local anaesthetics
