L13 Drugs Used To Treat Asthma

Question 1

How is respiration regulated?

Answer 1

• 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)

Question 2

What is the parasympathetic innervation in autonomic regulation of the lungs?

Answer 2

Bronchial and vascular smooth muscle and glands
- acetylcholine
- M3 cholinergic receptors
- stimulation results in bronchoconstriction and increased mucus secretions

Question 3

What is the sympathetic innervation in autonomic regulation of the lungs?

Answer 3

Bronchial smooth muscle
- circulating adrenaline from the adrenal medulla acts on b2 receptors on bronchial smooth muscle
- smooth muscle relaxation and bronchodilation

Question 4

What is NANC innervation?

Answer 4

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

Question 5

What factors can regulate respiration?

Answer 5

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

Question 6

How is the smooth muscle in airways regulated?

Answer 6

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

Question 7

What is asthma?

Answer 7

Recurrent reversible obstruction of the airways
in response to stimuli which are not themselves noxious and do not cause the syndrome in non- asthmatic

Question 8

What are the symptoms of asthma?

Answer 8

Shortness of breath
Wheezing
Coughing

Question 9

What causes asthma?

Answer 9

Acute airway obstruction cased by contraction of thr airway smooth muscle

Mucus hypersecretion and thickening/plugging

Airway inflammation

Question 10

What are the two phases in asthma?

Answer 10

1) immediate phase - bronchoconstriction on exposure to allergen

2) late phase - inflammation in response to inflammatory mediators

Question 11

What causes the bronchospasm in the immediate phase?

Answer 11

Bronchospasm due to interaction with mast cells
- release of spasmogens-histamine, leukotrienes
-bronchospasm and mucus secretion
- release chemotaxins, LTB4 attraction of leucocytes

Question 12

What causes the inflammation in the delayed phase?

Answer 12

The influx of cytokine releasing lymphocytes and eosinophils
- long lasting damage to the epithelium of bronchial tissue
- hyper-reactivity of bronchial tissue

Question 13

What can be used to target and treat the bronchospasms in the immediate phase?

Answer 13

Bronchodilators
- beta2 agonists
- muscarinic antagonists
- xanthines

Question 14

How do b2 adrenergic agonists dilate the bronchi?

Answer 14

Direct action on the b2 receptors on the bronchial smooth muscle - mimics the circulation of adrenaline

Also inhibits mediator release from mast cells

Question 15

How are beta2 adrenergic agonists given to patients and what are there side affects?

Answer 15

Given by inhalation
- short acting salbutamol 4-6hr
- long acting salbutamol 12hr

Side effects
- tolerance
- tremor

Question 16

What is the action of salbutamol and salmeterol on b2 adrenoreceptors?

Answer 16

Smooth muscle relaxation via G-protein coupled receptor
- stimulation of b2 receptor results in activation of Adenylyl cyclase
- increases second messenger cAMP

Question 17

How do muscarinic antagonists treat asthma?

Answer 17

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

Question 18

How do xanthines treat asthma?

Answer 18

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

Question 19

What is the role of glucocorticoids?

Answer 19

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

Question 20

What are the side effects of glucocorticoids?

Answer 20

Opportunistic infections
Cushing like syndrome when taken orally

Question 21

What is the role of sodium cromolyn?

Answer 21

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

Question 22

What is cough?

Answer 22

A reflex triggered by mechanical or chemical stimulation of upper respiratory tract

Serves to expel foreign bodies and unwanted material from airways

Question 23

How is a cough regulated?

Answer 23

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

Question 24

Which drugs reduce the sensory receptor sensitivity in a cough?

Answer 24

• menthol vapour
• eucalyptus oil
• topical local anaesthetics

Question 25

Which drugs target the cough centre in the brain?

Answer 25

• regulated by opioid receptors
• opioid receptor agonists