Drugs used to treat asthma L12

Question 1

How can respiration be regulated

Answer 1

1. spontaneous rhythmic discharge from respiratory centre in medulla
   - involuntary
2. voluntary control
   - involves cortex to motor neurones and diaphragm
3. Autonomic regulation
   - Respiratory centre modulated by a variety of factors (Pco2, Po2, afferents from lungs)
   - Regulation of bronchial smooth muscle (efferent pathways to lungs)

Question 2

how does parasympathetic NS control respiratory system

Answer 2

ACH released and binds to muscarinic 3 receptors stimulating bronchoconstriction and increased mucus secretions

Question 3

how does sympathetic NS control respiratory system

Answer 3

adrenaline from adrenal medulla or noradrenaline acts on B2 receptors on bronchial smooth muscle
- smooth muscle relaxation and bronchodilation

Question 4

how does NANC (nonadrenergic noncholinergic) affect respiratory system
- Variety of peptides, and other mediatiors

Answer 4

1. Inhibitory: NO on bronchial smooth muscle
   Smooth muscle relaxation & bronchodilation
2. Excitatory: substance P, neurokinin A
   Smooth muscle contraction, bronchoconstriction

Question 5

what do sensory receptors in airways do

Answer 5

regulate afferent pathways
1. Exogenous chemical
- Ammonia, sulphur dioxide,
2. Endogenous stimuli
- Inflammatory mediators
3. Physical stimuli
- Cold air

Question 6

what is asthma

Answer 6

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 7

what is the pathology of asthma

Answer 7

1. Acute airway obstruction caused by contraction of the airway smooth muscle
2. Mucus hypersecretion and thickening /plugging
3. Airway inflammation

Question 8

what are the symptoms of asthma

Answer 8

Dyspnoea (particularly breathing out)
Wheezing
Coughing

Question 9

what are the two phases of asthma

Answer 9

1. immediate phase
   - Bronchoconstriction on exposure to stimuli/allergen
2. late/delayed phase
   - Inflammation/damage in response to inflammatory mediators

Question 10

what is Bronchospasm

Answer 10

part of the immediate phase
the initial response to allergins/irritants
these things interact with mast cells causing bronchospasm

Question 11

what happens when allergins interact with mast cells

Answer 11

Release of spasmogens-Histamine, leukotrienes (LTC4 LTD4)
BRONCHOSPASM/MUCUS SECRETION
Release Chemotaxins, LTB4 attraction of leucocytes
- these are inflammatory mediators

Question 12

what happens in delayed phase

Answer 12

Vasodilation, oedema and mucus secretion
there is an influx of cytokine releasing lymphocytes (Th2) and eosinophils
- they normally work in immune response
- but in asthma, they cause damage to epithelium of bronchi tissue and causes it to become hyper-reactive as it exposes sensory receptors

Question 13

what drug can effect mast cells, bronchospasm and inflamation

Answer 13

MC: chromolyn
BS: Bronchodilators
- B2 agonists, M antagonists, Xanthines
- target immediate phase
I: glucocorticoids

Question 14

how do B2 adrenergic agonists treat asthma

Answer 14

Dilate the bronchi
Direct action on the β2 receptors on bronchial smooth muscle (mimic circulating adrenaline)
Also inhibits mediator release from mast cells

Question 15

how are B2 adrenergic agonists given and what are their side effects

Answer 15

Given by inhalation
- Short acting-Salbutamol 4-6 hr
- Long acting Salmeterol 12 hr
Side effects
- Tolerance
- Tremor

Question 16

how do Salbutamol and Salmeterol activate B2 receptors

Answer 16

G-protein coupled receptor
Stimulation of β2 receptor results in activation of adenalyl cyclase and an increase in the second messenger cAMP, leading to smooth muscle relaxation and bronchodilation

Question 17

why does Salmeterol have a longer half life

Answer 17

it has a long carbon chain with lipophilic end
- Lipophilic end anchors its self into membrane – not metabolised as quickly, can react on receptor

Question 18

what are the effects of muscarinic antagonists

Answer 18

bronchodilation
- Block the M3 stopping bronchoconstriction
Decrease mucus secretion
- Blocks M3 stops smooth muscle contraction

Question 19

give an example of muscarinic antagonist
- how is it given

Answer 19

Ipratropium
Given by inhalation
Relatively non selective but not well absorbed so doesn’t get into circulation and cause many side effects

Question 20

what would happen if Ipratropium did get into systemic circulation

Answer 20

normal effects of muscarinic antagonist
- dilating pupils and bronchi
- increased cardiac output
- decreased GI motility
- decreased gland secretion

Question 21

what are Xanthines

Answer 21

derivatives of caffeine and theobromine

Question 22

what do Xanthines cause

Answer 22

Bronchodilation
Proposed to block phosphodiesterase family of enzymes
Blocking phosphodiesterase III and IV increases cAMP leading to bronchodilation

Anti-inflammatory properties
Phosphodiesterases also associated with inflammatory processes

Question 23

give an example of Xanthines
- how is it given
- what are the side effects

Answer 23

Theophylline
well absorbed orally
Narrow therapeutic window
Side effects include, chronotropic and inotropic stimulation, CNS stimulation, GI disturbances

Question 24

what do glucocorticoids do

Answer 24

Suppress the inflammatory response and bronchospasm
Induce synthesis of polypeptide lipocortin which inhibits phospholipaseA2 so decreases production of inflammatory mediators
LTC4 LTD4 – spasmogens
LTB4 – chemotaxins
PGE2, PGI2 vasodilators, cytokines (stimulate lymphocytes
effective in both phases

Question 25

give 3 examples of glucocorticoids

Answer 25

Beclomethasone
- by inhalation
Prednisolone
- orally (short term)
Hydrocortisone
- injection

Question 26

what are the side effects of glucocorticoids

Answer 26

Opportunistic Infections e.g. oral candidiasis (if inhaled)
Typical glucocorticoid side effects (Cushing like syndrome) when taken systemically.

Question 27

what does Sodium Cromolyn do

Answer 27

first thought to be a mast cell stabiliser
now though to to also inhibit hyper-responsivity
by depressing neuronal reflexes triggered by irritant receptors

Question 28

what does Cysteinyl-leukotriene (CysLT1) receptor antagonists do

Answer 28

Supposed to target both phases
Effective for mild persistent asthma
Not as effective as glucocorticoids