PED1003/L13 Drugs in Asthma

Question 1

What centre regulates spontaneous rhythmic discharge?

Answer 1

Respiratory centre in medulla oblongata

Question 2

What 3 factors modulate the respiratory centre?

Answer 2

PCO2, PO2, afferents from lungs

Question 3

Describe parasympathetic innervation of lungs. (4)

Answer 3

Bronchial and vascular SM and glands
Acetylcholine
M3 cholinergic receptors (increased IP3)
Stimulation results in bronchoconstriction and increase mucus secretions

Question 4

Describe sympathetic innervation of lungs. (3)

Answer 4

Bronchial SM
Circulating adrenaline acts on B2 receptors (increased cAMP) on bronchial SM
SM relaxation and bronchodilation

Question 5

Describe the non-adrenergic, non-cholinergic pathway (NANC). (3)

Answer 5

Variety of peptides and other mediators
Inhibitory NO on bronchial SM
Excitatory substance P, neurokinin A

Question 6

Give 3 other factors that regulate respiration.

Answer 6

Exogenous chemicals e.g., ammonia sulphur dioxide
Endogenous stimuli e.g., inflammatory mediators
Physical stimuli e.g., cold air

Question 7

Define 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-asthmatics

Question 8

Give 3 symptoms of asthma.

Answer 8

Dyspnoea
Wheezing
Cough

Question 9

Describe the pathology of asthma. (3)

Answer 9

Acute airway obstruction caused by contraction of airway SM
Mucus hypersecretion and thickening/plugging
Airway inflammation

Question 10

Give the 2 phases of asthma disease process.

Answer 10

Immediate phase - bronchoconstriction on exposure to stimuli
Late/delayed phase - inflammation/damage in response to inflammatory mediators

Question 11

What occurs in the immediate phase of asthma? (3)

Answer 11

Bronchospasm
Release of spasmogens - histamine, leukotrienes (LTC4, LTD4)
Release chemotaxins, LTB4 attraction of leucocytes

Question 12

What occurs in the late/delayed phase of asthma?

Answer 12

Vasodilation, oedema, mucus secretion
Influx of cytokine releasing lymphocytes and eosinophils

Question 13

What long-term effects can occur as a result of the late/delayed phase of asthma? (2)

Answer 13

Long-lasting damage to epithelium of bronchial tissue
Hyper-reactivity of bronchial tissue, perhaps exposing sensory receptors

Question 14

What drugs can be used to treat the immediate phase in bronchospasm?

Answer 14

B2 agonists
Muscarinic antagonists
Xanthines

Question 15

What effect do B2 adrenergic agonists have? (2)

Answer 15

Dilate bronchi
Inhibit mediator release from mast cells

Question 16

How are B2 adrenergic agonists administered?

Answer 16

By inhalation
Short-acting Salbutamol 4-6h
Long-acting Salmetrol 12h

Question 17

Give 2 side effects of B2 adrenergic agonists.

Answer 17

Tolerance
Tremor

Question 18

Why does Salmetrol act for longer than Salbutamol? (2)

Answer 18

Long carbon chain with a phenolic group on the end
Phenolic group binds membrane and prevents dispersion of molecule

Question 19

How do muscarinic antagonists help asthma? (2)

Answer 19

Dilate bronchi - block M3
Decrease mucus secretion - block M3

Question 20

How is Ipratropium administered and how does it help asthma? (3)

Answer 20

Inhalation
Muscarinic antagonist
Relatively non-selective but not well-absorbed so causes little side effects

Question 21

How do xanthines cause bronchodilation and anti-inflammation? (2)

Answer 21

Block phosphodiesterase enzymes
Blocking phosphodiesterase III and IV increases cAMP
Phosphodiesterases also inflammatory

Question 22

Give an example of a xanthine.

Answer 22

Theophylline
Well absorbed orally
Narrow therapeutic window
Side effects - chronotropic & inotropic stimulation, CNS stimulation, GI disturbances

Question 23

How do glucocorticoids help treat asthma? (3)

Answer 23

Suppress inflammatory response
Induce synthesis of lipocortin which inhibits phospholipase A2
Decreases production of inflammatory mediators

Question 24

Give 3 kinds of inflammatory mediators in asthma.

Answer 24

Spasmogens - LTC4, LTD4
Chemotaxins - LTB4
Vasodilators, cytokines - PGE2, PGI2

Question 25

Give an example of a glucocorticoid in asthma treatment.

Answer 25

Beclomethasone - inhalation
Prednisolone - orally (Short-term)
Hydrocortisone - injection

Question 26

Give 2 side effects of glucocorticoids in asthma treatment.

Answer 26

Opportunistic infections
Typical glucocorticoid side effects (Cushing’s) when taken systemically

Question 27

How does sodium cromolyn help asthma? (2)

Answer 27

Mast cell stabiliser
Prevents release of histamine and inflammatory mediators
Inhibits hyper-responsivity
Depresses neuronal reflexes triggered by irritant receptors

Question 28

How do cysteinyl-leukotrienes (CysLT1) receptor antagonists help asthma?

Answer 28

Target both phases
Effective for mild persistent asthma
Not as effective as glucocorticoids