PED1003/L13 Drugs in Asthma Flashcards
What centre regulates spontaneous rhythmic discharge?
Respiratory centre in medulla oblongata
What 3 factors modulate the respiratory centre?
PCO2, PO2, afferents from lungs
Describe parasympathetic innervation of lungs. (4)
Bronchial and vascular SM and glands
Acetylcholine
M3 cholinergic receptors (increased IP3)
Stimulation results in bronchoconstriction and increase mucus secretions
Describe sympathetic innervation of lungs. (3)
Bronchial SM
Circulating adrenaline acts on B2 receptors (increased cAMP) on bronchial SM
SM relaxation and bronchodilation
Describe the non-adrenergic, non-cholinergic pathway (NANC). (3)
Variety of peptides and other mediators
Inhibitory NO on bronchial SM
Excitatory substance P, neurokinin A
Give 3 other factors that regulate respiration.
Exogenous chemicals e.g., ammonia sulphur dioxide
Endogenous stimuli e.g., inflammatory mediators
Physical stimuli e.g., cold air
Define asthma.
Recurrent reversible obstruction of the airways in response to stimuli which are not themselves noxious and do not cause the syndrome in non-asthmatics
Give 3 symptoms of asthma.
Dyspnoea
Wheezing
Cough
Describe the pathology of asthma. (3)
Acute airway obstruction caused by contraction of airway SM
Mucus hypersecretion and thickening/plugging
Airway inflammation
Give the 2 phases of asthma disease process.
Immediate phase - bronchoconstriction on exposure to stimuli
Late/delayed phase - inflammation/damage in response to inflammatory mediators
What occurs in the immediate phase of asthma? (3)
Bronchospasm
Release of spasmogens - histamine, leukotrienes (LTC4, LTD4)
Release chemotaxins, LTB4 attraction of leucocytes
What occurs in the late/delayed phase of asthma?
Vasodilation, oedema, mucus secretion
Influx of cytokine releasing lymphocytes and eosinophils
What long-term effects can occur as a result of the late/delayed phase of asthma? (2)
Long-lasting damage to epithelium of bronchial tissue
Hyper-reactivity of bronchial tissue, perhaps exposing sensory receptors
What drugs can be used to treat the immediate phase in bronchospasm?
B2 agonists
Muscarinic antagonists
Xanthines
What effect do B2 adrenergic agonists have? (2)
Dilate bronchi
Inhibit mediator release from mast cells
How are B2 adrenergic agonists administered?
By inhalation
Short-acting Salbutamol 4-6h
Long-acting Salmetrol 12h
Give 2 side effects of B2 adrenergic agonists.
Tolerance
Tremor
Why does Salmetrol act for longer than Salbutamol? (2)
Long carbon chain with a phenolic group on the end
Phenolic group binds membrane and prevents dispersion of molecule
How do muscarinic antagonists help asthma? (2)
Dilate bronchi - block M3
Decrease mucus secretion - block M3
How is Ipratropium administered and how does it help asthma? (3)
Inhalation
Muscarinic antagonist
Relatively non-selective but not well-absorbed so causes little side effects
How do xanthines cause bronchodilation and anti-inflammation? (2)
Block phosphodiesterase enzymes
Blocking phosphodiesterase III and IV increases cAMP
Phosphodiesterases also inflammatory
Give an example of a xanthine.
Theophylline
Well absorbed orally
Narrow therapeutic window
Side effects - chronotropic & inotropic stimulation, CNS stimulation, GI disturbances
How do glucocorticoids help treat asthma? (3)
Suppress inflammatory response
Induce synthesis of lipocortin which inhibits phospholipase A2
Decreases production of inflammatory mediators
Give 3 kinds of inflammatory mediators in asthma.
Spasmogens - LTC4, LTD4
Chemotaxins - LTB4
Vasodilators, cytokines - PGE2, PGI2
