What are the different classes of asthma treatments?
- B2 agonists
- Muscarinic Recpetor Antagonists
- Lukotriene antagonist
How do B2 adrenergic receptors agonists work?
- Direct action on B2 adrenocepors on bronchiole smooth muscle to relax
- Inhibit mediator release from mast cells and monocyes - reduce 2nd phase
- May act on cilia to increase mucus secretion
Name the short-acting B2 agonists
Max effect within 30 mins - last 4-6hrs PRN
-Tremor (activation of B2 in skeletal muscle)
-Tolerance in B2 recpetors develops
Name the long-acting B2 agonists
- duraion of action is 12hrs - 2x a day
- SIDE EFFCTS - temour (activation of B2 in skeletal muscle) and tolerance in B2 receptors devolps
How is theophylline used to treat asthma?
- Mechanism unclear - phosphodiesteras inhibitor which meabolises cAMP to AMP
- 2nd line drug - used with steroids if B2 inadequate - given IV in acute severe athsma
SIDE EFFECTS = CNA stimulant (tremour, insomina) stimulates heart causing vasodilation, causes anorexia and N+V
How do muscarinic receptor antagonists work?
- Poorly absorbed in systemic circulation
- Fewer side effects
- Relaxes bronchial smooth muscle
- Inibits elevated mucous secretion
- Blocks action of endogenous ACh at muscle receptors - low levels of ACh normally released from cholinergic nerves in airway which relax smooth muscle and open airways
- High levels of ACh released in asthma causing muscarinic receptors to activate, smooth muscle contracted and narrowed airways
How do leukotriene receptor antagonists work?
Montelukast (1x daily)
Zafirlukast (2x daily)
- Prevents exercise-induced and aspirin-sensitive asthma
- Add-on for uncontrolled, mild-moderate asthma
- Prevents leukotriene bonding to receptors (leukotriene cause bronchoconstriction)
- Act as cysteinyl-leukotriene receptors on brinchiole smooth muscle to prevent the action of LTC4 and LTD4 which are bronchial spasmogens and stimulate mucous secretion
- SIDE EFFECTS = HEADACHES, GI DISTURBANCE
What are examples of Glucocorticoids
- Beclameasone diproprionate
- Fluticosone proprionate
How do glucocorticoids work?
- Reduce production of inflammatory agents (chemokine, spasogens TLC4 AND LTD4, leucocytes, chemotaxins)
- Reduce bronchospasm and the recruitment and actvation of inflaammatory cells
- Enter cells (lipid-soluble) and bind to intracellular rceptors in cytoplasm
SIDE EFFECTS - oropharyngeal thruch, dysphonia adrenal suppression with prolonged use
Nedocromil Sodium/Sodium Cromoglicate
- Reduce bronchial hyper-reactivity
- Effective in asthma caused by antigen, exercise and irritants
- Mast cells stabiliser, reduces neuronal reflexes - bronchospasm, inhibits the release of T-cell cytokines
- SIDE EFFECTS = irritation of upper RT, hypersensitivity
Explain biological agents
- Recombinant DNA-derived humanized IgG1 monoclonal antibody
- Sub cut injection 2-3 weeks
- Binds to IgE (protein that recognises antigen nd starts inflammartoy response)
- Inhibts binding of IgE to receptor on the surface of mast cells and basopils
- Inhibits IgE-mediated casacde of asthma
- SIDE EFFECTS = Anaphlyaxis (allergic reaction to proteins) and malignancies
Theophyilline is used in the treament if acute asthma attacks. It works by blocking..
Cyclic Nucleotide Phosphodiesterase
Which drug blocks the spasmogenic effects of cysteinyl leukotrienes - releasing bronchioles and reducing mucous secretion?
Which drug inhibits IgE binding to prevent mast cell activation?
What effects is associated with inhaled muscarinic antagonists (ipratropium)
Reduction in elevated mucus secretion caused by asthma