Asthma Treatments Flashcards
What are the different classes of asthma treatments?
- B2 agonists
- Glucocorticoids
- Muscarinic Receptor Antagonists
- Cromoglicate
- Theophylline
- Leukotriene Antagonists
- Biologics
How do B2 adrenergic receptor agonists work?
- Direct action on B2 adrenoceptors on bronchiole smooth muscle to relax.
- Inhibit mediator release from mast cells and monocytes (reduce 2nd phase also.)
- May act on cilia to increase mucous secretion.
Name the short-acting B2 agonists
- Salbutamol, Terbutaline
- Max effect within 30 mins - last 4-6hrs PRN
- SIDE EFFECTS - tremor (activation of B2 in skeletal muscle) and tolerance in B2 receptors develops.
Name the long-acting B2 agonists
- Salmetrol
- Duraction of action is 12hrs - 2x a day.
- SIDE EFFECTS - tremor (activation of B2 in skeletal muscle) and tolerance in B2 receptors develops.
How is theophylline used to treat asthma?
- Mechanism unclear - inhibits phophodiesterase (PDE) which metabolises cAMP to AMP.
- 2nd line drug - used with steroids if B2 inadequate. - Given IV in acute severe asthma.
- SIDE EFFECTS - CNA stimulant (tremor, insomnia), stimulates heart causin vasodilation, causes anorexia and N+V.
How do muscarinic receptor antagonists work?
- Ipratropium
- Poorly absorbed in systemic circulation - fewer side effects.
- Relaxes bronchial smooth muscle
- Inhibits 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 (1xdaily)
- Zafirlukast (2xdaily)
- Prevents exercise-induced and aspirin-sensitive asthma.
- Add-on for uncontrolled, mild-moderate asthma.
- Prevents leukotrienes bonding to receptors (leukotrienes cause bronchoconstriction)
- Act as cysteinyl-leukotriene receptors on bronchiole 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
- Beclametasone diproprionate
- Budesonide
- Fluticosone proprionate
- Prednisolone
- Hydrocortisone
How do glucocorticoids work?
- Reduce production of inflammatory agents (chemokines, spasmogens (TLC4 and LTD4), leucocyte chemotaxins).
- Reduce bronchospasm and the recruitment and activation of inflammatory cells.
- Enter cells (lipid-soluble) and bind t intracellular receptors in cytoplasm.
- SIDE EFFECTS - oropharyngeal thrush, dysphonia (use spacer) adrenal suppression with prolonged use.
Explain Cromoglicates
- Nedocromil Sodium/Sodium Cromoglicate
- Reduce bronchial hyper-reactivity.
- Effective in asthma caused by antigen, exercise and irritants.
- Mast cell stabiliser, reduces neuronal reflexes - bronchospasm (desensitise to irritants), inhibits the release of T-cell cytokines.
- SIDE EFFECTS - irritation of upper RT, hypersensitivity.
Explain biological agents?
- Omalizumab
- Recombinant DNA-derived humanised IgG1 monoclonal antibody.
- Subcutaneous injection every 2-3 weeks.
- Binds to IgE (protein that recognises antigen and starts inflammatory response.
- Inhibits binding of IgE to receptor on the surgace of mast cells and basophils.
- Inhibits IgE-mediated cascade of asthma.
- SIDE EFFECTS - anaphylaxis (allergic reaction to proteins) and malignancies (higher rate than usual.
Theophyilline is used in the treatment 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?
Montelukast.
Which drug inhibits IgE binding to prevent mast cell activation?
Omalizumab
What effect is associated with inhaled muscarinic antagonists (Ipratropium)?
Reduction in elevated mucus secretion caused by asthma.
