MW L3 Asthma treatment 3 Flashcards
Anti-allergens
Anti-allergen therapy options
Cromones
Cromones e.g. (2)
nedocromil and DSCG (disodium cromoglycate)
How do chromones work?
Mast cell stabilising - inhibit mediator release from lung mast cells
In what stage are chromones effective?
early AND late stage in about half of people
Other actions of chromones?
inhibit sensory nerve fibres and neuronal reflex (inhibits bronchoconstriction via BK, NKA, S02)
AND
inhibits eosinophil chemotaxis
What nerve does DSCG inhibit?
Vagus sensory
Do we use H1 agonists in asthma?
NO,
except maybe ketotifen - which enhances beta receptor sensitivity - reverses the reduced response in asthma
Anti-IgE antibody is called
omalizumab - approved for severe asthma (i.e. not responsive to steroids)
Where does omalizumab bind?
Fc portion of IgE
Prevent binding to mast cells
How is omalizumab administered?
Sub-cut
Future therapies (5)
gene therapy leukocyte adhesion blockers mast cell signalling inhibitors PDE inhibitors mediator antagonists (neurokinin and cytokine)
How does beta adrenoreceptor polymorphism affect therapy?
some people get continued response, for others it trails off - this is a problem for regular salmeterol use
How does a polymorphism in 5 lipoxygenase alter response?
no response to leukotriene antagonists - probably why these have not proven very good
6 targets of asthma therapy
1 Antigen presentation
2 Th2 cell stimulation and cytokine release
3 Mast cell activation
4 Eosinophil recruitment and activation
5 Upregulation of adhesion molecule expression (in blood vessels and endothelium)
6 Activation of resident cells such as bfibroblasts
