1MB Resp Flashcards
Salbutamol is?
Short acting B2 agonist
How do SABAs work?
Bind to B2 adrenoreceptors causing a cascade which causes MLCK to stay phosphorolysed as well as MLK and Ca2+ influx is decreased.
Relaxing ASM and causing Vasodilation
When would you use a SABA?
First line in asthma
Also used in COPD
What is formoterol and salmetorol examples of?
LABAs
What is the mechanism of action of formoterol and salmetorol?
They both act the same as SABAs (by binding to B2 adrenoreceptors) however their action lasts longer. (<12hrs)
Montelukast and zafirlukast are examples of?
CysLT1 receptor antagonists, otherwise known as leukotriene receptor antagonists.
How does montelukast work?
Stop the CysLTs that have been released from inflammatory cells (e.g. eosinophils) from acting on the CysLT1 receptor (will bind onto this receptor competitively) and so prevent bronconstriction, mucus production and pulmonary oedema.
When would you administer a drug such as montelukast?
Late add on therapy in mild persistent asthma, also in rhinitis and rhinorrhoea.
Give an example of a xanthine.
Menoxanthines such as aminophylline and theophylline.
How do Xanthines work?
Theophylline activates histone deacetylase (HDAC) which may potentiate the anti-inflammatory action of glucocorticoids.
It is a competitive non-selective phosphodiesterase inhibitor, increasing cAMP which activates pKA that inhibits TNF-alpha and leukotriene synthesis.
Reducing inflammation and causing bronchodilation
When to use a xanthine
They are second line in the treatment of asthma and should be used in conjunction with a B2 adrenoreceptor and glucocorticoid.
Side affects of xanthines
Frequently causes nausea, vomiting, abdominal discomfort and headache.
Side affects of xanthines
Frequently causes nausea, vomiting, abdominal discomfort and headache.
The side affects of montelukast and zafirlukast
Sometimes report of headache and gastrointestinal symptoms.
Where are glucocorticoids produced?
Zona fasiciulata (in the adrenal cortex beneath zona glomerulosa)
Give examples of glucocorticoids
Prednisolone, Beclometasone, Budesonide, Flucticasone
Mechanism of action of Glucocorticoids
Glucocorticoids signal via nuclear receptors (class 1), specifically GR glucocorticoids increase transcription of genes encoding anti-inflammatory proteins and decrease transcription of genes encoding inflammatory proteins.
Has an anti-inflammatory action
When to use glucocorticoids
Mainstay of treatment in the prophylaxis of asthma and are preferably delivered by the inhalational route to minimise adverse systemic effects.
Mainstay in rhinitis and rhinorrhoea – however unlike in asthma, it is a topical nasal spray (note these can be used in combination with anti-histamines for moderate to severe rhinitis).
What family of drugs does sodium cromoglicate belong to?
Cromones
When to use sodium cromoglicate
Asthma, also can be used for maintenance treatment of allergic rhinitis (intra-nasal administration) with an onset of action of 4 to 7 days, but weeks may be required for full effect – not as effective as corticosteroids
How do cromones work
Are often described as ‘mast cell stabilizers’ (i.e. agents that supress histamine release from mast cells).
A decrease in the sensitivity of irritant receptors associated with sensory C-fibres that trigger exaggerated reflexes and reduction of cytokine release are potential mechanisms.
Has an anti-inflammatory effect
Example of Anti-IgE
Omalizumab (requires intravenous administration)
How does omalizumab work?
Monoclonal antibody directed against IgE. Binds IgE via Fc to prevent attachment to Fc receptors – suppresses mast cell response to allergens Reduces the expression of Fc receptors on various inflammatory cells
Mepolizummab is an example of?
Anti-IL5
How does mepolizumab work?
Monoclonal antibody directed against IL-5
When to use an Anti-IL5
Recently introduced treatment for asthma associated with severe eosinophilia – very expensive
Name Anticholinergics
Short acting (3-5hrs): Ipratropium, oxitropium
Long acting (<10hrs): Tiotropium
How do anticholingerics work?
They inhibit cholinergic receptors (M1/2/3) in airways which when stimulated cause muscle contraction and submucosal gland activation (mucus production).
They relax ASM and decrease mucus production
What is the similarity and difference between tiotropium and oxitopium
Similarity - both M3 selective Difference - tiotropium is a LAMA, oxitopium is a SAMA
When to use a SAMA/LAMA
Treatment of COPD
These also work in PAR and SAR (not non-allergic) – this is due to the blocking of post-ganglionic neurones reducing mucosal secretion (in non-allergic it is increased mucosal blood flow that leads to secretions not excess mucus production).
Note, this medication for rhinitis would be topical.
Example of PDE4
Rofumilast
How does rofumilast work?
A selective PDE4 inhibitor,
Suppresses inflammation and emphysema
When to use a PDE4 such as rofumilast
Can use in severe COPD when accompanied by chronic bronchitis
Effects of rofumilast
Can have very limiting adverse effects on the GI system
Anti-histamine examples
Intranasal - azelastine
Oral - Loratidine, fexofenadine, cetirizine
How do anti-histamines work?
Competitive antagonists of H1 receptors reduce effects of mast cell derived histamine that include: vasodilatation and increased capillary permeability, activation of sensory nerves, mucus secretion from submucosal glands.
Inhibit vasodilation and mucus secretion
When to use anti-histamines
SAR, PAR and episodic AR, but less so for non-allergic rhinitis
Why chose an oral anti-histamine like loratidine, instead of intranasal?
Due to reduced sedation (do not cross the blood brain barrier) and lack of anti-cholinergic effects
What is oxymetazoline?
Vasoconstrictor
Mechanism of oxymetazoline
Act as direct, or indirect, sympathomimetics to mimic the effect of noradrenaline. Produce vasoconstriction via activation of 1-adrenoceptors to decrease swelling in vascular mucosa.
Causes vasocontriction
When to use a vasoconstrictor
Short term in rhinitis - to reduce congestion
