Respiratory Drugs Flashcards
What are LABAs combined with?
GCS
Which are more effective bronchodilators in asthma, beta adrenoceptors agonists or muscarinic receptor agonists?
Beta adrenoceptor agonists
What is theophylline?
Phosphodiesterase inhibitor
Smooth muscle relaxant
Adenosine inhibitor
What are LABAs? and uLABAs?
Long acting beta2 adrenoceptors agonists
uLABA - ultra long acting beta2 adrenoceptor agonist
What are some adverse effects of oral GCS?
Osteoporesis
Diabetes,
Muscle wasting
Hypertension
Growth suppression
Suppresion of adrenal, hypothalamus and pituitary axis
Need to wean off them
How does transrepression work?
GCS bound to its receptor bind to AP-1 downstream from its activation by inflammatory cytokines - the inhibits AP-1 activating inflammatory transcription factors
What are SAMAs and LAMAs?
Short and long acting murcarinic receptor agonists
How does GCS transactivation work on a molecular level?
They diffuse into cells >
Dimerize with a co-factor >
Activate transcription factors that encode anti-inflammatory products
T/F, combining inhaled GCS and LABAs improves symptoms, quality of life and exacerbation rate more than their use individually?
True
What is the treatment for idiopathic pulmonary fibrosis?
None available
O2
Which are more effective are providing symptomatic relief, SABAs or LABAs?
LABAs
The end of GCS transrepression is …
Repressed transcription of:
Cytokines and their receptors
Inducible enzymes for inflammatory mediators (eg COX-2)
Adhesions molecules
Compare the histopathology of severe asthma and COPD
Asthma:
More SM
More BM
COPD
More fibrosis
Loss of alveolar tethering
Both:
High Inflammation
Which are more effective bronchodilators in COPD, beta adrenoceptors agonists or muscarinic receptor agonists?
Muscarinic are equally or more effective than adrenoceptor
When are phosphodiesterase inhibitors used?
In severe and very severe COPD as it can reduce exacerbations
What are the clinical effects of GCS treatment in COPD patients?
Improves symptoms
Better quality of life
Less frequent exacerbations
But it is associated with an increased risk of pneumonia
What are the most important inhaled GCSs?
Budesonide
Fluticasone propionate
They are available in combinations with LABAs
What is the difference between indacaterol, and salmeterol and formoterol
Indacaterol lasts an extra 12 hours (24 cf to 12hours)
Where are muscarinic receptor in airways?
Smooth muscle (M3)
What is the effect of LABAs?
Not 100% clear but they reduce the rate of exacerbations
Maybe anti-inflammatory
Chronically bronchodilate
What ligand acts on muscarininc receptors in the airways?
ACh
What are some other interventions for COPD?
Exercise
O2
Pulmonary rehab
Lung transplantation
What are the two ways GCS are administered?
Inhaled (topical)
Oral (systemic)
When are LABAs indicated?
Asthma, COPD
Prophylaxis only
What are three LABAs?
Salmeterol and Formoterol and Indacaterol
Why don’t anti-histamines work for asthma?
Because there are many mediators in these conditions, histamine isn’t an importnat mediator of bronchospasm
in asthma despite it working on H1 receptors on smooth muscle. Cystenile leukotriene can constrict the muscle for a much longer time, parasympathetic, comple
ment system.
Do GCS only transactivate?
No, they can also perform tranrepression
What are some anti-inflammatory products that GCS activate the expression of?
Annexin-1 - turns off on going inflammation and recruitment
Serpin A3 - anti-protease
Beta2-adrenoceptor - to maintain agonist’s effects
Do LABAs improve survival in COPD patients? Why/why not?
No, because they don’t prevent remodelling
When are GCS indicated?
If inhaled beta agonists are required >3 times per week
Glucocorticoids overall affect in asthma is to
Reduce inflammatory cell number and activation
Decrease the probability and severity of episodes of asthma
What are some adverse effects of inhaled GCS?
Dysphonia
Oral candidiasis
Reduced serum cortisol
What are some other treatments for COPD?
Antibiotics - for infections
Antioxidants agents
Mucolytics agents
Antitusives
Vasodilators (for hypertension)
What makes LABAs long acting?
They are lipid soluble
When are oral GCS indicated in asthma
Acute exascerbations
Severe chronic asthma
What is the difference between salmeterol and formoterol?
Salmeterol has a slow onset while formoterol has a fast onset
What are the 4 effects of glucocorticoids on the inflammatory cells in asthma?
Reduce activity, recruitment and survival of eosinophils and T cells
Reduce mast cell cytokine production
Reduce macrophage cytokine production
Reduce proliferation, cytokine production and collagen production by fibroblasts and smooth muscle cells
Does tolerance to LABAs develop? If so then how?
Yes
Reduced number of receptors
What is the most common SABA?
Salbutamol
