MW L5 COPD treatment Flashcards
Most effective treatment for COPD?
Stop smoking :|
Do we use bronchodilators in COPD?
Yes, but limited effect as bronchoconstriction is not a major cause of airway obstruction
Do we use muscarinic atnagonists for COPD?
Yes
Ipratropium bromide & Tiotropium
What is new licensed in 2013 and not in the notes?
Aclidinium (fast M2 off time)
What M do we ideally want to block?
M3 (M2 block would antagonise its effects as M2 is negative feedback on ACh release)
What can we used for excessive mucus secretion?
Muscarinic antagonists
What is shown to be good for mucus secretion in trials? (2)
Neurokinin antagonists
Agents inhibiting sensory fiber activation
EGF stands for
Epidermal growth factor
EGF receptor is in pathway to ….
mucus production
What form is active EGF receptor
Phosphorylated (EGFR kinase inhibitors are used in cancer, being trialed for COPD)
Do we use corticosteroids in COPD?
Some benefit in reducing hospitalisation… not much
What does PDE III do?
What does PDE IV do?
III - broncoconstric
IV - increased cAMP
What PDE inhibitors are used in COPD?
Theophylline (non-selective)
Rofulimast (PDE IV selective)
to avoid acute exacerbations pt with COPD have
vaccinations
Some emphysema pt have what treatment….
Alpha1 antitrypsin augmentation therapy - if they are deficient, but most patients are not
Are elastase inhibitors used?
disappointing results
What antioxidants are a ‘potential’
Vit E and C
N-acetyl cysteine
Antibiotic that also has beneficial action (unrelated to antibiotic activity)
clarithromycin
- alveolar protection in smoke
Retinoic acid works by
Stimulates alveolar regeneration (only in animal models)
What recombinant tech is being looked at for COPD
Recombinant Keratinocyte Growth Factor - induces alveolar growth (animal models)
Other treatments for COPD - non-drugs (2)
O2
Physiotherapy
Mucolytics such as ….. work by….
N-acetylcysteine
break disulphide bonds in mucin
Do we use DNAase?
No
Why don’t glucocorticoids work for COPD?
Occlusion not due to bronchoconstriction but due to tissue remodelling and secretion
Why is there decreased steroid sensitivity in COPD?
Oxidative stress
What is the negative effect of steroid therapy
Neutrophil apoptosis is inhibited by steroids
compared with asthma where eosinophil apoptosis is promoted by glucocorticoids
How is NFKB produced?
Inflammatory stimuli lead to IkB phosphorylation and liberation of NFkB
What does NFkB do?
Migrates to the nucleus and interacts with inflammatory genes - activates and causes transcription of inflammatory proteins
What does HAT do?
Histone acetyltransferase (HAT) acetylates histones
- unpacks chromatic and allows RNA polymerase binding to DNA
- cooperates and amplifies NFKB action
What does HDAC do?
Histone deacetylase (HDAC) represses inflammatory gene expression - Major pathway for glucocorticoid action
What does histone do to DNA?
constrains in causing transcriptional supression
What drun enhances HDAC activity?
Theophyline (although no change in NFKB, falls in TNF and IL8)
What does acetylates histone do to DNA?
Prompts the unwinding of chromatin, allowing transcriptional complexes to bind to DNA
Inflammtory stimuli increases …..
Oxidative stresses decreases…
Increased HAT
Decreased HDAC
