PT6: COPD Mechanisms & Pharmacology Flashcards Preview

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Flashcards in PT6: COPD Mechanisms & Pharmacology Deck (25)
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1
Q

what is COPD

A

a disease state characterised by progressive airflow limitation that is not fully reversible, associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily cigarette smoke

2
Q

what are some other conditions associated with COPD

A
chronic bronchitis (productive cough, excessive sputum produciton)
emphysema (alveolar wall destruction, irreversible enlargement of terminal air space)
3
Q

what are the long term consequences of COPD

A

pulmonary hypertension, cyanosis, hypoxia, right heart failure

4
Q

what are the pharmocological characteristics of COPD

A
reduced airflow and little variation
limited hyperresponsivemess
neutrophil-rich sputum
Th1 & Tc1 activation
goblet cell hyperplasia
peribroncial fibrosis
5
Q

what are the acute exacerbations of COPD

A

bacterial infection in up to 50% of stable COPD

viral infection is associated with acute exacerbation

6
Q

what are the mechanisms of airflow reduction in COPD

A

occlusion of airway by mucous

thickened airway wall, inflammatory cell infiltrate, peribronchial fibrosis, increased airway smooth muscle

7
Q

how is mucous formed

A

by mucous glands (glandular structure in airway wall)

by goblet cells (found on airway surface)

8
Q

what is the cause of mucous hypersecretion in COPD

A

goblet cell hyperplasia/metaplasia, enlargement of mucous gland, reduces airflow through bronchi

9
Q

how is mucous production controlled

A

by neuronal input and inflammatory mediators

10
Q

what is the therapy for COPD

A

mycolytics:
n-acetyl cysteins (breaks disulphide bonds in mucin, anti-oxidant activity, limited benefit)
DNAse (no efficacy on mucous removal demonstrated in COPD but are used in CF)
muscarinic antagonists:
block parasympathetic stimulation of secretion

11
Q

what is responsible for COPD inflammation

A

leukocyte infiltration, leukocyte products, increased cytokines

12
Q

what are the consequences of inflammation

A

epithelial damage leading to decreased ciliary funciton, increased mucous secretion from goblet cells, mucous cell hyperplasia, increased bronchial permeability
stimulation of sensory nerves, leading to neurogenic inflammation and cough

13
Q

what is the mechanism of COPD

A

machrophages and neutrophils release proteases, reactive oxygen species
macrophages and epithelial cells also release fibroblast growth factors
cytotoxic T cells

14
Q

what is the function of proteases in COPD

A

break down connective tissue, stimulate mucous hypersecretion, proteases are normall balances by inhibitors

15
Q

what is the function of reactive oxidant species in COPD

A

damage epithelium, activate inflammatory genes, further damage

16
Q

what bronchodilators are used in COPD

A

bronchoconstriction not major cause of airway obstruction, so B2 agonists often have a limited effect
muscarinic antagonists used

17
Q

what muscarinic antagonists are used

A

ipratropium bromide gives some improvement, tiotropium & aclindinium have pharmacokinetic advantages

18
Q

what is the effect of phosphodiesterasespde III & IV in airway smooth muscle

A

inhibition leads to bronchodilation

19
Q

what is the effect of PDE IV in leukocytes

A

PDE inhibitors increase intracellular cAMP; inhibits chemotaxis, granule release, respiratory burst, inhibits TNFalpha release

20
Q

why do bronchodilators not work in COPD

A

occlusion not due to bronchoconstriction (tissue remodelling, secretion)

21
Q

why do anti-inflammatory glucocorticoids not work in COPD

A

oxidative stress results in decreased steroid sensitivity (impaired glucocorticoid receptor function)
neutrophil apoptosis inhibited by glucocorticoids

22
Q

what is emphysema

A

permanent enlargement of airspaces distal to the terminal bronchiole, destruction of alveolar walls

23
Q

what are lung elastases

A

strongly implicated in emphysema, derived from neutrophils and macrophages, degrade elastin/basement membrane/connective tissue, increased after smoking, serpins (serine protease inhibitors) inactivated by oxidant stress

24
Q

what are antiproteases

A

alpha1-antitrypsin augmentation therapy in patients with deficiency
elastase inhibitors

25
Q

what are antioxidants

A

vit C & E
N-acetyl cysteine
omega 3