COPD Flashcards
What is the pathology of COPD?
Inflammation causes the mucosa to become engorged and causes obstruction
Circular smooth muscle constricts
Collapse of airway integrity
Emphysema
What are the features of COPD
Inflammation
Tissue damage
Mucocilliary dysfunction
What two conditions does COPD compromise of and what is their effect?
Chronic bronchitis:
Chronic neutrophil inflammation
Mucous hyper secretion
Smooth muscle spams
Emphysema: alveolar destruction impaired gas exchange Loss of bronchial support Irreversible
How does emphysema occur?
Protease is increased
Increased beyond the normal size of airspaces distal to the number of terminal bronchiole
Leads to destruction of acinial pouching in alveolar sacs
What pharmacological treatments are used for COPD?
LAMA - tiotropium LABA - salmeterol PDE41 - rofumilast Mucolytic - carbocisteine Antibiotics - azithromycin
What is the disease process of COPD?
Cigarette smokes causes alveolar macrophages to produce cytokines
This is detected by CD8+ cells that are activated and produce Proteases
Neutrophils are activated by chemotactic factors (IL8)
Proteases cause alveolar wall destruction and increase mucus secretions
Increase in macrophage population, increased release of metalloproteinases (e.g. Elastase)
Release of free radicals
What is the response to bronchodilators and corticosteroids in COPD?
Poor
What type of spirometry pattern is seen in COPD?
Obstructive spirometry pattern
What type of cell response is COPD?
CD8
What mucarinic antagonists are used in COPD and how do they function?
Ipratropium - M1, M2, M3 antagonist
Tiotropium - M3 specific antagonist
These drugs workday blocking the ACh on the M3 receptors which surpasses the cough reflex.
How are SAMA and LAMA’s given?
Orally - to reduce systemic effects
What type of chemical structure is ideal in drugs to prevent systemic effects?
Quaternary amine groups
Describe the cough reflex?
Irritant stimulant arrives in the airways
Causes depolarisation of the sensory nerve terminals
Action potentials go the brain stem via the vagus nerve
Action potentials arrise in the parasympathetic pre-ganglionic neurone which synapse via the post - works on the M3 receptor
How is a Muscarinic antagonist generally administered?
In combination with bronchodilators and steroids e.g. with Indaceterol
What is expressed by T cells and Macrophages which causes inflammation?
Phosphodiesterase 4 (PDE4) - cause inflammation