COPD Flashcards
what are the receptors in the airways
muscarinic acetylcholine receptors
M1, M2, M3
location of M1 receptor in the airways
Ganglia
role of M1 receptor
Facilitate fast neurotransmission mediated by ACh acting on nitcotinic receptors (nAChR)
Increase action potential frequency from nicotinic receptor stimulation
location of M2 receptors
postganglionic neurone terminals
role of M2 receptors
inhibitory autoreceptors reduce release of Ach (blockade)
Increase release of Ach
Location of M3 receptors
airway smooth muscle
role of M3 receptors
mediate contraction in response to Ach
present on mucus secreting cells causing increased secretion
what is COPD
increased resistance to airflow during expiration (no problem breathing in only on exhalation)
why does a person with COPD struggle to exhale
airways + alveoli lose elastic quality
walls between alveoli destroyed
airway walls inflamed
airways clogged by mucus
what causes COPD and airway obstruction to progress
muscular dysfunction
inflammation
Tissue damage
what two conditions contribute to COPD
emphysema + chronic bronchitis
what is emphysema
Alveolar destruction (loss of alveoli walls) Impaired gas exchange Loss of bronchial support
emphysema is reversible/irreversible
irreversible
how does emphysema occur
protease -> alveolar destruction -> emphysema
what is chronic bronchitis
chronic neutrophilic inflammation
Mucus hypersecretion
Mucociliary dysfunction
Altered lung microbiome
what cells are a marker for COPD
neutrophils
chronic bronchitis is reversible/irreversible
(partly) reversible
what effect does chronic bronchitis have on airway smooth muscle
smooth muscle spasm + hypertrophy
who gets COPD
smokers, those exposed to smoking, pollutants, chemical fumes, dusts or AAT deficient people
list the symptoms
Daily mucus/sputum cough Progressive Breathlessness Wheezing (chronic bronchitis) Chest tightness Lips & fingers blue/grey = hypoxic Exacerbations Reduced lung function Chronic symptoms: not episode reduced breath sounds (emphysema) Dysponea (difficult/laboured breathing)
main symptoms of chronic bronchitis
wheezing
main symptom of emphysema
reduced breath sounds
what tests are used to diagnose COPD
spirometry (pulmonary function test) Chest X ray Chest CT scan Arterial blood gas test (measures O2) Blood Test: neutrophils present
how is spirometry carried out
patient blows into spirometer after max inspiration as hard and fast as possible
how is spirometry used to tell if a patient has COPD
airways more constrictive in COPD so FVC reduced due to gas trapping/decreased residual volume
FVC & FEV1 both reduced
In a patient with COPD their FEV1 in response to a B2 agonist is
less than 15%
what effect does smoking cessation have as treatment for COPD
FEV1 falls gradually in non-smokers, FEV1 in smoker is rapid, FEV1 cannot be restored but ht falling FEV1 rate can be reverted to normal after long period of not smoking early screening nicotine patches bupropion Varenicline
What immunisations help protect against COPD patients
pneumococcal
influenza
what is the aim O2 sats for a COPD patient
88% - 92%
what mask must COPD patients get O2 from
venturi
what percentage of oxygen must COPD patients be given
24% - 28%
why must COPD patients be given controlled Oxygen
prevent hypercarbia (COPD patients cannot efficiently get rid of CO2 - poor ventilation - so CO2 builds up) causing respiratory acidosis
how does renal compensation work
high conc of CO2 in blood detected by kidneys and renal secretion of HCO3 to counterbalance
how are muscarinic antagonists used to treat COPD
inhaled
block post junctional end plate M3 receptor activation by preventing contraction (bronchoconstriction) by preventing Ach binding to receptor
Antagonist of M3 smooth muscle receptor activation in response to ACh released from postganglionic parasympathetic fibres and epithelial cells
benefit of muscarinic antagonists acting against M3
high therapeutic ratio (Safe)
reduces exacerbations
describe the steps of airway smooth muscle contraction Brought about by the binding of Ach to M3
Ach binds to M3 receptor, signal to Gq/11 signal to PLC causing PIP2 -> IP3, IP3 causes release of calcium from sacropasmic reticulum, intermediate steps involve calmodulin and MLCK leading to contraction
types of muscarinic antagonsits
Ipratropium (SAMA - short acting)
LAMA: tiotropium, Glycopyrronium, Aclidinium, Umedlidinium, Aclidinium bromide
how does ipratropium work
delayed bronchodilator - reduces bronchospasm
non-selective blocker of M1, M2, M3
what is the effect of treating a patient with a LAMA or SAMA
decreased mucus secretion
no effect on COPD progression
how is ipratropium given
high nebulised dose
ipratropium and tiotropium have a quaternary ammonium group what is the benefit of this
reduces absorption/systemic exposure
avoids multiple AP adverse effects of a generalised parasympathetic block
what does atropine posses
tertrial amine
how do B2 agonists help COPD patients
b-adrenoceptors inhaled causing bronchodilation
does salbutamol help reduce inflammation
NO! only bronchodilation
what are the short acting B2 agonists
salbutamol 4-6h
what are the long acting B2 agonists
salmeterol/formoterol (2x day)
indacaterol/olodaterol (ultra LABA) once daily
most effective way to relax the airways of a COPD patient during exacerbation
LABA/LAMA combo inhaler
increases FEV1
both drugs in same airway location (act on same ligand)
what treatment would be given to a COPD patient having few (<2 exacerbation)
Glycophyrronium/indacterol
what treatment would be given to a COPD patient having sever/frequent (>2) exacerbations
LABA and/or LAMA + ICS (co-adminstered with glucocorticoid)
what effect does administering a glucocorticoid have on COPD patient
reduces inflammation
when would glucocorticoid be co-administered with LAMA/LABA
high eosinophil count
when can glucocorticoid be unresponsive in COPD patients
Oxidative/nitrative stress due to chronic inhalation of tobacco or if HDAC2 reduced
what is an adverse effect of co-administering a glucocorticoid
can cause pneumonia as local immune suppression altered microbiome and impairs MC clearance
why is fluticasone more likely to cause predisposition to pneumonia
it causes prolonged lung retention
give examples of ICS/LABA/LAMA triple inhaler
beclomethasone
formoterol
glycopyrronium
when would a triple inhaler like beclomethasone, formoterol or glycopyrronium be used
once daily for moderate/severe COPD
NOT for asthma/acute bronchospasm
what would be given as an add on therapy, given orally, to reduce exacerbations in people with severe COPD + chronic bronchitis
Rofumilast:
inhibitor of PDE4 (PDE4 expressed on neutrophils, T cells and macrophages surpasses inflammation and emphysema
adverse effects of rofumilast
GI effects, nausea, headache
What add on therapy is used to reduce exacerbations by reducing sputum viscosity and aide sputum expectoration
mucolytis: oral carbocisteine or erdosteine
how would you treat a patient with acute COPD
nebulised high dose salbutamol (LABA) + ipratropium (LAMA)
oral prednisolone (steroid)
antibiotic (amoxycillin/doxycycline) if infection eg. high eosinophils
24-28% O2 via Venturi against PaO2/PaCO2
physic to aide sputum expectoration
Non-invasive ventilation allowing higher FiO2 (inspired O2)
ITU intubated assisted ventilation (only if reversible component eg. Pneumonia)
what does the prognosis of COPD depend on
FEV1: higher the FEV1 = decreased exacerbations = good prognosis
describe the chronic cascade in COPD
Progressive fixed airflow obstruction
Impaired alveolar gas exchange
Respiratory failure: decreased PaO2 Increased PaCO2
Pulmonary hypertension
Right ventricular hypertrophy/failure (i.e. cor pulmonale)
Death
