therapeutics - COPD week 1

Question 1

what is COPD?

Answer 1

chronic - progressive and long lasting

obstructive - narrowing of airways that causes airflow limitation

pulmonary - small airways and/or alveoli destruction

disease - multicomponent illness with extra-pulmonary effects (effects other organs)

Question 2

how is COPD characterised?

Answer 2

airflow limitation which is not fully reversible

progressive and associated with abnormal inflammatory responses of the lungs to noxious particles and gases

airflow limitation is caused by small airway disease and parenchymal destruction: chronic bronchitis and emphysema

Question 3

what are risk factors for COPD?

Answer 3

smoking

environmental pollution

genetic factor

occupational exposure

frequent infections of the airway

age > 35

poor diet

socio-economical deprivation

Question 4

what are the symptoms of COPD?

Answer 4

progressive and exertional breathlessness (dyspnea) - difficulty whilst exercising

chronic cough -

sputum production

wheezing and chest tightness

frequent winter bronchitis

upper respiratory infection (purulent sputum)

pulmonary hypertension

Question 5

what are the symptoms in severe COPD?

Answer 5

weight loss - anorexia

asymptomatic rib fractures

ankle swelling

depression, anxiety

Question 6

how do you diagnose COPD?

Answer 6

age - considered if over 35

risk factors - smoker

respiratory symptoms - exertional breathlessness, chronic cough, sputum production, winter bronchitis

test airflow obstruction - post bronchodilator spirometry

Question 7

what is the COPD pathophysiology?

Answer 7

chronic bronchitis and bronchiolitis - inflammation of central airways (trachea/bronchi) and smaller airways (bronchioles)

hypertrophy (increase in size) and hyperplasia (increase in number) in mucus secreting glands and smooth muscles

small airway become obstructed by intraluminal mucus, mucosal oedema and airways wall fibrosis

the obstruction and the mucus increase resistance to airflow and cause chronic viral and bacterial colonisation in the retained mucus

Question 8

what is emphysema?

Answer 8

persistent inflammation destroys alveoli at the end of the small airways

permanent enlargement of the air spaces distal to the terminal bronchial accompanied by destruction of their walls

destruction of the parenchyma decreases the area for gas exchange and lung elasticity

hypertrophy of capillaries reduces ability to absorb oxygen and may increase blood pressure

Question 9

pathogenesis of COPD

Answer 9

1. inflammatory cells and mediators - chronic inflammation
2. oxidative stress - reactive oxygen and nitrogen species
3. protease-antiprotease imbalance
   a1-antitrypsin deficit

Question 10

aims of managing stable COPD?

Answer 10

prevent and control symptoms

reduce the frequency and severity of exacerbations

improve general health status and exercise tolerance

Question 11

non pharmacological management of COPD?

Answer 11

offer treatment and support to stop smoking

offer pneumococcal and influenza vaccinations

offer pulmonary rehabilitation if indicated

co-develop a personalised self management plan

optimise treatment for comorbidities

Question 12

start inhaled therapies only if:

Answer 12

all the above interventions have been offered

inhaled therapies are needed to relieve breathlessness and exercise limitation and,

people have been trained to use inhalers and can demonstrate satisfactory technique

offer SABA and SAMA as required

SABA (short acting inhaled beta agonists)

SAMA (short acting muscarinic antagonists)

Question 13

muscarinic receptors in the lungs:

Answer 13

M1 receptors may mediate bronchodilator, by the release of a relaxing agent from respiratory epithelia or pulmonary nerves

M2 autoreceptors, on post-ganglionic cholinergic nerves: provide negative feedback to reduce acetylcholine release

M3 on airway smooth muscles and glands: mediate bronchocontriction and mucus secretion

Question 14

inhaled anticholinergic drugs ?

Answer 14

mechanism of action:
block muscarininc acetylcholine receptors (M3) to cause bronchodilator and reduce mucus secretion

short-acting antimuscarinic drugs:
ipratropium bromide (SAMA) - onset after 20 minutes within 30-60 minutes, and duration of action 3-6 hours

long acting antimuscarinic drugs:
tiotropium bromide (LAMA) - onset of action 30 minutes, peak effect within 3-4 hours and 24 hour duration of action

Question 15

side effects produced by anticholinergic drugs?

Answer 15

common: dry mouth, arrhythmia, cough, dizziness, headache, nausea
uncommon: constipation, dyshphonia, glaucoma, palpitations, skin reactions, stomatitis, urinary disorders, vision blurred

caution:
tiotropium - arrhythmia, heart failure, myocardial infarction

Question 16

for treatment refer to powerpoint slides

Answer 16

for treatment refer to powerpoint slides

Question 17

treatment options for COPD

Answer 17

oral corticosteroid therapy is not recommended

mucolytic therapy - considered in patients with a chronic cough productive of sputum

long acting phosphodiesterase-4-inhibitor:

theophylline: after a trial of inhaled combination therapy in patients unable to use inhaled therapy

roflumilast

Question 18

oral inhibitor for phosphodiesterase-4

Answer 18

roflumilast (daxas)

mechanism of action:
selective inhibition of the PDE4 isoenzyme in lung cell

use:
oral add on to bronchodilator therapy for severe COPD associated with chronic bronchitis and prevention of exacerbations

side effects:
common: diarrhoea, weight loss and nausea
increase in psychiatric adverse reactions