phys pharm - Asthma:

Question 1

asthma =

Answer 1

chronic inflammatory disorder of the airways associated with smooth muscle hyperresponsiveness and obstruction

= wheezing, breathlessness, chest tightness, coughing

Question 2

bronchial asthma =

Answer 2

recurrent, ‘reversible’ obstruction of the airways in response to a stimulus (e.g. cold air, exercise, pollen, dust) that is innocuous to a non-asthmatic individual

Question 3

chronic asthma =

Answer 3

irreversible changes in airways calibre through hypertrophy and hyperplasia of the smooth muscle

= hypersecretion of mucus
= thickened basement membrane
= increased volume of smooth muscle

Question 4

allergen response in asthma:

Answer 4

During an asthma attack the airways narrow and the sufferer has problems breathing out. This respiratory difficulty can be quantified by measuring FEV1 (Forced Expiratory Volume in 1 second)

after a few minuites of attack = early phase

further effects hours later = late phase

Question 5

Modern Treatment Strategies in Asthma:

Answer 5

1. Prophylaxis

2. Symptomatic Relief

Question 6

1. Prophylaxis:

Answer 6

Prevent/reduce inflammation using anti-inflammatory agents,

e.g. using corticosteroids (beclomethasone
OR fluticasone)

Question 7

Problems associated with chronic corticosteroid dosing…

Answer 7

Cushing’s syndrome

Thinning of skin / easy bruising / oedema / ulceration

Poor wound-healing / increased risk of infection

Increased appetite / increased abdominal fat / muscle wasting

Negative Ca2+ balance/osteoporosis

Question 8

2. Symptomatic Relief

Answer 8

Rapid reversal of bronchoconstriction (using β2-selective adrenoceptor agonists)

E.G. salbutamol, terbutaline, salmeterol

Question 9

β2-selective adrenoceptor agonists

Answer 9

• relax bronchoconstriction irrespective of the cause
• Inhibit mucus secretion and stimulate mucus clearance
• Decrease tissue oedema
• possess some anti-inflammatory activity

Question 10

Airways Smooth Muscle Contraction controlled by …

Answer 10

 acetylcholine
 histamine
 leukotrienes

These agents interact with specific G protein-coupled receptors in
the smooth muscle to cause Ca2+
influx = Ca2+/calmodulin-dependent activation of
myosin light chain kinase and myosin phosphorylation to
promote contraction

Question 11

Airways Smooth Muscle Relaxation…

Answer 11

β2-adrenoceptor activation causes adenylyl cyclase activation (via a Gs protein) to increase cyclic AMP/cyclic AMP-dependent protein kinase activity leading to:

 decrease in [Ca2+] (through activation of Ca2+ efflux pathways and/or inhibition of Ca2+ influx pathways)

 inhibition of myosin phosphorylation by myosin light chain kinase

 promotion of myosin dephosphorylation

Therefore, if a β2-adrenoceptor agonist is delivered to the airways it will relax the airways smooth muscle

Question 12

Long-acting β2-adrenoceptor agonists…

Answer 12

e.g. salmeterol

= may offer 24 hour prophylaxis against asthma attack

poorly effective in revering acute asthma attack but prevents bronchospasm

The long-acting = due to the long hydrophobic tail of the molecule that acts like a leash, tethering the molecule to the β2-adrenoceptor

Question 13

Most common asthma therapy currently is..

Answer 13

combined inhaled LABA + corticosteroid

e.g.
SALMETEROL + FLUTICASONE