Physiology and Pharmacology: (Challis) 11 Asthma

Question 1

What is asthma and what does it result in

Answer 1

Chronic inflammatory disease of the airways

• results in airways hyperresponsiveness
• further resulting in ‘reversible’ airway obstruction
• though hypertrophy/hyperplasia

Question 2

How can difficulty breathing be quantified?

Answer 2

Measured through FEV1 (Forced expiratory volume in 1 second)

Question 3

What effect does an allergen have on response with regards to time?

Answer 3

Initial response in attack termed ‘early phase’
- around %60 FEV1 capacity

Some sufferers experience late phase hours later
- more severe broncho-constriction than early phase

Question 4

Mechanism of early phase attack

Answer 4

Eliciting agent
-> stimulates mast cells

• > release of spasmogens, chemotaxins and chemokines
• > spasmogens cause bronchospasm

Question 5

Mechanism of late phase attack

Answer 5

Infiltration of cytokine releasing TH2 cells + inflammatory cells e.g. eosinophils

• > mediators, EMBP, ECP released
• >

Question 6

Define prophylaxis

- example of agents used

Answer 6

Prevent/reduce inflammation using anti-inflammatory agents e.g. using corticosteroids

• beclomethasone
• fluticasone

Question 7

Problems associated with chronic corticosteroid dosing

• newer corticosteroids minimize risks how? example of one?

Answer 7

• Cushing’s syndrome
• Thinning of skin / easy bruising
• Increased risk of infection
• Increased abdominal fat
• Negative Ca2+ balance -> osteoporosis

New steroid Fluticazone minimises side effects by

• direct delivery to lungs
• favourable pharmacokinetics (poor systemic absorbance, hangs around in airways, any in blood quickly metabolised by liver)

Question 8

Treatments for symptomatic relief? Examples + why they are effective

Answer 8

Rapid reversal of bronchoconstriction -> Beta2-selective adrenoceptor agonists

e.g. salbutamol, terbutaline, salmeterol

Effective because they relax bronchoconstriction irrespective of cause

• stimulates muscle relaxation
• inhibit mucus secretion
• decrease tissue oedema
• may possess some anti-inflammatory activity

Question 9

Why choose a B2 selective agonist when treating asthma over a non-selective B adrenoceptor agonist?

Answer 9

Minimise side effects -> non-selective agonist will relieve symptoms but also stimulate heart beat speed, contractile strength

Question 10

Explain the long-acting nature of salmeterol

Answer 10

Due to the long hydrophobic tail of the molecule that acts like a leash, tethering the molecule to the receptor

this means that the agonist can later re-assert agonist action when the site is free, regardless if a molecule was bound to the site beforehand