S11) Pharmacology of Airway Control

Question 1

Describe the autonomic innervation of the airway smooth muscle

Answer 1

• Parasympathetic (dominant) – bronchoconstriction, vascular dilatation, increased secretion from mucus glands
• Sympathetic – innervates vascular smooth muscle & glands (doesn’t affect airway, but β-adrenoreceptors found in airway smooth muscle)

Question 2

What does asthma control mean?

Answer 2

• Minimal symptoms during day and night
• Minimal need for reliever medication
• No exacerbations
• No limitation of physical activity
• Normal lung function (FEV₁ and/or PEF >80% predicted or best)

Question 3

Outline the stepwise treatment approach for asthma

Answer 3

• Step 1 – short acting β₂ agonists, consider low dose ICS
• Step 2 – regular low dose ICS
• Step 3

A. LABA + low dose ICS

B. LABA + ↑ dose ICS / stop LABA if no effect

• Step 4 – LABA + high dose ICS (can add LTRA/aminophylline)
• Step 5 – daily oral steroid + high dose ICS + consider others

Question 4

What is used to treat mild intermittent asthma in Step 1 of asthma control?

Answer 4

Mild intermittent asthma – short-acting β₂-agonists e.g. salbutamol, terbutaline

Question 5

Describe the Step 1 treatment aims in asthma control

Answer 5

• Symptom relief through reversal of bronchoconstriction
• Used on an as-required basis (not regularly)

Question 6

Describe the site and/or mechanism of action of β₂ agonists in Step 1 of asthma control

Answer 6

• Acts predominantly on airway smooth muscle
• Potentially inhibits mast cell degranulation (if used intermittently)

Question 7

Illustrate the β₂ receptor function in airway smooth muscle

Answer 7

Question 8

Classify the different inhaled β₂ agonists in terms of the speed of onset and the duration of action

Answer 8

Question 9

Identify some side effects of β₂ agonists

Answer 9

Adrenergic i.e. tachycardia, palpitations, tremor

Question 10

What is used as regular preventer therapy in Step 2 of asthma control?

Answer 10

Regular preventer therapy – inhaled corticosteroids

Question 11

What are the four conditions one must consider before starting Step 2 in the asthma control for a patient?

Answer 11

• Using β₂ agonist ≥ 3 times/week
• Symptoms ≥ 3times/week
• Waking ≥ 1time/week
• Exacerbation requiring oral steroids in last 2 years

Question 12

What are the aims of Step 2 treatment in asthma control?

Answer 12

• Improve symptoms
• Improve lung function
• Reduce exacerbations
• Prevent death

Question 13

Illustrate the systemic availability of inhaled drugs

Answer 13

Question 14

Provide some examples of inhaled corticosteroids

Answer 14

• Budesonide
• Beclomethasone
• Fluticasone

Question 15

Provide an example of a combined LABA and steroid

Answer 15

Symbicort

Question 16

Provide an example of a leukotriene receptor antagonists

Answer 16

Montelukast

Question 17

What are some ADRs for leukotriene receptor antagonists?

Answer 17

• Angioedema
• Dry mouth
• Anaphylaxis
• Arthralgia
• Fever

Question 18

Describe the mechanism of action for LTRAs

Answer 18

• LTRAs lock the effect of cysteinyl leukotrienes in the airways at the CysLT1 receptor
• Leukotrienes are released by mast cells/eosinophils, induce bronchoconstriction, mucus secretion and mucosal oedema and promote inflammatory cell recruitment

Question 19

Provide some examples of methylxanthines

Answer 19

• Theophylline
• Aminophylline

Question 20

Describe the mechanism of action for methylxanthines

Answer 20

• Antagonise adenosine receptors
• Inhibit phosphodiesterase
• Increase cAMP

Question 21

What are the ADRs for methylxanthines?

Answer 21

• Common – nausea, headache, reflux
• Potentially life-threatening toxic complications – arrhythmias, fits

Question 22

What possible drug interactions might methylxanthines have?

Answer 22

Levels increased by CYP450 inhibitors e.g. erythromycin, ciprofloxacin

Question 23

Provide some examples of long acting anticholinergics

Answer 23

• Tiotropium bromide
• Glycopyrronium

Question 24

What are the indications for LAMAs?

Answer 24

• COPD
• Severe asthma

Question 25

Describe the mechanism of action for long acting anticholinergics

Answer 25

LAMAs bind to M₃ muscarinic receptor and block it’s action (prevent bronchoconstriction)

Question 26

What are the ADRs of LAMAs?

Answer 26

**Anticholinergic** – dry mouth, urinary retention, glaucoma

Question 27

Describe the mechanism of action of omalizumab (anti-IgE)

Answer 27

**Biological therapies:** - Prevents IgE binding to high affinity IgE receptor - Cannot bind to IgE already bound to receptor, so cannot cross-link IgE and activate mast cells

Question 28

Describe the mechanism of action of reslizumab (Anti IL-5)

Answer 28

**Biological therapies:** - Reduce peripheral blood and airway eosinophil numbers - Most effective at reducing rate of severe asthma exacerbations