11. Pharmacology of Airway Control

Question 1

What are the components of asthma pathophysiology?

Answer 1

Inflammation -> mucosal oedema, bronchoconstriction, mucus plugging, and airway remodelling, and bronchial hyperresponsiveness.

Question 2

In what ways is asthma a heterogenous disease?

Answer 2

Pathologically, symptom patterns and triggers of exacerbations, and response to treatment.

Question 3

What are the five steps involved in management of asthma in adults?

Answer 3

Mild intermittent asthma, regular preventer therapy, add-on therapy, persistent poor control, continuous or frequent use of oral steroids.

Question 4

What is meant by asthma control?

Answer 4

Minimal symptoms day and night, minimal need for reliever medication, no exacerbations, no limitation of physical activity, normal lung function.

Question 5

Before starting a new drug therapy for asthma, what should be checked?

Answer 5

Compliance with existing therapies, inhaler technique, eliminate trigger factors.

Question 6

What is step 1 of asthma management?

Answer 6

Short-acting B2-agonists - salbutamol, terbutaline.

Question 7

What are the goals of step 1 in asthma management?

Answer 7

Symptom relief by reversing bronchoconstriction, prevent bronchoconstriction.

Question 8

What is a risk of using SABAs regularly in asthma control?

Answer 8

They reduce control with regular use - mast cell degranulation promoted.

Question 9

What is the action of SABAs?

Answer 9

Relax airway smooth muscle, inhibit mast cell degranulation if intermittent use.

Question 10

What is the mechanism of action of SABAs?

Answer 10

MLCK and PKA cause relaxation and inhibition of agonist-induced contraction.

Question 11

What are the ADRs of SABAs?

Answer 11

Adrenergic so tachycardia, palpitations, tremor.

Question 12

What is step 2 of asthma management?

Answer 12

Inhaled corticosteroids.

Question 13

When should treatment of asthma step up to step 2?

Answer 13

If using B2 agonist >3 times/week, symptoms >3 times/week, waking >1/week, exacerbation requiring oral steroids in last 2 years.

Question 14

What is the purpose of corticosteroid use in asthma therapy?

Answer 14

Improve symptoms, improve lung function, reduce exacerbations, prevent death.

Question 15

What is the mechanism of action of corticosteroids?

Answer 15

Transactivation on B2 receptors, transrepression of inflammatory mediators.

Question 16

What is the systemic availability of inhaled drugs dependent on?

Answer 16

Drug entering systemic circulation via absorption from lungs and drug from swallowed fraction that is metabolised in gut and liver.

Question 17

Which subgroup of asthma patients respond better to inhaled steroids?

Answer 17

Those with eosinophilic asthma.

Question 18

What is step 3 of asthma management?

Answer 18

Long acting B2 agonist (formoterol, salmeterol), add in LABA when patients not controlled on ICS.

Question 19

What are the effects of LABA used in asthma therapy?

Answer 19

Reduced asthma exacerbations, improved asthma symptoms, improved lung function.

Question 20

Why do LABAs need to prescribed in conjunction with inhaled steroids?

Answer 20

They’re not anti-inflammatory on their own.

Question 21

Why should LABA and ICS be combined in a single inhaler?

Answer 21

Easier to use, compliance, potentially cheaper, safer.

Question 22

What are the alternative step 3/4 add-ons to LABA?

Answer 22

High dose ICS, leukotriene receptor antagonists, theophylline, tiotropium.

Question 23

What is the action of LTC4 on airways?

Answer 23

LTC4 release by mast cells and eosinophils can cause bronchoconstriction, mucus secretion and mucosal oedema, and promotes inflammatory cell recruitment.

Question 24

What is the mechanism of action of leukotriene receptor antagonists in asthma therapy?

Answer 24

Block effect of cysteinyl leukotrienes in airways at CysLT1 receptors.

Question 25

What are the ADRs of leukotriene receptor antagonists?

Answer 25

Angioedema, dry mouth, anaphylaxis, arthralgia, fever, GI disturbance, nightmares

Question 26

What is the mechanism of action of methylxanthines in asthma therapy?

Answer 26

Antagonises adenosine receptors so inhibits phosphodiesterase, increases cAMP.

Question 27

Why are methylxanthines not used commonly in asthma therapy?

Answer 27

Poorly efficacious, narrow therapeutic window, ADRs, life-threatening toxic complications, DDIs.

Question 28

What are the frequent ADRs of methylxanthines?

Answer 28

Nausea, headache, reflux.

Question 29

What are the potentially life-threatening toxic complications of methylxanthines?

Answer 29

Arrhythmias, fits.

Question 30

What are the DDIs of methylanthines?

Answer 30

Levels increased by CYP450 inhibitors.

Question 31

When are LAMAs used?

Answer 31

COPD and severe asthma to reduce exacerbations.

Question 32

What are the ADRs of LAMAs?

Answer 32

Dry mouth, urinary retention, glaucoma.

Question 33

What is step 5 of asthma management?

Answer 33

Oral steroids, or biological therapies (anti-IgE or anti-IL-5).

Question 34

What are the criteria for anti-IgE use in asthma therapy?

Answer 34

Strict - atopy, IgE in strict range.

Question 35

What is the mechanism of action of anti-IgE in asthma therapy?

Answer 35

Prevents IgE binding to high affinity IgE receptors.

Question 36

What is the effect of anti-IL-5 use in asthma therapy?

Answer 36

Reduces peripheral blood and airway eosinophil numbers, reduces severe asthma exacerbations.

Question 37

When is stepping down recommended in asthma therapy?

Answer 37

Once asthma is controlled so patients are maintained at lowest possible dose of inhaled steroid.

Question 38

Why does size of particles matter in drug delivery via inhaler devices?

Answer 38

Too big (10 micron) - deposit in mouth and oropharynx. Too small (0.5 micron) - inhaled to alveoli and exhaled without deposition in lungs. Right size (1-5 micron) - most effective as they settle in small airways.

Question 39

What are the criteria for classification as severe asthma in adults?

Answer 39

Unable to complete sentences, pulse >110bpm, respiration >25/min, peak flow 33-50% of best/predicted.

Question 40

What are life-threatening features of an asthma attack?

Answer 40

Severe asthma + PEF <33%, sPO2 <92, PaO2 <8kPa, PaCO2 >4.5kPa, silent chest, cyanosis, feeble respiratory effort, hypotension, bradycardia, arrhythmia, exhaustion, confusion, coma.

Question 41

What is the treatment of acute severe asthma?

Answer 41

Oxygen high flow to keep sats 94-98%; nebulised salbutamol; oral prednisolone; nebulised ipratroprium bromide; IV aminophyllin; IV magnesium sulphate.