Drugs for Airway Control

Question 1

Outline the pathophysiology of asthma

Answer 1

Th2-driven/eosinophilic inflam –> airway remodelling –> bronchial hyper-responsiveness

Mucosal oedema

Bronchoconstriction

Mucus plugging

Question 2

Briefly outline asthma treatment

Answer 2

Smooth muscle dysfunction = short acting BA (salbutamol), long acting BA (formoterol)

Inflam = inhaled CS (budesonide), oral CS (prednisolone)

Question 3

Before initiating new asthma drug therapy, what need to be assessed?

Answer 3

Compliance with existing therapies

Inhaler technique

Eliminate trigger factors

Question 4

Briefly outline the stepwise approach to asthma treatment

Answer 4

Step 1 = SABA – consider low dose ICS

Step 2 = Low dose ICS

Step 3 = (a) LABA + low dose ICS,
(b) LABA + increased dose ICS/stop LABA if no effect

Step 4 = LABA + high dose ICS
can add LTRA/aminophylline

Step 5 = Oral steroid + high dose ICS

Question 5

Outline the treatment for step 1: mild intermittent asthma

Answer 5

Short acting BA (salbutamol)

Symptom relief = bronchoconstriction reversal

Intermittent use = inhibit mast cell degranulation

Chronic use = mast cell degranulation increases

Mechanism = immediate, prevent bronchoconstriction, relaxing airway smooth muscle – bind to B2 adrenoceptors

Question 6

What are the ADRs of BA?

Answer 6

Adrenergic =

Tachycardia

Palpitations

Tremor

Question 7

Outline the treatment for step 2: regular preventer therapy

Answer 7

Inhaled corticosteroids = stop inflam

Start when = using BA <3 a week, symptoms >3 a week, waking >1 a week

Molecular action of steroids = binds intracellular receptor glucocorticoid receptor alpha = 1) transactivation (produce anti inflam molecules), 2) transrepression (stop translation of pro-inflam molecules)

Question 8

Outline the treatment for step 3: add on therapy

Answer 8

Long-acting BA (formoterol, salmeterol)

Question 9

What is symbicort?

Answer 9

Combined LABA and steroid

Question 10

Outline the alternative step3/4 add-ons

Answer 10

High dose ICS

Leukotriene receptor antagonists = montelukast

Methylxanthines = theophylline

LAMAs long acting anticholinergics = tiotropium (spiriva)

Question 11

What is the mechanism of leukotriene receptor antagonists?

Answer 11

leukotrienes are released by mast cells/eosinophils and induce bronchoconstriction, mucus secretion and mucosal oedema, and promote inflam cell recruitment.

LTRAs block the effect of cysteinyl leukotrienes in the airways at the CysLT1 receptor

Question 12

Outline the mechanism of methylxanthines

Answer 12

antagonise adenosine receptors

inhibit phosphodiesterase – increase cAMP = bronchodilation

Question 13

What is the mechanism of long acting anticholinergics?

Answer 13

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

Reduces exacerbations in both COPD and asthma

Question 14

Outline the treatment for step 5

Answer 14

Oral steroids

Biological agents = omalizumab (prevents IgE binding), reslizumab (anti IL-5)

Question 15

Outline treatment of acute severe asthma

Answer 15

High flow oxygen

Nebulised salbutamol

Oral prednisolone

Nebulised ipratropium bromide

IV aminophylline

Question 16

What is iprotrapium bromide (atrovent)?

Answer 16

Anticholinergic

Shorter acting anti-muscarinic

Question 17

Briefly outline the drugs that treat asthma

Answer 17

SABA (short acting beta agonist) = salbutamol

LABA (long acting beta agonist) = formoterol

LAMA (long acting anticholinergics) = tiotropium brombide

Short acting anticholinergic = iprotrapium bromide

Leukotriene receptor antagonists = montelukast

Methlxanthines = theophylline

Biological = omalizumab