Drug for Asthma and COPD

Question 1

What is the class of first-line bronchodilator drugs for asthma?

Answer 1

Beta-2 adrenoceptor agonists

Question 2

What is the class of first-line anti-inflammatory drugs for asthma?

Answer 2

Corticosteroids

Question 3

What is the class of first-line anti-inflammatory drugs for COPD?

Answer 3

Corticosteroids

Question 4

What is the class of first-line and second line bronchodilator drugs for patients with stable COPD who show increasing frequency of acute exacerbations (more than two serious exacerbations in the last year or one leading to hospitalisation)?

Answer 4

Long-acting muscarinic antagonist (LAMA) for first line; LABA (second line)

LAMA: tiotropium bromide
LABA: indacaterol

Question 5

Name an example of a short-acting inhaled bronchodilator drug.

Answer 5

Salbutamol (5-15 min onset, 4-6 hours duration, SABA)

Question 6

Name an example of a long-acting inhaled bronchodilator drug that is also fast-acting used as both a controller and reliever for asthma?

Answer 6

Formoterol (2-3 min onset, 12 hours duration, LABA)

Question 7

Name an example of an ultra-long-acting bronchodilator drug that is also fast-acting used for COPD.

Answer 7

Indacaterol (5 min onset, 24 hrs duration LABA)

Question 8

Name an example of a long-acting inhaled bronchodilator drug that is slow-acting used for asthma.

Answer 8

Salmeterol (12 h LABA)

Slow-acting so used only as controller NOT reliever

Question 9

What is the MOST dangerous adverse effect of beta-2 agonists in asthma?

Answer 9

Downregulation of beta-2 receptors results in reduced efficacy of beta-2 agonist-induced bronchodilation when required to relieve acute asthma attack.

The risk of receptor downregulation is greatest with LABAs. LABAs used alone increase the risk of death from asthma.

Question 10

What must be co-prescribed with LABAs to reduce the risk of downregulation of beta-2 agonists?

Answer 10

A corticosteroid must always be co-prescribed with LABAs for asthma.

The LABAs are formulated in combined inhalers together with corticosteroids to ensure that the two drugs are taken together.

The concern even extends to SABAs if they are over-used. Increasingly for patients ≥12 years-old, salbutamol is being replaced with formoterol+ budesonide inhaler.

Question 11

Name a SAMA that can be combined as an adjunct with beta-2 agonist to produce greater bronchodilation in asthma?

Answer 11

Ipratropium bromide (SAMA)

Question 12

List common adverse effects of inhaled muscarinic receptor antagonists.

Answer 12

Limited systemic side effects as not well absorbed into systemic circulation when taken by inhalation
Unpleasant taste
Typical parasympatholytic effects:
Dry mouth
Urinary retention (especially in the elderly)

Question 13

Briefly explain the mechanisms of action of methylxanthines such as theophylline.

Answer 13

Inhibits phosphodiesterases (PDEs)

Blocks adenosine receptors

↑ Epinephrine release from adrenal medulla

CNS stimulant action on respiration

NOT used clinically as an anti-inflammatory but it has some weak anti-inflammatory effects

Effects on mast cells and T-cells

↓ Microvascular leakiness

Question 14

List adverse effects of methylxanthines such as theophylline.

Answer 14

Narrow therapeutic window (therapeutic range for theophylline: 5-20 mg/L)

Many drug-drug interactions: Caution for potential drug interactions

Gastrointestinal: Nausea, vomiting, abdominal discomfort, anorexia

CNS: Nervousness, tremor, anxiety, insomnia, seizures

Cardiovascular: Arrhythmias

Question 15

Name an example of a soft steroid

Answer 15

Ciclesonide

Question 16

What is a soft steroid?

Answer 16

An inhaled prodrug that is converted by esterases in the lungs into the active steroid (e.g., ciclesonide).

As the drug is only active in cells expressing esterases adverse effects are minimised even if the drug escapes into the systemic circulation.

Question 17

List SEVEN more common adverse effects of inhaled corticosteroids.

Answer 17

Oropharyngeal candidiasis (opportunistic infection due to localised immunosuppression)

Dysphonia (enfeebled voice due to localised muscle wasting)

Cough / throat irritation
Adrenal suppression (e.g. fluticasone)

Easy bruising (especially in elderly)

Posterior subcapsular cataracts (especially in elderly)

Osteoporosis (especially in elderly)

Question 18

Name an example of a 5-lipoxygenase inhibitor

Answer 18

Zileuton

Question 19

Name an example of a CysLT receptor antagonist

Answer 19

Montelukast

Question 20

What class of drugs is particularly useful as an adjunct anti-inflammatory in NSAID-exacerbated respiratory disease or aspirin-sensitive asthma?

Answer 20

Leukotriene pathway inhibitors (e.g., zileuton)

Question 21

Q
What class of drugs is both anti-inflammatory and weakly bronchodilator?

Answer 21

CysLT receptor antagonists (e.g., montelukast)

Question 22

What types of asthma respond well to cromoglicic acid?

Answer 22

Cromoglicic acid is a mast cell stabiliser. Allergic (antigen), cold, dry air and exercise challenge-induced asthma often responds well to a dose of cromoglicic acid before the challenge.

Question 23

Name a monoclonal antibody drug for allergic asthma

Answer 23

Omalizumab (anti-IgE monoclonal antibody)

Question 24

What are the common limitations or adverse effects when using omalizumab?

Answer 24

Expensive. Associated with a small increase in the risk of heart attack, transient ischaemic attacks (TIA) and blood clots. Potential for anaphylaxis.

Question 25

Name ONE anti-IL5 signalling monoclonal antibody for severe, persistent eosinophilic asthma

Answer 25

Reslizumab (anti-IL-5, IV)

Mepolizumab (anti-IL-5, SC)

Benralizumab (anti-IL-5 receptor)

Question 26

List adverse effects or limitations when using reslizumab to treat asthma

Answer 26

Only approved for severe, persistent eosinophilic asthma in patients ≥18 years old

Expensive

Oropharyngeal pain

As for all monoclonal antibodies, potential for anaphylaxis

Question 27

Name a PDE-4 inhibitor used in the treatment of COPD

Answer 27

Roflumilast

Question 28

Briefly explain the mechanisms of action of roflumilast.

Answer 28

Inhibition of PDE-4 prevents breakdown of cAMP resulting in:
- Reduced inflammatory cell activity
- Inhibition of fibrosis
- Relaxation of smooth muscle

Question 29

List adverse effects of roflumilast

Answer 29

Headaches, dizziness, insomnia

Weight loss, diarrhoea, nausea, decreased appetite

Rarely: anxiety, depression, and suicidal ideation

Caution in patients with hepatic impairment

Question 30

List advantages of azithromycin in treatment of COPD

Answer 30

Macrolide antibiotic prevents bacteria from growing by interfering with their protein synthesis - prevention and treatment of acute exacerbations due to bacterial infection

Additionally, anti-fibrotic and airway smooth muscle relaxant through mechanisms that are not completely understood

Question 31

List adverse effects of azithromycin

Answer 31

• Common: Diarrhoea, nausea, vomiting
• Severe: Cardiac arrhythmia
• Contraindicatedhistory of cholestatic jaundice or hepatic dysfunction

Question 32

Name a thiol mucolytic used in COPD

Answer 32

Erdosteine

Question 33

What are the adverse effects of beta-2 agonist bronchodilators? (3)

Answer 33

1. Tremour (most common) and muscle cramps
2. Peripheral vasodilation –> flushing
3. Palpitation and tachycardia (beta-1 adrenoceptor effects)

Question 34

What are the first line drugs for asthma (bronchodilators and anti-inflammatory drugs)?

Answer 34

Bronchodilation
* Fast-acting β2 agonists [SABA] (relievers)
* Long-Acting β2 agonists [LABA] (controllers)

Anti inflammatory
* Glucocorticoids (Corticosteroids / Steroids)

Question 35

What are the second line drugs for asthma (brochodilators and anti-inflammatory drugs)?

Answer 35

Bronchodilation
* Muscarinic receptor antagonists
* Theophylline (methylxanthines)
* Leukotriene receptor antagonists (weak)

Anti-inflammatory
* Mast cell stabilisers – Cromoglicic acid
* Leukotriene pathway inhibitors/receptor antagonists
* Anti-IgE antibody
* Anti-Interleukin-5/Interleukin-4 signalling antibodies

Question 36

Name 3 inhaled corticosteriods. (first line anti inflammatory drug for asthma)

Answer 36

1. Budesonide
2. Fluticasone
3. Ciclesonide

Question 37

What are the classes of drug (and theri examples) used in COPD management?

Answer 37

1. Bronchodilators SAMA, SABA, LAMA (1st) and LABA (2nd)
2. Anti-inflammatories: inhaledcorticosteriods
3. Theophylline (bronchodilator)(class: methylxanthines)
4. Phosphodiesterase-4 inhibitors (roflumilast)
5. Azithromycin
6. Mucolytics (erdostein)