Drugs for Asthma

Question 1

What are the 2 major forms of asthma?

Answer 1

1) Allergic asthma (Type 1 HS/IgE-mediated)

2) Eosinophilic asthma (Type 2 HS/Cell-mediated)

Question 2

Why does the use of LABAs alone make asthma outcomes worse and how is it prevented?

Answer 2

ß2-adrenoceptor tolerance

Must take with ICS to upregulate ß2-adrenoceptor expression

Question 3

What are the 1st line drugs in for asthma?

Answer 3

1) SABA (salbutamol)
2) LABA (formoterol, salmeterol)
3) ICS (eg. budesonide, fluticasone)

Question 4

What is used as a “reliever” in an acute asthma attack?

Answer 4

Fast-acting SABAs (Salbutamol)

Question 5

What is the given as a “controller” in chronic asthma or to prevent progression from early to late?

Answer 5

LABA (Formoterol/Salmeterol) + ICS (Budesonide, Fluticasone)

Question 6

What is the moa of ß2-adrenoceptor agonists used in asthma?

Answer 6

1) Airway smooth muscle relaxation → bronchodilation
2) Mast cell stabilization
3) ↓Microvascular leakiness
4) ↑ Mucociliary clearance

Question 7

What do you give to a px having an anaphylactic rxn?

Answer 7

IM Adrenaline (IV/SC if possible)

Question 8

How are SABAs and LABAs usually administered?

Answer 8

Inhalation
(but also oral if cannot use inhaler)
- and IV in emergency

Question 9

What are 3 AEs of ß2-agonists used in asthma?

Answer 9

Sympathomimetic:
1) Tremor (commonest side effect) and muscle cramps

2) Peripheral vasodilatation (e.g. flushing)

3) Palpitations & tachycardia (ß1-adrenoceptor effects)

4)HypoK+/Hypergly
– Usually transient and/or insignificant but beware of DDIs with other drugs causing hypoK+/hypergly

5) ***ß2-adrenoceptor tolerance

Question 10

ß-agonists are (1st/2nd) line in asthma but usually (1st/2nd) line in COPD.

Answer 10

1st line in asthma
2nd line in COPD (group A but LABAs first line with LAMAs in B and E)

Question 11

What are 2 bronchodilators used in 2nd line for asthma?

Answer 11

SAMA: Ipratropium bromide
LAMA: Tiotropium bromide

Question 12

What are 2 methylxanthines used in asthma treatment for bronchodilation?

Answer 12

1) Theophylline (Oral-ER and IV)
2) Aminophylline (Oral-ER, IV and rectal)

Question 13

When are methylxanthines used to treat asthma?

Answer 13

IV in acute severe asthma

Question 14

What are 2 AES of methylxanthines used in asthma?

Answer 14

1) Narrow therapeutic window (therapeutic range: 5-20 mg/L)
2) Many DDIs
3) GI: Nausea, vomiting, abdominal discomfort, anorexia
4) CNS: Nervousness, tremor, anxiety, insomnia, seizures (in children)

5) CVS: Arrhythmias

Question 15

What is the use of magnesium sulphate in asthma treatment?

Answer 15

Adjunct treatment of severe acute asthma

Question 16

What is the moa of Magnesium sulphate in asthma?

Answer 16

1) Relaxes airway smooth muscle
2) ↓ release of acetylcholine and histamine
3) Anti-inflammatory effect

Question 17

What are 3 factors that make budesonide, fluticasone and ciclesonide good choices as ICS in asthma treatment?

Answer 17

1) High receptor binding affinity (very low dose required)
2) Extensive first pass metabolism (less systemic side effects)
3) Highly lipophilicity

Question 18

What is the moa of ICS in asthma?

Answer 18

1) ↑anti-inflammatory mediators:
- ↑ Annexin A1
- ↑ ß2 adrenoceptors

2) ↓Pro-inflammatory mediators
- ↓ T cell, mast cell, eosinophils
- ↓shedding of epithelial cells
- ↓ mucus secretion
- ↓ inflammatory cytokines
- ↓ phospholipase A2
- ↓ COX2 → prostaglandins
- ↓ 5-LOX → leukotrienes
- ↓ NO synthase

Question 19

What are 2 uses of ICS for asthma?

Answer 19

1) 1st line prophylactic for asthma treatment
2) Nocturnal asthma

Question 20

What are 4 AEs of ICS used in asthma?

Answer 20

1) Oropharyngeal candidiasis (due to localised immunosuppression)
2) Dysphonia (enfeebled voice due to localised muscle wasting)
3) Cough / throat irritation
4) Adrenal suppression (e.g., fluticasone)
5) Easy bruising (especially in elderly)
6) Posterior subcapsular cataracts
7) Osteoporosis

Question 21

How are leukotriene pathway inhibitors administered?

Answer 21

Oral

Question 22

What are 2 leukotriene pathway inhibitors?

Answer 22

1) Montelukast - Cysteinyl-Leukotriene (CysLT) receptor antagonist
2) Zileuton - 5-lipoxygenase (5-LOX) inhibitor

Question 23

What are 2 uses of leukotriene pathway inhibitors (eg. Montelukast, Zileuton) used in asthma?

Answer 23

1) Prophylaxis & chronic treatment of asthma
2) Aspirin-induced/NSAID exacerbated asthma
3) Exercise-induced asthma

Question 24

What are 2 AEs of leukotriene pathway inhibitors (eg. Montelukast, Zileuton) used in asthma?

Answer 24

Few and mild
1) Headache
2) GI disturbance

a/w Churg-Straus syndrome
3) Suicidal thinking and neuropsychiatric adverse effects in some patients

Question 25

Leukotriene pathway inhibitors (eg. Montelukast, Zileuton) used in asthma are (weak/strong) bronchodilators?

Answer 25

Weak

Question 26

What are the moas of Cromoglicic acid used in asthma?

Answer 26

Mast cell stabiliser:
1) Controls Cl- channels to inhibit cellular activation

2) mast cell degranulation induced by IgE-mediated FcεRI crosslinking

3) ↓secretion of inflammatory mediators from eosinophils, neutrophils and macrophages

4) ↑ annexin A1 secretion
– Annexin A1 inhibits prostaglandin and leukotriene production

Question 27

What are 2 uses of cromoglicic acid in asthma?

Answer 27

1) Prophylactic control of asthma (by inhalation route only)

2) Prophylactic control of allergic rhinitis, allergic conjunctivitis, and vernal keratoconjunctivitis

Question 28

What are 2 mAbs used in asthma treatment?

Answer 28

1) Omalizumab (Anti-IgE)
2) Reslizumab (Anti-IL-5)

Question 29

What is the moa of Omalizumab used in asthma?

Answer 29

Anti-IgE
Used for severe asthmatics with allergies and an elevated IgE level

Subcutaneous injection every 2 to 4 weeks

Depletes levels of free IgE in serum

Decreases FcεRI/ expression on mast cells (basophils)

Question 30

What are 2 drawbacks of using omalizumab for asthma treatment?

Answer 30

1) Expensive
2) a/w small increase in risk of heart attack, transient ischaemic attacks (TIA) and blood clots.
3) Potential for anaphylaxis

Question 31

When is reslizumab indicated?

Answer 31

severe, persistent eosinophilic asthma in px ≥18 y/o

Question 32

What are 2 drawbacks of using reslizumab for asthma treatment?

Answer 32

1) Expensive
2) Oropharyngeal pain
3) Potential for anaphylaxis