asthma

Question 1

How is asthma characterised?

Answer 1

Reversible airflow obstruction, airway inflammation, and hyperresponsiveness.

Question 2

What causes airway obstruction in asthma?

Answer 2

Smooth muscle contraction, inflammation, oedema, mucus, structural changes.

Question 3

What are the acute symptoms of asthma?

Answer 3

Acute exacerbations (asthma attacks).

Question 4

Major symptoms of asthma?

Answer 4

Wheezing, chest tightness, dyspnoea, cough, hypoxaemia.

Question 5

Main cells in inflamed airways?

Answer 5

Eosinophils and neutrophils.

Question 6

What changes occur in chronic asthma?

Answer 6

Oedema, dilated blood vessels, mucus buildup, eosinophil & neutrophil accumulation.

Question 7

What are the two phases of asthma attacks?

Answer 7

Immediate and late phases.

Question 8

Describe the immediate phase of asthma.

Answer 8

Trigger ➝ mast cells/monocytes activated ➝ spasmogens (cysLTs, histamine, PGD2) ➝ bronchospasm + chemokines released.

Question 9

Describe the late phase of asthma.

Answer 9

Infiltration of eosinophils, Th2 cells, cytokines ➝ mediators (cysLTs, NO, EMBP, etc.) ➝ epithelial damage, inflammation, hyper-reactivity.

Question 10

Co-factors that damage the epithelium in late phase?

Answer 10

Eosinophil cationic protein (ECP) and eosinophil major basic protein (EMBP).

Question 11

Main therapeutic targets in asthma?

Answer 11

1) Smooth muscle relaxation, 2) Inflammatory cascade inhibition.

Question 12

Drugs for smooth muscle relaxation?

Answer 12

Beta agonists, PDE blockers, leukotriene receptor antagonists.

Question 13

Drugs for inflammation blockade?

Answer 13

Corticosteroids, leukotriene antagonists, PDE blockers, targeted biologics.

Question 14

MOA of β2 agonists?

Answer 14

Activate β2 GPCR ➝ ↑ cAMP ➝ PKA activation ➝ bronchodilation.

Question 15

Examples of β2 agonists?

Answer 15

Adrenaline (non-selective), isoprenaline (selective).

Question 16

Routes of β2 agonist admin?

Answer 16

Inhalation (solution or powder), oral, IV/SC/IM.

Question 17

Short-acting β2 agonists (SABAs)?

Answer 17

Salbutamol, terbutaline — acute relief, 3–5 hr duration.

Question 18

Long-acting β2 agonists (LABAs)?

Answer 18

Salmeterol, formoterol — ~12 hr duration, adjunct to ICS.

Question 19

Side effects of β2 agonists?

Answer 19

Tremor, tachycardia, dysrhythmias, paradoxical bronchospasm.

Question 20

What is SRS-A?

Answer 20

“Slow reacting substance of anaphylaxis” — now known to be leukotrienes.

Question 21

Where are leukotrienes produced from?

Answer 21

Mast cells (from arachidonic acid).

Question 22

Role of cysteinyl LTs (LTC4, LTD4) in asthma?

Answer 22

Bronchoconstriction, ↑ mucus, vascular leakage, eosinophil chemoattraction.

Question 23

LTB4 function?

Answer 23

Potent neutrophil chemoattractant.

Question 24

3 main leukotriene modulators?

Answer 24

Zafirlukast, montelukast (LTRA), zileuton (5-LOX inhibitor).

Question 25

Zafirlukast & montelukast MOA?

Answer 25

Block CysLT1 receptor (LTC4/LTD4) — no effect on LTB4.

Question 26

Zileuton MOA?

Answer 26

Inhibits 5-lipoxygenase ➝ ↓ LTA4 and downstream leukotrienes.

Question 27

Limitations of leukotriene modulators?

Answer 27

Weak bronchodilation, weak anti-inflammatory effects.

Question 28

Clinical use of leukotriene modulators?

Answer 28

Mild/mod asthma (basal symptom relief); not useful alone in severe asthma.

Question 29

Contraindications/usage guidelines for leukotriene modulators?

Answer 29

Montelukast: >6 months Zafirlukast: >5 years Zileuton: >12 years Not for acute attacks.

Question 30

Why some respond, some don’t?

Answer 30

Polymorphisms in 5-LOX, LTC4 synthase, CysLT1 receptors.

Question 31

Antimuscarinics used in asthma?

Answer 31

Ipratropium (SAMA), tiotropium (LAMA).

Question 32

MOA of muscarinic antagonists?

Answer 32

Block M3 receptor ➝ bronchodilation + ↓ mucus secretion.

Question 33

Short-acting (SAMA) vs long-acting (LAMA)?

Answer 33

SAMA: Ipratropium, ~6–8 hr LAMA: Tiotropium, glycopyrronium, umeclidinium, aclidinium.

Question 34

Side effects of SAMAs/LAMAs?

Answer 34

Dry mouth, GI upset, tachycardia, nausea.

Question 35

Anti-inflammatory mechanisms of corticosteroids?

Answer 35

↓ cytokines, chemokines ↓ eosinophils, IgE, LT, COX Inhibit NF-κB via HDAC2 and GR complex.

Question 36

Inhaled corticosteroids (ICS)?

Answer 36

Beclomethasone, budesonide.

Question 37

ICS advantages?

Answer 37

Local effect, fewer systemic effects, long-term control.

Question 38

ICS disadvantages?

Answer 38

Adrenal suppression, ↓ bone density, oral candidiasis.

Question 39

Oral corticosteroids?

Answer 39

Prednisolone, hydrocortisone — short-term/severe attacks only.

Question 40

Side effects of long-term oral steroids?

Answer 40

Cushingoid features, osteoporosis, hyperglycaemia, growth suppression.

Question 41

What do eosinophils release in asthma?

Answer 41

Th2 cytokines, ROS, LTC4/LTD4, PGD2, TGF-β, MBP.

Question 42

IL-5 blockers?

Answer 42

Mepolizumab (IgG1) Reslizumab (IgG4) Benralizumab (anti-IL5Rα).

Question 43

Indications for IL-5 blockers?

Answer 43

Severe eosinophilic asthma ↓ eosinophils Fewer exacerbations Steroid-sparing Slight lung function improvement.