L14. Respiratory pharmacology

Question 1

What are the underlying causes of asthma symptoms- the two phases of asthma

Answer 1

Phase 1: bronchospasm
- Hypertrophy and constriction of smooth muscle= airway obstruction
Phase 2:
- Hyper-reactivity to stimulus causing chemokines –>excess inflammation, mucus build up

Question 2

What are the approaches to treating asthma

Answer 2

Bronchodilator: early phase of asthma attack
Glucocorticoids for late phase inflammation (in conjunct w LABA)
1. ShortActingBetaAgonist
2. Corticosteroid
3. LABA
4. Methylxanthine, Muscarinic antagonist, Leukotrine antagonist

Question 3

What is the difference between short acting and long acting beta agonists

Answer 3

SABA: fast onset and short duration - more water soluble, moves quickly to site of action but is washed away quickly too

LABA: slow onset and long duration: more lipid soluble, takes longer to diffuse to the receptors, but gets stuck in the membrane so stored for a while.

Question 4

What are the adverse effects of B2 agonist

Answer 4

• Gets systemic absorption:
• tremor- stim B2 on skeletal muscle
• tachycardia- stim B1 receptors due to lack of selectivity.

Question 5

What are methylxanthines mechanism, and give an example of one.

Answer 5

It is a Bronchodilator: eg. theophylline

• prevents breakdown of cAMP by inhibiting Phosphodiesterase. This allows accumulation of cAMP -> inhibition of smooth muscle contraction
• Antagonise Adenosine which causes contraction of smooth muscle, stops some inflammation (by helping some histone deacetylase)

Question 6

What are muscarinic antagonist mechanism, and give an example

Answer 6

Eg. ipratropium. Blocking receptor for ACh to bind

• inhibit bronchoconstriction
• inhibit mucus secretion
• no effect on inflammatory phase 2 but much less systemic cross over because it is poorly absorbed

Question 7

What are glucocorticoids mechanism, give an example

Answer 7

eg. Beclometasone

Increase transcription of anti-inflammatory genes, and repress inflam genes for cytokines/chemokines by inhibiting acetylation and turning on histone deacetylase. This takes acetyl groups off histones which turns the gene transcription off.
Therefore dampening inflammation- late phase of asthma.

-Adverse effects: oropharyngeal candidiasis (thrush) and sore throat because repressing the immune system in the throat

Question 8

What is used to treat COPD - can’t be cured

Answer 8

• Stop smoking
• Bronchodilators for relief dyspnoea,
• Glucocorticoids don’t slow disease progression but help reduce inflam. They have reduced effeciency for smokers because smoking downregulates the histone deacetylase enzymes which help repress inflam gene transcription
• Oxygen therapy as well

Question 9

What is cough

Answer 9

Cough is protective response to foreign particles or mucus secretions. Controlled by the cough centre in the medulla.

Question 10

How is cough treated (useless)

Answer 10

Antitrussive agents

• Demulcents: lozenges coat the airways, make it easier for mucus to move
• Opioids: eg. codeine - low doses suppress cough
• Mucolytics: eg. carbocisteine - thin the mucus, easy to remove

Question 11

What is the mechanism of Beta2 agonist and give example

Answer 11

It is a physiological antagonist- stimulates another pathway which counteracts bronchoconstriction.
It binds to B-adrenergic receptor, activates cAMP-dependent pathway which inhibits smooth muscle contraction. It also opens a potassium channel which allows K+ to leave the cell - hyperpolarising it, which reduces likelihood of voltage gated calcium channels opening, inhibiting contraction.

eg. Salbutamol (SABA) or Salmeterol (LABA)