Airway pharmacology

Question 1

What can drugs treat/reduce severity of symptoms of?

Answer 1

• Reverse airway smooth muscle contraction
• Reduce mucus secretion
• Reduce allergic inflammation of the airways
• Reduce sensitivity to irritating stimuli

Question 2

What aspects of acute airway pathology can be treated with drugs?

Answer 2

• Contraction of smooth muscles
• Excess mucus secretion
• Oedema
• Irritation of sensory neurones

Question 3

Drugs used to treat airway smooth muscle contraction

Answer 3

Bronchodilators:

• (Beta-2 adrenergic receptor agonists)
  
  • SABA(e.g. salbutamol)
  • LABA(e.g. Salmeterol)
  • Ultra-LABA(e.g. indacaterol)
• Long acting muscaranic receptor antagonists(e.g. tiotropium)
• Phosphodiesterase inhibitors(e.g. theophylline)

Question 4

How do bronchodilators act?

Answer 4

Act by relaxing smooth muscle cells

Question 5

What happens in relaxation of bronchioles?

Answer 5

• Increase in luminal area
• Decrease in resistance
• Increase in airflow

Question 6

What happens in contraction of bronchioles?

Answer 6

• Decrease in luminal area
• Increase in resistance
• Decrease in airflow

Question 7

What does inflammatory mediators induce?

Answer 7

Induce ASMC contraction

Question 8

Pathway of ASMC contraction

Answer 8

• Contractile mediators bind to GPCR like M3
• Gq subunit binds to sarcoplasmic reticulum, increasing Ca2+ mobilisation and sensitivity
• This results in muscle contraction

Question 9

What does beta 2 adrenergic receptor activation induce?

Answer 9

Induces ASMC relaxation via AC and PKA

Question 10

Pathway of ASMC relaxation

Answer 10

• Beta 2 agonist like salbutamol binds to beta 2 adrenoreceptor
• Gs subunit interacts with adenylyl cyclase which converts ATP into cAMP
• cAMP interacts with PKA resulting in a decrease in Ca2+ mobilisation and sensitivity
• This results in muscle relaxation

Question 11

How do muscaranic receptor antagonists relax ASMC’s?

Answer 11

-Relax ASMCs by inhibiting the contractile effects of ACh at the M3 receptor

Question 12

What are corticosteroids used as?

Answer 12

Used as preventer medication to reduce airway inflammation

Question 13

Examples of inhaled corticosteroids

Answer 13

• Fluticasone
• Buedesonide
• Beclometasone

Question 14

Examples of oral/systemic steroids

Answer 14

• Prednisone

- Dexamethasone

Question 15

What do corticosteroids affect and to reduce what?

Answer 15

Corticosteroids affect the function of various immune and structural cells to reduce inflammation

Question 16

Steps involved in the increase or decrease of gene expression via corticosteroids

Answer 16

• CS diffuses through membrane and binds intracellular GR
• Drug receptor complex translocates to the nucleus
• Drug receptor complex binds DNA and affects transcription
• There’s altered transcription of the gene
• Corticosteroids increase or decrease transcription depending on the specific gene/protein
• Translation of gene into protein

Question 17

How do beta 2 agonists induce side effects?

Answer 17

Induce side effects by activating receptors in extra-respiratory tissues

Question 18

What does salbutamol activate in SA node and myocardium?

Answer 18

Activate beta-1 receptors at higher concentrations

-Results in Tachycardia, palpatations

Question 19

What does salbutamol activate in smooth muscles of the airways?

Answer 19

Activate beta 2 receptors

-Result in bronchodilation

Question 20

What does salbutamol activate in skeletal muscles?

Answer 20

Activates beta-2 receptors

-Results in tremors, muscle growth

Question 21

What are the long term side effects of corticosteroids?

Answer 21

• Growth retardation
• Skin ulcers
• Depression
• Osteoporosis
• Hypercortisolism

Question 22

How is asthma pharmacotherapy administered?

Answer 22

Administered in a stepwise manner

Question 23

What are the steps involved in asthma pharmacotherapy?

Answer 23

Step 1:SABA as required
Step 2:Add ICS
Step 3:Add LABA, Increase ICS dose, Add LTRA, PDEi
Step 4:Max ICS dose, Add fourth drug
Step 5:Add oral CS, Refer to specialist care, Anti-IgE

Question 24

How is COPD therapy administered?

Answer 24

Administered in a progressive manner