Airway pharmacology Flashcards
What can drugs treat/reduce severity of symptoms of?
- Reverse airway smooth muscle contraction
- Reduce mucus secretion
- Reduce allergic inflammation of the airways
- Reduce sensitivity to irritating stimuli
What aspects of acute airway pathology can be treated with drugs?
- Contraction of smooth muscles
- Excess mucus secretion
- Oedema
- Irritation of sensory neurones
Drugs used to treat airway smooth muscle contraction
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)
How do bronchodilators act?
Act by relaxing smooth muscle cells
What happens in relaxation of bronchioles?
- Increase in luminal area
- Decrease in resistance
- Increase in airflow
What happens in contraction of bronchioles?
- Decrease in luminal area
- Increase in resistance
- Decrease in airflow
What does inflammatory mediators induce?
Induce ASMC contraction
Pathway of ASMC contraction
- Contractile mediators bind to GPCR like M3
- Gq subunit binds to sarcoplasmic reticulum, increasing Ca2+ mobilisation and sensitivity
- This results in muscle contraction
What does beta 2 adrenergic receptor activation induce?
Induces ASMC relaxation via AC and PKA
Pathway of ASMC relaxation
- 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
How do muscaranic receptor antagonists relax ASMC’s?
-Relax ASMCs by inhibiting the contractile effects of ACh at the M3 receptor
What are corticosteroids used as?
Used as preventer medication to reduce airway inflammation
Examples of inhaled corticosteroids
- Fluticasone
- Buedesonide
- Beclometasone
Examples of oral/systemic steroids
- Prednisone
- Dexamethasone
What do corticosteroids affect and to reduce what?
Corticosteroids affect the function of various immune and structural cells to reduce inflammation
Steps involved in the increase or decrease of gene expression via corticosteroids
- 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
How do beta 2 agonists induce side effects?
Induce side effects by activating receptors in extra-respiratory tissues
What does salbutamol activate in SA node and myocardium?
Activate beta-1 receptors at higher concentrations
-Results in Tachycardia, palpatations
What does salbutamol activate in smooth muscles of the airways?
Activate beta 2 receptors
-Result in bronchodilation
What does salbutamol activate in skeletal muscles?
Activates beta-2 receptors
-Results in tremors, muscle growth
What are the long term side effects of corticosteroids?
- Growth retardation
- Skin ulcers
- Depression
- Osteoporosis
- Hypercortisolism
How is asthma pharmacotherapy administered?
Administered in a stepwise manner
What are the steps involved in asthma pharmacotherapy?
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
How is COPD therapy administered?
Administered in a progressive manner
