Airway pharmacology Flashcards
What are bronchodilators?
Drugs used to treat airway smooth muscle contraction by relaxing airway smooth muscle cells.
Give example of types of bronchodilators.
Beta 2 Agonists
- SABA (short acting): salbutamol
- LABA (long acting): salmetarol
- Ultra-LABA (ultra long acting): indacaterol
Long acting muscarinic receptor antagonists
-tiotropium
Phosphodiesterase Inhibitors
-theophylline
Describe the beta 2 agonist mechanism.
Binds beta 2 adrenoceptor (aGs)
Stimulates aGs pathway, producing cAMP
cAMP activates PKA
PKA decreases Ca2+ mobilisation and sensitivity, causing airway smooth muscle relaxation.
What is the use of SABA?
First-line therapy in asthma and are administered when required as reliever therapy (e.g. when the patient experiences an asthma attack) by metered-dose inhaler.
What is the use of LABA?
Bind to M3 G-protein coupled receptors and inhibit aGq pathway, preventing Ca2+ release from sarcoplasmic reticulum and therefore preventing muscle contraction, causing for airway smooth muscle relaxation.
Describe the LAMA muscarinic antagonist mechanism.
Bind to M3 G-protein coupled receptors and inhibit aGq pathway, preventing Ca2+ release from sarcoplasmic reticulum and therefore preventing muscle contraction, causing for airway smooth muscle relaxation.
Why are LAMA drugs less effective bronchodilators in asthma therapy?
They rely on contraction being caused by acetylcholine, however there are other factors which drive smooth muscle contraction such as prostaglandins and leukotrienes and the LAMA doesn’t affect those.
For this reason, they are less effective as bronchodilators in asthma therapy, where acetylcholine has a more minor role in airway smooth muscle contraction.
What is the role of corticosteroids?
Treat allergic airway inflammation in asthma by affecting the function of various immune and structural cells to reduce inflammation.
Give examples of inhaled corticosteroids.
- fluticasone
- budesonide
- beclometasone
Give examples of oral of systematic steroids. (which have a higher efficacy than inhaled)
- prednisone
- dexamethasone
Explain the mechanism of corticosteroids.
Bind to glucocorticoid receptors within cytosol of immune and structural cells.
Drug-receptor complex migrates to nucleus where it binds DNA, modulating transcription, translation and protein expression
can either increase expression of proteins or decrease the level of protein through affecting transcription of genes
(increase anti-inflammatory proteins or decrease pro-inflammatory proteins)
Why are drugs used in asthma administered by metered inhaler dose?
To try and reduce adverse effects in respiratory diseases, as metered inhaler dose applies the drug directly to the target tissue (airways/lungs) and so the greatest dose is present at that site.
Why does the metered inhaler dose not fully stay within the respiratory system?
Due to poor inhaler technique, a large quantity of the drug is generally swallowed rather than inhaled, and the drug is absorbed from the lungs and GI tract, both of which are richly innervated by blood vessels, ensuring the drug reaches the systemic circulation, causing for systemic side effects.
What are the adverse effects with beta 2 agonists?
1) Activates Beta 1 receptors in the heart, causing tachycardia and palpitations
2) Activates Beta 2 receptors in skeletal muscle, posing risk of tremors and also muscle growth (hypertrophy).
What are long acting Beta 2 agonists used in combination with?
Long acting Beta 2 agonists are used in combination with corticosteroids to reduce risk of sudden death
