Asthma Therapy Flashcards
How do B2 agonists work?
They activate B2 adrenergic receptors and cause bronchodilation
Which B2 agonists are short acting?
Salbutamol
Which B2 agonists are long acting?
Salmeterol and Formoterol
Name a non selective B agonist
Isoprenaline
Why is it important for B agonists to be selective?
To prevent stimulation of the heart
occurs with isoprenaline
How does salbutamol achieve selectivity?
It has an extended catechol group by one carbon
Why are salmeterol and formoterol longer acting?
They have an extended side chain
This increases the lipophilicity of the drugs and allows them to interact with the cell membrane, increasing their residence time
Why is salbutamol short acting?
It is not lipophilic so doesnt interact with the membrane
Acts as a soluble receptor at the B2 GPCR
Why is Formoterol intermediate acting?
Acts as both a soluble ligand and deposits into the lipid membrane around the receptor
Why does Salmeterol have a slower onset and the longest action?
It does NOT act as a soluble ligand
It must first diffuse into the membrane where it interacts with the receptor while adjacent to it
What is the mechanism of action of B agonists?
They bind to the B2 receptor which is Gs linked to AC AC increases the levels of cAMP Activates PKA PKA inactivates MLCK Muscle cannot contract
What type of drug is Theophylline?
Phosphodiesterase inhibitor
How do Phosphodiesterase inhibitors work?
Inhibit PDEIII which is an enzyme that breaks down cAMP
Therefore increased levels of cAMP -> Muscle cannot contract as well
They also inhibit PDEIV in leukocytes which increases intracellular cAMP and decreases leukocyte activation (especially eoinophils and macrophages)
What are the main problems with Phosphodiesterase inhibitors?
PDEIII is not just in the airways
It is also in the CNS so can cause adverse effects there
Why are Glucocorticoids useful in asthma?
They reduce inflammation
