Beta Agonists Flashcards
Give an example of a SABA.
Salbutamol
Give an example of a LABA.
Salmeterol
What are the bonds involved at the Adrenergic Binding Site?
Salt Bridge formation: Ammonium ion on adrenaline and residue on Aspartic acid.
Pi Stacking: Benzene on adrenaline and benzene on Phenylalanine
H Bonding: OH on benzene on adrenaline to TWO serine residues
What are the main binding groups on an adrenaline molecule?
- Ionised amine
- Chiral alcohol
- Benzene
- Hydrogen binding groups on a benzene (-OH)
What can be done to an adrenaline molecule to make it more selective to a beta receptor rather than alpha receptor?
Add an isopropyl substituent to the amine on the adrenaline.
Give an example of a molecule of adrenaline with an isopropyl substituent added to it.
Isoprenaline
How is can a molecule with an isopropyl substituent be more selective to a beta receptor than an alpha receptor?
Beta receptors have a hydrophobic pocket where the substituent can fit into. Alpha receptors don’t have this.
How can we increase potency in an adrenaline molecule?
Add a distant hydrogen bonding group.
When can adrenaline be used?
- Cardiac emergencies
- Anaphylactic reactions
Why is salbutamol useful as a treatment for asthma and why is adrenaline/noradrenaline not?
Adrenaline/noradrenaline are not selective enough.
-> side effects
No suitable duration of action
-> Metabolised by COMT -> methylation of OH on benzene -> inactive metabolite
True or False: For active B2-agonists the most suitable isomer of the molecule is the s isomer.
False. R isomer is the most suitable.
How do you know if a molecule is an s or r isomer?
- Find the chiral centre
- Label the group with the highest atomic number 1 and the lowest 4
- If it goes clockwise (right) = r isomer
If it goes anticlockwise = s isomer
-> make sure the lowest priority group is at the back
Which is better: salbutamol or levalbuterol?
Levalbuterol
Compare the structure of salbutamol and adrenaline.
Very similar in chemical structure -> still want it to be able to bind to the receptor.
Tertiary methyl on amine -> more beta selectivity over alpha
OH on Benzene moves out with extra CH2 in between -> Prevents reaction with COMT
What does COMT stand for?
Catechol O-methyl transferase
Give a drug which is a B2 agonist and explain how the molecule is structured to prevent methylation by COMT.
Terbutaline
-> phenol moves position to different carbon on benzene. Can till bind to serine residues.
What is the main alternative to salbutamol?
Salmeterol
-> effective when it comes to the ‘morning dip’
What are the 2 possible reasons why salmeterol has a longer duration of action?
- Long hydrophobic chain which can fit into the receptor binding pocket
- Anchor into the membrane of the lungs
What molecule structure does COMT target?
Catechol
Why is formoterol a useful LABA?
Preventer and a reliever
-> rapid onset of action and longer duration of action
