Anticholinergics Flashcards
(22 cards)
How is Ach made at the synapse?
- Fusion of acetic acid and choline at the presynaptic nerve.
- Placed into vesicles
- Vesicles moved to synaptic cleft and is released.
- Ach binds to receptor on postsynaptic nerve, producing a signal.
How is Ach broken down at the synapse?
- Binds to acetylcholinesterase on postsynaptic nerve and is broken down.
- Broken fragments go back to presynaptic nerve and are recycled.
What can be done generally at the synapse to prevent the breakdown of Ach?
Block acetylcholinesterase.
Which enzyme is involved in the synthesis of acetycholine?
Choline acetyltransferase
Why can we not use acetylcholine as a cholinergic receptor agonist?
- Hydrolysis in stomach and blood -> won’t go to were needed
- Can bind to many different adrenergic/cholinergic receptors -> side effects
What are the 2 types of receptors acetylcholine can bind to?
- Nicotinic
- Muscarinic
Why can acetylcholine bind to either the nicotinic or muscarinic receptors?
It has no rings so it is flexible.
-> Can sometimes form a nicotine or muscarine shape.
What are the bonds involved at the muscarinic receptor binding site?
- Hydrogen bonding
- Ionic bonding
- Hydrophobic pockets
True or False: Ach can adopt different conformations and can bind to different receptors.
True
How is acetycholine broken down in the body?
By ester hydrolysis.
What enzyme prevents the breakdown of acetylcholine?
Anticholinesterases
What bonds are involved in the acetylcholinesterases to help maintain its structure?
Disulphide bonds
Give a natural product with anticholinesterase activity.
Physostigmine
What is atropine?
Cholinergic receptor antagonist
-> More bulkier structure due to extra binding groups. Can interact with receptor to bind but to block it.
-> no conformational change
True or False: Having a Quat salt on a molecule can help it to cross the blood brain barrier.
False. It cannot pass the BBB
Give an example of a SAMA and what is it used as?
Ipratropium
->Bronchodilator
Out of many drug structures, how do you know which molecule is a LAMA/SAMA?
It has a Quat salt.
Give an example of a LAMA.
Tiotropium
How do you know the difference between an ipratropium and tiotropium molecule?
Ipratropium: Isopropyl unit on the end
Tiotroipium: Sulphur in pentagon structure (thiophene)
Why does a LAMA last longer than a SAMA?
Thiophene has electronegativity which allows it to bind and stabilise with a tyrosine residues in the receptor.
Give some examples of ultra LAMAs.
Aclidinium Bromide
Umlecidinium Bromide
Glycopyrronium Bromide
What are the main structure required on a LAMA?
- Quat Salt
- Esters to mimic ester of acetylcholine
- Bulky parts of structure for antagonism
