PHARM - Pharmacology of the Autonomic Nervous System: Cholinergics - Week 3 Flashcards
Describe how Ach is made (4).
-Choline is taken up by the diet via choline carriers.
-Mitochondria release Acetyl-CoA as a metabolic byproduct.
-Choline-acetyltransferase combine the two to release Ach and CoA.
-Ach is transported via an ACh carrier.
What is the action of botulinum toxin?
Prevents the release of ACh
Define blepharospasm, and what can be used to treat it.
Overreactive blinking. eyes need to be physically held up to see.
Botulinum toxin can be used to help open them.
How does botulinum toxin act?
Vesicles must fuse with the pre-synaptic membrane to release the ACh.
There are a family of SNARE proteins on this vesicles. The action potential is a que for them to change conformation and induce exocytosis.
Botox gets selectively uptaken into neurons and cleaves SNARE proteins.
Why is botox so potent?
Its a protease that can cleave many SNARE proteins. New SNAREs must be synthesised to counter its action.
What degrades excess ACh and where is it found?
Found embedded into the post-synaptic membrane called acetylcholinesterase.
What can happen if you block acetylcholinesterase?
Upregulation of ACh can cause many problems including bronchiospasms and can lead to death quickly.
Define myasthenia gravis.
Individuals develop an immune response against their own nicotinic receptors. Antibodies bind to them, and lead to a loss of their activation and can lead to paralysis.
How can an anti-acetylcholinesterase drug help in a myasthenia gravis case?
It helps prevent the break down of ACh, allowing the remaining functional nicotinic receptors to make the best use of the upregulated ACh.
Describe the tensilon test.
It is a test to see if someone has myasthenia gravis.
In humans, the individual’s arms are raised, and a gentle downward pressure is applied to them.
They are given tensilon, which is a kind of edrophonium - a short-acting anti-cholinesterase.
If they have myasthenia gravis, they can more easily resist the downward pressure.
What is an edrophonium?
Short-acting anti-cholinesterase.
Name 8 general parasympathetic agonistic effects on the body.
Salivation
Lacrimation
Urination
Defaecation
Sweating
Slowing heart rate
Bronchoconstriction
Miosis
Why is tachycardia symptom of an anti-parasympathetic drug? Describe in terms of a fit/unit person.
A fit person will have a slower basal heart rate, and thus the parasympathetic response is likely to be dominating here. When this action is blocked, the sympathetic response will take over, and result in tachycardia.
In unfit individuals, they have a higher basal heart rate, thus a more dominant sympathetic response, and when their parasympathetic response is blocked, it is unlikely to affect their heart rate.
Give two examples of muscarinic antagonists, and what two plants they can be isolated from.
Atropine and hyoscine.
Deadly nightshade has mainly atropine and some hyoscine.
Angel’s trumpet has mainly hyoscine and some atropine.
Give an example of a nicotinic antagonist, and where it can be found.
D-tubocurarine isolated from curare.
