The ANS 2 Flashcards
What are the basic steps in neurotransmission?
1) Uptake of precursors
2) Synthesis of transmitter
3) vesicle storage of transmitter
4) depolarisation by propagated action potential
5) depolarisation-dependant influx of Ca2+
6) exocytotic release of neurotransmitter
7) diffusion to post-synaptic membrane
8) interaction with post-synaptic receptor
9) inactivation of transmitter
10) degradation or re-uptake of transmitter
11) interaction with pre-synaptic receptors
What is the process of Acetylcholine synthesis in Cholinergic transmission?
Acetyl CoA + Choline = Acetylcholine and Coenzyme A
Uses enzyme choline acetyltransferase (CAT)
What is the process of ACh degradation after cholinergic transmission?
Acetylcholine = acetate + choline
Uses acetylcholinesterase enzyme (AChE)
It’s an extracellular enzyme that coats the synapse membrane
Give an example of a drug that works on nAChR’s at autonomic ganglia?
Trimethaphan is a ganglion-blocking drug uses in hypertensive emergencies to produce controlled hypotension in surgery.
Why don’t drugs work at the nAChR’s on both the autonomic ganglia and the neuromuscular junction?
As the nAChR’s differ in structure so the drugs can only be specific to one
How many subtypes of mAchR’s are there?
5
These are M1 to M5 this is why drug selectivity is important as the different receptors have different actions.
Give an example of a new drug that DOES display limited tissue selectivity (on mAcHR’s)
Tolterodine is an mACHR agonist and is used to treat “overactive bladder”
How can the actions of endogenously released Ach be enhanced?
By using AChE (acetylcholinesterase enzyme) inhibitors. For example, Pyridostigmine is use to treat myasthenia gravis and Donepezil is used to treat Alzheimer’s.
Why are cholinergic drugs only used very selectively/
As their lack of selectivity often causes unwanted side effects.
Eg a non-selective muscurinc ACh receptor agonist is likely to cause autonomic side effects like, low heart rate+output, increased bronchi-constriction +peristalsis, salivation + sweating
What is SLUDGE a mnemonic for?
Mnemonic for the pathological effects of a massive discharge from the parasympathetic nervous system
What are the symptoms of SLUDGE syndrome?
Salivation Lacrimation (tears, eye water) Urination Defecation Gastrointestinal upset Emisis (vomiting)
When is SLUDGE syndrome eneocuntered?
Drug overdose
Ingestion of magic mush rooms
Exposure to organophophorus insecticides (parathion)
Nerve gases (sarin or Novichok)
How is SLUDGE syndrome caused?
One way may be by a substance covalently modifiying ACHE stoping the breakdown of Ach so receptors in parasympathetic system are constantly innervated.
Symptoms primary due to chronic stimulation f mAchR in organs/muscles innervated by parasympathetic nervous system.
How is sludge treated?
Atropine (blocks mAchR’s)
Pralidoxime (gets rid of bound agents, releasing AchE)
Other anti-cholinergic agents (break down the Ach)
Give some examples and clinical uses of mAChR agonists (activators).
Pilocarpine and Bethanechol are used to treat glaucoma and to stimulate bladder emptying