The ANS 2

Question 1

What are the basic steps in neurotransmission?

Answer 1

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

Question 2

What is the process of Acetylcholine synthesis in Cholinergic transmission?

Answer 2

Acetyl CoA + Choline = Acetylcholine and Coenzyme A

Uses enzyme choline acetyltransferase (CAT)

Question 3

What is the process of ACh degradation after cholinergic transmission?

Answer 3

Acetylcholine = acetate + choline

Uses acetylcholinesterase enzyme (AChE)

It’s an extracellular enzyme that coats the synapse membrane

Question 4

Give an example of a drug that works on nAChR’s at autonomic ganglia?

Answer 4

Trimethaphan is a ganglion-blocking drug uses in hypertensive emergencies to produce controlled hypotension in surgery.

Question 5

Why don’t drugs work at the nAChR’s on both the autonomic ganglia and the neuromuscular junction?

Answer 5

As the nAChR’s differ in structure so the drugs can only be specific to one

Question 6

How many subtypes of mAchR’s are there?

Answer 6

5

These are M1 to M5 this is why drug selectivity is important as the different receptors have different actions.

Question 7

Give an example of a new drug that DOES display limited tissue selectivity (on mAcHR’s)

Answer 7

Tolterodine is an mACHR agonist and is used to treat “overactive bladder”

Question 8

How can the actions of endogenously released Ach be enhanced?

Answer 8

By using AChE (acetylcholinesterase enzyme) inhibitors. For example, Pyridostigmine is use to treat myasthenia gravis and Donepezil is used to treat Alzheimer’s.

Question 9

Why are cholinergic drugs only used very selectively/

Answer 9

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

Question 10

What is SLUDGE a mnemonic for?

Answer 10

Mnemonic for the pathological effects of a massive discharge from the parasympathetic nervous system

Question 11

What are the symptoms of SLUDGE syndrome?

Answer 11

Salivation 
Lacrimation (tears, eye water)
Urination 
Defecation 
Gastrointestinal upset 
Emisis (vomiting)

Question 12

When is SLUDGE syndrome eneocuntered?

Answer 12

Drug overdose
Ingestion of magic mush rooms
Exposure to organophophorus insecticides (parathion)
Nerve gases (sarin or Novichok)

Question 13

How is SLUDGE syndrome caused?

Answer 13

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.

Question 14

How is sludge treated?

Answer 14

Atropine (blocks mAchR’s)
Pralidoxime (gets rid of bound agents, releasing AchE)
Other anti-cholinergic agents (break down the Ach)

Question 15

Give some examples and clinical uses of mAChR agonists (activators).

Answer 15

Pilocarpine and Bethanechol are used to treat glaucoma and to stimulate bladder emptying

Question 16

Give some examples and clinical uses of mAchR antagonists (de-activators/blockers)

Answer 16

Ipratropium and Tiotropium used to treat asthma and COPD.

Tolterodine, Darifenacin and Oxybutynin used for overactive bladder

Question 17

What neurotransmitter do the majority of post-ganglionic sympathetic neurones release?

Answer 17

Noradrenaline

Question 18

What are vascorities?

Answer 18

Highly branched atonal networks on post-ganglionic sympathetic neurones. They’re a specialised site for Ca2+ dependant noradrenaline release

Question 19

What happens in noradrenaline transmission following Ca2+ release?

Answer 19

NA diffuses across synaptic cleft and interacts with adrenorecepotrs on ports-synaptic membrane to initiate signaling.

Na intersects with post-synaptic adrenoceptors to regulate processes in the nerve terminal

Question 20

How is NA removed form the synaptic cleft?

Answer 20

By noradrenaline transporter proteins.
Two transporter mechanisms “uptake 1” and ‘uptake 2”.
“Uptake 1” is aa Na+ dependant, high affinity transporter
“Uptake 2” is a lower affinity, non-neural mechanism

Another route is that any Na not taken up by vesicles in the re-synaptic terminal is susceptible to metabolism by the 2 enzymes = MAO and COMTa

Question 21

Give an example of. B2-drenoceptor gonist used clinically nd explain why its selectivity is important?

Answer 21

Salbutamol is used in sthm to reverse/oppose bronchoconstriction.

Selectivity is important s it limits possible cardiovascular side effects (positive iontropic nd chronotropic actions)