Autonomic Nervous System 2

Question 1

Briefly outline the basic steps of neurotransmission.

Answer 1

Uptake of precursors
Synthesis of transmitter
Vesicular storage of transmitter
Degradation of transmitter
Depolarisation by propagated action potential
Depolarisation-dependent influx of Ca2+
Exocytotic release of transmitter
Diffusion to post-synaptic membrane
Interaction with post-synaptic receptors
Inactivation of transmitter
Re-uptake of transmitter
Interaction with pre-synaptic receptors

Question 2

Where in the steps of neurotransmission is the most common site for drugs to intervene?

Answer 2

On degradation of transmitter
Interaction with postsynaptic receptors
Inactivation of transmitters
Re-uptake of transmitters
Interaction with pre-synaptic receptors

Question 3

What types of receptors are found in sympathetic preganglionic receptors?

Answer 3

Cholinergic

Question 4

What types of receptors are found in sympathetic postganglionic receptors?

Answer 4

Cholinergic but mostly adrenergic receptors

Question 5

What types of receptors are found in parasympathetic preganglionic receptors?

Answer 5

Cholinergic

Question 6

What types of receptors are found in parasympathetic postganglionic receptors?

Answer 6

Cholinergic

Question 7

How is acetylcholine synthesised?

Answer 7

Acetyl CoA + Choline -> acetylcholine + coenzyme A

With the help of the enzyme choline acetyltransferase

Question 8

How is acetylcholine degraded?

Answer 8

Acetylcholine -> acetate + choline

With the help of the enzyme acetylcholinesterase

Question 9

What are the consequences of cholinergic drugs?

Answer 9

They usually lack selectivity. This means that if you try to treat something there may be unwanted side-effects.

Question 10

What is a non-selective muscarinic ACh receptor agonist likely to cause? Give examples.

Answer 10

Autonomic side-effects such as:
Heart:
Heart rate and cardiac output going down
Smooth muscle:
Bronchoconstriction and GI-tract peristalsis increases
Exocrine glands:
Sweating and salivation going up

Question 11

What is SLUDGE syndrome?

Answer 11

A mnemonic for the pathological effects indicative of massive discharge of the parasympathetic nervous system which is a consequence of organophosphate poisoning where acetylcholinesterase is inhibited.
Salivation
Lacrimation
Urination
Defecation
Gastrointestinal upset
Emesis

Question 12

How can SLUDGE syndrome come about?

Answer 12

Drug overdose
Ingestion of magic mushrooms
Expose to organophosphorus insecticides

Question 13

Why do you get the symptoms of SLUDGE?

Answer 13

Du to chronic overstimulation of muscarinic acetylcholine receptors in organs and muscles innervated by the parasympathetic nervous system.

Question 14

How can SLUDGE be treated?

Answer 14

Anti-cholinergic agents such as atropine and pralidoxime

Question 15

mACh receptor agonists and antagonists can be used clinically. Give examples of how the agonists can be used.

Answer 15

Agonists such as pilocarpine and bethanechol are respectively used to treat glaucoma and acutely to stimulate bladder emptying

Question 16

Gives examples of how the antagonists can be used.

Answer 16

To treat some forms of asthma and chronic obstructive pulmonary disease (COPD)
Also to treat an overactive bladder

Question 17

How do noradrenergic varicosities work in release of neurotransmitter?

Answer 17

Tyrosine goes into the varicosity and becomes DOPA and then dopamine. It is then stored in a vesicle and turns into noradrenaline. Noradrenaline is the released and acts on a post-junctional adrenoceptor.

Question 18

Where is noradrenaline converted into adrenaline?

Answer 18

Within the adrenal medulla in the chromaffin cells.

Question 19

What are the two fates of noradrenaline in noradrenergic transmission?

Answer 19

Termination or metabolism

Question 20

Outline how termination works.

Answer 20

NA actions are terminated by re-uptake into the pre-synaptic terminal by a Na+-dependent high affinity transporter.
NA that is not recaptured by the Na+ transporter is taken up by a lower affinity non-neuronal mechanism.

Question 21

Outline how metabolism works.

Answer 21

Within the pre-synpatic terminal NA that is not taken up into vesicles again and reused is susceptible to metabolism by monoamine oxidase and catechol-O-methyltransferase.

Question 22

Where can you pharmacologically manipulate noradrenergic transmission?

Answer 22

Inhibiting metabolism (MAO inhibitors). Inhibit NA synthesis by inhibiting Tyrosine converting into DOPA.
alpha2-receptor antagonists and agonists to either increase or decrease re-uptake of NA. Inhibition of post-synaptic receptors to bind to NA.

Question 23

Why are beta2-adrenoceptor-selective agonists’ selectivity important?

Answer 23

It is used in asthma for example to cause bronchodilation.
However if they weren’t selective they could act on beta1-adrenoceptors found in the heart as well causing tachycardia and positive inotropy.
However there are also b2-adrenoceptors in the heart so it is not entirely possible to limit side-effects.

Question 24

Why would you use alpha1-adrenoceptor-selective antagonists and beta1-adrenoceptor-selective antagonists?

Answer 24

Used to treat a number of cardiovascular disorders such as hypertension.

Question 25

Where can alpha1-adrenoceptors be found?

Answer 25

In smooth muscle. Agonists cause constriction and antagonists cause dilation. Smooth muscle found in blood vessels have these receptors.