The Autonomic Nervous System and Drugs

Question 1

Where in the spine do parasympathetic fibres originate from?

Answer 1

Cranio-sacral

Question 2

Are the pre-ganglionic fibres of the parasympathetic system long or short?

Answer 2

Long myelinated

Question 3

Are the post ganglionic fibres of the parasympathetic system long or short

Answer 3

Short, unmyelinated

Question 4

Where are the ganglia of parasympathetic fibres located?

Answer 4

In the tissues

Question 5

What is the main neurotransmitter of the parasympathetic nervous system

Answer 5

ACh

Question 6

How many ACh molecules need to bind to a nicotinic AChR in order for it to open

Answer 6

2

Question 7

From what region of the spine to fibres of the sympathetic system originate from

Answer 7

Thoracolumbar

Question 8

Are the preganglionic fibres of the sympathetic nervous system long or short

Answer 8

Short

Question 9

Where are the sympathetic ganglia located

Answer 9

Paravertebral chain

Question 10

Are the postganglionic fibres of the sympathetic system long or short

Answer 10

Long unmyelinated

Question 11

What is the main neurotransmitter of the sympathetic nervous system

Answer 11

Noradrenaline

Question 12

How is noradrenaline synthesised? What is the rate limiting step

Answer 12

Tyrosine–> L-DOPA –> Dopamine –> Noradrenaline (–> adrenaline)

Rate limiting step is the reaction of tyrosine –> L-DOPA by tyrosine hydroxylase
The final step occurs in the vesicles

Question 13

Why is tyrosine considered an essential amino acid

Answer 13

As it is not one that we can make ourselves it has to come from the diet

Question 14

What else is tyrosine important in the synthesis of

Answer 14

Thyroxine

Question 15

What type of neurones can all pre-ganglionic neutrons be considered to be

Answer 15

Cholinergic

Question 16

What is the difference between muscarinic and nicotinic ACh receptors

Answer 16

Nicotinic = ligand gated
Muscarinic = GPCR

Question 17

Where will you find post-ganglionic neutrons that are not adrenergic

Answer 17

Sweat glands and hair follicles

Question 18

What is the name of the substances that can be co-released with NA or ACh and give an example of one

Answer 18

Non-adrenergic, non-cholinergic (NANC) transmitters

e.g. 5-HT (serotonin)

Question 19

Describe the sympathetic postganglionic neutrons at the adrenal glands

Answer 19

The neurones form chromatin cells which when stimulated by the release of ACh from the presynaptic neurone release adrenaline into the blood stream

Question 20

Describe the synthesis of ACh and where is occurs

Answer 20

Synthesised from choline and acetyl Co-A by the enzyme choline acetyltransferase (CAT)
In the cytoplasm of cholinergic terminals

Question 21

How is ACh broken down?

Answer 21

By acetylcholinesterase

to acetate and choline (which is largely recycled by reuptake through a choline transporter)

Question 22

Explain how acetylcholinesterase can be used as a drug target and give an example of one such drug

Answer 22

Inhibitors for acetylcholinesterase can be used to prevent the breakdown of ACh and therefore prolong the action at the postsynaptic membrane
This is useful in myasthenia gravis
e.g. pyridostigmine

Question 23

Name nicotinic cholireceptor antagonist that has action at the ganglion and give its action

Answer 23

Trimethapan ganglion-blocker which is used in hypertensive crisis during surgery

Question 24

Name a nicotinic AChR antagonist which has action at the neuromuscular junction

Answer 24

Tubocurarine –> muscle paralysis

Question 25

What is the action of pilocarpine and what receptors does it act on

Answer 25

Muscarinic AChR agonist used to treat glaucoma

Question 26

Name a muscarinic AChR antagonist and give its use

Answer 26

Ipratropium bromide and tiotropium used to treat asthma and COPD (prevent bronchoconstriction)

Question 27

What type of drug is donepezil and when is it used

Answer 27

Acetylcholinesterase inhibitor used in Alzheimer's disease

Question 28

What is the enzyme that is packaged in the vesicle that converts dopamine to noradrenalin

Answer 28

Dopamine beta hydroxylase

Question 29

What is a noradrenergic varicosity

Answer 29

A specialised site for Ca2+ dependent NA release on a highly branched axonal network

Question 30

Explain what Uptake 1 and Uptake 2 are

Answer 30

Two pathways of termination of the action of NA (proteins) Uptake 1 captures 90-95% of NA reuptake into the vesicle by Na+-dependent high affinity transporter Uptake 2 takes up that NA not captured by Uptake 1, lower affinity, non-neuronal

Question 31

What can happen to NA in the pre-synaptic terminal that is not taken up into vesicles

Answer 31

Can be metabolism by 2 enzymes: Monoamine oxidase (MAO) Catechol-O-methyltransferase (COMT)

Question 32

What is the action of alpha-methyl tyrosine

Answer 32

Competitive inhibition of tyrosine hydroxylase (prevents NA formation in pheochromocytoma)

Question 33

What is the action of alpha-methyl-DOPA

Answer 33

'False transmitter' accumulates in vesicles with NA and preferentially binds to pre-synaptic alpha 2 adrenoreceptor so exploited for treatment of hypertension

Question 34

What is the action of CarbiDOPA

Answer 34

Inhibits the action of DOPA decarboxylase in the periphery | Used in Parkinsons

Question 35

What are indirectly acting sympathomimetic agents and what is there use

Answer 35

They are structurally related to NA therefore recognised and taken up into the adrenergic terminal by Uptake 1 and into the vesicle --> leak of NA from the vesicle e.g. amphetamine

Question 36

What class of drugs are uptake 1 inhibitor

Answer 36

Tricyclic anti-depressants

Question 37

What is dobutamine and what are its actions

Answer 37

Selective beta 1 agoinst | Positive chronotropic and ionotropic effects in the heart

Question 38

What salbutamol an example of and what are its actions

Answer 38

Beta 2 agoinst | Bronchodilation

Question 39

What is ephedrine an example of and what are its actions

Answer 39

Selective alpha 1 agonist | Used as nasal decongestant

Question 40

Name a selective alpha 2 receptor agonist and give its action

Answer 40

Clonidine | Used as an anti-hypertensive

Question 41

Name an alpha antagonist and give its use

Answer 41

Phentolamine | Used for peripheral vasodilation to treat peripheral vascular disease

Question 42

Name a selective alpha 1 antagonist and give its use

Answer 42

Prazosin | Used to treat hypertension

Question 43

Name a beta blocker and give its use

Answer 43

Propranolol Used to treat hypertension, MI, angina Contraindicated in asthmatics as can cause bronchoconstriciton