Session 8 - The ANS

Question 1

What does the ANS do and how is it divided and where do these predominate?

Answer 1

Controls all vegetative (involuntary) functions
Parasympathetic:
- Regulates basal activities
- “rest and digest”
- Predominate from the Medullary and Sacral regions
Sympathetic:
- responds to stressful situations
- “fight or flight” response
- Predominates from Thoracic and Lumbar regions

Question 2

What are the anatomical divisions of the brain stem and spinal cord?

Answer 2

M - Medullary
C - Cranial
T - Thoracic
L - Lumbar
S - Sacral

Question 3

Describe the general structure of the ANS para/sympathetic systems.

Answer 3

Parasympathetic:
1) Originate in the lateral horn of the medulla and sacral spinal cord
2) Have long myelinated preganglionic fibres
3) Have short unmyelinated postganglionic fibres
4) Ganglia are located within the innervated tissues
5) Have action that sympathetic nervous system (generally)
Sympathetic:
1) Originate in the lateral horn of lumbar and thoracic spinal cord
2) Have short myelinated preganglionic fibres
3) Have long unmyelinated postganglionic fibres
4) Ganglia are located in the paravertebral chain close to the spinal cord
5) Have actions that oppose the parasympathetic nervous system

Question 4

What is the enteric system?

Answer 4

The possible 3rd division of the ANS. It controls the GI system and is capable of operating independently the CNS

Question 5

What are the principle neurotransmitters involved in the NAS and where?

Answer 5

Acetylcholine (ACh)
Noradrenaline (NA)
- All preganglionic neurons release ACh acts on NICOTINIC AChR (Ligand Gate Cation Channel)
- Parasympathetic Postganglionic neurons release ACh which acts on Muscarinic AChR (GPCRs)
- MOST Sympathetic Postganglionic Neurons release NA which acts on Adrenoreceptors (GPCRs)

Question 6

Which receptors are GPCRs?

Answer 6

M1-M5 ACHRs
Alpha 1 and 2 and Beta 1 and 2 Adrenoceptors
(not nAChR this is a ligand gate cation channel)

Question 7

Some sympathetic post-ganglionic neurones are cholinergic not noradrenergic. What do they act on?

Answer 7

-Sweat glands and hair follicles (piloerection)

Question 8

Describe the ANS innervation of the adrenal glands

Answer 8

• The adrenal medulla is innervated directly by preganglionic sympathetic neurons which release ACh to nAChR on chromaffin cells which release adrenaline into the bloodstream. As they are directly innervated by preganglionic sympathetic neurons, they can be considered as post ganglionic sympathetic neurones.

Question 9

Give some examples of the Parasympathetic release of ACh on receptors around the body

Answer 9

Heart (atria) - M2 AChR - Bradycardia, reduced cardiac conduction
Smooth Muscle - M3 AChR - bronchial contraction, increased intestinal mobility, bladder contraction, (general contraction)
Glandular - M1/M3 AChR - Increased sweat/ salivary/ lacrimal secretion

Question 10

What are the effects of the sympathetic release of Noradrenaline on the body?

Answer 10

Heart - Beta 1 - tachycardia, positive inotropy (increased force of contraction)
Smooth Muscle - Alpha 1 or Beta 1 - arteriolar contraction, bronchiolar/intestinal/ uterine relaxation, bladder sphincter contraction, radial muscle contraction
Glandular - increased (viscous) secretion
Kidney - renin release

Question 11

Outline the receptors involved in the sympathetic release in exercise and why

Answer 11

• positive chronotropic (heart rate) and inotropic (strength of contraction) by Beta 1 adrenoceptors
• Vasoconstriction of most blood vessels by Alpha 1 adrenoceptors
• Vasodilation to exercising muscles and airway Beta 2 Adrenoceptors

Question 12

What are the 5 most common sites of drug action during neurotransmission?

Answer 12

1) degradation of transmitter (after being synthesised in cell)
2) Interaction of neurotransmitter with post-synaptic receptor
3) Inactivation of transmitter (i.e. cholinesterase)
4) Re-uptake of transmitter
5) Interaction with pre-synaptic receptors

Question 13

Why does manipulating cholinergic function have such wide effects?

Answer 13

ACh is released in all pre-ganglionic neurones of the ANS and is also released from the post-ganglionic neurone of the parasympathetic system. As well as at neuromuscular junctions. As such it’s effects are very wide reaching

Question 14

What is trimethaphan and what does it act upon?

Answer 14

An antihypertensive drug that has selective autonomic nAChR blocking properties.
It is able to selectively antagonise autonomic ganglia nAChR rather than at neuromuscular junctions as they differ slightly in structure.

Question 15

What are pyridostigmine and donepezil?

Answer 15

They are AChE (acetyl cholinesterase) inhibitors and as such potentiate the signal

Question 16

What are the likely side effects of non-selective, muscarinic AChR aganists?

Answer 16

Heart: Decreased heart rate and cardiac output
Smooth muscle: increases bronchoconstriction, Gi tract peristalsis
Exocrine glands: increased sweating and salivation

Question 17

What causes “SLUDGE” syndrome and how can it be treated?

Answer 17

It is a massive discharge of the Parasympathetic nervous system. Primarily due to over stimulation of muscarinic acetyl choline receptors. It can be treated with anti-cholinergic agents such as atropine and pralidoxime

Question 18

Name 2 mAChR agonists and 4 antagonists and how their side effects can be limited

Answer 18

Administration locally will limit side effects:
Agonists: Pilocarpine, Bethanechol
Antagonists: Intratropium, tiotropium, tolterodine, darifenacin, oxybutynin, hyoscine (AKA scopolamine)

Question 19

What is salbutamol and how does it work?

Answer 19

It is a B2 adrenoceptor-selective agonist. It leads to oppose constriction and as such asthma.
It’s Bets 2 selectivity reduces it’s cardiovascular side effects as it doesn’t bind to Beta 1. It is also applied local

Question 20

Name an Alpha 1 and a Beta 1 adrenoceptor antagonist

Answer 20

Doxazosin - Alpha 1 - adrenoceptor antagonist

Atenolol - Beta 1 - adrenoceptor antagonist