ICPP 13 - The ANS (Part 2)

Question 1

How is ACh synthesised?

How is ACh degraded?

Answer 1

• Synthesised from Acetyl CoA & Choline via choline acetyltransferase (CAT)
• Degraded into acetate & choline via acetylcholinesterase (AChE)

Question 2

How can cholinergic transmission be intervened therapeutically? Give an example of a drug that does this.

Answer 2

• Blocking nAChR’s at autonomic ganglia, e.g.: trimethaphan used in hypertensive emergencies
• Blocking ACh breakdown via AChE inhibitors, e.g.: pyridostigmine in myasthenia gravis or donepezil in Alzheimers.

Question 3

Why is it important that we use selective mAChR agonists rather than non-selective?

Answer 3

As non-selective agonists will have significant autonomic side effects on various body systems, e.g.: a mAChR agonist

• Decreased HR + CO
• Increased bronchoconstriction
• Increased sweating + salivation

Question 4

What is “Sludge” syndrome?
When does it occur?
What is it treated with?

Answer 4

• The pneumonic for pathological effective due to prolonged over-stimulation of mAChR’s innervated by the parasympathetic NS.
• Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis
• Occurs in drug overdose, ingestion of magic mushrooms, exposure to insecticides and nerve agents
• Treated with anti-cholinergic agents such as atropine or pralidoxime.

Question 5

How is noradrenaline synthesised?

Answer 5

• Tyrosine (diet) –> DOPA via tyrosine hydroxylase
• DOPA –> Dopamine via DOPA decarboxylase
• Dopamine packaged into vesicle
• Dopamine –> NA (within vesicle) via Dopamine B-hydroxylase
• NA –> Adrenaline within the vesicle too
• NA –> AD within the adrenal medulla via PNMT

Question 6

How is NA released from the vesicle of a postganglionic neurone?

Answer 6

• Via Ca2+ dependent exocytosis

Question 7

How is NA transmission terminated?

Answer 7

1) By re-uptake into pre-synaptic terminal by Na+ dependent transporter (NET). Not all re-uptaken so required further re-uptake by. a lower affinity, non neuronal mechanism
2) Within pre-synaptic terminal NA taken up into vesicles susceptible to metabolism by MAO or COMT enzymes.

Question 8

Name a couple adrenoreceptor agonist and antagonists used clinically.

Answer 8

• Salbutamol (B2 agonist), causes bronchodilation to improve asthma symptoms
• Doxazosin (a1 antagonist) used to treat hypertension
• Propranolol/Atenolol (b1 antagonist) used to treat anxiety and hypertension respectively.

B1 in heart, B2 in lungs remember.