MCBG S9 Pharmacological Intervention In The ANS

Question 1

What is the overall equation to show ACh synthesis?

What enzyme is involved?

What is the overall equation to show ACh degradation?

What enzyme is involved

Answer 1

Acetyl CoA + Choline -> ACh + CoA

Choline acetyltransferase

ACh -> Acetate + choline

acetylcholinesterase

Question 2

Why do drugs that act on nAChRs have selective at autonomic ganglia compared to neuromuscular junctions?

Answer 2

nAChRs differ in structure and neuromuscular junctions compared to at autonomic ganglia.

Question 3

Actions of ACh can be enhanced by AChE Inhibitors.

Name 2 and what they treat.

Answer 3

Pyridostigmine - treat myasthenia gravis

Donepezil - treats Alzheimer’s disease.

Question 4

Lack of selectivity of _________ drugs causes unwanted side effects.

Name 6.

Answer 4

Decreased heart rate 
Cardiac output 
Bronchoconstriction
GI tract peristalsis 
Sweating
Salivation

Question 5

What does SLUDGE syndrome represent?

Answer 5

Mnemonic for the pathological effects indicative of massive discharge of the PSNS.

Salivation - salivary gland stimulation
Lacrimation - lacrimal gland stimulation
Urination - relaxation of urethral internal sphincter muscle and detrusor muscle contraction
Defecation
GI upset - smooth muscle tone changes
Emesis - vomiting

Question 6

SLUDGE syndrome can be encountered in cases of…

Answer 6

Drug overdose
Magic mushrooms
Insecticide exposure
Nerve gas exposure - Sarin and VX

Question 7

How do nerve gases act to cause SLUDGE syndrome?

Answer 7

Covalently modify AChE
Irreversibly deactivate the enzyme and raise ACh levels.
Prolonged interaction at synapse

Question 8

What may sludge syndrome be treated with?

Answer 8

Atropine - blocks receptor for ACh

Pralidoxime - reverses covalent Modification in AChE

Question 9

How can the lack of selectivity of mAChR agonists and antagonists be overcome by means of administration?

Answer 9

Administer them locally rather than systematically.

Question 10

Describe the steps in synthesis of noradrenaline that occurs within a post-ganglionic varicosity.

What extra step is present in the adrenal medulla?

Answer 10

Tyrosine is hydroxylase day to DOPA
DOPA decarboxylated by DOPA decarboxylase to Dopamine
Dopamine.
This occurs in the cytosol

Once packaged into a vesicle hydroxylation of dopamine by dopamine B-hydroxylase makes noradrenaline.

Converted to adrenaline by phenylethanolamine N-methyltransferase

Question 11

NA, once released into the synaptic cleft, interacts with pre-synaptic adrenoceptors aswell.

Why?

Answer 11

Regulator processes within the varicosity/ nerve terminal for example NA release.

Question 12

What 2 ways can NA be removed from the synaptic cleft?

Answer 12

Uptake 1 - re-uptake into pre-synaptic terminal by NA transporter.
High affinity

Uptake 2 - taken by low affinity, non-neuronal mechanism where the NA leaks away from the synapses and is taken in by surround I cells.

Question 13

NA that is taken back through Uptake 1 but isn’t taken into vehicles is metabolised by what enzymes?

Answer 13

Monoamine oxidase (MAO)
Catechol-O-methyltransferase (COMT)