16. Autonomic Nervous System 2

Question 1

Which steps in neurotransmission are the most common sites of drug action?

Answer 1

Degradation of transmitter
Interaction with post-synaptic receptors
Inactivation of transmitter
Re-uptake of transmitter
Interaction with pre-synaptic receptors

Question 2

Describe the reaction of acetylcholine synthesis

Answer 2

acetyl CoA + choline -> acetylcholine + coenzyme A

Uses enzyme choline acetyltransferase

Question 3

Describe the reaction of acetylcholine degradation

Answer 3

acetylcholine -> acetate + choline

Uses enzyme acetylcholinesterase

Question 4

How can myasthenia gravis be treated using cholinergic transmission?

Answer 4

The actions of endogenously released ACh can be enhanced by AChE inhibitors
Means there is more ACh present for longer

Question 5

What is a disadvantage of using cholinergic drugs?

Answer 5

Lack of selectivity so there can be unwanted side effects, limiting their usage

Question 6

What causes SLUDGE syndrome?

Answer 6

A massive discharge of the parasympathetic nervous system

Question 7

What is the SLUDGE mnemonic

Answer 7

Salivation - stimulation of salivary glands
Lacrimation - stimulation of the lacrimal glands
Urination - relaxation of urethral internal sphincter muscle
Defecation
Gastrointestinal upset - smooth muscle tone changes
Emesis- vomiting

Question 8

When is SLUDGE syndrome usually encountered?

Answer 8

Drug overdose
Ingestion of magic mushrooms
Exposure to organophosphorus insecticides or nerve gases

Question 9

How do nerve agents work?

Answer 9

They covalently modify acetylcholinesterase to irreversibly deactivate the enzyme and raise acetylcholine levels

Question 10

What are the features of post-ganglionic sympathetic neurons?

Answer 10

Possess a highly branching axonal network with numerous varicosities - each is a specialised site for calcium dependent noradrenaline release

Question 11

Describe noradrenergic transmission synthesis

Answer 11

Tyrosine -> DOPA -> Dopamine (then take up by vesicles) -> noradrenaline

Question 12

What happens following calcium dependent exocytotic release of NA?

Answer 12

• NA diffuses across synaptic cleft, interacts with adrenoceptors to imitate signalling in effector tissue
• NA interacts with pre-synaptic adrenoceptors to regulate processes within nerve terminal
• Rapidly removed from synaptic cleft by NA transporter proteins

Question 13

Termination of noradrenergic transmission

Answer 13

NA actions terminated by reuptake into pre-synaptic terminal by sodium dependent high affinity transporter (uptake 1)
NA not recaptured by uptake 1 is taken up by a lower affinity non-neuronal mechanism (uptake 2)

Question 14

Metabolism of noradrenergic transmission

Answer 14

Within pre-synaptic terminal NA not taken up into vesicles is susceptible to metabolism by 2 enzymes:

• monoamine oxidase
• catechism-O-methyltransferase

Question 15

What is an example of a subtype-selective agonist used clinically?

Answer 15

Beta-2-adrenoceptor-selective agonists

Salbutamol used in asthma to reverse/oppose bronchoconstriction

Question 16

What is an example of subtype-selective adrenoceptor antagonists used clinically?

Answer 16

Alpha-1-adrenoceptor-selective antagonists and beta-1-adenoceptor-selective antagonists
Used to treat number o cardiovascular disorders including hypertension