18. The Autonomic Nervous System Flashcards

1
Q

What are the 12 main steps in neurotransmission?

A
  1. Uptake of precursors. 2. Synthesis of transmitter. 3. Vesicular storage of transmitter. 4. Degradation of transmitter. 5. Depolarisation by propagated action potential. 6. Depolarisation-dependent influx of Ca2+. 7. Exocytotic release of transmitter. 8. Diffusion to post-synaptic membrane. 9. Interaction with post-synaptic receptors. 10. Inactivation of transmitter. 11. Re-uptake of transmitter. 12. Interaction with pre-synaptic receptors.
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2
Q

Which steps in neurotransmission are targeted pharmacologically?

A

Degradation of transmitter, interaction with post-synaptic receptors, inactivation of transmitter, re-uptake of transmitter, interaction with pre-synaptic receptor.

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3
Q

Which enzyme catalyses synthesis of acetylcholine?

A

Choline acetyltransferase.

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4
Q

Which enzyme catalyses degradation of acetylcholine?

A

Acetylincholinesterase.

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5
Q

How do drugs have selectivity at autonomic ganglia over nicotinic acetylcholine receptors at the neuromuscular junction?

A

The structures are different so drugs may only bind to one.

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6
Q

How many types of muscarinic acetylcholine receptors are there?

A

5: M1-M5.

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7
Q

How can the actions of endogenously released ACh be enhanced?

A

By AChE inhibitors as ACh is broken down slower so is the neuromuscular junction for longer to act longer.

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8
Q

What limits the useage of cholinergic drugs?

A

The lack of selectivity, as it means there are unwanted side-effects.

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9
Q

What is SLUDGE?

A

A mnemonic for the pathological effects indicative of massive discharge of the parasympathetic nervous system.

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10
Q

What are the symptoms in SLUDGE due to?

A

Chronic stimulation of muscarinic acetylcholine receptors in organs and muscles innervated by the parasympathetic nervous system.

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11
Q

What are the symptoms in SLUDGE?

A

Salivation, Lacrimation, Urination, Defecation, Gastrointestinal upset, Emesis (vomiting).

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12
Q

How can SLUDGE be treated?

A

With atropine, pralidoxime, or other anticholinergic agents.

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13
Q

What are some muscarinic ACh receptor agonists and their functions?

A

Pilocarpine - treats glaucoma. Bethanechol - stimulate bladder emptying.

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14
Q

What are some muscarinic ACh receptor antagonists and their functions?

A

Ipratropium and tiotropium - some types of asthma and COPD. Tolterodine, darifenacin, and oxybutynin - overactive bladder treatment.

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15
Q

How is noradrenaline synthesised?

A

In the cytosol: Tyrosine -> DOPA (tyrosine hydroxylase). DOPA -> Dopamine (DOPA decaroxylase). In the vesicle: Dopamine -> Noradrenaline (Dopamine B-hydroxylase).

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16
Q

How does NA act in the post-synaptic membrane?

A

It diffuses across the synaptic cleft and interacts with adrenoceptors to initiate signalling in the effector tissue.

17
Q

How does NA act in the pre-synaptic membrane?

A

It interacts with pre-synaptic adrenoceptors to regulate processes within the nerve terminal.

18
Q

Why has NA only have a very limited time to influence pre and post-synaptic adrenoceptors?

A

It is rapidly removed from the synaptic cleft by noradrenaline transporter proteins.

19
Q

How are NA actions terminated?

A

Uptake 1 - re-uptake into the presynaptic terminal by a Na+ dependent, high affinity transporter. Uptake 2 - taken up by a lower affinity, affinity, non-neuronal mechanism.

20
Q

How is NA metabolised?

A

In the pre-synaptic terminal, if NA isn’t taken up it is susceptible to metabolism by two enzymes: MAO (monoamine oxide) or COMT (catechol-O-methyltransferase).

21
Q

How can neurotransmitter release by inhibited?

A

By inhibiting Ca2+-dependent exocytosis.

22
Q

How do indirectly-acting sympathomimetic agents work?

A

They are taken up into noradrenergic synaptic vesicles and cause NA to leak from vesicles. NA then leaks into the synaptic cleft.

23
Q

How are effects of activation of B1-adrenoceptors in the heart mediated?

A

Through activation of the adenylyl cyclase/cyclic AMP signalling pathway.

24
Q

What are the drugs of choice for chronic heart failure?

A

Bisoprolol, metoprolol (B1-adrenoceptor selective antagonists). Carvedilol (mixed B1/B2/a1 adrenoceptor antagonist).