Acetylcholine and Parasympathetic System Flashcards

1
Q

Name the two compounds from which ACh is synthesized. Also state which one is the precursor.

A

Precursor, Choline (from diet) and acetyl-CoA

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2
Q

Name the enzyme that converts choline and acetyl-CoA to ACh

A

Acetyltransferase

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3
Q

From what is choline derived? And where

A

Diet, liver

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4
Q

Which transporter will transport choline into the nerve terminal?

A

High affinity Na-choline co-transporter

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5
Q

Which transport inhibitor can reduce the synthesis of Acetycholine?

A

Hemicholinium, a neuronal choline transporter inhibitor

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6
Q

Where is ACh stored after being synthesized?

A

ACh is transported by vesicle transporter to be stored in vesicles

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7
Q

Which drug can inhibit the vesicular transporter responsible for transporting ACh into vesicles?

A

Vesamicol

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8
Q

By which mechanism is ACh released into the synaptic cleft?

A

Ca- dependent exocytosis

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9
Q

How is the action of ACh in the synaptic cleft terminated?

A

The action of acetylcholine in the synapse is normally terminated by metabolism to acetate and choline by the enzyme acetylcholinesterase in the synaptic cleft.

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10
Q

What is the result when cholinesterase enzymes are blocked/inhibited?

A

Blockade of cholinesterase enzymes result in increased autonomic activity, primarily cholinergic activity. Increased effects at postganglionic nerve terminal with increased stimulation of muscarinic receptors, enhancing synaptic cholinergic activity, causes excessive salivation, bradycardia, bronchospasm and hypotension. Increasing NMJ activity causes muscle fasciculation and twitching and may result in a depolarisation block and paralysis

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11
Q

Name two receptors of ACh on postsynaptic neurons.

A

Nicotinic receptors

Muscarinic receptor

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12
Q

Where do you find nicotinic receptors?

A

Ganglia
Adrenal gland
Neuromuscular junction

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13
Q

Where do you find muscarinic receptors?

A

Cardiac
Smooth muscle
Exocrine glands

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14
Q

Which acetylcholinesterase inhibitor is commonly used?

A

Neostigmine

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15
Q

Name the Effects of blocking ACh vesicular release.

A

Inhibition of sweating, giving symptoms of a dry, warm skin
Inhibition of salivation with symptoms of dry mouth
Pupillary dilatation
Inhibition of vesicular release at the neuromuscular junction would lead to muscle paralysis

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16
Q

Which drugs results in Inhibition of vesicular release of ACh at the neuromuscular junction?

A

Streptomycin , neomycin

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17
Q

which poison causes parasympathetic paralysis with symptoms of a dry mouth and blurring of vision

A

Botulinum

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18
Q

Which venom causes parasympathetic paralysis with symptoms of a dry mouth and blurring of vision

A

Beta-bungarotoxin

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19
Q

What type of receptor are Nicotinic receptors?

A

ligand-gated ion channels

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20
Q

What type of receptor are Muscarinic receptors?

A

G-protein coupled receptors

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21
Q

From which cranial nerves does parasympathetic preganglionic fibres originate?

A

Cranial nerves III (oculomotor), VII (facial), IX (glossopharyngeal), and X (vagus)

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22
Q

From which spinal cord region does preganglionic parasympathetic fibres arise?

A

sacral region (S2 to S4) of the spinal cord

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23
Q

How many preganglionic parasympathetic fibres does the vagus nerve account for?

A

90%

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24
Q

Which areas of the body does the postganglionic neuron from the vagus nerve innervate?

A

most of the organs in the thoracic

and abdominal cavity.

25
Name the two groups of cholinergic drugs
Direct acting | Indirect acting - anticholinesterase agents
26
Name the two groups of direct acting cholinergic drugs
Choline Esters | Natural alkaloids
27
Name the two groups of anti-cholinesterase agents
Irreversible and reversible
28
Name two examples of choline esters
Acetylcholine | Bethanechol
29
What is the prototype for direct acting cholinergic drugs?
Acetylcholine
30
What is the prototype for indirect acting anticholinesterase inhibitors?
Neostigmine
31
Does bethanechol (quarternary compound) penetrate the BBB?
No
32
Why is bethanechol's action more prolonged than that of ACh?
It is not hydrolysed by cholinesterase
33
Give an example of natural alkaloids
Pilocarpine
34
In which occular disease is pilocarpine prefered?
Closed-angle glaucoma
35
The commonly used anticholinesterases are quaternary compounds that...
...do not pass the blood-brain barrier and have negligible central effects.
36
MOA of acetylcholinesterase
Acetylcholine binds to the active site of the esterase and is hydrolysed, producing free choline and acetylated enzyme. In second step, the covalent acetyl-enzyme bond split with the addition of water.
37
Why is pilocarpine effective in closed-angle glaucoma?
Pilocarpine reduce IOP by contracting the ciliary muscle. This pulls the sclera spur and result in the trabecular meshwork being stretched and separated. The fluid pathways are opened up and aqueous outflow is increased
38
All parasympathomimetic causes...
miosis (excessive pupillary constriction)
39
Name two drugs that reduce IOP by decreasing aqueous secretion
Timolol | Brimonidine
40
How does timolol decrease aqueous secretion?
Beta blocker, it blocks B-2 receptors on the ciliary processes and reduce aqueous production. They may block vessels supplying the ciliary processes. The resulting vasoconstriction produces reduced ultrafiltration and aqueous formation.
41
How does brimonidine decrease aqueous secretion?
Alpha 2 adrenoceptor agonists, they decrease aqueous by stimulating alpha 2 adrenoceptors on the adrenergic nerve terminal innervating the ciliary body
42
What is Myasthenia Gravis
Characterized by progressive weakening of skeletal muscles. It preferentially affects women and can be lethal if untreated. Symptoms are caused by an autoimmune-induced decrease (70-90%) in the number of nAChRs at the NMJ. Ptosis and weakness of smile are common early signs.
43
Which drug is diagnostic in early stages of Myasthenia Gravis?
Edrophonium (acetylcholinesterase inhibitor)
44
Can edrophonium be used as therapy for myasthenia gravis?
Yes, but neostigmine is preferred
45
Name the adverse effects of AChE inhibitors.
The same as sx of ACh excess - DUMBELS: diarrhea, urination, miosis, bronchoconstriction, excitation, lacrimation (flow of tears), salivation and sweating.
46
Name the two drugs that can be used for Myasthenia Gravis due to their higher affinity for the NMJ than the rest of the ANS
Neostigmine | Pyridostigmine
47
Give four examples of reversible anticholinesterase agents
Neostigmine Physostigmine (eserine) Pyridostigmine Edrophonium
48
Explain MOA of edrophonium
It binds by electrostatic forces to the active site of the enzyme. It does not form covalent bonds with the enzyme
49
Name the two groups of irreversible anticholinesterase agents
Organo Phosphorus Compounds | Carbamates
50
Name the three groups of anticholinergic drugs
Antimuscarinic Anti-nicotinic Cholinesterase regenerators
51
Give an example of a non-selective antimuscarinic drug
Atropine
52
Give an example of a cholinesterase regenerator drug and name its class
Pralidoxime - Oximes
53
Name the different effects of the parasympathetic nervous system
``` Constricts pupils Stimulates flow of saliva Constricts bronchi Slows heartbeat Stimulates peristalsis and secretion in stomach Stimulates bile release Contracts bladder ```
54
Atropine MOA, uses in therapeutics, effects/side-effects
Tertiary amine with competitive binding to muscarinic receptors Treatment of organophosphate poisoning Antispasmodic, antisecretory, mydriasis and cycloplegia
55
Glycopyrrolate - MOA, uses
Antimuscarinic/bronchodilator Quaternary amine, Used for reversal of neuromuscular blockade Preoperative medication Ophthalmology to produce mydriasis and cycloplegia
56
Give 5 examples of antimuscarinic drugs
``` Atropine Scopolamine Glycopyrrolate Oxybutynin (antispasmodic, urge incontinence, Post operative urinary spasms) Imipramine (reduces incontinence) ```
57
Ipratropium bromide - MOA, uses
anticholinergic/bronchodilator/nasal agent | asthma/COPD when not controlled by LABA, corticosteroids, spacer
58
Give an example of nicotinic agonist
succinylcholine - stimulates skeletal muscle contraction
59
Give an example of a nicotinic antagonist
Pancuronium - inhibits skeletal muscle contraction