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Autonomic Nervous System > Acetylcholine and Parasympathetic System > Flashcards

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
Q

Name the two groups of cholinergic drugs

A

Direct acting

Indirect acting - anticholinesterase agents

26
Q

Name the two groups of direct acting cholinergic drugs

A

Choline Esters

Natural alkaloids

27
Q

Name the two groups of anti-cholinesterase agents

A

Irreversible and reversible

28
Q

Name two examples of choline esters

A

Acetylcholine

Bethanechol

29
Q

What is the prototype for direct acting cholinergic drugs?

A

Acetylcholine

30
Q

What is the prototype for indirect acting anticholinesterase inhibitors?

A

Neostigmine

31
Q

Does bethanechol (quarternary compound) penetrate the BBB?

A

No

32
Q

Why is bethanechol’s action more prolonged than that of ACh?

A

It is not hydrolysed by cholinesterase

33
Q

Give an example of natural alkaloids

A

Pilocarpine

34
Q

In which occular disease is pilocarpine prefered?

A

Closed-angle glaucoma

35
Q

The commonly used anticholinesterases are quaternary compounds that…

A

…do not pass the blood-brain barrier and have negligible central effects.

36
Q

MOA of acetylcholinesterase

A

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
Q

Why is pilocarpine effective in closed-angle glaucoma?

A

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
Q

All parasympathomimetic causes…

A

miosis (excessive pupillary constriction)

39
Q

Name two drugs that reduce IOP by decreasing aqueous secretion

A

Timolol

Brimonidine

40
Q

How does timolol decrease aqueous secretion?

A

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
Q

How does brimonidine decrease aqueous secretion?

A

Alpha 2 adrenoceptor agonists, they decrease aqueous by stimulating alpha 2 adrenoceptors on the adrenergic nerve terminal innervating the ciliary body

42
Q

What is Myasthenia Gravis

A

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
Q

Which drug is diagnostic in early stages of Myasthenia Gravis?

A

Edrophonium (acetylcholinesterase inhibitor)

44
Q

Can edrophonium be used as therapy for myasthenia gravis?

A

Yes, but neostigmine is preferred

45
Q

Name the adverse effects of AChE inhibitors.

A

The same as sx of ACh excess - DUMBELS: diarrhea, urination, miosis, bronchoconstriction, excitation, lacrimation (flow of tears), salivation and sweating.

46
Q

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

A

Neostigmine

Pyridostigmine

47
Q

Give four examples of reversible anticholinesterase agents

A

Neostigmine
Physostigmine (eserine)
Pyridostigmine
Edrophonium

48
Q

Explain MOA of edrophonium

A

It binds by electrostatic forces to the active site of the enzyme. It does not form covalent bonds with the enzyme

49
Q

Name the two groups of irreversible anticholinesterase agents

A

Organo Phosphorus Compounds

Carbamates

50
Q

Name the three groups of anticholinergic drugs

A

Antimuscarinic
Anti-nicotinic
Cholinesterase regenerators

51
Q

Give an example of a non-selective antimuscarinic drug

A

Atropine

52
Q

Give an example of a cholinesterase regenerator drug and name its class

A

Pralidoxime - Oximes

53
Q

Name the different effects of the parasympathetic nervous system

A 
Constricts pupils
Stimulates flow of saliva
Constricts bronchi 
Slows heartbeat
Stimulates peristalsis and secretion in stomach
Stimulates bile release
Contracts bladder
54
Q

Atropine MOA, uses in therapeutics, effects/side-effects

A

Tertiary amine with competitive binding to muscarinic receptors
Treatment of organophosphate poisoning
Antispasmodic, antisecretory, mydriasis and cycloplegia

55
Q

Glycopyrrolate - MOA, uses

A

Antimuscarinic/bronchodilator Quaternary amine,
Used for reversal of neuromuscular blockade
Preoperative medication
Ophthalmology to produce mydriasis and cycloplegia

56
Q

Give 5 examples of antimuscarinic drugs

A 
Atropine
Scopolamine
Glycopyrrolate
Oxybutynin (antispasmodic, urge incontinence, Post operative urinary spasms)
Imipramine (reduces incontinence)
57
Q

Ipratropium bromide - MOA, uses

A

anticholinergic/bronchodilator/nasal agent

asthma/COPD when not controlled by LABA, corticosteroids, spacer

58
Q

Give an example of nicotinic agonist

A

succinylcholine - stimulates skeletal muscle contraction

59
Q

Give an example of a nicotinic antagonist

A

Pancuronium - inhibits skeletal muscle contraction

Autonomic Nervous System (5 decks)

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