Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology > Cholinergic system > Flashcards

Cholinergic system Flashcards

1
Q

What are the two groups that drugs affecting the ANS are divided into?

A
  • Cholinergic (act on ACh-activated receptors)
  • Adrenergic (norephinephrine/epinephrine-stimulated receptors)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Where are ACh receptors found?

A
  • Postganglionic sympathetic and parasympathetic neurons
  • Effector cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Use of ACh

A
  • Released from pre-ganglionic neurons in both sympathetic and parasympathetic ganglia.
  • Released from post-ganglionic neurons in parasympathetic system to stimulate effectors (eg. glands, smooth & cardiac muscles, fat & xliver cells)
  • Released from somatic efferents at NMJ to stimulate skeletal muscle (end-plate potential + action potential)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Function of ACh

A
  • Stimulates skeletal muscle
  • Stimulates parasympathetic input at low concentrations
  • Stimulates sympathetic input at high concentrations.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are cholinomimetic drugs?

A

Substances that stimulate the PNS - also called cholinergic drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How can cholinergic drugs act?

A
  • Directly by stimulating nicotinic/muscarinic receptors (mimicking ACh)
  • Indirectly by inhibiting cholinesterase, promoting ACH release
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

2 types of cholinergic receptors

A
  • Muscarinic receptors
  • Nicotinic receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What type of receptors are muscarinic?

A

Slow-acting metabotropic receptors i.e. 2nd messenger GPCR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Where are muscarinic receptors located?

A

On effect tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Where do muscarinic receptors receive transmission signals from?

A

Postsynaptic parasympathetic nerve terminals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What effects are muscarinic receptors responsible for?

A

Parasympathetic-like effects in effector tissue such as heart, smooth muscles, brain and exocrine glands.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the 5 subtypes of mAChR?

A
  • M1 (CNS & autonomic ganglia): excitatory signals in CNS & glandular tissues (eg. gastrc acid secretion)
  • M2 (cardiac): ↑ parasympathetic effects of heart (eg. cardiac depression)
  • M3 (glandular & smooth muscular): ↑ parasympathetic effects (eg. bronchoconstriction, GIT stimulation, eye accommodation & vasodilation)
  • M4 (CNS): inhibitory effects in CNS
  • M5 (CNS): excitatory effects in CNS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What do M1, M3 and M5 receptors act through to activate?

A

They act through GqPCR to activate IP3 pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What do M2 and M4 receptors act through and function?

A

They act through GiPCR, to inhibit adenylyl cyclase & ↑ K+ conductance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What type of receptors are nicotinic receptors?

A

Fast-acting ionotropic receptor channel i.e. ligand-gated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Where are nicotinic receptors found?

A
  • CNS
  • Sympathetic synapses with adrenal medulla
  • Autonomic ganglia
  • NMJ
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the 2 subtypes of nAChR?

A
  • Muscle subtype, Nm (found in skeletal muscle endplate region at NMJ)
  • found in neuronal membranes at ANS post-synaptic ganglia and CNS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What happens where nicotinic receptors are located?

A

Depolarising waves trigger postsynaptic firing and skeletal muscle contraction respectively.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are nicotinic receptors composed of?

A

Different subunits, with combinations varying depending on main 3 classes of nAChR: Muscular, Ganglionic and CNS types

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the structure of ACh?

A

A choline ester with a positively charged quaternary ammonium group and a negatively charged ester group.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Which compounds partially mimic the structural characteristics of ACh? and what does this allow?

A

Nicotine and muscarine - allows them to bind to cholinergic receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the side effects of agonists due to overstimulation of cholinergic receptors?

A

DUMBELS
- Diarrhea
- Urination
- Miosis/muscle weakness
- Bronchorrhea
- Emesis
- Lacrimation
- Salivation/Sweating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are muscarinic receptors affinities for cholinomimetic agents?

A

Muscarine > ACh > nicotine

(opposite for nicotinic receptors)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Direct-acting cholinomimetics characteristics?

A
  • Mimic ACh binding
  • Some have receptor specificity or decreased tendency to be metabolised by cholinesterases.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

7 direct-acting cholinomimetics?

A

BBM CAMP
- Butyrylcholine
- Bethanecol
- Muscarine
- Carbachol
- ACh
- Methacholine
- Pilocarpine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

About acetylcholine as a direct-acting cholinomimetic

A
  • Equal affinity for muscarinic & nicotinic receptors
  • Produces non-specific cholinergic effects, and rapidly broken down by AChE
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

About butyrylcholine as a direct-acting cholinomimetic.

A

Choline-based ester similar to ACh

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

About methacholine as a direct-acting cholinomimetic.

A
  • More muscarinic than nicotinic
  • Broken down by AChE
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

About carbachol as a direct-acting cholinomimetic.

A

More nicotinic than muscarinic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

About muscarine as a direct-acting cholinomimetic. (3))

A
  • Higher affinity for muscarinic receptors
  • Parasympathetic effects: cardiac depression, bronchoconstriction, miosis, acid & salivary secretion, sphincter relaxation, vasodilation
  • In muscarine poisoning, bradycardia with marked hypotension & vasodilation results in circulatory shock. It can be avoided completely by prompt diagnosis & treatment with atropine.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

About bethanecol as a direct-acting cholinomimetic.

A
  • Parasympathomimetic choline carbamate
  • Stimulate muscarinic receptors only
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

About pilocarpine as a direct-acting cholinomimetic.

A

– Parasympathomimetic alkaloid
Stimulate M3 receptors
- Pilocarpine stimulates the secretion of large amounts of saliva and sweat. It is used to treat dry mouth (xerostomia).
- Treatment of chronic open-angle glaucoma & acute angle-closure glaucoma. It acts on M3 receptor found on the iris sphincter muscle, causing the muscle to contract, leading to miosis.
- Acts on the ciliary muscle and causes it to contract, opening the trabecular meshwork to facilitate rate that aqueous humor leaves the eye to decrease IOP.
- Diagnosis of CF by stimulating sweat glands in a sweat test to measure [Cl-] & [Na+] that is excreted in sweat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Where do indirect-acting reversible cholinomimetics bind?

A

Bind to enzyme transiently instead of ACh

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Function of AChE

A

Cleaves ACh to acetate and choline to terminate its actions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Where is AChE located?

A

Pre and postsynaptically in nerve terminal where it is membrane bound

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What do inhibitors of AChE indirectly provide and how?

A

Cholinergic action by preventing degradation of ACh.

37
Q

Where do inhibitors of AChE bind to? and what does this cause?

A

To anionic and esteric site of cholinesterase, which reversibly blocks its active site so it can no longer hydrolyse ACh before they reach the postsynaptic receptors.

38
Q

What does accumulation of ACH in synaptic space provoke?

A

A responde at all cholinoreceptors in body (ANS receptors, NMJ and brain)

39
Q

Give 3 indirect-acting cholinomimetics

A
  • Physostigmine
  • Neostigmine
  • Donepezil
40
Q

Write about physostigmine

A

Tertiary amine naturally found in plants. It forms carbamoylated intermediate with AchE.
Indirectly stimulates both NN & muscarinic receptors in ANS
Can also enter & stimulate cholinergic sites in CNS
Action lasts 30mins – 2hrs
Enhance smooth muscle contraction (eg. GI) & pupil diameter
Used in treatment of overdoses of drugs with anticholinergic actions eg. atropine as it can antagonize the central effects of atropine on muscarinic receptors.

41
Q

Write about neostigmine

A

Indirectly stimulates both NM & muscarinic receptors
More polar, hence does not penetrate BBB, hence low propensity to cause CNS effects & does not absorb well from GIT
Stimulate bladder & GIT
Reverse anesthesia from neuromuscular blocking agents
Improve muscle tone in people with myasthenia gravis

42
Q

Write about donepezil

A

The precise mechanism of action of donepezil in patients with Alzheimer’s disease is not fully understood. Certainly Alzheimer’s disease involves a substantial loss of the elements of the cholinergic system and it is generally accepted that the symptoms of Alzheimer’s disease are related to this cholinergic deficit, particularly in the cerebral cortex and other areas of the brain. It is noted that the hippocampal formation plays an important role in the processes of control of attention, memory and learning. Just the severity of the loss of cholinergic neurons of the central nervous system (CNS) has been found to correlate with the severity of cognitive impairment.

43
Q

How do indirect-acting irreversible cholinomimetics bind?

A

Bind to the enzyme covalently; long lasting

44
Q

Example of indirect-acting irreversible cholinomimetics

A

Poisonous organophosphates – dyflos, sarin gas

45
Q

Write about poisonous organophosphates – dyflos, sarin gas

A

Effects: bind to similar sites to ach but phosphyrylate esteric site and it’s “irreversible. Act soon enough can give a drug that will reactivate enzyme.
Oxime reactivators, Pralidoxime (2-PAM), is typically used in organophosphate poisoning to remove anticholinesterases from the enzyme, by binding to it and decreasing its affinity for the cholinesterase.
Pralidoxime is often used with atropine (a muscarinic antagonist) to help reduce the parasympathetic effects of organophosphate poisoning. Pralidoxime is only effective in organophosphate toxicity (i.e. it does not have an effect if the acetylcholinesterase enzyme is carbamylated, as occurs with neostigmine or physostigmine). Pralidoxime has an important role in reversing paralysis of the respiratory muscles but due to its poor BBB penetration, it has little effect on centrally-mediated respiratory depression. This is why atropine, which has excellent BBB penetration, is concomitantly administered with Pralidoxime during the treatment of organophosphate poisoning.

46
Q

Cholinergic antagonists subtypes

A
  • Anti-muscarinic agents
  • Ganglionic blockers
  • Neuromuscular blockers
47
Q

4 Anti-muscarinic agents

A
  1. Atropine (atropa belladonna)
  2. Pirenzepine
  3. Methoctramine
  4. Solifenacin
48
Q

What is atropine?

A

A tertiary amine belladonna alkaloid that binds competitively with cholinergic receptors, preventing ACh from binding to those sites.

49
Q

What is a common phenomenon of atropine?

A

Low doses will cause a paradocical slowing of the heart, but the predominant effect will be to speed up the heart.

50
Q

What is atropine still available to treat, but why is it not preferable?

A

To treat GIT but not as effective due to better proton-pump inhibitors available.

51
Q

Affinity of atropine

A

High affinity for muscarinic receptors

52
Q

Mneumonic for anticholinergic toxidrome

A

Hot as a hare, blind as a bat, dry as a bone, red as a beet & mad as a hatter

53
Q

Atropine effects on PNS parasympathetic

A

Tachycardia, bronchodilation, constipation, inhibit acid & saliva secretions

54
Q

What is the predominant effect of atropine at low doses? and why?

A

Slight ↓HR due to blockade of M1 receptors on inhibitory presynaptic neurons, permitting ↑ACh release.

55
Q

What is the effect of atropine at high doses? and why?

A

Progressive ↑HR by blocking M2 receptors on SA node.

56
Q

What is atropine used to treat?

A
  • Organophosphate poisoning
  • Bradycardia (neostigmine)
  • Bladder incontinence
  • Produce mydriasis and cycloplegia prior to refraction
  • Suppress respiratory secretions prior to surgery
57
Q

What is atropine commonly used in combination with and why?

A

in combination with β2-agonists & inhaled corticosteroids for asthmatic patients

58
Q

Pirenzepine info (2)

A
  • M1 selective antagonist
  • Does not cross BBB
59
Q

When is pirenzepine prescribed and why?

A
  • In treatment of peptic ulcers
  • It reduces gastric acid secretion and reduces muscle spasm
60
Q

Where does methoctramine bind?

A

To pre-synaptic M2 receptors

61
Q

Name an anti-muscarinic agent that isn’t used clinically

A

Methoctramine

62
Q

Where does solifenacin bind?

A

To M3 receptors

63
Q

What is solifenacin used in the treatment of?

A

Overactive urinary bladder

64
Q

Where do ganglionic blockers specifically act? and effect

A

On nicotinic receptors of both sympathetic and parasympathetic autonomic ganglia and block the entire output of the ANS at the nicotinic receptor.

65
Q

What is nicotine?

A

It is a component of cigarette smoke without therapeutic benefit & delirious to health.

66
Q

What does nicotine lead to?

A
  • Postsynaptic neurons depolarisation and firing
  • Adrenal medulla activatino
67
Q

What is the initial stimulatory response of nicotine?

A

↑BP & HR, ↑ peristalsis & secretions

68
Q

What do high doses of nicotine result in?

A

↓BP, ↓ activity in both GIT & ceasing of bladder musculature

69
Q

What is the general effect of nicotine?

A

First causes stimulation due to release of transmitter from adrenergic terminal and adrenal medulla, followed by paralysis of all ganglia due to ganglionic blockade.

70
Q

Tubocurarine and hexametonium ‘effect’

A

non depolarising effect

71
Q

Where does hexamethonium act?

A

On pre-ganglionic sites in both sympathetic and parasympathetic NS

72
Q

Effect of atropine on arterioles and system

A

Sympathetic - vasodilation and dilation
Parasympathetic - tachycardia

73
Q

Effect of atropine on muscle and system

A

Parasympathetic - mydriasis and cycloplegia

74
Q

Effect of atropine on GIT and system

A

Parasympathetic - relaxation (constipation)

75
Q

Effect of atropine on urinary bladder and system

A

Parasympathetic - urinary retention

76
Q

Effect of atropine on salivary glands and system

A

Parasympathetic - dry mouth

77
Q

Effect of atropine on sweat glands and system

A

Sympathetic - anhidrosis

78
Q

What was hexamethonium formally used to treat and why is it not anymore?

A
  • Previously used to treat hypertension
  • Discontinued due to non-specificity and combined sympatholytic and parasympatholytic effects
79
Q

Trimetaphan effect

A
  • Non-depolarising
  • Short action, for controlled hypotension during surgery
80
Q

What is mecamylamine

A

Non-selective, non-competitive antagonist of nAChR

81
Q

What is Mecamylamine used as and why

A

Used as a research tool for addiction and neuropsychiatric disorders as it easily crosses BBB

82
Q

What is varenicline used for?

A

Smoking cessation

83
Q

What type of agonist is varenicline?

A

Partial agonist

84
Q

Function of neuromuscular blockers

A

Block cholinergic transmission between motor nerve endings and the nicotinic receptors on the skeletal muscle.

85
Q

Where do neuromuscular blockers act?

A

On receptors at the endplate of NMJ

86
Q

Why are neuromuscular blockers important clinically?

A
  • During surgery to facilitate tracheal intubation and provide complete muscle relaxation at lower anaesthetic doses -> more rapid recovery from anaesthesia
  • Reduces postoperative respiratory depression
87
Q

How do neuromuscular blockers act at low doses?

A

As competitive antagonist (can be overcome by anticholinesterases)

88
Q

How do neuromuscular blockers act at high doses?

A

As channel blocker at motor endplate (ability of anticholinesterases reduced)

Pharmacology (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions