Cholinoceptor Antagonists Flashcards

1
Q

Define Affinity.

A

The strength with which an agonist binds to a receptor

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

Define Efficacy.

A

Once the drug has bound to the receptor, the ability of the drug to transduce a response and activate intracellular signalling pathways is its efficacy

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

What is the difference between agonists and antagonists in terms of affinity and efficacy?

A

Agonists – have affinity and efficacy

Antagonists – have affinity but NOT efficacy

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

Where are nicotinic receptors found?

A

In ALL autonomic ganglia

At neuromuscular junctions

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

Where are muscarinic receptors found?

A

At parasympathetic effector organs and on sweat glands

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

What are the few clinically useful nicotinic receptor antagonists called and how do they block the receptor?

A

Ganglion Blockers
These block the ion channel itself, thus preventing the ions from moving through the pore (it doesn’t block the receptor but the channel itself)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Give two examples of ganglion blocking drugs.

A

Hexamethonium

Trimethaphan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What does ‘use-dependent block’ mean?

A

The drugs work most effectively when the ion channels are open.
This means that the more agonist is present at the receptor, the opportunity the antagonist has to block the channel, thus the more useful and effective the drugs can be

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

What determines the effect of ganglion blockade in a tissue?

A

It depends on which limb of the autonomic nervous system predominates in the particular tissue (at the time e.g. at rest)

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

Which tissues are sympathetic dominated?

A

Vasculature

Kidneys

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

What is the overall effect of ganglion blockade in terms of loss of sympathetic dominance?

A

Hypotension
The sympathetic-mediated vasoconstriction is taken away and the ability of the kidneys to increase renin secretion and increase sodium and water reabsorption is also taken away

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

Which tissues are parasympathetic dominated?

A

Lungs – causes bronchoconstriction
Eyes – maintains partial pupillary constriction at rest
Bladder, ureters and GI tract
Exocrine functions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What would the effect of ganglion blockage be on these tissues?

A
Bronchodilation  
Pupil dilation (blurred vision)  
Bladder dysfunction  
Loss of GI motility and secretions  
Decrease in exocrine secretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is hexamethonium?

A

It is a ganglion blocker that was the first anti-hypertensive
It has a generalised action and had loads of side-effects

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

What is trimethaphan and when is it used?

A

The only ganglion-blocking drug that is still in clinical use
It is very potent and used when a controlled hypotension is needed in surgery.
It is very short acting.

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

In what types of chemicals are nicotinic receptor blockade antagonists found?

A

Toxins and venoms

17
Q

How do receptor blockade antagonists have their effect?

A

These are irreversible – they bind covalently and prevent the ion channels from opening

18
Q

Give an example of a nicotinic receptor blockade antagonist.

A

Alpha-bungarotoxin (common krait snake venom)

19
Q

What are the targets of muscarinic receptor antagonists?

A

Parasympathetic effector organs and sweat glands

20
Q

Give four examples of muscarinic receptor antagonists.

A

Atropine
Hyoscine
Tropicamide
Ipratropium Bromide

21
Q

What effect do muscarinic receptor antagonists have on the CNS?

A

The parasympathetic nervous system is important in the CNS in terms of attention, memory and certain sleep pathways.
At low doses atropine can cause mild restlessness
At low doses hyoscine can be a good sedative
At high doses, both drugs can cause CNS agitation

22
Q

What is tropicamide used for?

A

It is used to dilate the pupil to observe the retina (it is used to examine the eye)

23
Q

What is an important use of muscarinic receptor antagonists with regards to surgery? Why is it useful in this circumstance?

A

Anaesthetic premedication
It causes dilation of the airways so it is easier to intubate the patient
It reduces secretions thus reducing the risk of aspiration
It also knocks out the effect of the parasympathetic nervous system in decreasing heart rate and contractility (because general anaesthetics will decrease heart rate and contractility anyway)

24
Q

What can hyoscine be used to treat? Explain how.

A

Motion Sickness
Muscarinic receptors are important in relaying information from the labyrinth in the inner ear to the vomiting centres.
Muscarinic receptor antagonists can reduce the flow of information from the labyrinth to the brain thus reducing the nausea.

25
Q

What degenerative disorder of the central nervous system can be treated by muscarinic receptor antagonists? Explain how.

A

Parkinson’s Disease
In Parkinson’s disease, many of the nigro-striatal dopamine neurones are lost (these are important in the fine control of movement)
Musarinic receptors have a negative effect on this dopamine signalling so by blocking the muscarinic receptors (knocking out the M4 receptors) you can remove this inhibitory effect and allow the remaining dopaminergic neurones to fire at the maximum rate.

26
Q

Explain the use of muscarinic antagonists in treating asthma andCOPD.

A

Ipratropium Bromide is used to treat asthma and COPD

It removes the parasympathetic mediated bronchoconstriction

27
Q

Explain the role of muscarinic antagonists in treating irritable bowel syndrome.

A

Muscarinic antagonists will reduce smooth muscle contraction, gut motility and gut secretions thus relieving the symptoms of IBS.

28
Q

State some general unwanted side-effects of muscarinic antagonists.

A

Hot as hell (decreased sweating affects thermoregulation)
Dry as bone (due to reduced exocrine secretions) Blind as a bat (due to effects on the accommodation ability of the ciliary muscle – cycloplegia)
Mad as a hatter (high doses will cause CNS agitation, restlessness, confusion etc.)

29
Q

How do you treat muscarinic receptor antagonist poisoning (e.g. atropine poisoning)?

A

Give an anticholinesterase e.g. physostigmine

30
Q

Describe how botulinum toxin causes paralysis.

A

It binds to the SNARE complex and prevents the fusion of the vesicles, containing acetylcholine, with the presynaptic membrane thus preventing the release of acetylcholine from the nerve terminal.
This leads to muscle paralysis

31
Q

State the overall effects of ganglion blocking drugs on a subject at rest.

A
Hypotension 
Pupil dilation 
Bronchodilation 
Bladder dysfunction  
Decreased GI tone  
Decreased GI secretions