Cholinoceptor Antagonists

Question 1

Where are nicotinic receptors found?

Answer 1

In ALL autonomic ganglia

At neuromuscular junctions

Question 2

Where are muscarinic receptors found?

Answer 2

At parasympathetic effector organs and on sweat glands

Question 3

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

Answer 3

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)

Question 4

Give two examples of ganglion blocking drugs.

Answer 4

Hexamethonium

Trimethaphan

Question 5

What does ‘use-dependent block’ mean?

Answer 5

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

Question 6

What determines the effect of ganglion blockade in a tissue?

Answer 6

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

Question 7

Which tissues are sympathetic dominated?

Answer 7

Vasculature

Kidneys

Question 8

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

Answer 8

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

Question 9

What is hexamethonium?

Answer 9

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

Question 10

What is trimethaphan and when is it used?

Answer 10

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.

Question 11

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

Answer 11

Toxins and venoms

Question 12

How do receptor blockade antagonists have their effect?

Answer 12

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

Question 13

Give an example of a nicotinic receptor blockade antagonist.

Answer 13

Alpha-bungarotoxin (common krait snake venom)

Question 14

What are the targets of muscarinic receptor antagonists?

Answer 14

Parasympathetic effector organs and sweat glands

Question 15

Give four examples of muscarinic receptor antagonists.

Answer 15

Atropine
Hyoscine
Tropicamide
Ipratropium Bromide

Question 16

What effect do muscarinic receptor antagonists have on the CNS?

Answer 16

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

Question 17

What is tropicamide used for?

Answer 17

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

Question 18

3 reasons why muscarinic receptor antagonists are good anaesthetic premedications

Answer 18

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)

Question 19

What can hyoscine be used to treat? Explain how.

Answer 19

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.

Question 20

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

Answer 20

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.

Question 21

Explain the use of muscarinic antagonists in treating asthma andCOPD.

Answer 21

Ipratropium Bromide is used to treat asthma and COPD

It removes the parasympathetic mediated bronchoconstriction

Question 22

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

Answer 22

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

Question 23

State some general unwanted side-effects of muscarinic antagonists.

Answer 23

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.)

Question 24

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

Answer 24

Give an anticholinesterase e.g. physostigmine

Question 25

Describe how botulinum toxin causes paralysis.

Answer 25

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

Question 26

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

Answer 26

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

Question 27

Feature of ipatropium bromide that makes it good for asthma

Answer 27

Very positively charged which localises it in lung