Cholinoceptor Antagonists

Question 1

Define Affinity.

Answer 1

The strength with which an agonist binds to a receptor

Question 2

Define Efficacy.

Answer 2

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

Question 3

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

Answer 3

Agonists – have affinity and efficacy

Antagonists – have affinity but NOT efficacy

Question 4

Where are nicotinic receptors found?

Answer 4

In ALL autonomic ganglia

At neuromuscular junctions

Question 5

Where are muscarinic receptors found?

Answer 5

At parasympathetic effector organs and on sweat glands

Question 6

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

Answer 6

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 7

Give two examples of ganglion blocking drugs.

Answer 7

Hexamethonium

Trimethaphan

Question 8

What does ‘use-dependent block’ mean?

Answer 8

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 9

What determines the effect of ganglion blockade in a tissue?

Answer 9

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

Question 10

Which tissues are sympathetic dominated?

Answer 10

Vasculature

Kidneys

Question 11

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

Answer 11

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 12

Which tissues are parasympathetic dominated?

Answer 12

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

Question 13

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

Answer 13

Bronchodilation  
Pupil dilation (blurred vision)  
Bladder dysfunction  
Loss of GI motility and secretions  
Decrease in exocrine secretion

Question 14

What is hexamethonium?

Answer 14

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

Question 15

What is trimethaphan and when is it used?

Answer 15

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 16

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

Answer 16

Toxins and venoms

Question 17

How do receptor blockade antagonists have their effect?

Answer 17

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

Question 18

Give an example of a nicotinic receptor blockade antagonist.

Answer 18

Alpha-bungarotoxin (common krait snake venom)

Question 19

What are the targets of muscarinic receptor antagonists?

Answer 19

Parasympathetic effector organs and sweat glands

Question 20

Give four examples of muscarinic receptor antagonists.

Answer 20

Atropine
Hyoscine
Tropicamide
Ipratropium Bromide

Question 21

What effect do muscarinic receptor antagonists have on the CNS?

Answer 21

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 22

What is tropicamide used for?

Answer 22

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

Question 23

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

Answer 23

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)

Question 24

What can hyoscine be used to treat? Explain how.

Answer 24

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 25

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

Answer 25

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 26

Explain the use of muscarinic antagonists in treating asthma andCOPD.

Answer 26

Ipratropium Bromide is used to treat asthma and COPD

It removes the parasympathetic mediated bronchoconstriction

Question 27

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

Answer 27

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

Question 28

State some general unwanted side-effects of muscarinic antagonists.

Answer 28

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 29

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

Answer 29

Give an anticholinesterase e.g. physostigmine

Question 30

Describe how botulinum toxin causes paralysis.

Answer 30

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 31

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

Answer 31

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