Cholinoceptor antagonists

Question 1

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

Answer 1

Ganglion Blockers

These block the ion channel itself (so not the receptor), thus preventing the ions from moving through the pore

Question 2

Give two examples of ganglion blocking drugs.

Answer 2

Hexamethonium

Trimethaphan

Question 3

What does ‘use-dependent block’ mean, in regards to nicotinic receptor antagonists?

Answer 3

The drugs work most effectively when the ion channels are open (i.e. when. more agonist is present at the receptor)

Question 4

What determines the effect of ganglion blockade in a tissue?

Answer 4

It depends on which limb of the autonomic nervous system (SNS or PNS) is dominant in the particular tissue (at the time e.g. at rest PNS is largely dominant)

Question 5

Which tissues are sympathetic dominated (at rest)?

Answer 5

Vasculature

Kidneys

Question 6

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

Answer 6

• Decreased sympathetic-mediated vasoconstriction
• Decreased renin secretion from kidneys (=decreased sodium and water reabsorption)

=> Hypotension

Question 7

Which tissues are parasympathetic dominated (at rest)? What effects does it have on the tissue?

Answer 7

Lungs – causes bronchoconstriction

Eyes – maintains partial pupillary constriction at rest

Bladder and ureters - contraction of detrusor; relaxation of trigone and sphincter (bladder emptying)

GI tract - increased motility and tone, increased secretions

Salivary glands - copious watery secretion

Question 8

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

Answer 8

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

Question 9

What is the clinical use of hexamethonium and trimetaphan?

Answer 9

Anti-hypertensive drug (no longer used due to the many side effects)

Hypotensive drug during surgery (short acting)

Question 10

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

Answer 10

Toxins and venoms

Question 11

How do receptor blockade antagonists work?

Answer 11

Irreversible covalent binding to the receptor preventing the ion channels from opening

Question 12

Give an example of a nicotinic receptor blockade antagonist

Answer 12

Alpha-bungarotoxin (from common krait snake venom)

Question 13

Give four examples of muscarinic receptor antagonists

Answer 13

Atropine (plant based)
Hyoscine (plant based)
Tropicamide
Ipratropium Bromide

Question 14

What effect does atropine have on the CNS (at normal and toxic doses)?

Answer 14

NORMAL dose: little effect

TOXIC dose: Mild restlessness and Agitation (Less M1 selective)

Question 15

What effect does hyoscine have on the CNS (at normal and toxic doses)?

Answer 15

NORMAL dose: Sedation, amnesia

TOXIC dose: CNS depression or paradoxical CNS excitation (associated with pain); greater permeation into CNS than atropine

Question 16

What is tropic amide used for?

Answer 16

It is used to dilate the pupil to examine the retina

Question 17

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

Answer 17

Anaesthetic premedication

• Causes dilation of airways so easier to intubate the patient
• Causes reduced secretion (saliva + oesophageal) so none gets in airways
• Knocks out the PNS effect in decreasing heart rate and contractility (so only anaesthetic is having thus effect)
• Sedation (for hyoscine)

Question 18

Why is hyoscine able to treat motion sickness?

Answer 18

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 19

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

Answer 19

Parkinson’s Disease

Muscarinic (M4) receptors have an inhibitory effect on Dopaminergic (D1) neurones. In Parkinson’s, nigro-striatal dopaminergic neurones are lost. By blocking the the M4 receptors, you allow the remaining dopaminergic neurones to fire at the maximum rate.

Question 20

Explain the use of muscarinic antagonists in treating asthma and COPD. State the specific antagonist used

Answer 20

Ipratropium Bromide

It removes the parasympathetic mediated bronchoconstriction

Question 21

Explain the role of muscarinic antagonists in treating irritable bowel syndrome. What is the specific Muscarinic receptor type?

Answer 21

Reduces smooth muscle contraction, gut motility and gut secretions

M3

Question 22

State some general unwanted side-effects of muscarinic antagonists.

Answer 22

Hot as hell - decreased sweating

Dry as a bone - decreased secretions

Blind as a bat - cycloplegia (loss of accommodation due to paralysis of ciliary muscle)

Mad as a hatter - CNS disturbance