Cholinoceptor Antagonists

Question 1

What are Nicotinic Receptor Antagonists known as?

Answer 1

Ganglion Blocking Drugs

Question 2

What part of the ANS do Nicotinic Receptor Antagonists target?

Answer 2

Both SNS and PNS - both use Nicotinic ACh receptors on the ganglia

Question 3

What term is used to describe the degree to which nicotinic receptor antagonists block?

Answer 3

Use-dependent Block - They work best when the ion channels are open (when more agonist is present)

Question 4

How do Hexamethonium and Trimetaphan work?

Answer 4

The enter the ion channels connected to nicotinic receptors and block the flow of ions through them

Question 5

What determines the effect of a Nicotinic receptor antagonist in a particular tissue?

Answer 5

Which branch of the ANS is dominant in that tissue

Question 6

What is the effect of Nicotinic Receptor antagonists in the Kidneys?

Which branch of the ANS is dominant?

Answer 6

Sympathetically dominated - Decreased Renin secretion leads gives hypotensive effect

Question 7

What is Hexamethonium?

Why is it no longer used?

Answer 7

First Anti-hypertensive. Nicotinic Receptor Antagonist.

Very generalised action and high side-effect profile - superseded by more selective agents

Question 8

What type of drug is Trimetaphan?

How is it used?

Answer 8

Ganglion blocking drug - Nicotinic receptor antagonist

Very potent hypotensive drug used in surgery

Question 9

Why are nicotinic receptor blockade antagonists not used as drugs?

Answer 9

Tend to be irreversible - lead to a loss of autonomic function.

Found in some snake venoms

Question 10

What branch of the ANS will Muscarinic Receptor Antagonists effect?

Answer 10

PNS (+ Cholinergic SNS)

Question 11

Name 3 Muscarinic Receptor Antagonists

Answer 11

Atropine

Hyoscine

Tropicamide

Question 12

What does Atropine cause at normal and toxic doses?

Answer 12

Normal: Little effect (mild restlessness)

Toxic: Agitation

Question 13

What does Hyoscine cause at normal and toxic doses?

Answer 13

Normal: Sedation

Toxic: CNS depression or paradoxical CNS excitation (associated with pain)

Question 14

Why do Atropine and Hyoscine particularly target the CNS?

Answer 14

They are M1 and M5 selectove

Question 15

What type of drug is Tropicamide and why is it used?

Answer 15

Muscarinic receptor antagonist - acts on receptors within the iris to cause pupil dilation

Used when examining the retina

Question 16

Why might Muscarinic Receptor antagonists be used as anaesthetic premedication?

Answer 16

Sedative effects

Dilation of airways and reductions in secretions to aid in intubation

Removes parasympathetic effects on the heart (reducing HR and contractility) which anaesthetic will do anyway - doubling of effect avoided

Question 17

What is a Hyoscine patch used to treat and how?

Answer 17

Motion Sickness

Muscarinic receptors are important in relaying information from the labyrinth of the inner ear to the vomiting centres.

Muscarinic receptor antagonists reduce the flow of information from the labyrinth to the brain - reducing nausea

Question 18

Name 5 conditions Muscarinic receptor antagonists can be used to treat:

Answer 18

Motion Sickness

Parkinsons

Asthma

COPD

Irritable bowel syndrome

Question 19

How can Muscarinic receptor antagonists be used in treating Parkinson’s disease?

Answer 19

Nigrostrial Dopamine neurones are lost in Parkinson’s

Muscarinic receptors have a negative effect on dopamine signalling from these neurones - good normally, but in Parkinson’s 60-70% of dopamine-producing neurones have been lost

Antagonists take out M4 receptors removing the inhibitory effect and the last few D1 dopamine neurones can fire at maximum rate

Question 20

Which muscarinic receptor antagonist is used in treating asthma and COPD?

How does it work?

Answer 20

Ipratropium bromide

It removes the effects of bronchoconstriction

Question 21

What is the difference between Ipratropium bromide and atropine?

What does this mean?

Answer 21

Ipratropium is like atropine but also has a large quaternary amine structure.

This makes it positively charged, meaning it is unable to cross the lipid membrane and is localised to the lungs only.

Question 22

What are the four main side effects of Muscarinic receptor antagonists?

Answer 22

Decreased sweating

Reduced secretions

Cycloplegia - Paralysis of ciliary muscle leading to loss in accommodation ability of the lens

Agitation, restlessness and confusion

Question 23

How can Muscarinic receptor antagonists be used to treat Irritable Bowel Syndrome?

Answer 23

Knocking out parasympathetic effects (M3) in the gut reduces smooth muscle contraction, gut motility and secretions, relieving symptoms of IBS

Question 24

What are the six main effects of Nicotinic receptor antagonists?

Answer 24

• Hypotension
• Pupil Dilation
• Bronchodilation
• Bladder Dysfunction
• Decrease in GI tone
• Decrease in secretions

Question 25

What is Botulinum toxin and how does it work?

Answer 25

Most deadly and potent toxin in the world

Binds to the SNARE complex preventing ACh vesicle exocytosis

Botox is used to paralyse skeletal muscle

Question 26

How is atropine poisoning treated?

Answer 26

With an anti-cholinesterase like Physostigmine

Prevents ACh breakdown so ACh will start to outcompete the atropine blocking the receptors