Cholinoceptor Antagonists Flashcards
What are Nicotinic Receptor Antagonists known as?
Ganglion Blocking Drugs
What part of the ANS do Nicotinic Receptor Antagonists target?
Both SNS and PNS - both use Nicotinic ACh receptors on the ganglia
What term is used to describe the degree to which nicotinic receptor antagonists block?
Use-dependent Block - They work best when the ion channels are open (when more agonist is present)
How do Hexamethonium and Trimetaphan work?
The enter the ion channels connected to nicotinic receptors and block the flow of ions through them
What determines the effect of a Nicotinic receptor antagonist in a particular tissue?
Which branch of the ANS is dominant in that tissue
What is the effect of Nicotinic Receptor antagonists in the Kidneys?
Which branch of the ANS is dominant?
Sympathetically dominated - Decreased Renin secretion leads gives hypotensive effect
What is Hexamethonium?
Why is it no longer used?
First Anti-hypertensive. Nicotinic Receptor Antagonist.
Very generalised action and high side-effect profile - superseded by more selective agents
What type of drug is Trimetaphan?
How is it used?
Ganglion blocking drug - Nicotinic receptor antagonist
Very potent hypotensive drug used in surgery
Why are nicotinic receptor blockade antagonists not used as drugs?
Tend to be irreversible - lead to a loss of autonomic function.
Found in some snake venoms
What branch of the ANS will Muscarinic Receptor Antagonists effect?
PNS (+ Cholinergic SNS)
Name 3 Muscarinic Receptor Antagonists
Atropine
Hyoscine
Tropicamide
What does Atropine cause at normal and toxic doses?
Normal: Little effect (mild restlessness)
Toxic: Agitation
What does Hyoscine cause at normal and toxic doses?
Normal: Sedation
Toxic: CNS depression or paradoxical CNS excitation (associated with pain)
Why do Atropine and Hyoscine particularly target the CNS?
They are M1 and M5 selectove
What type of drug is Tropicamide and why is it used?
Muscarinic receptor antagonist - acts on receptors within the iris to cause pupil dilation
Used when examining the retina
Why might Muscarinic Receptor antagonists be used as anaesthetic premedication?
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
What is a Hyoscine patch used to treat and how?
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
Name 5 conditions Muscarinic receptor antagonists can be used to treat:
Motion Sickness
Parkinsons
Asthma
COPD
Irritable bowel syndrome
How can Muscarinic receptor antagonists be used in treating Parkinson’s disease?
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
Which muscarinic receptor antagonist is used in treating asthma and COPD?
How does it work?
Ipratropium bromide
It removes the effects of bronchoconstriction
What is the difference between Ipratropium bromide and atropine?
What does this mean?
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.
What are the four main side effects of Muscarinic receptor antagonists?
Decreased sweating
Reduced secretions
Cycloplegia - Paralysis of ciliary muscle leading to loss in accommodation ability of the lens
Agitation, restlessness and confusion
How can Muscarinic receptor antagonists be used to treat Irritable Bowel Syndrome?
Knocking out parasympathetic effects (M3) in the gut reduces smooth muscle contraction, gut motility and secretions, relieving symptoms of IBS
What are the six main effects of Nicotinic receptor antagonists?
- Hypotension
- Pupil Dilation
- Bronchodilation
- Bladder Dysfunction
- Decrease in GI tone
- Decrease in secretions
What is Botulinum toxin and how does it work?
Most deadly and potent toxin in the world
Binds to the SNARE complex preventing ACh vesicle exocytosis
Botox is used to paralyse skeletal muscle
How is atropine poisoning treated?
With an anti-cholinesterase like Physostigmine
Prevents ACh breakdown so ACh will start to outcompete the atropine blocking the receptors
