Cholinoceptor Antagonists Flashcards
Where are nicotinic receptors present?
at all autonomic ganglia
What are nicotinic receptor antagonists also known as?
ganglion blocking drugs
What are the two ways in which ganglion blocking drugs work?
Antagonise the receptor and/or physically block the ion-channel itself (nicotinic)
What does use dependant blockage mean?
The drug works best when the channel is open so the more the receptor is used, the more it is blocked.
What is incomplete blocking?
Ion-channel blockade is only partial (as some ions still pass through)
Why do some GBDs not have affinity?
They don’t bind to the receptor, just block the ion-channel itself
What does the effect of GBDs depend on?
Which system is more dominant e.g. PNS or SNS
Give some of the effects of the PNS
eye: constriction of pupil and contraction of ciliary muscle
trachea and bronchioles: constriction
salivary glands: copious watery secretion
ureters and bladder: contraction of detrussor and relaxation of trigone and sphincter
heart: reduced HR and contractility
GI: increases motility/tone and more secretions
Give some of the effects of the SNS
eye: pupil dilation
trachea and bronchioles: dilation
salivary glands: thick viscous secretion
skin: piloerection and more sweating
adipose: lipolysis
liver: glycogenolysis and gluconeogenesis
kidney: increased renin
ureters and bladder: relaxation of detrussor and constriction of trigone and sphincter
heart: increased HR and contractility
GI: reduces motility/tone and less secretions
blood vessels (skeletal m): dilation
blood vessels (skin, mucous membrane and splanchnic area): constriction
What are the CVS effects of GBDs?
Hypotension – blood vessel vasoconstriction inhibited and kidney renin secretion inhibited
What are the smooth muscle effects of GBDs?
Pupil dilation, decreased GI-tone, bladder dysfunction, bronchodilation
What are the exocrine effects of GBDs?
Decreased secretions
Give examples of ganglion blocking drugs and what they were originally used for
hexamethonium and trimetaphan
Anti-hypertensives - both blocks channels and antagonise them
How did hexamethonium work and what was its flaw?
First anti-hypertensive drug used but lots of side effects as very general
An ion-channel blocker (so not a lot of affinity)
How did trimetaphan work and when was it used?
Used for when you want hypotension during surgery, IV-administered, short acting.
A receptor antagonist (so has affinity)
What is alpha bungarotoxin?
A GBD that is irreversible (used by snakes)
Binds mainly to somatic nicotinic receptors (NRs) whereas the GBDs above bind to autonomic NRs
What do muscarinic receptor antagonists mainly work on?
PNS - only found in SNS in sweat glands
Give two examples of MRAs (muscarinic receptor antagonists)
atropine
hyoscine
How can MRAs be useful in treating Parkinson’s? Explain briefly what Parkinson’s involves
- In Parkinson’s disease, the substantia nigra neurones are lost which usually produce dopamine for the striatum to allow fine movement control
- The lack of dopamine gives the Parkinson’s disease symptoms
- Muscarinic receptor antagonist drug decreases the negative inhibition on release of dopamine into the striatum from another source meaning dopamine can continue to be released into the striatum
What are the CNS effects of atropine and hyoscine (high and low doses)?
Atropine:
Normal dose – little effect
Toxic dose – mild restlessness and agitation
Hyoscine:
Normal dose – sedation, amnesia
Toxic dose – CNS depression or paradoxical CNS excitation (associated with pain). Maybe due to a greater permeability through the BBB into the brain
What are the opthalmic effects of tropicamide and how is this useful?
Used in examination of the retina – causes dilation/miosis
How can MRAs be used in anesthetic pre-medication?
The MRAs block the PNS and so block; bronchoconstriction (so bronchodilates), watery secretions (more thick secretions decreases chance of aspirations), decreased HR and contractility (protect the heart from slowing effects of other drugs) and also sedates the patient
How can hyoscine be used to treat motion sickness?
What causes motion sickness?
Inhibits the muscarinic receptors in the vomiting centre so the sensory mismatch (from a mismatch from what the eyes see and what the labyrinth reports in balance) cannot induce vomiting when suffering from motion sickness.
What are the respiratory effects of Ipratropium bromide and what is it used for?
What is its relationship to atropine and why is it preferred to atropine?
- Used for Asthma and COPD as it causes bronchodilation
- Similar molecular shape to atropine but has an extra nitrogen-containing polar group attached that allows it to linger more in the lungs as it cannot cross the mucosa as easily as atropine would
What are the GI uses of MRAs?
Treats irritable bowel syndrome as the MRA decreases GI tone and secretions.
What are the unwanted effects of MRAs?
Hot as hell – decrease in sweating and thermoregulation defects
Dry as a bone – decreased secretions
Blind as a bat – cyclopegia (paralysis of eye muscles so no accommodation/focusing)
Mad as a hatter – CNS disturbance (i.e. tremors etc.)
Which drug can be used to treat an atropine overdose?
A drug that either enhances ACh activity (anticholinesterase) or inhibits atropine so: 1. bethanechol (muscarinic receptor agonist),
ecothiopate (Irreversible anticholinesterase - less preferred as irreversible) and physostigmine (anticholinesterase)
What is botulinum toxin and what does it do?
Parasympatholytics - reduces the activity of the PNS
- One of the most toxic proteins known
- Binds to the ACh vesicles and stops them docking with the inner membrane forming a SNARE complex
