Cholinoreceptor Antagonists Flashcards
What is affinity?
ability to bind to a receptor - both agonist and antagonist
What is efficacy?
ability to induce a biological response - agonist only
Where are nicotinic receptors found?
ALL autonomic ganglia
What are the properties of glanglion blocking drugs (GBDs)?
(nicotinic receptor agonists)
GBDs can act to both antagonise the receptorAND/OR physically block the ion-channel itself.
Use-dependant blocks – the drug works best when the channel is open so the more the receptor is used, the more it is blocked (e.g
- Opposite to most with the more agonist meaning the less effective the drug is.
Incomplete blocking–Ion-channel blockade is only partial (as some ions still pass through)
Some GBDs do NOT have affinity as some types DON’T bind to the receptor, just block the ion-channel itself.
What are the effects of GBDs on the body (at rest)?
Depends on whether PNS or SNS is dominant at the time - e.g at rest after being given a GBD, you would expect to see an increased HR and bronchodilation
CVS effects: hypotension – blood vessel vasoconstriction inhibited and kidney renin secretion inhibited (so no AngII).
Smooth muscle effects: pupil dilation, decreased GI-tone, bladder dysfunction, bronchodilation.
Exocrine secretions: decreased secretions.
What are examples of GBDs?
Hexamethonium – the first anti-hypertensive drug used but LOTS of side effects as very general.
- Primarily an ion-channel blocker (so not a lot of affinity).
Trimetaphan – used for when you want hypotension during surgery, IV-administered, short acting.
- Primarily a receptor antagonist (so has affinity).
BOTH drugs can however both antagonise and block nicotinic receptors.
a-bungarotoxin is an example of a GBD that is irreversible (used by snakes).
- This drug binds mainly to somatic nicotinic receptors (NRs) whereas the GBDs above bind to autonomic NRs.
What are the CNS effects of muscarinic receptor antagonists (MRAs)?
Atropine:
- Normal dose – little effect.
- Toxic dose – mild restlessness -> agitation.
Hyoscine:
- Normal dose – sedation, amnesia.
- depression or paradoxical CNS excitation (associated with pain).
• Possibly due to a greater permeability through the BBB into the brain.
What are the opthalmic effects of MRAs?
Tropicamide:
- Used in examination of the retina – causes dilation/miosis.
How can MRAs be used as an anaesthetic 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 a hyosine patch be used to treat motion sickness?
motion sickness = mismatch between senses
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.
How can MRAs be used for Parkinson’s Disease?
In Parkinson’s disease, the substantia nigra neurones are lost which usually produce dopamine for the striatum. The lack of dopamine gives the Parkinson’s disease symptoms.
However, a muscarinic receptor antagonist drug decreases the negative inhibition on release of dopamine into the striatum from another source (muscarinic M4 receptor) meaning dopamine can continue to be released into the striatum.
What are the respiratory effects of MRAs?
Ipratropium Bromide:
- 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 gastrointestinal effects of MRAs?
Treats irritable bowel syndrome as the MRA decreases GI tone and secretions
What are some 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).
Mad as a hatter – CNS disturbance (i.e. tremors etc.).
Which drugs would you take to treat an atropine overdose?
Bethanechol – muscarinic receptor agonist.
Ecothiopate – Irreversible anticholinesterase.
Physostigmine – anticholinesterase (drug that’s actually used)
You would want to give a drug that either enhanced ACh activity (anticholinesterase) or inhibits atropine.
Atropine is competitive inhibitor for ACh - outcompetes at high doses - anticholinesterase -> build up of ACh -> more ACh receptor complexes - > parasympathetic response returns
