Cholinoceptor antagonists Flashcards
What are the few clinically useful nicotinic receptor antagonists called and how do they block the receptor?
Ganglion Blockers
These block the ion channel itself (so not the receptor), thus preventing the ions from moving through the pore
Give two examples of ganglion blocking drugs.
Hexamethonium
Trimethaphan
What does ‘use-dependent block’ mean, in regards to nicotinic receptor antagonists?
The drugs work most effectively when the ion channels are open (i.e. when. more agonist is present at the receptor)
What determines the effect of ganglion blockade in a tissue?
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)
Which tissues are sympathetic dominated (at rest)?
Vasculature
Kidneys
What is the overall effect of ganglion blockade in terms of loss of sympathetic dominance?
- Decreased sympathetic-mediated vasoconstriction
- Decreased renin secretion from kidneys (=decreased sodium and water reabsorption)
=> Hypotension
Which tissues are parasympathetic dominated (at rest)? What effects does it have on the tissue?
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
What would the effect of ganglion blockage be on these tissues?
Bronchodilation Pupil dilation (blurred vision) Bladder dysfunction Loss of GI motility and secretions Decrease in exocrine secretion
What is the clinical use of hexamethonium and trimetaphan?
Anti-hypertensive drug (no longer used due to the many side effects)
Hypotensive drug during surgery (short acting)
In what types of chemicals are nicotinic receptor blockade antagonists found?
Toxins and venoms
How do receptor blockade antagonists work?
Irreversible covalent binding to the receptor preventing the ion channels from opening
Give an example of a nicotinic receptor blockade antagonist
Alpha-bungarotoxin (from common krait snake venom)
Give four examples of muscarinic receptor antagonists
Atropine (plant based)
Hyoscine (plant based)
Tropicamide
Ipratropium Bromide
What effect does atropine have on the CNS (at normal and toxic doses)?
NORMAL dose: little effect
TOXIC dose: Mild restlessness and Agitation (Less M1 selective)
What effect does hyoscine have on the CNS (at normal and toxic doses)?
NORMAL dose: Sedation, amnesia
TOXIC dose: CNS depression or paradoxical CNS excitation (associated with pain); greater permeation into CNS than atropine
What is tropic amide used for?
It is used to dilate the pupil to examine the retina
What is an important use of muscarinic receptor antagonists with regards to surgery? Why is it useful in this circumstance?
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)
Why is hyoscine able to treat motion sickness?
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.
What degenerative disorder of the central nervous system can be treated by muscarinic receptor antagonists? Explain how.
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.
Explain the use of muscarinic antagonists in treating asthma and COPD. State the specific antagonist used
Ipratropium Bromide
It removes the parasympathetic mediated bronchoconstriction
Explain the role of muscarinic antagonists in treating irritable bowel syndrome. What is the specific Muscarinic receptor type?
Reduces smooth muscle contraction, gut motility and gut secretions
M3
State some general unwanted side-effects of muscarinic antagonists.
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
