Pharm 7 - Cholinoceptor Antagonists Flashcards
Define affinity.
the strength with which an agonist binds to a receptor
Define efficacy.
once the drug has bound to a receptor, the ability of the drug to produce a response and activate intracellular signalling pathways
Agonists have…
affinity and efficacy
Antagonist have…
affinity but no efficacy
Where are nicotinic receptors found?
all autonomic ganglia
at neuromuscular junctions
Where are muscarinic receptors found?
at parasympathetic effector organs and sweat glands
What are nicotinic receptor antagonists called?
Ganglion blockers
block the ion channel itself so prevent ions going through
Give 2 examples of ganglion blocking drugs.
Hexamethonium
Triemethaphan
What does use dependent block mean?
drugs work more effectively when the ion channels are open
e.g. if agonist there to open the channel, antagonist will work more effectively
What dominates the effect of ganglion blockade in a tissue?
Which limb of ANS dominates in the tissue
Which tissues are sympathetic dominated?
Vasculature
Kidneys
What is the overall effect of ganglion blockade in terms of loss of sympathetic dominance?
hypotension
as takes away the ability of kidneys to produce renin
Which tissues are parasympathetically dominated?
Eyes - maintains partial pupillary constriction at rest
Lungs - causes bronchoconstriction
Bladder, ureters and GI tract
Exocrine functions
What would the effect of ganglion blockage be on these tissues?
Bronchodilation Pupil dilation Bladder dysfunction Loss of GI motility and secretions Decrease in exocrine secretion
What is hexamethonium?
ganglion blocker that was used as anti-hypertensive
What is trimethaphan?
only ganglion blocking drug still in clinical use
causes hypotension - needed for surgery
In what types of chemicals are nicotinic receptor blockade antagonists found?
Toxins and venoms
How do receptor blockade antagonists have their effect?
irreversible
Give an example of nicotinic receptor blockade antagonist.
Alpha bungarotoxin
What are the targets of muscarinic receptor antagonists?
Parasympathetic effector organs and sweat glands
Give 4 examples of muscarinic receptor antagonists?
Atropine
Hyoscine
Tropicamide
Ipratropium Bromide
What effect do muscarinic receptor antagonists have on the CNS?
atropine = low dose = restlessness
hyoscine = sedation
high dose = CNS agitation
What is tropicamide used for?
used to dilate the pupil to observe the retina
What is an important use of muscarinic receptor antagonists with regard to surgery?
Anaesthetic premedication
causes dilation of airways so easier to intubate patient
reduces secretion so less risk of aspiration
knocks out parasympathetic nervous system in decreasing heart rate and contractility
What can hyoscine be used to treat?
Motion sickness
muscarinic receptors relay information from labyrinth in the inner ear to vomitting centre
so blocking these will reduce nausea
What degenerative disorder can be treated using muscarinic receptor antagonists?
Parkinson’s disease
Muscarinic receptors have inhibitory impact on the dopamine neurones in the nigro-striatal
Explain the use of muscarinic antagonists in treating asthma and COPD?
Ipratropium bromide
removes parasympathetic mediated bronchoconstriction
so used to treat COPD and asthma
Explain the role of muscarinic antagonists in treating IBS?
reducing smooth muscle contraction, gut motility and gut secretions
State some general unwanted side effects f
Hot as hell
Dry as a bone
Blind as a bat
Mad as a hatter
How would you treat muscarinic receptor antagonist poisonin?
anticholinesterase e.g. physostigmine
Describe botulinum toxin causes paralysis.
binds to SNARE complex and prevents fusion of vesicles containing acetylcholine
so prevents acetylcholine release into nerve terminal
muscle paralysis
State the overall effects of ganglion blocking drugs on a subject at rest?
Hypotension Pupil dilation Bronchodilation Bladder dysfunction Decreased GI tone Decreased GI secretions
