PHARM 7: Cholinoceptor Antagonists Flashcards
define affinity
the strength with which an agonist binds to a receptor
- to form a drug receptor complex
define efficacy
once a drug has bound to the receptor,
the ability to transduce a response and activate intracellular signaling pathways
affinity is shown by:
and
efficacy is shown by:
affinity is shown by: both agonists + antagonists
efficacy is shown by: agonist only
What are the 2 groups of cholinoceptors ?
- Nicotinic
- Muscarinic
What are the 2 ways in which you can interfere with an ion channel linked receptor ?
a) block receptor (receptor blockade antagonists)
- -> prevents ion channels from opening
- -> causes total loss of autonomic function
b) block ion channel itself (ganglionic blocking drugs)
How do ganglion blocking drugs work?
- Ganglion blockage drugs block the ion channel
- prevents ions from moving through the channel pore
- it interferes with both Para + Sympa action
How do ganglion blocking drugs work?
- Ganglion blockage drugs block the ion channel
- prevents ions from moving through the channel pore
- it interferes with both Para + Sympa action
What is Use dependent block?
- if more agonist = present at the receptor,
- there is more opportunity for antagonists to block the channel so these drugs become more effective
- i.e means that the drug is more effective when the channels are open
note: this is an ‘incomplete block’ - slows it down
Which of the following effects would be observed at rest after treatment with a ganglion blocking drug?
a) Increased heart rate
b) Pupil constriction
c) Bronchodilation
d) Detrusor contraction
e) Increased gut motility
answer =
a) Increased heart rate
c) Bronchodilation
- AT REST –> so opposite of that
what was hexamethonium previously used as?
why is it no longer used?
- previously used as anti hypertensive
- no longer used as side effect profile = v large
note: more of a channel blocker
What are some uses of Trimetaphan?
is it long lasting or short acting?
- used during surgery when controlled hypotension is needed
- short acting
note: more of a receptor blocker
What effect does alpha bungarotoxin have on the body?
- alpha bungarotoxin = snake venom
- it is a nicotinic receptor blockade antagonist
- targets skeletal muscle of the somatic nervous system
- causing paralysis of skeletal muscle + diaphragm
- leading to suffocation + death
In normal doses, atropine causes:
In normal doses, hyoscine:
in higher does both cause:
atropine
- little CNS effect
Hyoscine
- good sedative
high dose atropine = agitation
high dose hyoscine = CNS depression
- -> different responses may be due to atropine being less M1 selective
- so hyoscine = more effective on m1
- also hyoscine = more lipid soluble than atropine
What is Tropicamide?
and what is its use
Tropicamide = Muscarinic receptor antagonist
- acts on receptors in iris
- causes pupil dilation –> useful for retinal examination
Why are muscarinic receptor antagonists good as an anesthetic premedication ?
- causes airways to dilate (useful for gas mask + intubation)
- dries throat –> reduces risk of aspiration
- reduces secretion in the lungs (+ mouth + saliva)
- removes parasympathetic effect on the heart (anesthetic reduced rate + contractility anyways –> so to reduce doubling effect of slowing down heart parasympathetic influence = removed)
other than as a sedative, why is hyoscine used as a patch for motion sickness?
- neurological effect
- muscarinic receptors = important in relaying info from inner ear –> vomiting centers
- muscarinic receptor ANTAGONISTS reduce flow of info from inner ear labyrinth (periphery) –> brain
- reducing nausea.
note: hyoscine patch interferes with the vomiting signal –> less nausea
How do muscarinic receptor antagonists act as a treatment method for parkinson’s disease?
- in parkinson’s nigrostrial dopamine neurons = lost
- nigrostrial dopamine neurons (in basal ganglia) –> important in fine control of movement
NORMALLY: muscarinic receptors have inhibitory effect on dopamine signaling
- if person has parkinson’s, they have already LOST these neurones so we don’t want these inhibitory effect anymore
SO
- antagonists take out M4 receptors
- which causes inhibitory effect to be lost
- and so remaining D1 dopamine neurons can fire at max rate
parkinson - u lose dopaminergic neurones
- so d1 receptor stimulation is less effective
- so fine control of movement is lost
- drug –> enhances the D1 receptor
How do muscarinic receptor antagonists act as a treatment method for asthma + COPD?
give an example
- administered as an aerosol
- aerosol = +vely charged
- -> so doesn’t get out of lungs very well
- so it is held localized in the lungs
e. g IPRATROPIUM BROMIDE –> removed effects of bronchoconstriction
- helps in obstructive airway diseases.
How do muscarinic receptor antagonists act as a treatment method for Irritable Bowel Syndrome (IBS) ?
- it knocks out parasympathetic effect in gut
- and reduces smooth muscle contraction/gut motility/ gut secretions
- relieves symptoms
List unwanted side effects of muscarinic receptor antagonists
- decreased sweating
- reduced secretions (e.g saliva, mucous)
- affects accommodation ability of colliery muscle (cycloplegia)
- high dose: CNS agitation/restlessness/confusion
- risk of poisoning
note: hot as hell
dry as bone
blind as a bat
mad as a hatter
Describe the mechanism of botulinum toxin
- NORMALLY: SNARE complex allows vesicles to fuse with memb + release ACh
BUT
- Botulinum toxin binds to SNARE complex –> prevents release of ACh –> vesicle remains in nerve
–> very potent
how is botulinum toxin used clinically?
- botox = injected in the face to remove wrinkles
- locally paralyses skeletal muscle
Why might nicotinic antagonists cause hypotension?
- increase in HR
- interference with vasoconstriction
- so there is more vasodilation and TPR goes down –> hypotension
- renin release decreases
- -> hypotension
What is the effect of nicotinic antagonists on exocrine secretions?
- decrease in secretions
Which of the following drugs would you administer to treat an atropine overdose? a) Bethanechol b) Ecothiopate c) Hyoscine d) Physostigmine e) Pralidoxime
ANSWER: d) Physostigmine
technically both Ecothiopate + Physostigmine work
but b = irreversible (long + lasting effects) and usually you want a drug that is reversible
How does physostigmine
used for atropine poisoning?
- in atropine poisoning, you have are no. of atropine binding to muscarinic receptor
- so you get muscarinic side effects
- if you use physostigmine
- which blocks acetyl cholinesterase reversibly
- so Ach becomes dominant
- and it outcompetes atropine
- so normal function is restored
Give two examples of ganglion blocking drugs
- Hexamethonium
- Trimetaphan
What are ganglionic blocking drugs also known as ?
Nicotinic receptor antagonists
describe the characteristic of side effects of Trimetaphan
- depends on whether SNS / PSN is dominant
