7: Cholinoceptor Antagonists Flashcards
Define competitive antagonist
except it doesn’t induce a response. Increasing the concentration of the antagonist = increases likelihood of the antagonist binding to a receptor (as opposed to agonist binding)
Interefering w nicotinic cholinoceptors can affect which part of ANS
PS + S depending on which is dominant
How can nicotinic receptors act
- blocking the nicotinic receptors and so prevents ACh from interacting - the drug has affinity to the receptor
- Block the ion channel itself thus they’re called ‘ion channel blockers’. They get into the ion channel and prevent the ions from passing through. If the majority of the action is through ion channel blockade, then the affinity is irrelevant- it is a physical blockade of the receptor.
Define use-dependent block
term referring to the fact that these drugs work most effectively when ion channels are open.
Sympathetically dominated tissues include + effect of nicotnic receptor antagonists:
Kidneys (increase renin secretion, Na and H2O reabsorption) + Blood vessels (particularly vasoconstriction in the gut).
Showsa hypotensive effect. The BP falls because these sympathetically driven responses in the kidneys and blood vessels to increase BP are reduced.
PS dominated tissues include:
Eyes, lungs, bladder, ureters, GIT, exocrine secretions
Effects of nicotinic receptor antagonists on eyes
• Parasympathetic action acts to maintain a level of partial pupil constriction at rest. This allows them to dilate or constrict further when necessary. Administering ganglion blocking drugs will hence cause pupils to dilate.
Effects of nicotinic receptor antagonists on lungs
. The bronchioles are always partially constricted under parasympathetic control so that further dilation or constriction can occur when required. These drugs tend to cause bronchodilation when the parasympathetic effect is lost.
Effects of nicotinic receptor antagonists on bladder, ureter, GIT
Bladder dysfunction, loss of GI motility, tone and secretions
Effects of nicotinic receptor antagonists on exocrine secretions
Reduced secretions overall. S driven sweating will decrease so ability to thermoregulate is affected
Hexamethonium action
Ion channel blockage mechanism is predominant.
First anti-hypertensive drug but many side effects
Trimetaphan
predominant mechanism is receptor antagonism.
Given when pt needs hypotensive during surgery/ given in specific situations
How does alpha-bungarotoxin work
targets the skeletal muscle of the somatic NS. This causes paralysis of the skeletal muscle and diaphragm which leads to suffocation and death.
Muscarinic receptor antagonists have effects on which part of ANS
PNS
Give examples of nicotinic receptor antagonists
hexamethonium + trimetaphan
Give examples of muscarinic receptor antagonists
atropine + hyoscine + topicamide
Effects of high dose atropine
restlessness + CNS agitation
Effects of hyoscine at normal and high dose
Normal: sedative and amnesia
High: CNS depression and paradoxical CNA excitation
How do you treat motion sickness
Hyoscine patch blocks muscarinic receptors in vomiting centre to stop feeling nausea.
Which, atropine/hyoscine, penetrates brain better?
hyoscine - more lipid soluble
Topicamide uses
a muscarinic receptor antagonist for the eye. The PNS causes iris constriction which then causes the pupil to get smaller. With the use of an antagonist, the pupil will dilate instead.
This is used in eye exams to examine the retina.
Uses of muscarinic receptor antagonists
COPD + Asthma
Parkinsons
Anaesthetic premedication
What is ipratropium bromide
Muscarinic receptor antagonist - easier to trap in the lungs when inhaling. It is quite difficult for this drug to cross membranes. The drug has its blocking effect on the muscarinic receptors in the airways and due to its polar molecule attached, it cannot cross through into the blood so it doesn’t have a muscarinic side effects. It’s chosen over atropine bc of quaternary N – v polar.
Muscarinic receptor antagonist unwanted effects
- Hot as Hell Causes decrease in sweating and loss of thermoregulation
- Dry as a bone Reduced secretions (PNS regulates these)
- Blind as a bat Ability to focus on near objects is PNS driven so if the muscarinic receptors are blocked, the ability to focus is lost (Cyclopegia)
- Mad as a hatter CNS disturbance
Which medication used to treat atropine poisioning
Physostigmine - blocks acetylcholinesterases. Increase in ACh in synapse outcompetes atropine
How does botulinum toxin work
Prevents ACh from being exocytosed and getting to the synapse. It interferes with the SNARE complex. Botulinum prevents the vesicles docking with the membrane and then getting out. It is very dangerous toxin and potent
