Cholinoceptor antagonists Flashcards
(31 cards)
what is the definition of affinity?
ability of drug to bind to receptor and produce drug-receptor complex
Do both agonists and antagonists have affinity?
Yes
Also remember that the stronger the affinity, the more longer-lasting the complex
What does efficiacy mean?
the ability of drug to induce a biological response
Do agonists and antagonists have efficiacy?
NO agonists have efficiacy and antagonists do not.
What is a common muscarinic antagonist?
atropine
What do nicotinic receptor antagonists do?
Mostly block the receptor (classic antagonist) but some act as physical channel blockers (they are technically ion channel blockers- not classic antagonist).
Another word for nicotinic receptor antagonist is ‘ganglion blocking drug’
Give 2 examples of nicotinic receptor antagonists
- Hexamethonium (primarily blocking ion channel- there is not a lot of affinity)
- Trimetaphan (better at blocking the receptor- has affinity).
What does use-dependent block mean?
The more open the channels are the more effective the drugs are.
I.e. the more competitive agonists around, the more the channel will be used and therefore the better the drug works (because the channel will be open). There will never be complete blockade- the drug just makes it more difficult for molecules to pass through.
What is the difference between antagonism and a physical blockade?
Sitting in the channel pore is a physical blockade.
Note that not all nicotinic receptor antagonists will have affinity as some will just act by blocking ion channel itself.
What is the main effect of nicotinic antagonists?
Nicotinic receptor antagonists can cause hypotension.
Vasoconstriction is inhibited- TPR goes down and so does BP. Reduces renin secretion too. Therefore, there is less aldosterone and less water reabsorption.
What are the other effects of nicotinic receptors?
They will also dilate your pupils (light-sensitive), will interfere with GI and bladder function (causing constipation), and reduced secretions (make it difficult to produce saliva, gut secretions and sweat).
are hexamethonium and trimetaphan reversible?
yes
Why is hexamethonium not used as an anti-hypertensive?
As there are too many side effects and the drug is too general. Still used carefully today. Trimetaphan used to control blood flow during surgery.
What is an irreversible nicotinic antagonist? and what happens to the body?
Alpha- bungarotoxin binds very strongly to the receptor, blocking it irreversibly. Found in snake venom.
This toxin mainly binds to somatic nicotinic receptor (NRs) whereas the nicotinic receptors above are for the autonomic nervous system.
Toxins are designed to target skeletal muscle (diaphragm doesn’t work and causes paralysis and death).
A general note about muscarinic receptor antagonists
Generally, they are PNS antagonists because the only muscarinic receptors found in the SNS are found in sweat glands.
What are the 2 most common muscarinic antagonists (hint in the cards before)?
- Atropine
- Hyoscine
What are the CNS effects of atropine?
Normal dose – Little effect
Toxic dose - Mild restlessness –> Agitation
(Less M1 selective)
What are the CNS effects of hyoscine?
Normal dose – Sedation, amnesia- useful therapeutic effects
Toxic dose – CNS depression or paradoxical CNS excitation (associated with pain- not common)
(Greater permeation into CNS. Influence at
therapeutic dose)
Why is there a difference between the CNS effects of hyoscine and atropine?
Hyoscine is more M1 selective and will get there faster. It is also theorised that hyoscine is more lipid-soluble and can penetrate deeper into the brain.
What are the ophthalmic effects of tropicamide (muscarinic antagonist)?
Use of tropicamide to examine the back of the retina. It paralyses the muscle which causes muscle constriction so the pupil dilates
What is the role of muscarinic antagonists as anaesthetic premedication?
It blocks bronchoconstriction and you have dilated airways (useful if you are inhaling anaesthetic.
Also blocks the production of watery secretions- saliva- possibility for saliva to go down the airways causing choking so don’t want that in surgery.
It also reduces the rate and contractility of the heart. Protects the heart from slowing effects of other drugs and acts like a sedation.
What is the role of muscarinic antagonists in motion sickness aid?
Motion sickness is an information mismatch- between the visual and the labyrinth in the ear. The mismatch is relayed to the vomiting sensor (activates cholinergic nerve).
people with motion sickness often use a hyoscine patch. The patch inhibits muscarinic receptors in the vomiting centre reducing motion sickness.
How do muscarinic antagonists help with Parkinson’s disease?
Caused by loss of dopaminergic neurones. Therefore, less dopamine release- not detected by D1 Receptors.
Increases the D1 receptors so the little dopamine Is more effective.
What is the muscarinic antagonist action with regards to D1 receptors?
The muscarinic antagonist is given to reduce M4 receptors leaving the D1 receptors alone, allowing it to sense the dopamine.
