Cholinoceptor Antagonists Flashcards
define affinity
y is the ability to bind to a receptor – both agonist and antagonist.
define efficacy
is the ability to induce a biological response – agonist only.
o i.e. ACh has efficacy for the muscarinic acetylcholine receptor.
where are nicotinic receptors always present?
Nicotinic receptors are present at ALL autonomic ganglia.
what are nicotinic receptor antagonists also called?
Also called ganglion blocking drugs
what are the two groups of cholinoreceptors?
nicotinic
-present on all autonomic ganglia
muscarinic
-present within the effector organs of the parasympathetic nervous system as well as the sweat glands innervated by the SNS
how can the ganglion blocking drugs act to work?
there are two ways in which you can interfere with an ion-channel linked receptor; blocking the receptor or the ion channel itself.
GBDs can act to both antagonise the receptor AND/OR physically block the ion-channel itself.
GBDs block the ion channel thus preventing ions from moving through the channel pore.
what does use-dependent block mean?
Use-dependant blocks – the drug works best when the channel is open so the more the receptor is used, the more it is blocked. Opposite to most with the more agonist meaning the less effective the drug is.
More agonist present = more opportunity for the antagonist to block the channel. But hence these drugs only result in incomplete block.
define incomplete blocking
Incomplete blocking – Ion-channel blockade is only partial (as some ions still pass through).
do all GBD have affinity?
Some GBDs do NOT have affinity as some types DON’T bind to the receptor, just block the ion-channel itself.
examples of GBDs
Hexamethonium
Trimetaphan
what are the effects of GBD on the body
CVS effects; hypotension – blood vessel vasoconstriction inhibited and kidney renin secretion inhibited (so no AngII).
§ Smooth muscle effects; pupil dilation, decreased GI-tone, bladder dysfunction, bronchodilation.
§ Exocrine secretions; decreased secretions.
why do GBDs cause hypotension?
reduced renin secretion from the kidney
vasodilation
*the more dominant pathways lost
clinical use of hexamethonium
Hexamethonium – the first anti-hypertensive drug used but LOTS of side effects as very general.
o Primarily an ion-channel blocker (so not a lot of affinity).
clinical use of trimetaphan
Trimetaphan – used for when you want hypotension during surgery, IV-administered, short acting.
o Primarily a receptor antagonist (so has affinity).
what is a-bungarotoxin?
a-bungarotoxin is an example of a GBD that is irreversible (used by snakes).
o This drug binds mainly to somatic nicotinic receptors (NRs) whereas the GBDs above bind to autonomic NRs.
what are muscarinic receptors antagonists?
Muscarinic Receptor Antagonists (MRAs):
§ This is mainly a PNS antagonist as the only muscarinic receptor in the SNS is found in sweat glands.
o So expect mainly inhibition of PNS.
what are two types of MRAs?
Two examples of MRAs are:
o Atropine.
o Hyoscine.
what are the CNS affects of atropine?
Atropine:
§ Normal dose – little effect.
§ Toxic dose – mild restlessness à agitation.
what are the CNS effects of hyoscine?
Hyoscine:
§ Normal dose – sedation, amnesia.
§ Toxic dose – CNS depression or paradoxical CNS excitation (associated with pain).
· Possibly due to a greater permeability through the BBB into the brain.
what are the ophthalmic effects of MRAs and what is the drug used?
Tropicamide:
§ Used in examination of the retina – causes dilation/miosis.
how can MRAs be used in anaesthetic pre-medication? what are the effects?
The MRAs block the PNS and so block; bronchoconstriction (so bronchodilates), watery secretions (more thick secretions decreases chance of aspirations), decreased HR and contractility (protect the heart from slowing effects of other drugs) and also sedates the patient
what can the hyoscine patch be used in?
Inhibits the muscarinic receptors in the vomiting centre so the sensory mismatch (from a mismatch from what the eyes see and what the labyrinth reports in balance) cannot induce vomiting when suffering from motion sickness.
how can MRAs be used in Parkinson’s disease?
Neurological – Parkinson’s Disease – lack of dopamine in the CNS:
o MRA drug:
§ In Parkinson’s disease, the substantia nigra neurones are lost which usually produce dopamine for the striatum. The lack of dopamine gives the Parkinson’s disease symptoms. However, a muscarinic receptor antagonist drug decreases the negative inhibition on release of dopamine into the striatum from another source meaning dopamine can continue to be released into the striatum.
what effects can ipratropium bromide have?
Ipratropium Bromide:
§ Used for Asthma and COPD as it causes bronchodilation.
§ Similar molecular shape to atropine but has an extra nitrogen-containing polar group attached that allows it to linger more in the lungs as it cannot cross the mucosa as easily as atropine would.
