Cholinoreceptor antagonist Flashcards
affinity
ability to bind to a receptor
stronger affinity= longer lasting complex
agonist and antagonist
efficacy
ability to induce biological response
agonists only
where are nicotinic receptors present?
all autonomic ganglia
what are nicotinic receptor antagonists called
ganglion blocking drugs (GBD)
two main action of GBDs
1) anatagonise the receptor
2) physically block off the ion-channel it is linked to
- use dependent
- incomplete
concept of use-dependent blocks (ion channel)
drug is more effective when the channel is open so the more the receptor is used , the more it is blocked
[for receptors, more drug does not mean more effectiveness as they compete for the same receptor]
incomplete blocking (ion channel)
partial ion channel blockage (some ions can still pass_
why can some GBDs be said to have no affinity?
they don’t bind to the receptor but block the ion-channel only
CVS effects of GBD
hypotension- blood vessel vasoconstriction is inhibited and renin secretion is inhibited (no ANG II)
smooth muscle effects of GBD
- pupil dilation
- decreased GI tone
- bladder dysfunction
- bronchodilation
exocrine secretion effects of GBD
decreased secretion
examples of GBDs
hexamethonium- 1st antihypertensive but lots of side effects
trimetaphan- uses for hypertension during surgery, short acting and IV
hexamethonium
ion channel blocker
not alot of affinity
trimetaphan
receptor antagonist therefore has affinity
irreversible GBD
alpha- bungarotoxin of the common krait snake
how is alpha bungarotoxin different to the other GBDs
binds to mainly somatic nicotinic receptors
(to immobilise the prey’s skeletal muscles)
the other GBDs bind to autonomic nicotinic receptors
what are muscarinic receptor antagonists (MRA)?
PNS antagonists (except sweat glands musc receptors)
therefore mainly inhibits PNS stimulation
examples of MRA
- atropine
- hyoscine
CNS effect of atropine
normal dose- little effect
toxic dose- mild restlessness–> agitation
CNS effect of hyoscine
normal dose- sedation, amnesia
toxic dose- CNS depression (or paradoxical CNS excitation, associated with pain- possibly due to greater permeability through BBB)
how do hyoscine and atropine have varying effects despite their similar structures
hyoscine is more M1 selective than atropine
what is used to examine the retina
tropicamide
dilation/mydriasis of the eye (constriction in inhibited) so the pupil expands so the retina can be examined
use of MRAs in anaesthetic pre medication
block PNS block bronchoconstriction block watery secretions decreased heart rate and contractility sedation
treating motion sickness (neurological)
hyoscine patch
- inhibits the muscarine receptors of the vomiting centre
- sickness due to sensory mismatch between eyes and labyrinth)
treatment of Parkinson’s (lack of dopamine)
PD involves the substantial Niagra neurones (Which are lost) producing dopamine for the striatum
MRA decreases the negative inhibition of dopamine release into striatum from another source so dopamine can be released continually
D1 receptors are upregulated by blocking M4 receptors
what MRA is used to treat asthma and COPD
ipratropium bromide
-causes bronchodilation
similar in shape to atropine
-has extra nitrogen-containing polar group attached that allows it to linger more in the lungs without crossing the mucosa in to the blood, like atropine would
GI effects of MRA
treatment of IBS
- MRA decreases GI tone and secretions
unwanted effects of MRA
1) hot- due to decreased sweating and thermoregulation defects
2) dry- decreased secretions
3) blind- cyclopegia (paralysis of eye muscles, no accommodation)
4) mad- CNS disturbance
which drugs would be used to treat atropine poisoning?
1) physostigmine (anti cholinesterase)
2) ecothiopate (irreversible anti cholinesterase)
3) bethanechol (muscarinic receptor agonist)
atoprine competes with ACh, having anti cholinesterase means more ACh remains to outcompete the atropine
what does the botulinum toxin do?
blocks the SNARE complex (ACh vesicles) stopping them from docking and being exocytosed.
