Cholinergic Transmission Flashcards
Synthesis of acetylcholine:
choline precursor is transporter into pre-synaptic nerve endings, transport is rate-limiting step in Each synthesis
Storage of Acetylcholine:
ACh is transported into and stored in nerve terminal vesicles; uptake is mediated by H+-ACh antiporter
Release of Acetylcholine:
arrival of action potential and depolarization of the terminal; influx of calcium and initiation of exocytosis
What drug inhibits release of acetylcholine?
onabotulinumtoxin: Botulinum toxin
T/F. Botulinum toxin is a protein.
TRUE.
What is the mechanism of botulinum toxin?
is a protein that is taken up into cholinergic nerve terminals by receptor-mediated endocytosis; inactive synaptic vesicle protein required for vesicle docking with presynaptic membrane; produced reversible state of cholinergic denervation
T/F. Botulinum toxin produces flaccid paralysis of skeletal muscle.
TRUE.
What is the street name for botulinum toxin?
Botox.
How is botox given and what is it used for?
IM, therapeutic uses for muscle spasms/dystonias, cosmetic, excessive perspiration, overactive bladder
What are side effects of botox?
distant spread beyond injection site can cause serious dysphagia and breathing difficulties, allergic reactions, loss of facial expression
What are the two cholinergic receptor subtypes?
muscarinic and nicotinic
What are the most common muscarinic receptors?
M2 and M3 (there are M1-M5)
Which drug selectively STIMULATES muscarinic receptors?
muscarine (agonist)
Which drug selectively BLOCKS muscarinic receptors?
atropine (antagonist)
What is an example of using atropine?
eye drops in the eye to dilate pupils; antagonists of muscarinic receptor = iris sphincter
What are the most common nicotinic receptors?
Nn(neuronal, ganglia) and Nm(neuromuscular junction)
How is the Nn (neuronal) different than Nm (neuromuscular)?
Nn = 2 alpha and 3 beta, Nm = 2 alpha, beta, GAMMA, and DELTA; nicotine ONLY stimulates Nn, whereas nicotine stimulates AND blocks in Nm
If nicotine persistently blocks the Nn receptors what can occur?
desensitization (depolarizing blockade)
What is a cholinergic antagonists (blocker) of Nn receptor?
mecamylamine
What is a competitive antagonist of Nm
d-tubocurarine
Termination of cholinergic transmission: acetylcholinesterase RAPIDLY terminate cholinergic transmission by what?
Hydrolysis (choline is recycled)
Butyrylcholinesterase functions as what?
drug metabolizing enzyme
What is a ganglionic blocking agent?
mecamylamine
Characteristics of mecamylamine:
antihypertensive (lowers high BP); withdrawn from sales
Mechanism of mecamylamine:
noncompetitive antagonist of Nn receptors; has no effect on Nm receptors; blocks activation of postganglionic PNS and SNS nerve fibers
