7 Cholinergics I Flashcards
Where are the three types of muscarinic receptors found in the body?
M1: Postganglionic neurons of autonomic gangliaM2: Heart, primarily smooth muscleM3: Glands, smooth muscle, endothelium
Where are the two types of nicotinic receptors found in the body?
N1/Nn: postganglionic neurons of autonomic ganglia (including adrenal medulla)N2/Nm: neuromuscular junction of skeletal muscles
What are the cholinergic receptor subtypes, and what are these subtypes based on?
Muscarinic and nicotinic, based on selectivity for muscarine or nicotine
What type of receptors are nicotinic receptors?
nicotinic receptors are ligand-gated ion channels
What is the mechanism of action for nicotinic receptors?
2 ACh molecules bind to receptor and cause the Na+ channel to open, which in turn triggers an EPSP.
What type of receptors are muscarinic receptors?
7 transmembrane domain receptors coupled to G proteins
ACh and other cholinergic drugs mimic stimulation of the ______ nervous system via ______ receptors.
parasympathetic, muscarinic
Why does ACh have no real therapeutic application?
It has limited therapeutic use because of its diffuse action and its rapid breakdown by cholinesterase.
T or F: Synthetic choline esters and natural alkaloids are both examples of cholinergic drugs.
T
Which natural alkaloids are selective for muscarinic receptors? Nicotinic receptors?
Muscarinic: muscarine and pilocarpineNicotinic: nicotine and varenicline
Name as many of the normal physiological functions of the parasympathetic nervous system as you can.
decrease heart rate, decrease blood pressure, activation of GI movements, emptying of bladder and rectum, activation of mucosal cells and salivary and lacrimal glands, constriction of bronchi, constriction of pupil and lens
The rate of ACh synthesis is controlled by the rate of _____.
choline uptake
Which enzyme catalyzes ACh synthesis?
Choline acetyltransferase (ChAT)
Which two enzymes can catalyze the hydrolysis of ACh?
Acetylcholinesterase (AChE) and plasma cholinesterase (aka pseudocholinesterase and butyrylcholinesterase)
Name the four directly-acting muscarinic receptor agonists (aka cholinomimetics).
acetylcholine, methacholine, carbachol, bethanechol
Which of the cholinomimetics are susceptible to cholinesterase? Which are unaffected by cholinesterase?
Acetylcholine and methacholine are susceptible to cholinesterase, while carbachol and bethanechol are not
Why are carbachol and bethanechol longer acting than the other cholinomimetics?
duration of action of cholinergic agonists is based primarily on susceptibility to cholinesterase; carbachol and bethanechol are not effectively hydrolyzed by cholinesterase.
Where is acetylcholinesterase primarily found?
high concentrations are found at cholinergic synapses, neuromuscular junctions, and in RBCs
Where is plasma cholinesterase primarily found?
plasma and liver, with limited expression in other tissues
Which enzyme hydrolyzes ingested esters from plant sources and ACh that escapes from cholinergic synapses?
plasma cholinesterase
Name the four competitive inhibitors of cholinesterases
edrophonium, neostigmine, pyridostigmine, physostigmine
T or F: cholinesterase inhibitors are agonists of the parasympathetic nervous system that operate through direct stimulation.
F; cholinesterase inhibitors indirectly stimulate the parasympathetic nervous system by prolonging the activity of ACh in the synapse
Name the three major types of noncompetitive cholinesterase inhibitors.
Organophosphate (O-P) derivatives, insecticides, and nerve gases
O-P insecticides react first with _______, while O-P nerve gases react first with _______.
O-P insecticides react first with plasma cholinesterase while O-P nerve gases react first with AChE.
