Ch. 9 Cholinergic Flashcards
Hemicholinium-3
Blocks high-affinity transporter for choline and thereby prevents uptake of choline required for ACh synthesis
RESEARCH ONLY
Vesamicol
Blocks the ACh-H+ antiporter used to transport ACh into vesicles
RESEARCH ONLY
Botulinum toxin
Degrades synaptobrevin = prevents vesicle fusion on presynaptic membrane
Edrophonium
Inhibitor of ACh Degredation: Inhibits acetylcholinesterase (AChE) by binding to enzyme’s active site
Neostigmine
Inhibitor of ACh Degredation: Inhibits AChE by binding to enzyme’s active site
Pyridostigmine
Inhibitor of ACh Degredation: Inhibits AChE by binding to enzyme’s active site
Ambenonium
Inhibitor of ACh Degredation: Inhibits AChE by binding to enzyme’s active site
Physostigmine
Inhibitor of ACh Degredation: Inhibits AChE by binding to enzyme’s active site
Diisopropyl fluorophosphate
Inhibitor of ACh Degredation: Inhibits AChE by binding to enzyme’s active site
organophosphate used as insecticide, nerve gas, former topical miotic medication
Tacrine
Inhibitor of ACh Degredation: Inhibits AChE by binding to enzyme’s active site
Donepezil
Inhibitor of ACh Degredation: Inhibits AChE by binding to enzyme’s active site
Rivastigmine
Inhibitor of ACh Degredation: Inhibits AChE by binding to enzyme’s active site
Also affects butyrylcholinesterase by forming a carbamoylate complex with the enzymes
Galantamine
Inhibitor of ACh Degredation: Inhibits AChE by binding to enzyme’s active site
Also acts as a nonpotentiating ligand of nicotinic receptors
Methacholine
Muscarinic Receptor Agonist: Stimulates muscarinic receptor activity
Carbachol
Muscarinic Receptor Agonist: Stimulates muscarinic receptor activity
Cannot be used systemically
Bethanechol
Muscarinic Receptor Agonist: Stimulates muscarinic receptor activity
Almost completely selective for muscarinic receptors
Cevimeline
Muscarinic Receptor Agonist: Stimulates muscarinic receptor activity
Pilocarpine
Muscarinic Receptor Agonist: Stimulates muscarinic receptor activity
Succinylcholine
Nicotinic Receptor Agonist: Stimulate opening of nicotinic ACh receptor channel and produce depolarization of the cell membrane.
Persists at the neuroeffector junction and activates the nicotinic receptor channels continuously –> inactivation of voltage-gated Na+ channels = cannot open to support further APs
Short duration = DOC for paralysis during intubation.
Another name for action of succinylcholine
“Depolarizing blockade”
Atropine
Muscarinic Receptor Antagonist: Selectively antagonizes muscarinic receptor
Scopolamine
Muscarinic Receptor Antagonist: Selectively antagonizes muscarinic receptor
Pirenzepine
Muscarinic Receptor Antagonist: Selectively antagonizes muscarinic receptor
Methscopolamine
Muscarinic Receptor Antagonist: Selectively antagonizes muscarinic receptor
Glycopyrrolate
Muscarinic Receptor Antagonist: Selectively antagonizes muscarinic receptor
Ipratropium
Muscarinic Receptor Antagonist: Selectively antagonizes muscarinic receptor
Tiotropium
Muscarinic Receptor Antagonist: Selectively antagonizes muscarinic receptor
Oxybutynin
Muscarinic Receptor Antagonist: Selectively antagonizes muscarinic receptor - nonspecific
Propantheline
Muscarinic Receptor Antagonist: Selectively antagonizes muscarinic receptor - nonspecific
Terodiline
Muscarinic Receptor Antagonist: Selectively antagonizes muscarinic receptor - nonspecific
Fesoterodine
Muscarinic Receptor Antagonist: Selectively antagonizes muscarinic receptor - nonspecific
Trospium
Muscarinic Receptor Antagonist: Selectively antagonizes muscarinic receptor - nonspecific
Darifenacin
Muscarinic Receptor Antagonist: Selectively antagonizes muscarinic receptor - M3 selective
Solifenacin
Muscarinic Receptor Antagonist: Selectively antagonizes muscarinic receptor - M3 selective
Pancuronium
Nicotinic Receptor Antagonist: Selectively antagonizes nicotinic receptor preventing endogenous ACh binding and subsequent muscle cell depolarization (“Nondepolarizing blockade”)
LONG ACTING
Tubocurarine
Nicotinic Receptor Antagonist: Selectively antagonizes nicotinic receptor preventing endogenous ACh binding and subsequent muscle cell depolarization (“Nondepolarizing blockade”)
LONG ACTING
Vecuronium
Nicotinic Receptor Antagonist: Selectively antagonizes nicotinic receptor preventing endogenous ACh binding and subsequent muscle cell depolarization (“Nondepolarizing blockade”)
INTERMEDIATE ACTING
Rocuronium
Nicotinic Receptor Antagonist: Selectively antagonizes nicotinic receptor preventing endogenous ACh binding and subsequent muscle cell depolarization (“Nondepolarizing blockade”)
INTERMEDIATE ACTING
Mivacurium
Nicotinic Receptor Antagonist: Selectively antagonizes nicotinic receptor preventing endogenous ACh binding and subsequent muscle cell depolarization (“Nondepolarizing blockade”)
SHORT ACTING
Trimethaphan
Nicotinic Receptor Antagonist: Selectively antagonizes nicotinic receptor preventing endogenous ACh binding and subsequent muscle cell depolarization (“Nondepolarizing blockade”)
Administered when ganglionic blockade is desired - HTN acute aortic dissection
Mecamylamine
Nicotinic Receptor Antagonist: Selectively antagonizes nicotinic receptor preventing endogenous ACh binding and subsequent muscle cell depolarization (“Nondepolarizing blockade”)
Administered when ganglionic blockade is desired - HTN acute aortic dissection
Types of cholinergic receptors
Muscarinic and Nicotinic
Muscarinic receptors are
G protein coupled receptors
Nicotinic Receptors are
ligand-gated ion channels
M1, M3, and M5 mAChR
Gq/11 –> PLC –> increased IP3 and DAG –> increased Ca2+ and increased PKC = excitatory
M2 and M4 mAChR
Beta/gamma of G protein –> inhibition of adenylyl cyclase and increased K+ channel opening = suppress cellular excitability
Location of M1
Autonomic ganglia = late excitatory postsynaptic potential
CNS = arousal, attention, analgesia
Location of M2
Heart:
- SA node = slowed spontaneous depolarization; hyperpolarization
- AV node = decrease conduction velocity
- Atrium = decrease refractory period, decrease contractile force
- Ventricle = slight decrease in contractility
Location of M3
Smooth muscle = contraction
Location of M4
CNS
Location of M5
CNS
Nicotinic receptors
Ligand-gated ion channels –> net inward Na+ depolarizing the cell
-Direct ligand-gated conductance
- requires binding of 2 ACh to 1 nAChR –> conformational change of 2 alpha subunits
2 alpha, 1 beta, 1 delta, 1 epsilon (mature skel m) OR 1 gamma (embryonic
Nicotinic Nm receptor Location
NMJ - skeletal muscle
- opening of Na+/K+ channels –> skeletal muscle contraction
Nicotinic Nn receptor location
Autonomic ganglia
- opening of Na+/K+ channels –> depolarization and firing of postganglionic neuron
Adrenal medulla
- opening of Na+/K+ channels –> secretion of catecholamines
CNS
- opening of Na+/K+ channels –> arousal, attention analgesia
2 cholinesterases
- AChE - postsyn membrane
2. Butyrylcholinesterase (BuChE) secondary role, may be involved in path of Alzheimer’s
Latency of mAChR
100 - 250 msec
Latency of nAChR
5 msec
Principle neurotransmitter at the NMJ that is released by alpha motor neurons –> binding of nicotinic receptors and motor end-plate depolarization
ACh
- extent of depolarization depends on QUANTITIY of ACh
Effect of Gaglionic Blockade on ARTERIOLES
(mainly adrenergic sympathetic tone) –> Vasodilation, increased peripheral blood flow, hypotension
Effect of Gaglionic Blockade on VEINS
(mainly adrenergic sympathetic tone) –> vasodilation, pooling of blood, decreased of venous return, decreased cardiac output
Effect of Gaglionic Blockade on HEART
(mainly parasymp cholinergic tone) –> tachycardia
Effect of Gaglionic Blockade on IRIS
mainly parasymp cholinergic tone –> Mydriasis (pupil dilation)
Effect of Gaglionic Blockade on CILIARY MUSCLE
mainly parasymp cholinergic tone –> cycloplegia (focused to far vision)
Effect of Gaglionic Blockade on GI TRACT
Mainly parasymp cholinergic tone –> decreased tone and motility; constipation; decreased secretions
Effect of Gaglionic Blockade on URINARY BLADDER
Mainly parasymp cholinergic ton –> urinary retention
Effect of Gaglionic Blockade on SALIVARY GLANDS
Mainly parasymp cholinergic tone –> xerostomia (dry mouth)
Effect of Gaglionic Blockade on SWEAT GLANDS
Mainly symp cholinergic tone –> Anhidrosis (absence of sweating)
Effects of ACh on VASCULATURE (endothelial cells)
Release of NO and vasodilation
Effects of ACh on EYE IRIS (pupillae sphincter muscle)
Contraction and miosis (constriction of pupil)
Effects of ACh on CILIARY MUSCLE
Contraction and accommodation for near vision
Effects of ACh on SALIVARY AND LACRIMAL GLANDS
Thin and watery secretions
Effects of ACh on BRONCHI
Constriction
Increased secretions
Effects of ACh on HEART
Bradycardia
Decreased conduction velocity
AV block at high doses
Slight decrease in contractility
Effects of ACh on GI TRACT
Increased Tone
Increased secretions
Relaxation of sphincters
Effects of ACh on URINARY BLADDER
Contraction of detrusor muscle
Relaxation of sphincter
Effects of ACh on SWEAT GLANDS
Diaphoresis (sweating)
Effects of ACh on REPRODUCTIVE TRACT, MALE
Erection
Effects of ACh on UTERUS
Variable
