Cholinergic Flashcards
Choline transporter into neuron terminal
Na-Dependent membrane choline receptor (CHT)
Potent CHT inhibitor
hemicholiniums
Enzyme that synthesizes ACh from acetyl CoA and choline
choline acetyltransferase (ChAT)
ACh transport vesicle
Vesicle-associated transporter (VAT)
Inhibitor of VAT
vesamicol
What can be stored inside VATs
ACh, peptides, ATP, proteoglycan
v-SNARE proteins on vesicles
synaptobrevin
t-SNARE proteins on neuronal cell membrane
syntaxin, SNAP-25
ACh release is dependent on
Calcium
ACh release into synaptic cleft inhibited by
Botulinum toxin
Primary terminator of ACh
Acetylcholinesterase
Muscarinic receptor signaling type
G-protein coupled
Nicotinic receptor signaling type
Na channels (5 subunits: 2a, B, y, d)
M1, M3 G protein
Gq
M2 G protein
Gi
M3 activation of papillary sphincter
Contraction - miosis, open Canal of Schlemm (decrease intraocular pressure)
M3 activation of ciliary muscle
Contraction - accommodation for near vision
M2 activation of SA/AV node
Decreased HR, decreased velocity, decreased ventricular contraction
M3 activation of bronchioles
Contraction - bronchospasm
M3 activation of glands
Increased secretions
M3 activation of stomach
motility, cramps
M3 activation of intestines
contraction - diarrhea, involuntary defecation
M3 activation of bladder
detrusor contraction, sphincter relaxation, voiding, incontinence
M3 activation of blood vessel endothelium
dilation
What receptors are found ECL cells
M1
What receptors are found on parietal cells
M3
Contraindications for treatment with cholinomimetic drugs
peptic ulcers, GI tract disorders, asthma
Why does ACh have very limited clinical use
Must be administered intravenously due to very rapid destruction by AChE
Receptor type for ACh
nicotinic/muscarinic
Effects of ACh
short lasting miosis vasodilation, decreased TPR, reflex tachycardia bronchial constriction/secretion Saliva/sweat/tears bladder constriction
Bronchiolar hypersensitivity diagnosis
Inhalation of Metacholine causes bronchoconstriction at low doses
Belladonna alkaloid poisoning diagnosis
subcutaneous dose of Metacholine causes sign/symptoms of muscarinic cholinoceptor activation
No response in poisoned individual
Receptor type for Carbachol
nicotinic/muscarinic
Therapeutic uses for Carbachol
glaucoma treatment - decrease intraocular pressure
High doses of carbachol cause
Cardiac arrest
Receptor type for Bethanechol
primarily M3
Effects of Bethanechol
GU: increased detrusor tone
GI: increased motility/secretion
Muscarine poisoning symptoms
increased saliva/sweat/tears within minutes
Larger doses cause abdominal pain, nausea, diarrhea, blurred vision, dyspnea
Symptoms subside in 2 hours
Effects of Pilocarpine
Contracts iris sphincter muscle - miosis
Frees entrance to canal of Schlemm (N-A glaucoma)
Enhances tone of trabecular network (W-A glaucoma)
Contracts ciliary muscle - accommodation/loss of far vision
Clinical uses for pilocarpine
glaucoma and xerostomia
Pilocarpine tests to diagnose parasympathetic dysfunction
Direct acting cholinomimetics
ACh Metacholine Bethanechol Carbachol Muscarine Pilocarpine Nicotine
Nicotine action on Nm receptors
Skeletal muscle contraction
Fasciculations
Depolarizing blockade
Nicotine action on Nn receptors
Cardiac: increase HR via stimulation of renal medulla (E/NE)
Vascular: peripheral vasoconstriction
GI: increase motility/secretion
Carotid bodies: increased respiratory rate
Medullary emetic chemoreceptors: nausea/vomiting
Edrophonium and MG
Improvement of MG symptoms after administration of edrophonium; negative test indicates cholinergic crisis
AChE inhibitors as treatment for MG
Pyridostigmine and neostigmine - quarternary amines
Treatment for Paralytic Ileus and Urinary Retention
Neostigmine - used to treat abdominal distension, atony of detrusor
Contraindication for neostigmine
urinary bladder obstruction
Treatment for Alzheimer’s
Tacrine and Donepezil
AChE inhibitor intoxication symptoms
DUMBBELSS Diarrhea Urination Miosis Bradycardia Bronchoconstriction Excitation of CNS Lacrimation Sweat Saliva
AChE inhibitor intoxication treatment
Atropine
Atropine relieves
Secretions
Bronchoconstriction
Bradycardia
CNS excitation
AChE reactivators
Pralidoxime (2-PAM)
Does not work with pyridistigmine and neostigmine
Muscarinic antagonists
Atropine
Ipratropium
Benztropine
Effects of Atropine
Peripheral vasoconstriction Mild vagal stimulation Decreased secretion Mydriasis/cycloplegia Hyperthermia Tachycardia Sedation Urinary Retention Hallucinations
Clinical Uses of Atropine
Antispasmodic, antisecretory, AChE inhibitor overdose, antidiarrheal, ophthalmology, prevent vagal reaction
Treatment of Atropine Poisoning
Physostigmine
Effects of Ipratropium
Decreases bronchoconstriction
Decreases bronchosecretions
Clinical uses of Ipratropium
First line therapy for chronic obstructive lung disease
Second line therapy for asthma
Effects of Benztropine
re-establish dopaminergic-cholinergic balance in pts with Parkinson’s
Decrease GU/GI secretions, motility and increase HR
Ganglionic blocking agents
Hexamethonium and mecamylamine
Effects of ganglionic blocking agents
Arterioles: vasodilation, hypotension Veins: dilation, decreased VR, decreased CO Heart: Tachycardia Iris: mydriasis Ciliary muscle: cycloplegia GI: decreased tone/motility - constipation Bladder: urinary retention Salivary glands: xerostomia Sweat glands: anhidrosis
Non-depolarizing blocking agents action
prevent channel opening
Depolarizing blocking agents action
prevent channel closing
Non-depolarizing blocker
D-tubocurarine
Depolarizing blocker
succinylcholine
Phase 1 blockade
binding of depolarizing blocker to Nm receptor causes persistent depolarization - paralysis
Augmented by AChE inhibitors
Phase 2 blockade
following long paralysis, endplate repolarizes but next depolarization is difficult due to channel desensitization
Clinical uses of NM blockers
decrease neuromuscular transmission during anesthesia
Tracheal intubation
Control of ventilation
Treatment of convulsions
Side effects of NM blockers
CV: hypotension (systemic histamine) Hyper-K: pts with burns, nerve damage, NM disease etc respond to blockers by releasing K into blood - cardiac arrest Intraocular pressure increase Increased intragastric pressure Myalgia
