PHARM Chapter 9 - Cholinergic Pharmacology Flashcards
ME of hemicholinium-3 and vesamicol
Inhibit the synthesis, storage, or release of ACh
Uses of Hemicholinium 3 and vesamicol
Utilized only in research settings
ME of Botulinum toxin
Inhibits the synthesis, storage, and release of ACh, degrades SNAP25 which prevents vesicle fusion presynaptically
Uses of Botulinium Toxin
Focal dystonias, torticollis, achalasia, stabismus, etc.
What produces botulinum toxin
clostridium botulinum
Inhibitors of ACh Degradation
Edrophonium Neostigmine Pyridostigmine Ambenonium Physostigmine Diisopropyl fluoro-phosphate Tacrine Donepezil Rivastigmine Galantamine
ME of inhibitors of ACh Degradation
Inhibit AChE by binding to enzyme’s active site, causes increase in ACh in cleft which activates nearby receptors
Uses for Edrophonium, Neostigmine, Pyridostigmine, Ambenonium, Physostigmine
Diseases of muscle weakness (edrophoium)
Urinary or GI motility agent, NMJ diseases, glaucoma (neostigmine, pyridostigmine, ambenoium)
Reversal of anticholinergic toxicity or induced paralysis in surgery (physostigmine)
Short acting with rapid onset of action inhibitor of ACh degradation
Edrophonium
Topical application of cholinesterase inhibitors to the cornea has what effect?
decreases intraocular pressure by facilitating outflow of aqueous humor
Why is physostigmine used for treating CNS antichlinergic toxicity
nonpolar structure
2 carbamic acid ester AChE inhibitors
neostigmine and physostigmine
1 organophosphate AChE inhibitor
diisopropyl flurophosphate
Aging
oxygen-phosphorus bonds within the inhibitor are broken spontaneously in favor of stronger bonds between the enzyme and the inhibitor - essentially irreversible
Eaton-lambert syndrome
autoantibodies against calcium channels
how does tubocurare cause weakness or paralysis
acts as competitive antagonist for nAChR preventing ACh from binding to the receptor and causing nondepolarizaing blcokade of cholinergic transmission
Effect of AChE inhibitors on the GI system
increase smooth muscle motility because it enhances ganglionic transmission at auerbach’s plexus
SE of diisopropyl fluoro-phosphate
respiratory paralysis
organophosphate compound used as insecticide
diisopropyl fluoro-phosphate
Uses of tacrine, donepezil, rivastigmine, galantamine
mild to moderate Alzheimer’s disease dementia
Affects both AChE and butyrylcholinestarase by forming a carbamoylate complex with the enzymes
rivastigmine
ME of methacoholine
stimulate muscarinic receptor activity - selective for cardiovascular muscarinic cholinergic receptors
Uses of methacholine
diagnosis of asthma
ME of carbachol, bethanechol, cevimeline, pilocarpine
Stimulate muscarinic receptor activity
Uses for carbachol
glaucoma - cannot be used systemically because it is unpredicatble
Uses for bethanechol
Urinary tract motility agent - due to selective agent for muscarinic receptors
Uses for cevimeline and pilocarpine
xerostomia in sjogren’s syndrome
FDA approved to treat parkinson’s disease with dementia
rivastigmine
how can the GI effects of AChE inhibitors be minimized
administer w/ meal or in combination w/ memantine an NMDA channel blocker
This drug is a vasodilator and is cardiac vagomimetric
(mimics cardiac response to vagus nerve = parasympathetic stimulation = methacholine
Has enhanced nicotinic action relative to other choline esters
carbachol
Most clinically used alkaloid is ___ which is a miotic agent and sialogogue (saliva inducing) used to treat xerostomia
pilocarpine
ME of succinylcholine
nicotinic receptor antagonist - stimulates opening of nAChR channel and produces depolarization of cell membrane - persists at neuroeffector junction and activates nicotinic receptor channels continuous resulting in inactivation of voltage-gated sodium channels (depolarizing blockade)
uses of succinylcholine
induction of neuromuscular blockade in surgery, intubation
ME of Atropine
selectively antagonize muscarinic receptors, marginal nicotinic affect
Uses of atropine
AChE overdose, acute bradycardia, premedication for anesthetic procedure, excessive salivation during surgery, antidote to mushroom poisoning
ME of scopolamine
selectively antagonizes muscarinic receptors - significant CNS effects
Uses of scopolamine
motion sickness, nausea/vomiting
ME of pirenzepine, methscopolamine, glycopyrrolate
selectively antagnoize muscarinic recpetors
Uses of pirenzepine, methscopolamine, glycopyrrolate
PUD, surgically induced/vagally induced bradycardia (glycopyrrolate)
ME of ipratropium and tiotropium
selectively antagonize muscarinic receptors
Uses of ipratropium and tiotropium
COPD and asthma (tiotropium more superior)
Uses of oxybutyin, propantheline, terodiline, tolterodine, fesoterodine, rospium, darifenacin, solifenacin
hyperrefelxic and overactive bladder, urge incontinence
ME of oxybutyin, propantheline, terodiline, tolterodine, fesoterodine, rospium, darifenacin, solifenacin
selectively antagonize muscarinic receptors
M3 receptor antagonists
darifenacin and solifenacin
used clinically to dilate eyes (mydriasis)
atropine
benztropine and trihexyphenidyl ME
muscarinic receptor antagonist
uses of benztropine and trihexyphenidyl
commonly used to treat extrapyramidal symptoms and akathisia associated w/ neuroleptics
acute cholinesterase inhibitor toxcicity
due to exposure of organophosphate pesticides - vomiting, diarrhea, profuse sweating, hypersalivation, miosis, bronchoconstriction followed by nicotinic toxciity
Why are anticholinergic drugs contraindicated in elderly
many commonn drugs possess small measure of anticholinergic activity
elderly sensitive to choinergic blockade
polypharmacy is common practice in geriatrics, may induce acute encephalopathy, falls, urinary retension, constipation, cognitive deficits
ME of pancuronium, tubocuraranie, vecuronium, rocuronium, mivacurium
selectively antagonize nicotinic recpetors preventing endogenous ACh binding and subsequent muscle cell depolarization
Uses of pancuronium, tubocurarine, vecuronium, rocuronium, mivacurium
induction of neuromuscular blockade in surgery, intubation
Long acting nicotinic receptor antagonists
pancuronium and tubocurarine
Medium acting nicotinic receptor antagonists
vecuronium and rocuronium
Short acting nicotinic receptor antagonists
mivacurium
what can reverse the nondepolarizing blocking agent adverse effects
AChE inhibitors
ME of trimethaphan and mecamylamine
selectively antagonize nicotinic receptors, preventing endogenous AChE binding and subsequent muscle cell depolarization
Uses of trimethaphan and mecamylamine
hypertension in patients with acute aortic dissection
When would mecamylamine and trimethaphan be administered
ganglionic blcokade is desired - lowers bp while blunting sympathetic reflexes
Arterioles
Predominant tone:
Effect of ganglionic blockade
sympathetic
vasodilation, hypotension
Veins
Predominant tone:
Effect of ganglionic blockade
symapthetic
vasodilation, pooling of blood, decreased venous return and cardiac output
Heart
Predominant tone:
Effect of ganglionic blockade
Parasympathetic
Tachycardia
Iris
Predominant tone:
Effect of ganglionic blockade
Parasympathetic
Mydriasis (pupil dilation)
Ciliary muscle
Predominant tone:
Effect of ganglionic blockade
Parasympathetic
cycloplegia = focused to far vision
GI
Predominant tone:
Effect of ganglionic blockade
Parasympathetic
Decreased tone and motility, constipation
Urinary bladder
Predominant tone:
Effect of ganglionic blockade
parasymaptheitc
urinary retention
Salivary glands
Predominant tone:
Effect of ganglionic blockade
parasympathetic
dry mouth
Sweat glands
Predominant tone:
Effect of ganglionic blockade
Symapthetic
anhidrosis
Effect of ACh on vasculature
release NO = vasodilation
Effect of ACh on Eye iris
contraction and miosis
Effect of ACh on Ciliary muscle
contraction and accommodation of lens to near vision
Effect of ACh on Salivary and lacrimal galnds
thin and watery secretions
Effect of ACh on bronchi
constriction, increased secretion
Effect of ACh on heart
bradycardia, decreased conduction velocity, AV block at high doses
Effect of ACh on GI
increased tone, relaxation of sphincters
Effect of ACh on urinary bladder
contraction of detrusor, relaxation of sphincter
Effect of ACh on sweat glands
diaphoresis
Effect of ACh on penis
erect
