Cholinergics Flashcards
Acetylcholine MOA
Direct-acting cholinomimetic
Bethanechol MOA
Direct-acting cholinomimetic
Carbachol MOA
Direct-acting cholinomimetic
Methacholine MOA
Direct-acting cholinomimetic
Cevimeline MOA
Direct-acting cholinomimetic
Pilocarpine MOA
Direct-acting cholinomimetic
Varenicline MOA and generic name
Chantix, Direct-acting cholinomimetic
Ambenonium MOA
Cholinesterase inhibitor
Donepezil MOA
Cholinesterase inhibitor
Echothiophate MOA
Cholinesterase inhibitor
Edrophonium MOA
Cholinesterase inhibitor
Galantamine MOA
Cholinesterase inhibitor
Neostigmine MOA
Cholinesterase inhibitor
Physostigmine MOA
Cholinesterase inhibitor
Pyridostigmine MOA
Cholinesterase inhibitor
Rivastigmine MOA
Cholinesterase inhibitor
Tacrine MOA
Cholinesterase inhibitor
Pralidoxime MOA
Cholinesterase regenerator
Scopolamine MOA and clinical use
antimuscarinic, motion sickness and ophthalmology
Atropine MOA and clinical use
antimuscarinic, GI disorders and ophthalmology, cholinergic poisoning
Dicyclomine MOA and clinical use
antimuscarinic, GI disorders
Glycopyrrolate MOA and clinical use
antimuscarinic, GI disorders
Hyoscyamine MOA and clinical use
antimuscarinic, GI disorders
Cyclopentolate MOA and clinical use
antimuscarinic, ophthalmology
Homatropine MOA and clinical use
antimuscarinic, ophthalmology
Tropicamide MOA and clinical use
antimuscarinic, ophthalmology
Ipratropium MOA and clinical use
antimuscarinic, resp disorders
Tiotropium MOA and clinical use
antimuscarinic, resp disorders
Darifenacin MOA and clinical use
antimuscarinic, urinary disorders
Fesoterodine MOA and clinical use
antimuscarinic, urinary disorders
Oxybutynin MOA and clinical use
antimuscarinic, urinary disorders
Solifenacin MOA and clinical use
antimuscarinic, urinary disorders
Tolterodine MOA and clinical use
antimuscarinic, urinary disorders
Trospium MOA and clinical use
antimuscarinic, urinary disorders
Benztropine MOA and clinical use
antimuscarinic, movement disorders
Biperiden MOA and clinical use
antimuscarinic, movement disorders
Orphenadrine MOA and clinical use
antimuscarinic, movement disorders
Procyclidine MOA and clinical use
antimuscarinic, movement disorders
Trihexyphenidyl MOA and clinical use
antimuscarinic, movement disorders
Mecamylamine MOA
ganglion blockers
MOA of Ach mimetics
mimic actions of ACh on nicotinic and muscarinic acetylcholine receptors
M1 receptor location and mechanism
nerves, GPCR - Gq
M2 receptor location and mechanism
heart, nerves, smooth muscle; GPCR - Gi
M3 receptor location and mechanism
glands, smooth muscle, endothelium; GPCR - Gq
M4 receptor location and mechanism
CNS, GPCR - Gi
M5 receptor location and mechanism
CNS, GPCR - Gq
Nm receptor location and mechanism
skeletal muscle, NMJ; pentamer - Na, K depolarizing ion channel
Nn receptor location and mechanism
Postganglionic cell body, dendrites, CNS; alpha and beta, depolarizing ion channel
Effects of direct-acting cholinergic agonists on skeletal muscle
nAChRs will cause muscle contraction, prolonged agonist will cause flaccid paralysis
Effects of direct-acting cholinergic agonists on parasympathetics
miosis, negative inotropy and chronotropy, dilation of vessels, bronchoconstriction, increased GI motility, detrusor contraction, secretion from glands increases
Effects of direct-acting cholinergics on eye
contraction of iris and ciliary muscle, increasing aqueous humor outflow
Effects of direct-acting cholinergics on CV system
reduce PVR and changes heart rate, endothelium-derived relaxing factor is released and relaxes smooth muscle
Effects of direct-acting cholinergics on GI and GU
increase in glandular secretions, smooth muscle contraction and smooth muscle relaxation
Effects of direct-acting cholinergics on CNS
moderate doses cause an increase in cognitive function, higher concentrations can cause tremors and analgesia
Effects of direct-acting cholinergics on PNS
activation of autonomic ganglia, sympathomimetic on CV system and parasympathomimetic on GI/GU
Clinical uses of direct-acting cholinergic agonists
Glaucoma, esotropia, GI/GU disorders
Direct-acting cholinergic agonists in glaucoma
contraction of ciliary body, facilitating aqueous humor outflow
Direct-acting cholinergic agonists in GI/GU disorders
Bethanechol used for postoperative ileus, megacolon, urinary retention; pilocarpine and cevimeline increase salivary secretion
Toxicity of muscarinic direct-acting choliniomimetics
nausea, vomiting, diarrhea, urinary urgency, salivation, sweating, bronchoconstriction
Major contraindications of mAChR agonists
asthma, hyperthyroidism, coronary insufficiency, acid-peptic disease
Acute toxicity of nicotinic stimulants
CNS stimulation, NMJ depolarization leading to resp paralysis, hypertension, cardiac arrhythmias
Chronic toxicity of nicotinic stimulants
increased risk of vascular disease, sudden coronary death, ulcer recurrences
Acetylcholine clinical use
causes miosis
Methacholine clinical use
bronchial airway hyperreactivity
Bethanechol clinical use
urinary retention and heartburn
Carbachol clinical use
glaucoma, produce miosis during surgery
Cevimeline clinical use
xerostomia in pts with Sjogrens
Pilocarpine clinical use
xerostomia, miosis during ophthalmic procedures, glaucoma
Varenicline clinical use
smoking cessation
Varenicline intrinsic activity
partial agonist that binds to a4B2 nicotinic receptors
Varenicline causes the release of what NT?
dopamine - stimulating reward pathway
AE of varenicline
neuropsych sxs such as agitation, depression, suicide ideation
Chemical subgroups of AChE inhibitors
alcohols and carbamic acid esters, which reversibly bind to AChE; organophosphates, which irreversibly bind to AChE
MOA of AChE Inhibitors
inhibition of AChE, resulting in ACh accumulation throughout the body and activation of nAChRs and mAChRs
Duration of action of AChE Inhibitors
alcohols and carbamic acid esters - short duration of action due to noncovalent bonds; organophosphates - very long duration, forms a very stable bond
Organ systems effected by AChE inhibitors
stimulate autonomic effector organs, stimulate CNS, depression after stimulation of CNS
Effects of AChE inhibitors on CV system
bradycardia, decrease in cardiac output, modest increase in BP
Therapeutic uses of AChE inhibitors
diseases of eye, GI and GU disorders, NMJ, heart, and Alzheimer’s
AChE toxicity
cutaneous vasodilation, anhidrosis, anhydrotic hyperthermia, nonreactive mydriasis, delirium, hallucination
Common antidote for AChE Inhibitors
physostigmine
AChE Inhibitor interaction with succinylcholine
enhance phase 1 block, antagonize phase 2 block
AChE inhibitor interaction with nondepolarizing NMBA
diminish neuromuscular blockade
AChE inhibitor interaction with cholinergic agonists
enhance effects of cholinergic agnoists
AChE inhibitor interaction with B-blockers
enhance bradycardic effects
AChE inhibitor interaction with systemic corticosteroids
enhance muscle weakness
Acute intoxication of AChE inhibitors
miosis, salivation, sweating, bronchial constriction, vomiting, diarrhea; CNS involvement may follow rapidly
Antidote for AChE Inhibitor poisoning
atropine, cholinesterase regenerator
Cholinesterase regenerator MOA
regenerate active enzyme from organophosphorus-cholinesterase complex via removal of phosphorous group
Prophylactic agent for AChE inhibitor
pyridostigmine
Pyridostigmine side effects
stomach cramps, diarrhea, nausea, frequent urination, HA, dizziness, SOB, peptic ulcer, blurred vision, watery eyes
MOA of mAChR blockers
parasympatholytic, block effects of PS autonomic discharge
Clinical use of tertiary amines - mAChR-blockers
eye or CNS
Clinical use of quaternary amines - mAChR-blockers
peripheral nervous system
Half life and excretion of atropine
2 hours; 60% excreted in urine, 40% eliminated by phase I and II reactions
Intrinsic activity of atropine
reversible antagonist
Tissues most sensitive to atropine
salivary, bronchial, sweat glands
mAChR blockers on CNS
longer lasting sedative effect, can reduce tremor associated with Parkinson’s disease, prevents motion sickness
mAChR blockers on eye
block papillary constrictor muscle resulting in dilation, weaken contraction of ciliary muscle which prevents accommodation, and reduces lacrimal secretion
mAChR blockers on CV system
tachycardia may occur, no significant changes
mAChR blockers on respiratory
bronchodilation and reduced secretion
mAChR blockers on GI
decrease salivary secretion, other GI secretions are most unaffected, gastric emptying is prolonged, smooth muscle relaxation
mAChR blockers on GU
relax smooth m. of ureters and bladder to slow voiding
mAChR blockers on sweat glands
suppression of thermoregulatory sweating, inhibits sympathetic cholinergic nerve fibers
Cholinergic antagonists for parkinson disease
reduce tremor, benzotropine and trihexyphenidyl
Cholinergic antagonists for motion sickness
vestibular disorders, scopolamine
Cholinergic antagonists for anesthesia
atropine blocks vagal reflexes
Cholinergic antagonists for ophthalmologic disorders
retina examination facilitated by mydriasis
Cholinergic antagonists for respiratory disorders
ipratropium used as first-line therapy, tiotropium may also be used
Cholinergic antagonists in CV disorders
atropine used for symptomatic bradycardia and hyperactive carotid sinus reflexes
Cholinergic antagonists in GI disorders
travelers diarrhea, conditions of hypermotility
Cholinergic antagonists in urinary disorders
relief of urinary urgency; generally will be selective for M3 receptor
cholinergic poisoning antidote
pralidoxime
AE of mAChR antagonists
block of parasympathetic function, hyperthermic effects
Contraindication of mAChR antagonists
glaucoma, men with prostatic hyperplasia, acid-peptic diseases (can slow gastric emptying)
Pirenzepine selectivity and MOA
M1, inhibits gastric secretion by acting at the ganaglia
Chemistry of ganglion-blocking drugs
synthetic amines
MOA Ganglion-blocking drugs
block action of ACh and similar agonists at nAChRs of both parasympathetic and sympathetic autonomic ganglia, block autonomic outflow
Nerve effects of ganglion-blocking drugs
enhance sympathetic tone, sedation, tremor, choreiform movements, mental aberrations
Eye effects of ganglion-blocking drugs
cycloplegia with loss of accommodation, moderate dilation of pupil
CV system effects of ganglion blocking drugs
decrease in vascular tone, decrease in BP, diminished contractility, moderate tachycardia
GI effect of ganglion blocking drugs
reduced secretion and inhibited motility
GU effect of ganglion blocking drugs
urination retention or hesitancy, erection may be prevented
Clinical applications of ganglion blocking drugs
may be used for hypertension, but patients are not typically willing to use them due to toxicity
