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NEURO3 drugs - cholinergic agonists & antagonists

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beddowme's version from 2012-06-05 16:28

general

Question Answer
2 general types of cholinomimeticsdirect-acting (bind cholinoceptor) & indirect-acting (inhibit AChE)
undesirable effects of cholnergic agentssalivation, sweating, defecation, HA, loss of accomodation
contraindications of M & N receptor agonistspeptic ulcer, asthma, coronary insufficiency, hyperthryoidism
parasympathetic akacranio-sacral
sympathetic akathoraco-lumbar
preganglionic transmitter for allACh (except somatic b/c there is no ganglia)
ganglionic receptor for allnicotinic (except somatic b/c there is no ganglia)
neuroeffector transmitter of sympathetics, & receptorNE on adrenergic receptor (except sweat glands)
neuroeffector transmitter of sweat glands & receptorACh, muscarinic receptor
neuroeffector transmitter of adrenal medulla & receptorepi & NE released in blood from adrenal medulla, onto adrenergic receptors
neuroeffector transmitter of parasympathetics & receptorACh on muscarinic or nicotinic receptor
neuroeffector transmitter of somatics & receptorACh on nicotinic receptor of striated muscle
where does choline come from?recycled or dietary
ACh is made fromcholine & acetyl-CoA
what blocks the entry of choline into presynaptic neuron, therefore preventing synthesis of ACh?hemicholinium (never prescribed)
prevents ACh uptake into storage vesiclesvesamicol (never prescribed)
blocks release of ACh (& give MOA)botulinum toxin, breaks down synaptobrevin, destroying nn that enabling breathing & swallowing
ACh release enhanced byspider venom
AChE degrades ACh intocholine & acetate
uses for botulinum toxinstrabismus & esotropia, wrinkles, stroke paralysis, migraines, facial tics, stuttering, lower back pain, incontinence, writer's cramp, carpal tunnel, tennis elbow, morbid obesity, ulcer prevention, vaginal muscle spasms, clubfoot, spastic vocal cords, cervical dystonia
ocular misalignment is calledstrabismus
crossed eyesesotropia
what enzyme makes Ach?choline acetyl transferase
main use of muscarinic agoniststreat glaucoma (pilocarpine)
memorize

sympathetic & parasympathetic actions

Question Answer
sympathetic eyepupil dilates
sympathetic lacrimal gland-
sympathetic salivary glandsthick & viscous secretion
sympathetic lungs (trachea & bronchioles)dilates, facilitates breathing
sympathetic heartinc rate & contractility
sympathetic GIdecreased motility & tone, sphincters contract
sympathetic blood vessels in skeletal musclesdilate (more blood to mm)
sympathetic blood vessels in skin, mucous membranesconstrict (blood is diverted from periphery to legs to run!)
sympathetic female genitaliauterus relaxes (nonpregnant) or contracts (pregnant)
sympathetic male genitaliaejaculation
sympathetic ureters & bladderdetrusor relaxes, trigone and sphincter contract
parasympathetic eyepupil constricts; accomodation
parasympathetic lacrimal glandsstimulates tears
parasympathetic salivary glandsprofuse, watery secretion
parasympathetic lungs (trachea & bronchioles)constricts, increases secretion
parasympathetic heartdecreased rate & contractility
parasympathetic GIinc motility, tone, secretions, & peristalsis
parasympathetic blood vessels-
parasympathetic female genitaliaengorgement
parasympathetic male genitaliaerection
parasympathetic ureters & bladderdetrusor contracts, trigone and sphinter relax (facilitates urine excretion)
memorize

cholinergic agonists

Question Answer
name the direct-acting muscarinic receptor agonistsmuscarine, ACh, bethanechol, pilocarpine
name the direct-acting nicotinic receptor agonistsnicotine (at low doses), ACh
name the reversible anticholinesterasesphysostigmine, edrophonium, pyridostigmine, donepezil
name the irreversible anticholinesterasesechothiophate, organophosphates, nerve gases
mechanism of both types of nicotinic receptorspentameric ion channels that inc permeability to Na+ & Ca2+ leading to depolarization and excitation
types of nicotinic receptors and where they are foundNm (muscle type; at NMJ) & Nn (neuronal type; autonomic ganglia & adrenal medulla)
types of muscarinic receptorsM1 (neural), M2 (cardiac), M3 (glandular)
how do M1 receptors work?inc IP3 & DAG to depolarize autonomic ganglia, nerves, & gastric parietal cells
how do M2 receptors work?dec cAMP & inc K efflex to dec HR, contractility, and conduction
how do M3 receptors work?inc IP3 & DAG (and therefore Ca)... contraction of circular (miosis) & ciliary (accomodation) muscle, bronchoconstriction
which drug resists AChE? what is it used for?bethanecol, to increase GI motility (used after surgery to "wake the gut up", treats adynamic ileus & urinary retention)
ACh clinical usesnot much
bethanechol & pilocarpine adverse effectsbronchospasms, increase in exocrine secretions
pilocarpine clinical usesglaucoma & dry mouth treatment
nicotine low/high doselow doses stimulates nicotinic receptors, high dose inhibits nicotinic receptors and may cause death
varenicline is used for _ and is a _smoking cessation (Chantix), nicotinic receptor agonist
memorize

anticholinesterases

Question Answer
2 different cholistesterasespseudocholinesterase/butyrlcholisterase/plasma cholinesterase (in blood plasma) AND true/acetylcholinesterase (@ cholinergic synapses & on RBCs)
effects are similar to that caused by muscarinic agonists BUTpotentiate transmission @ NMJ, less vasodilation, only large toxic doses produce bradycardia & hypotension
anticholisterases classified byduration of action (short, medium, long/irreversible)
edrophonium durationshort-acting
neostigmine, physostigmine durationmedium-acting
organophosphates/echothiophate durationirreversible
which one crosses bbb and can be absorbed orally?physostigmine
acetylcholinesterase acts onACh only
butyrylcholinesterase acts onACh, benzylcholine, & succinylcholine
toxic dose of anticholinesteraseextreme nicotinic stimulation, depolarizing neuromuscular blockade, if lipid soluble then convulsions/coma/respiratory arrest
physostigmine is antidote foratropine poisoning
medium-acting are calledcarbamates
MOA of carbamatesreact with AChE, leaving a carbamyl group attached to the enzyme, which will spontaneously hydrolyze off in a few hours, reactivating the enzyme
isoflurophate is used forglaucoma
nerve gasessoman, sarin
echothiophate is used forglaucoma
parathion & malathion are what and MOAinsecticides... must be converted to active metabolites (insects can't do that well)
edrophonium MOAdoesn't react with cholinesterase; instead, it binds to enzyme by electrostatic force
antidote for exposure to nerve gases/insecticidepralidoxime (doesn't work after some time b/c phosphate group ages and loses organic moiety)
irreversible/long-lasting anticholinesterases leave what attached to AChE?phosphate group
acute glaucoma is also calledangle-closure, closed-angle, narrow-angle
acute glaucoma caused byfolded iris blocks exit of aqueous humor from anterior chamber (pressure on trabecular meshwork)
acute glaucoma Sxextreme pain, blurred vision, red eye, dilated pupil, nausea/vomiting, permanent blindness in 2-5 days
chronic glaucoma is also calledopen-angle or wide-angle
chronic glaucoma caused byobstruction in Schlemm's canal...slowly, often bilateral, genetic determinant
chronic glaucoma Sxgradual loss of peripheral vision, sometimes HA, blurred vision/dull pain
how can a cholinomimetic treat closed-angle glaucoma?cause contraction of iris constrictor muscle & ciliary muscle, thus facilitating drainage of aqueous humor (& circular ciliary muscle contraction decreases secretion)
most commonly effected areas in myasthenia gravisareas around eyes & mouth (first symptoms are usually ptosis & diplopia)
myasthenia gravia caused byautoimmune: circulating Ab to nicotinic ACh receptors (Nm)
myasthenia gravis associated withlupus, hyperthyroidism, hyperplasia of thymus gland or thymoma
myasthenia is more prevalent in what gender (at younger ages)women
diagnose myasthenia gravisedrophonium
myasthenia is worse when (and why?)at the end of the day, b/c overnight, the body replenishes NTs (including ACh)
treat myasthenia gravisneostigmine/pyridostigmine (anticholinesterases), thymectomy, plasmapheresis, immunosuppressives (glucocorticoids/azathioprine)
what produces the antibodies you don't want in myasthenia gravis?thymus
pyridostigmine & edrophonium adverse effectincrease in ACh may cause cholinergic crisis
pyridostigmine & edrophonium are antidotes totubocurarine
pralidoxime used forregenerating free & active AchE and treatment of cholinergic crisis (with atropine)
pralidoxime adverse effectsblurred vision, tachycardia, dizziness
cholinergic crisistoo much anticholinesterase -- stimulation of muscarinic receptors.. salivation, lacrimation, poor vision, muscle weakness
treat glaucoma with eye drops of which anticholinesterase?echothiophate
use which anticholinesterase to reverse action of non-depolarizing neuromuscular-blocking drugs in anesthesia?neostigmine (does not cross bbb)
memorize

cholinergic antagonists

Question Answer
contraindications for cholinergic antagonists at muscarinic sitesglaucoma, obstruction of GI tract
cholinergic antagonists are also calledAch receptor antagonists, anticholinergic agents
antimuscarinics usesto produce mydriasis & cycloplegia, in motion sickness, bronchodilators, adjuncts to general anesthesia, GI hypersensitivity/secretion, excessive salivation
examples of antimuscarinicsatropine, scopolamine, ipratropium
low dose atropine causes _ and high dose _bradycardia, tachycardia
scopolamine producesdizziness/amnesia
toxic doses of either scopolamine or atropineexcitement, agitation, hallucination, coma
antagonists at autonomic ganglianicotine (both agonist & antagonist) and trimethaphan/hexamethonium (use limited by severe SE)
antimuscarinics arecompetitive antagonists, reversible
Nn blockertrimethaphan
competitive Nm blockerpancuronium
depolarizing Nm blockersuccinylcholine
what is given to overcome atropine poisoning?physiostigmine (competes!)
ipratropium is used to treatasthma, COPD; it dilates the bronchial tubes (blocks M3 receptors)
scopolamine treatsmotion sickness
atropine toxicity mnemonicdry as a bone, red as a beet, blind as a bat, mad as a hatter, hot as a hare
a clear distant vision that helps in measuring refraction is called what and caused bycycloplegia, muscarinic antagonists
use this drug to dilate pupil for retinal examtropicamide
use for irritable bowel syndromedicyclomine
use for urinary incontinencetolterodine
muscarinic agonist/antagonist causes occlusion of canal of Schlemm, raising intraocular pressure?antagonist
muscarinic agonist/antagonist causes improved drainage of the eye?agonist
Paralysis of the ciliary muscles of the eye that results in the loss of visual accommodationcycloplegia
used as a measure of smoking habitscotinine (inactive metabolite)
fatal dose of nicotine40mg (5 cigarettes)
potential therapeutic uses of nicotineAlzheimer's, prevent Parkinsons, ulcerative colitis, schizophrenia
nicotine elicits discharge of what from the adrenal medulla, causing what?epinephrine, accelerates HR & inc BP
difference in MOA of hexamethonium & trimethaphan (both used to treat what)both block Nn of ganglia, but hexa is a channel blocker and trimetha is a competitive Ach receptor blocker; both used for htn (hexa htn, trimetha hypertensive crisis)
what is used NOW to treat hypertensive emergency?sodium nitroprusside
mecamylamine is usedin patches w/ nicotine for smoking cessation; competitive Ach blocker
competitive blockers of Nmpancuronium, tubocurarine
depolarizing blockers of Nmsuccinylcholine (closes sodium channels)
difference between Ach and succinylcholine at NMJsuccinylcholine is not immediately hydrolyzed so it occupies Nm receptor for much more time (phase I: persistent partial depolarization)
tubocurarine adverse effectcauses histamine release (allergies)
ganglionic-blocking drugs, clinical useobsolete! but produce hypotension
present in black widow spiderlatrotoxin (causes explosive release of Ach)
memorize

predominant tone & effects of autonomic ganglion blockade

Question Answer
predominant tone of arteriolessympathetic (adrenergic)
predominant tone of veinssympathetic (adrenergic)
predominant tone of heartparasympathetic (cholinergic)
predominant tone of irisparasympathetic (cholinergic)
predominant tone of ciliary muscleparaympathetic (cholinergic)
predominant tone of GIparasympathetic (cholinergic)
predominant tone of urinary bladderparasympathetic (cholinergic)
predominant tone of salivary glandsparasympathetic (cholinergic)
predominant tone of sweat glandssympathetic (cholinergic)
predominant tone of genital tractsympathetic & parasympathetic
effect on arteriolesvasodilation, hypotension
effect on veinsdilation, decreased venous return so dec cardiac output
effect on hearttachycardia
effect on irismydriasis
effect on ciliary musclecycloplegia (focus to far vision)
effect on GIreduced tone and motility, constipation, dec gastric & pancreatic secretions
effect on urinary bladderurinary retention
effect on salivary glandsxerostomia
effect on sweat glandsanhidrosis
effect on genital tractdec stimulation
memorize

 

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