Modulation of the Parasympathetic System and NMJ Flashcards
Direct acting cholinomimetics
acetylcholine, bethanechol, carbachol, cevimeline, nicotine, pilocarpine, varenicline
Short acting anticholinesterase
edrophonium
Intermediate acting anticholinesterase
donepezil, galantamine, neostigmine, physostigmine, pyridostigmine, rivastigmine
Long acting anti cholinesterase
echothiophate, malathion, parathion, sarin
Reactivation of acetylcholinesterase
pralidoxime
Cholinoceptor blocking drugs
atropine, cyclopentolate, dicyclomine, homatropine, ipratropium, oxybutynin, scopolamine, tiotropium, tropicamide
Which neurotransmitter is used at the presynaptic terminal of para and sympathetic systems?
acetylcholine
What receptor is found at the post synaptic terminal of both para and sympathetic systems?
nicotinic
Which neurotransmitter is found at the parasympathetic effector cell?
acetylcholine
Which neurotransmitter is found at the sympathetic effector cell?
norepinephrine
Which receptor is found at the parasympathetic effector organ?
muscarinic
Which receptor is found at the sympathetic effector organ?
adrenergic
What do cholinesterase inhibitors do?
inhibit the hydrolysis of endogenous acetylcholine thereby increasing the availability of naturally occurring ACh in the synapse
All cholinergic agonists are metabolized by cholinesterase in what three places?
at the receptor, in the blood, and in the liver
ACh, Carbachol, and Bethanechol pharmokinetics
not lipid soluble/highly charged, often have to inject it where you want it, ACh is rapidly broken down while the other two have a longer duration
Pilocarpine, nicotine, and muscarine pharmokinetics
readily absorbed from most sites of administration, excreted by kidney
Which direct cholinomimetic is not seen clinically because of toxicity and crossing the BBB?
muscarine
What receptor is on the presynaptic nerve terminal of para and sympathetic systems?
muscarinic receptor, activation cause inhibition of neurotransmitter release
T/F muscarinic receptors are g protein coupled and produce 2nd messenger cascade that directly affects organ function
true
T/F nicotinic receptors are ion channel and activation produces depolarization of the nerve cell or NMJ
true
What is the result of prolonged agonist binding to the nicotinic post ganglion neuron?
desensitization/depolarizing blockade, prevents recovery
What is the muscarinic effect on the eye?
miosis (contraction of sphincter), accommodation, opening of TM (lower IOP)
What is the muscarinic effect on the heart?
decrease in heart rate (hyperpolarization of SA and AV node)
What is the muscarinic effect on blood vessels?
indirect vasodilation and decrease in peripheral resistance (in atherosclerosis will cause vasoconstriction)
What is the muscarinic effect on the respiratory system?
contraction of bronchial smooth muscle aka broncho-constriction and increased mucous secretion
What is the muscarinic effect on the GI tract?
increase smooth muscle motility and relax most sphincters, stimulate salivary and gastric glands to secrete
What is the muscarinic effect of the urinary tract?
stimulate detrusor and relax trigone and sphincter aka promote urination
What is the muscarinic effect on other glands?
SECRETION sweat, lacrimal, nasopharyngeal
T/F activation of nicotinic receptors often resembles simultaneous discharge on both para and sympathetic system
true be careful of drug side effects
Activation of nicotinic receptors in autonomic ganglia cause simultaneous…
sympathomimetic cardiovascular activity (increase HR and BP) AND parasympathomimetic GI and Urinary activity (nausea, vomiting, diarrhea, and urination)
What is the nicotinic effect at the NMJ?
depolarization followed by depolarization blockage aka desensitization
T/F most indirect acting cholinomimetics are simple alcohols or esters
true
T/F derivatives of phosphoric acid (organophosphates) have the shortest duration of action
false
What is the administration of indirect cholinomimetics?
any including IV
Where are organophosphates absorbed from?
skin, lung, gut, and conj – dangerous to humans
Which intermediate indirect drug is well absorbed from all sites and can be used topically in the eye?
physostigmine
T/F organophosphates are distributed to the CNS
true, CNS toxicity is common
Which organophosphate does not cross the CNS?
echothiophate
Why is edrophonium short acting?
forms a reversible bond with the enzyme but is not actually a substrate for ACh-esterase
What is the MOA of intermediate acting drugs?
neostigmine, physostigmine, and pyridostigmine are resistant to part of the enzyme action so it takes longer
What is the MOA of echothiophate, malathion, parathion, and sarin?
forms phosphorylated enzyme complex that strengthens the bond with the drug aka completely deactivates ACh-ase
What effect do low concentrations of indirect acting drugs have?
alerting response
What effect do high concentrations of indirect acting drugs have?
convulsions
What happens to the cardiovascular system when indirect acting drugs are used?
increased activity in both sympathetic and parasympathetic ganglia as well as increased activity at muscarinic receptors
Which system dominates the cardiovascular response to indirect acting cholinergic agonists?
parasympathetic because of direct muscarinic innervation aka decreased HR and decreased cardiac output
What is the indirect cholinergic agonist effect at the NMF?
prolong and intensify actions of acetylcholine, strengthen muscle contraction=helpful in myasthenia gravis
T/F the NMJ can be desensitized by high or prolonged concentrations
true
Which cholinomimetics can treat glaucoma?
carbachol, pilocarpine, echothiophate(obsolete)
Which cholinomimetic treats urinary retention?
bethanechol or neostigmine
Which cholinomimetic treats dry mouth?
cevimeline, pilocarpine
Which cholinomimetics treat myasthenia gravis?
edrophonium (diagnosis) and pyridostigmine maybe neostigmine
T/F cholinomimetics may help treat alzheimer’s?
true (donepezil, galantamine, rivastigmine)
How do cholinomimetics work in the eye?
cause contraction of the ciliary body +miosis to increase aqueous outflow
What cholinomimetic can reverse neuromuscular blockage produces during surgical anesthesia?
neostigmine and edrophonium
What are adverse effects of direct acting cholinomimetics?
nausea, vomiting and diarrhea (increase GI activity) urinary urgency, salivation and sweating (increase secretions) flushing of skin from vasodilation and bronchial constriction
What are adverse effects of cholinesterase inhibitors?
same as direct + muscle weakness (NMJ), convulsions (CNS) and respiratory failure
What are symptoms of organophosphate poisoning?
same as cholinesterase inhibitors
What are the effects of cholinergic blockers (muscarinic antagonists)?
interrupt parasympathetic nerve impulses and prevent ACh from stimulating cholinergic receptors
T/F Cholinergic blockers can be divided into muscarinic and nicotinic subgroups
true
What is an example of a naturally occurring muscarinic antagonists?
atropine, derived from nightshade plant
What is an example of a synthetic muscarinic antagonist?
tropicamide
What is the absorption of cholinergic blockers?
most are well absorbed in the gut, conj and across skin
What is the distribution of cholinergic blockers?
widely distributed with CNS penetration
Where are muscarinic antagonists eliminated?
kidney
What is the MOA of cholinergic blockers?
block acetylcholine action at muscarinic receptors, moderately selective for receptor subtypes
Is atropine selective or nonselective?
nonselective, useful in treating cholinomimetic toxicity like from organophosphates
Which muscarinic antagonist has minimal CNS effects and which has marked effects?
minimal atropine, marked scopolamine
What are scopolamine’s side effects and why does it have them?
drowsiness and amnesia, also reversal of vestibular disturbances, side effect because it crosses the BBB
What are cholinergic blocker effects on the cardiovascular system?
increased HR
What are cholinergic blocker effects on the eye?
mydriasis from blocking muscarinic activation of pupillary constrictor muscle allowing unopposed sympathetic dilator activity— also cycloplegia from weakening ciliary muscle– and reduction in lacrimal secretion
What are muscarinic antagonist effects on the respiratory system?
bronchodilation and decrease in secretions
What are muscarinic antagonist effects on GI tract?
decreased salivation and stomach acid, decreased smooth muscle tone and less propulsive movements
What are cholinergic blocker effects on the urinary tract?
relax bladder smooth muscle which slows voiding
What do cholinergic blockers do to sweat glands?
reduces sweating and can induce fever in younger patients
What CNS disorders are antimuscarinic drugs used for?
parkinsons and treatment of motion sickness
What antimuscarinic drugs are used for accurate refraction?
cyclopentolate or homatropine
What antimuscarinic drugs are used for dilated fundus exam?
tropicamide or cyclopentolate
What antimuscarinic drugs are used for uveitis and prevention of synechia?
homatropine or cyclopentolate
What are characteristics of iris synechia?
irregular pupil and increased IOP possible
What is the duration of eye drop dilation effects?
atropine 7-10 days, homatropine 1-3 days, cyclopentolate 1 day, tropicamide 6 hours
What antimuscarinic drugs are used as pre-anesthesis to prevent airway secretions?
atropine or scopolamine
What antimuscarinic drugs treat COPD and asthma because of bronchodilation?
ipratropium or tiotropium
What antimuscarinic drugs treat urinary urgency or bladder spasm?
oxybutynin
T/F antimuscarinic drugs treat bradycardia and some arrhythmias
true
What is cholinergic poisoning?
long acting indirect poisoning
What drug has an antimuscarinic effect used to treat cholinergic poisoning?
atropine because its nonspecific, multiple doses required
What cholinesterase regenerator can treat cholinergic poisoning if used rapidly?
pralidoxime because it can regenerate phosphorylated enzyme
What are adverse effects of antimuscarinic drugs?
mydriasis and light sensitivity, decreased accommodation, dry mouth, tachycardia, flushed skin, agitation, delirium, elevated body temp
T/F Cholinoreceptor agonists cause SLUD
true, salivation, lacrimation, urination, diarrhea
What are the cholinoreceptor antagonists? (opposite effect of SLUD)
dry mouth, dry eyes, urinary retention, constipation
