Autonomic System and Cholinergic Transmission Flashcards
Describe the autonomic nervous system, the divisions and the function
- involuntary
- sympathetic and parasympathetic
- handles visceral functions
- 2 neurons in series: pre and post ganglionic
- all preganglionic fibers release Ach
describe the sympathetic nervous systm
- fight or flight
- runs on norepinephrine
- increases CO, BP, RR, blood flow and BG
- decreases RBF, digestive process
- fires at once
- short pre and lost post
describe parasympathetic nervous system
- normal maintenance and anabolic metabolism
- incremental activation
- vagal stimulation
- long pre and short post
describe the somatic nervous system and its function
- voluntary
- controls movement, respiration and posture
- always excitatory
- no ganglia
describe cholinergic fibers and what they do
- synthesize and release Ach
- all preganglionic efferent and somatic motor fibers to skeletal muscle
- most parasympathetic postganglionic fibers
what do adrenergic fibers do and what fibers are these
- release NE
- most sympathetic postganglionic fibers
what NT is released in the somatic nervous system and what is the effector organ and effect
- Ach
- skeletal muscle
- stimulatory
what NT is released in sympathetic nervous system
NE
what NT is released in parasympathetic nervous system
Ach
what is the difference between a neurotransmitter and a neurohormone
a NT is released at the effector organ. a neurohormone is released into the blood that is then carrier to the effector organ
what is an example of a neurohormone in the sympathetic nervous system
the adrenal medulla releasing epi and NE into blood stresm
the effect from the autonomic nervous system depends on:
NT and receptors on effector organs
what are the steps to cholinergic transmission
- acetyl CoA + choline = ACh
- transported to cytoplasm, prepped for release
- calcium triggers release of Ach
- Ach binds to cholinergic receptor
- acetylcholinesterase degrades Ach into choline and acetate
what is the mechanism of adrenergic transmission
tyrosine gets converted to dopamine which gets converted to NE
- calcium induces NE release
does NE get broken down by acetylcholinesterase
no
what are the autonomic receptors
-cholinergic receptors
- adrenergic receptors
what are the cholinergic receptors
- nicotinic (ganglionic)
- muscarinic
what are the adrenergic receptors
-alpha
- beta
- dopamine
what are the 3 main classes of nicotinic receptors
- muscle
- ganglionic
- CNS
what is the effect of nicotinic receptors
excitatory
what is the mechanism of action in nicotinic receptors
sodium influx causes activation
what are the muscarinic receptors and what do each do
- M1- neural: CNS excitation, gastric secretion
- M2- atrial: cardiac and neural inhibition, decrease in HR and inotropy
- M3: glandular/smooth muscle: increased gastric acid, salivary secretion, GI contraction, ocular accomodation, vasodilation
-M4 and M5- CNS
which division of the autonomic nervous system causes pupil dilation (mydriasis)
sympathetic
what is another name for cholinergics
muscarinic agonists
describe cholinergic drugs and the 2 types
- parasympathomimetic
- direct acting: binds directly to nicotinic Ach receptor and muscarinic receptor
- indirect acting: inhibits acetylcholinesterase. amplifiers of endogenous Ach
what are the direct acting cholinergics
- pilocarpine (salagen)
- bethanechol (urecholine)
- cevimiline (evoxac)
what does pilocarpine (salagen) do
- glaucoma tx
- causes miosis, lowers IOP
- dental use- radiation induced xerostomia
what is bethanechol (urecholine) used for
post operative urinary retention
- used in sx to decrease secretions for a clear field
which direct acting cholinergic is most resistant to cholinesterase
bethanechol (urecholine)
what is cevimiline (evoxac)
- selective for M3
- more selective for exocrine glands
- chronic dry mouth use
- radiation induced xerostomia; sjogrens syndrom
what are the indirect acting cholinergics
- acetylcholinesterase inhibitors
- reversible: stigmine agents, donepezil (aricept), galantamine (razadyne)
- irreversible: organophosphates
indirect acting cholinergics used for the treatment of:
- myasthenia gravis
- glaucoma
- GI motility
- reversal of neuromuscular blockade
-anticholinergic toxicity - alzheimers
what are the reversible ACHE inhibitors
- pyridostigmine (Regonol)
- neostigmine (Prostigmin)
- physostigmine (antilirium)
- edrophonium (tensilon)
- galantamine, rivastigmine, donepezil
what are the indications for and the duration of pyridostigmine
- myasthenia gravis- 1st line
- nerve agent prophylaxis
- 4-6h duration
what are the indications for neostigmine and what type of amine is it
- myasthenia gravis
- post op ileus/urinary retention
- neuromuscular blockade reversal
- quaternary amine
what are the indications for physostigmine, what type of amine is it and why isnt it routinely used
- anticholinergic activity
- tertiary amine
- not used due to CNS activity
what is the indication for edrophonium, what type of amine is it and why isnt it routinely used
- diagnosis of myasthenia gravis
- quaternary amine
- not used for tx because short half life of 5 minutes
what is the indication for galantamine, rivastigmine, and donepezil
- mild to moderate alzheimers disease
- more selective ACHe for management of cognitive dysfunction
- modest clinical benefits
describe organophosphates and the kinds
- irreversible Ache
- long lasting
- insecticides: parathion, malathion
- nerve agents: sarin, soman tabun, VX
- Novichok agents
what is the mechanism of ACHe
breaks down acetylcholine and binds at the esteric site
- phosphorus binds irreversible to serine at the esteric site
- OP attached to ACHe preventing Ach binding
when cholinesterase is blocked by organophosphates what 3 things can happen
- hydrolyze to original state (slow)
- regenerate with an oxime (fast)
- age (cannot regenerate)
what are the muscarinic symptoms using the acronym SLUDGE in cholinergic toxicity
- Salivation
- Lacrimation
-Urination - Diarrhea
- GI discomfort
- Emesis
what are the muscarinic symptoms using the acronym DUMBBELS for cholinergic toxicity
- Diarrhea
- Urination
- Miosis/muscles wek
-Bronchorrhea
-Bradycardia
-Emesis
-Lacrimation
-Salivation/Sweating
what are the nicotinic symptoms of cholinergic toxicity
- Muscle cramps
-Tachycardia
-Weakness
-Twitching
-Fasciculations
what is the synonym and aging half life for sarin
- GB
- 5 hours
what is the synonym and aging half life for soman
- GD
- 2 minutes
what is the synonym and aging half life for tabun
- GA
- more than 40 hours
what is the synonym and aging half life for VX
- none
- over 40 hours
what can you adminster in cholinergic toxicity and what does each do
- pralidoxime (2-pam): regenerates ACHE
- atropine: muscarinic antagonism only, wont correct nicotinic symptoms like paralysis
- pyridostigmine: prophylaxis only
what is the problem with atropine
it requires a really large dose
what is another name for anticholinergics
muscarinic antagonists
what do anticholinergics do
binds muscarinic receptors, blocks Ach
what are the types of anticholinergics and what does each do
- tertiary amines: have central effects and get into CNS easier
- quaternary amines: peripheral effects
what drugs are examples of tertiary amines
- atropine
- scopolamine, benzotropine, dicyclomine
what drugs are examples of quaternary amines
- glycopyrrolate
-titotropium
describe atropine
- prototypical anticholinergic
- muscarinic selectivity
- no effect on S/P heart transplant
what are the indications for atropine
- bradycardia
- OP toxicity
what is the minimum dose of atropine and why
0.5mg because it can cause paradoxical bradycardia
what is atropine derived from
jimson weed and deadly nightshade
what is the mechanism of atropine
- binds M2 receptor and blocks AcH so it reduces ACH effect on the heart thus increasing HR
where is scopolamine found, what type of amine it is and what are its indications
- found in hyoscyamus niger (henbane)
- tertiary amine
- uses: motion sickness and voodoo zombification
- blocks short term memory
what type of amine is glycopyrrolate and what is it used for
- quaternary amine, fewer central effects
- used to dry secretions in surgery and ketamine treatment
- adjunct for reversal of neuromuscular blockers
what are the uses of anticholinergic drugs
- opthalmology: mydriasis, cycloplegia, increased IOP
- GI/GU: antispasmodic, antidiarrheal, urinary incontinence
- cardiovascular: vagolytic ( increases HR)
- secretions: decreases all, surgery and dental use
- antidote: reversal of cholinergic toxicity in OP poisoning
- pulmonary: COPD/ asthma treatment (bronchodilation)
what are the anticholinergic effects
- CNS: drowsiness, amnesia, agitation, hallucinations, coma. scopolamine > atropine
- Eye: mydriasis, cycloplegia, reduced lacrimal secretion
- CV: tachycardia (vagal inhibition)
- respiratory: bronchodilation, reduced airway secretions
- GI: decreased motility, xerostomia
what is another name for nicotinic drugs
ganglion stimulating drugs
what are the effects of too much nicotine
- seizure
- respiratory arrest
- coma
- paralysis
how much nicotine can be fatal
1 drop of pure liquid = 40mg
what type of drug is varenicline (chantix)
a nicotinic drug
describe varenicline
- partial agonist/antagonist
-long half life and high affinity for nicotinic acetylcholine receptors - inhibits nicotine binding, withdrawal symptoms and dopamine release
what are the two types of neuromuscular blockers
- depolarizing
- nondepolarizing
what are the depolarizing neuromuscular blockers
succinylcholine
what are the nondepolarzing neuromuscular blockers
- rocuronium
- vecuronium
- pancuronium
- cisatricurium
what do neuromuscular blockers do
inhibit binding of ACH at NMJ
what does succinylcholine do, what is the onset, duration and dose
- opens sodium channels
- onset of 60 seconds
- duration of 5 minutes
- 1.5mg/KG IV
- give more is hypotensive
what is the caution with succinylcholine
- hyperkalemia
- denervation supersensitivity
what happens in denervation supersensitivity
- potassium increase of 5-10 mEq/L
- takes 3-5 days
what does rocuronium do, what is the onset, duration and dose
- nondepolarizing
- reversal agent with no ADR
- onset 60 seconds
- duration 45 minutes
- 0.6-1.2MG/KG
which nondepolarizing NMDs are not frequently used and why
- vecuronium, pancuronium and cisatracurium because they have slow onset
what can pancuronium cause
tachycardia
what is cisatracurium used for
therapeutic temperature management
what is rocuronium used for
- excellent intubating conditions
