NDNMB reversals Flashcards
2 parts of the CNS
-brain-spinal cord
2 parts of the PNS
somatic nervous system (SNS)Autonomic nervous system (ANS)
Which system conveys information from receptors to the CNS
Afferent system
which system conveys information from the CNS to the muscles and glands
Efferent system
what are the 2 main areas the efferent system sends information to?
the somatic nervous system (SNS)and Autonomic nervous system (ANS)
what does the somatic nervous system (SNS) do
conveys informatin from the CNS to the skeletal muscles
what does the ANS do
conveys information from the CNS to smooth musclecardiac muscleand glands
diagram of CNS and PNS
C Brain Spinal Cord N ^ v S Afferent Efferent V V P Somatic Autonomic N Nervous Nervous S System System V V SNS PNS
2 parts of the ANS
Sypathetic nervous system and the parasympathetic nervous system
ACh is stored where at the synaptic cleft
in vesicles at motor end plate
the nicotinic ACh receptor consist of how many gycoprotein subunits to form an ion channel? what are the named?
5
2 alpha, 1 beta, 1 delta, and 2 gamma (epsilon)
how many alpha glycoprotein subunits on the nicotinic receptor need to bound to for ACh to open the channel?
(both) 2
how many alpha glycoprotein subunits on the nicotinic receptor need to bound to for NDMBs to block the channel?
1
how many alpha glycoprotein subunits on the nicotinic receptor need to bound by Sux to cause a block?
both (2)
how is reversal of NMB (neuro muscular blockade) achieved?
by competitive antagonism–competition b/t NMBA and ACh for the motoer end plate receptor at the NMJ- whichever is the greatest wins
what is RECURARIZATION?
was a problem with long acting NMBAs whose effects outlasted the reversal agents
what is ENCAPSULATION reversal
cyclodextrin surrounds and bonds NMBA in plasma -the concenration gradient reversed drawing NMBAs off receptors into plasma and then quickly bound
side notes about cholinesterase inhibitors: what were they derived from?
what were they used for?
precursor of what? (give ex)
- derived from Calabar beanused in West africa as a poison precursor for organphosphates
- insecticides
- nerve gas
what class of drugs are reversal agents
cholinesterase inhibitors
basic way cholinesterase inhibitors work for reversals
competitive antagonism - inhibits acetylcholinesterase (and other chilinesterases), so it increases the concentration of ACh at the NMJ
Name 4 cholinesterase inhibitors
edrophonium (enlon)
neostigmine (prostigmin)
pyridostigmine
physostigmine (antilerium)
what is the most rapid acting cholinesterase inhibitor?
edrophonium
which cholinesterase inhibitor binds REVERSIBLY to the negative charged enzyme site (cholinesterase enzyme)?
edrophonium
why is the duration of binding short with edrophonium (Enlon)?
b/c once it binds it is liberated finds another site to bind to, and so on
Why is edrophonium (Enlon) not recommended for deep blocks?
b/c of the type of bonds it makes (reversable it’s not a covalent bond)
does edrophonium require attenuation of muscarinic response to ACh accumulation?
yes
just b/c shores may ask what is the basic chemical make up of edrophonium (Enlon)?
simple alcohol with quaternary ammonium group
just b/c shores may ask (b/c he is jealous that jake is a fucking wizard) what is the basic chemical make up of Neostigmine?
Quaternary ammonium compound
Does Neostigmine (Prostigmine) cross the BBB
No
What kind of bond does Neostigmine (Prostigmine) make?
IRREVERSABLE enzymatic deactivation (covalent)
lipid solubility of Neostigmine: good or poor?
poor
Does Neostigmine (Prostigmine) require attenuation of muscarinic response to ACh accumulation?
you bet your ass it does
which Cholinesterase inhibitor is used for myasthenia gravis??? Hmmmmm
pyridostigmine
is pyridostigmine a long acting or short acting cholinesterase inhibitor ?
long
is pyridostigmine used in anesthesia
no (remember myasthenia gravis)
what is a cholinesterase that is a precusor of neostigmine and is a teriary amine?
physostigmine (antilerium)
seems important b/c it is totally differentwhat is special about physostigmine (antilerium)
it crosses the BBB increasing the ACh in the brain causing:confusionlethargyweaknessCHOLINERGIC CRISIS*
what is physostigmine (antilerium) used for??
counteract delerium caused by benzos and barbs
hint: physostigmine (antiLERIUM)=deLERIUM
all cholinesterase inhibitors are eliminated where?
renal: endophonium 70%, Neostigmine 50%
Side effects of cholinesterase inhibitors?
Bradycardia, bronchospasm, increased airway secretions, nausea/vomiting, abd cramping, miosis (constriction of pupil), vision disturbance, micturation (voiding, peeing, weeing, pissing, etc).
so basically you go into a cholinergic chrisis, SLUDGE (too much ACh at postsynaptic cleft thus extreme PNS activation)
Neostigmine (Prostigmine) dose, max dose, onset, peak, duration, Renal excretion %?
dose: 0.04 - 0.07 mg/kg
max dose: 5 mg
onset: 5 - 10 minutes
peak: 10 minutes
duration: 1 hour
Renal excretion: 50%
Endrophonium (Enlon) dose, max dose, onset, peak, duration, Renal excretion %?
dose: 0.5 - 1 mg/kg
max dose: 40 mg
onset: 30 - 60 seconds
peak: 1 minute
duration: 45 minutes
Renal excretion: 70%
If you had to get your patient reversed as quick as possible what would you give???
endrophonium
whats another name for cholinesterase inhibitor “antidotes”?
anticholinergic agents or parasympatholytics
what are 3 main anticholinergic agents, and there basic chemical compound?
atropine-tertiary amine
scopolamine- tertiary amine
gylcopyrrolate- quaternary amine
should you give cholinesterase inhibitors without an anticholinergic?
no
why is scopalamine rarely used
b/c of its significant central effects
What is the general dosage recommendation for gylcopyrrolate (Robinul)?
Glyco 0.2mg for each 1mg of Neostigmine given.
(glycopyrrolate- 7mcg/kg–general rule of thumb neo and glyco are equal proportions 1cc to 1cc, because glyco is packaged as 0.2mg/cc and neo is packaged as 1mg/cc)
What is the general dosage recommendation for atropine?
7-15 mcg/kg, given with endrophonium.
typical dose is 1 - 2 mg
How do you reverse children, or anyone for that matter?
you always give your anti-cholinergic, wait for an increased HR, then give the cholinesterase inhibitor
side effects of anti-cholinergic drugs
tachycardia dry mouth mydriasis (dilated pupils) vision disturbance **CONFUSION***
(opposite of cholinesterase inhibitors)
**what shores whats us to know about sugammadex ( he stated in his lecture just know this)
-cyclodextrin structure -not used in the US-causes encapsulation
How is neostigmine (Prostigmine) metabolized?
50% renal, 50% hepatic
How is edrophonium (Enlon) metabolized?
75% renal, 25% hepatic
Glycopyrrolate (Robinul) dose, onset, peak, duration?
dose: 0.2 mg / 1 mg Neostigmine given
onset: 4 minutes
peak: 5 minutes
duration: 2 - 7 hours
Glycopyrrolate (Robinul) mechanism of action.
muscarinic receptor antagonist - competitively antagonizes muscarinic acetylcholine receptors, displacing acetylcholine, and preventing parasympathetic stimulation by acetylcholine
How is glycopyrrolate (Robinul) metabolized?
hepatic metabolism
renal elimination
Does glycopyrrolate (Robinul) cross the blood brain barrier?
no
Scopalomine dose, onset, peak, duration?
dose: 0.2 - 1 mg (usually given IM)
onset: 5 - 10 minutes
peak: 20 - 60 minutes
duration: 2 hours
Scopalomine mechanism of action.
muscarinic receptor antagonist - competitively antagonizes muscarinic acetylcholine receptors, displacing acetylcholine, and preventing parasympathetic stimulation by acetylcholine
Does scopalomine cross the blood brain barrier?
yes
How is scopalomine metabolized?
hepatic metabolism
renal elimination
Pulmonary, cardiac, and neuro effects of scopalomine?
pulmonary - bronchodilation
cardiac - increases CO
neuro - decreases motion-induced nausea; the best at decreasing secretions, increasing amnesia, and increasing sedation
What is contraindicated with scopalomine use?
closed-angle glaucoma
Atropine dose, onset, peak, duration?
dose: 0.01 mg/kg
onset: 1 minute
peak: 2 minutes
duration: 1 - 4 hours
Atropine mechanism of action.
muscarinic receptor antagonist - competitively antagonizes muscarinic acetylcholine receptors, displacing acetylcholine, and preventing parasympathetic stimulation by acetylcholine
How is atropine metabolized?
hepatic metabolism
renal elimination
Pulmonary and cardiac effects of atropine?
pulmonary - bronchodilation
cardiac - increased HR (d/t vagal inhibition of SA / AV node conduction)
Why is atropine given with edrophonium?
d/t its similar rapid onset
