Week 4: NMBAs Flashcards
Neuromuscular junction consists of (3):
Prejunctional motor nerve ending
Synaptic cleft (contains acetylcholinesterase (AChAse))
Highly folded Postjunctional muscle fiber
In nerve stimulation: depolarization reaches nerve terminal and voltage gated __________ channels open and _________ enters the nerve terminal
Calcium; calcium
In nerve stimulation: storage quanta Vesicles (presynaptic) release ____________ into the cleft
acetylcholine (ACh)
In nerve stimulation: ACh diffuses across the synaptic cleft and binds to the ________________ receptor at the postsynaptic end plate and start of muscle contraction
nicotinic cholinergic
The release of ACh quanta is antagonized by _________ and _________.
Hypocalcemia ; Hypermagnesimia
1 ACh quanta contains __________ to ___________ ACh molecules.
5,000 to 10,000
Post-junctional receptors have ______ subunits.
5
Postjunctional receptors with 2 alpha, 1 beta, 1 delta, and 1 epsilon (Fetal or “Adult”)?
Adult
** mature - after birth
Postjunctional receptors with 2 alpha, 1 beta, 1 delta, and 1 gamma (Fetal or “Adult”)?
Fetal
**immature/fetal-isommer
The two ___ subunits of the receptor contain the ACh-binding sites
a ( the a-recognition site )
If both “a” subunits are occupied then a ________ change happens and a _______ channel opens
conformational ; central
Sodium (and Calcium) move _________ the cell and Potassium moves __________ the cell. Action potential occurs and a muscle contraction happens.
in to ; out of
When a nerve impulse arrives at the neuromuscular junction (NMJ), voltage-gated ion channels open, leading to an influx of __________ within the terminal that causes several hundred vesicles of acetylcholine to fuse with the nerve membrane.
Calcium
The acetylcholine within the vesicles is released into the synaptic cleft, combining with and activating _______________ receptors on the motor endplate, the activation of which opens ion channels on the muscle membrane and depolarizes the membrane.
nicotinic
The release of ________ from intracellular stores stimulates an interaction between actin and myosin, resulting in muscle contraction.
Calcium
Increased Extrajunctional Receptors is called:
Upregulation
Upregulation occurs when?
When frequency of stimulation of NMJ decreases over days or longer.
What could decrease the frequency of stimulation of NMJ? (6)
- Prolonged use of NMBAs in ICU
- Immobilization
- Severe burns
- CVAs (stroke)
- Infection
- Sepsis
In up-regulation, the number of ___________ nAChRs increases
immature
In upregulation: The number of immature nAChRs will have increased sensitivity to _______ and _______ and decreased sensitivity to ___________.
ACh and SCh ; nondepolarizers
The channel opening time of the immature nAChRs is up to 10-fold longer than that of mature receptors and may allow systemic release of lethal doses of intracellular _______ in response to administration of _________.
K+ (Potassium) ; Succinylcholine (SCh)
When does Downregulation of mature nAChRs occur? give example.
During periods of sustained agonist stimulation.
Chronic neostigmine use.
In what condition is neogtigmine chronically used?
Myasthenia gravis
Sustained agonist stimulation leads to __________ to SCh but __________ sensitivity to nondepolarizing NMBAs.
Resistance; extreme .
Uses of muscle relaxants (4):
- Optimize surgical conditions
- Prevent unwanted movement
- Facilitate tracheal intubation
- Improve mechanical ventilation
Primary purpose of muscle relaxants:
Primary purpose is to achieve adequate relaxation of the upper airway, vocal cords, and diaphragm to facilitate intubation and surgery
Neuromuscular blocking agents (NMBA) are NOT ________ and DO NOT cause _______.
anesthetics ; amnesia.
NMBA do not cause awareness; not enough _________ causes awareness
anesthesia
T/F: Complete paralysis is not required for all surgical cases.
True :)
Other ways to produce muscle relaxation besides NMBAs?
- Inhalational agents: iso, sevo, des
- Blocks : regional, spinal
Main site of action of NMBA is on the ________________ receptor at the ________ of the muscle.
nicotinic cholinergic ; endplate
median dose that corresponds to 50% twitch reduction
ED50
corresponds to 95% block (useful relaxation when twitch abolished)
ED95
Characteristics of Neuromuscular Blockers(NMB)
- potency
- onset of action
- duration of action
- recovery index
- intubating condition
relationship between twitch depression and dose
potency
time to maximal blockade
Onset of Action
Time of injection to return of 25% twitch height
( Dose dependent )
Duration of Action
Time interval between 25% and 75% twitch height
( Speed of recovery )
Recovery Index
Two types of Neuromuscular Blocking Agents:
Depolarizing & Nondepolarizing
Depolarize at postsynaptic nAChRs
Depolarizing NMBAs
Example of depolarizing NMBA:
Succinylcholine
Compete for active binding sites on nAChRs
Nondepolarizing NMBAs
Two types of nondepolarizing NMBAs
Aminosteroid & Benzylisoquinolinium
Aminosteroid - Nondepolarizing NMBAs:
Pancuronium
Rocuronium
Vecuronium
Benzylisoquinolinium - Nondepolarizing NMBAs:
- Mivacurium
- Atracurium
- Cisatracurium
made up of two ACh molecules joined end to end; acts as a “false transmitter,” mimicking ACh.
Succinylcholine
Succinylcholine(SCh) (__________)
Anectine
_____________ agent creates an overwhelming persistent stimulation to nAChRs.
Depolarizing agent
with ___________ agents membranes become exhausted and unresponsive to ACh. Muscle contraction cannot recur until return of __________ state.
depolarizing ; resting
Which drug activates the prejunctional receptors to release ACh and it also mimics ACh.
Succinylcholine (SCh) - (Anectine)
Succinylcholine (Anectine) produces sustained depolarization of the __________ membrane and __________ receptors.
Postjunctional; extrajunctional
Succinylcholine causes prolonged depolarization of the motor end-plate which inactivates ________ channels and increases influx of ________.
Na; Sodium
*** exist of potassium from cell
Succinylcholine(SCh)/Anectine was introduced in what year?
1949
How does SCh mimic ACh?
it has Two ACh molecules joined end to end
When given may cause fasciculations before total paralysis, specially in patients with a lot of muscle.
Succinylcholine(SCh)/Anectine
Succinylcholine IV dose
1 -1.5 mg/kg IV
Succinylcholine IM dose in children.
4 -5 mg/kg IM
Why give IM succinylcholine?
Good for laryngospasm
Succinylcholine IV dose in kids.
1.5-2 mg/kg
**children are more resistant.
Succinylcholine IV dose in infants.
up to 3 mg/kg
Infants need an increased amount of SCh becaue
Not enough muscle and larger volume of distribution.
Onset of Succinylcholine(SCh)/Anectine
~ 1 minute ( 30 - 60 seconds).
Duration of Succinylcholine(SCh)/Anectine
5-15 minutes (dose dependent)
Infants need an increased amount of SCh becaue
Not enough muscle and larger volume of distribution.
Hydrolysis of SCh by ______________ occurs in the plasma, where almost ______% of the IV dose of SCh is hydrolyzed before reaching the NMJ,
Butyrylcholinesterase ( AKA Pseudocholinesterase or plasma cholinesterase) ;
90%
Succinylcholine(SCh)/Anectine is broken down by butyrylcholinestarese to :
- Choline
- Succinylmonocholine
Only _____% of SCh administered reaches the NMJ
10%
Recovery occurs when SCh _______ away from the NMJ
Diffuses
Butyrylcholinesterase is synthesize in the _________ and found in the __________
Liver ; Plasma
Factors that lower Butyrylcholinesterase:
Burns
Oral contraceptives
Anticholinesterase
Severe liver disease
Reglan
Advanced age
Malnutrition
Pregnancy
Neostigmine (lesser extent edrophonium) profoundly decreases the pseudocholinesterase activity (at 30 min after administration only 50% normal activity) which means it:
Prolongs SCh block.
Abnormal genetic variant of butyrylcholinesterase (over 20 mutations in the coding of the plasma cholinesterase gene) can cause prolonged muscle relaxation after __________ and _____________.
succinylcholine and mivacurium
Probably won’t know you have the gene until it happens.
Abnormal Plasma Cholinesterase
One way to test for it is to check for Abnormal Plasma Cholinesterase
“Dibucaine number”
Dibucaine number
The percentage of pseudocholinesterase enzyme activity that is inhibited by Dibucaine
Dibucaine number reflects __________ of cholinesterase enzyme (ability to hydrolyze SCh) not the ___________ that is circulating in plasma
quality ; NOT quantity
Types of Butyrylcholinesterase
Homozygous Typical
Heterozygous Atypical
Homozygous Atypical
Butyrylcholinesterase: Homozygous Typical
Dibucaine Number
Response to SCh
D#: 70- 80
R: Normal
Butyrylcholinesterase: Heterozygous Atypical
Dibucaine Number
Response to SCh
D#: 50-60
R: lengthened 50-100%
Butyrylcholinesterase: Homozygous Atypical
Dibucaine Number
Response to SCh
D#: 20- 30
R: Prolonged to 4-8 hrs
It is an agonist at the nicotinic receptor of the NMJ and binds with a high affinity, preventing membrane repolarization and thus subsequent action potentials.
Succinylcholine Block
(Phase I Block)
With continued dosing of a depolarizing NMBA, a type I block can develop into a:
Type II block / nondepolarizing
Cardiovascular Side Effects of SCh
Sinus Bradycardia
Junctional Rhythm
Premature ventricular escapes
ASYSTOLE
** treat with atropine
Cardiovascular Side Effects of SCh are more common with
redosing and in children ;
** a second dose given within 5 minutes of the first
Cardiovascular side effects reflect the actions of succinylcholine at cardiac ______________ receptors where the drug mimics the physiologic effects of acetylcholine.
muscarinic cholinergic
can occur to 80-90 % of patients if not pretreated with nondepolarizer or NSAID before giving SCh.
Faciculations
- Disorganized muscle contractions
In patients given SCh, what is very common 1-2 days postoperatively and can occur in 50-60% of the patients, probably due to fasciculations.
Myalgias
** usually big skeletal muscles
SCh administration associated with elevation in the plasma level of potassium of ______mEq/L in healthy patients
0.5
Severe hyperkalemia after SCh administration in patients with (4):
- Burns
- Severe abdominal Infections
- Severe metabolic acidosis
- Conditions associated with UPREGULATION of extrajunctional AChR.
Conditions associated with UPREGULATION of extrajunctional AChR.
Guillian-Barre syndrome
Hemiplegia
Muscular dystrophies
Burns
Paraplegia
“Guillian & Hemi Must Buy Pasta”
Because of the risk of massive ________, _________ , and ________ in children with undiagnosed muscle disease, succinylcholine is not recommended for use in children except for emergency tracheal intubation
rhabdomyolysis ; hyperkalemia;
death
Patients can develop myoglobinuria from muscle damage after ___________ administration.
SCh.
** most of the patients with rhabdomyolysis and myoglobinuria were subsequently found to have malignant hyperthermia or muscular dystrophy.
increase in tone of the masseter muscle may be an early indicator of ___________ (especially in children)
malignant hyperthermia
It is suggested that the high incidence of masseter spasm in children given succinylcholine may be due to _________ succinylcholine dosage
inadequate;
** probably not enough to cause muscle relaxation
Succynylcholine can ________ intragastic pressure and lower esophageal tone (LES).
Increase
**maybe dpends on the intensity of fasciculations, pre-dose of NDMR.
Succynylcholine can ________ intraocular pressure.
Peak time:
And return time:
Increase
** Peaks at 2-4 min after administration and returns to normal by 6 min
The use of succinylcholine is not widely accepted in open eye injury meaning:
when the anterior chamber is open.
SCh can causes __________ in intracranial pressure.
Increase
SCh side effects: (12)
Sinus Bradycardia
Junctional arrest
Premature ventricular escapes
ASYSTOLE
Fasciculations
Myalgias
Hyperkalemia
Myoglobinuria
Masseter spasm
Increase intragastric pressure and lower esophageal tone (LES).
increased intraocular pressure.
Increased intracranial pressure.
Defasciculating Doses used to be called
Curare Dart
A defasciculating dose of ___________ muscle relaxant administered prior succinylcholine decrease its side effects (Including fasciculations and postoperative myalgias).
non-depolarizing
Order of meds in a rapid sequence when giving Defasciculating dose:
- defasciculating dose.
- sedation (ex. propofol)
- Succynylcholine
__________ after a defasciculating dose
Premature muscle weakness
_____________ acts to block ACh receptor sites in an overwhelming, competitive manner.
Non-depolarizing
Two classes of ND-NMBA
- aminosteroids
- Benzylisoquinolinium
Aminosteroids NMDRs
Pancuronium
Pipercuronium
Vecuronium
Rocuronium
Benzylisoquinoliium NMDRs
Mivacurium
Atracurium
Cisatracurium
Competitively antagonize the presynaptic receptors to decrease release of Ach (fade on TO4)
Nondepolarizing Muscle Relaxants
Nondepolarizing Muscle Relaxants compete with ACh for binding on __________ of the alpha subunits of the nAChRs.
one or both
NDMR are classified according to:
How fast they act:
- long, intermediate, short.
&
Their durationt:
- depending on metabolism, redistribution, elimination and dose given .
Nondepolarizing Muscle Relaxants are almost always given ________
Intravenously.
Rocuronium (_________)
Zemuron
Rocuronium (Zemuron) ___________ action
intermediate
Rocuronium (Zemuron) has RARE histamine release (T/F)?
True :)
*could still cause it but RARE!
Rocuronium (Zemuron) has _______ effect of BP and HR
NO effect.
can be used to defasciculate with SCh,
Rocuronium (Zemuron)
Rocuronium (Zemuron) has low potency which means the ________ plasma concentration achieved after a bolus ________ quickly.
high ; decreases
Rocuronium (Zemuron) has real metabolites (T/F)?
False :(…. no real metabolites.
Rocuronium has a ______ onset making it good for RSI sequence (can even replace SCh) if dose is doubled.
Rapid
*** (Variable onset) prolonged duration at this dose.
In laparoscopic procedures, the duration of neuromuscular block produced by rocuronium is increased by approximately ________.
25%
** prolongs duration.- attributed to the effects of pneumoperitoneum on hepatic perfusion and blood flow.
The most common thing to cause anaphylaxis is said to be NMBAs specially…
Rocuronium
Rocuronium (Zemuron) Intubating dose:
and duration:
0.6 mg/kg
** ~ 30 mins or up to 70 min (after RSI dose)
Rocuronium (Zemuron)
RSI dose
Duration:
1.2 mg/kg
**up to 70 minutes after RSI dose
Rocuronium (Zemuron) comes in a _____ mg vial.
Does it need reconstituing?
50
No.
Rocuronium (Zemuron) dose for defasciculating dose with SCh.
5 mg
Rocuronium maintenance/repeat dose :
0.1 mg/kg as needed
Rocuronium onset:
1-2 min depending on dose
Rocuronium is ______% eliminated by the liver and _____% by the kidneys.
70% and 30%
Vecuronium (Norcuron) isn an ________ NMB although it last a little longer than Rocuronium.
Intermediate
__________ this NMBA would be good to give to an asthmatic patient because it does NOT cause histamine release.
Vecuronium (Norcuron)
Which NMBA is a very cardiac stable?
Vecuronium (Norcuron)
Vecuronium (__________)
Norcuron
Vecuronium (Norcuron) might _________ with Thiopental.
precipitate
Vecuronium (Norcuron) is ___________ potency.
Medium
Vecuronium (Norcuron)
intubation/induction dose:
0.1 mg/kg
Vecuronium (Norcuron)
vial:
Does it need reconstituing?
10mg vial
Yes, needs reconstituting into 10mL syringe for 1mg/cc
Vecuronium: Pretreatment/priming with ______ of intubation dose given 3-5 min before intubation dose
10%
Vecuronium - Maintenance dose for surgical relaxation:
0.01 mg/kg
Vecuronium Onset
Intubating conditions:
Maximal blockade:
2-3 minutes - good intubating conditions.
3-5 minutes - maximal blockade
T/F: Vecuronoium last longer than Rocuronium?
True :)
Vecuronium duration for 25% recovery and 95% recovery?
25-40 min (25% recovery);
45-60 min(95% recovery).
Vecuronium metabolite:
3-desacetyl:
** 60% potency of vecuronium
Pancuronium (_________)
Pavulon
Pancuronium (Pavulon) is a _________ acting.
Long
T/F: Pancuronium (Pavulon) has histamine release.
False…. no histamine release
Pancuronium (Pavulon) has vagolytic effects causing modest ________ due to antimuscarinic stimulation.
tachycardia
** do not give to patient who can’t tolerate changes in HR.
Pancuronium (Pavulon) has direct sympathomimetic effects = _________ release and reduced uptake of __________ by adrenergic nerves
Norepinephrine ; norepinephrine.
With Pancuronium be careful to give to any patient that will not tolerate an increase in ________ and ___________.
HR and cardiac output
Pancuronium is used in _______________ to counteract the bradycardia associated with high-dose opioid dosing.
Cardiac surgery
Pancuronium has the potential for significant
_________ ________ blockade, because it last a long time.
postoperative residual
Pancuronium initial dose and maintenance:
0.1 mg/kg - initial
0.02mg/kg - maintenance
Pancuronium onset and duration:
2-5 minutes.
60 - 100 minutes.
Pancuronium hepatic metabolism of ________ % and renal ________%.
20%
40-70%
Inhalational agents can help speed NMBAs because they cause:
muscle relaxation
Metabolite (3-OH pancuronium): ______ potency of Pancuronium
50%
__________ of a drug is determined by the dose required to produce a certain effect. For NMBAs, the effect (response) is depression of normal __________.
Potency ; Muscle contraction.
relationship between twitch depression and dose
potency
median dose that corresponds to 50% twitch reduction
ED50
corresponds to 95% block (useful relaxation when twitch abolished).
ED95
Hofmann elimination is ________, ___________, __________ chemical breakdown at physiologic temperature and pH.
spontaneous,
non-enzymatic,
non-organ dependent.
In hofmann elimination
when temperature increases and pH increases……. metabolism ___________.
increases.
in hofmann elimination
when temperature decreases and pH decreases……. metabolism
decreases.
Mivacurium (_________)
Mivacron
Mivacurium (Mivacron) will cause ______________ when given quickly. Pt. may develop bronchospasm.
Histamine release
Spontaneous recovery from the Mivacurium (Mivacron) block is rapid (T/F)
True
**Hofmann elimination
Mivacurium (Mivacron) metabolism
Hydrolysis by plasma cholinesterase.
Mivacurium (Mivacron) intubating dose and infusion?
0.2 mg/kg (intubation)
5-8 mcg/kg/min infusion
** “if stupid enough to use as infusion haha.”
Mivacurium (Mivacron)
onset and duration:
onset: 1 minute
duration: 10-20 minutes
Atracurium metabolism is by the same enzymes that degrades ________ and_________.
esmolol ; remifentanil.
Atracurium (_______)
Tracrium
Atracurium is ___________ acting?
Intermediate acting
Atracurium metabolized Hofmann Elimination ______% and ester hydrolysis _______%.
30%;
60%
Atracurium releases _______ histamine with potential for skin flushing, tachycardia and hypotension
SOME
Atracurium (Tracrium) dose:
0.5 mg/kg
Atracurium (Tracrium) onset and duration:
& 95% recovery in:
2-3 minutes - onset
20-35 minutes duration.
95% recovery in 60-70 min
Atracurium (Tracrium)’s primary metabolite is _________, which can produce rare _______activity.
Laudanosine;
Seizure
Atracurium (Tracrium) is a _____________ amine which means it can cross BBB and act as a __________.
Tertiary;
CNS stimulant.
Cisatracurium (_________)
Nimbex
Cisatracurium is _______ acting , a little longer than Atracurium.
intermediate
Cisatracurium (Nimbex) is metabolized 30% __________,
and 60%___________.
Hofmann elimination;
Ester hydrolysis.
Cisatracurium (Nimbex) has ______ histamine release and no changes in ______.
NO;
BP & HR
Cisatracurium: Potent cis-cis isomer of __________.
Atracurium
Cisatracurium (Nimbex) dose:
0.15-0.2 mg/kg IV
Cisatracurium (Nimbex) onset and peak :
2-5 min onset; (for intubation)
4-7 min peak
Cisatracurium (Nimbex) duration:
40-70 min;
20-35 min to begin recovery: up to 93 min for 90% return
How to enhance NMBA effects: “SAN -LIAM- HAHA”
Streptomycin
Aminoglycoside
Neomycin
Local anesthetics.
Inhalational agents.
Antibiotics.
Magensium
Hypercarbia
Acidosis
Hypothermia
Anticonvulsants (acute administration).
Local anesthetics potentiate both ________and _______ by potentiating pre- and postsynaptic effects.
NMDA and Depolarizers
inhalational agents have a direct effect on __________ receptors.
postjunctional
Antibiotics that depress the NMJ
streptomycin
neomycin
aminoglycosides
magnesium is a muscle ________
relaxant.
Hypothermia prolongs the duration of NMBAs by decreasing receptor _______ and _______ mobilization.
sensitivity ; ACh
Hypothermia decreases the force of muscle _______. Reduces _______&_______ metabolism. and reduces ___________ elimination.
*altered responses to NMBA
contraction;
renal & hepatic
Hofmann
Aging results in ________ total body water and serum albumin concentration, reducing the ___________ of NMBAs.
Decreased ; volume of distribution
** needing less as opposed to children who large VD and need more.
In aging: The decreased ______ function, _______, and __________ decrease the rate of NMBA elimination.
CV ;
renal filtration,;
liver blood flow.
Hypokalemia: ________ NMBA and can decrease the effectiveness of anticholinesterases (__________) on reversal (antagonizing nondpolarizing block).
potentiates;
Neostygmine
Hypermagnesemia: prolongs duration of action of NMBA by inhibiting _____ channels
calcium
Acidosis: interferes with effects of ____________ in reversing
nondepolarizing block.
anticholinesterases
Hypercarbia: leads to acidosis and interferes with NMBA ______.
antagonism
All drugs with significant hepatic and renal metabolism (___________) will be affected and their duration of action is prolonged by liver and kidney dysfunction.
Aminosteroids
_________________- class NMBAs are preferred in patients with organ dysfunction.
Benzyllisoquinolinium
*Ex. Atracurium; Cisatracurium
Patients with __________ have altered responses to NMBAs; they are already relaxed!! Give less!!
Myasthenia Gravis
Do not give ___________ to burn patients after the first 24- 40 hours.
Succinylcholine
**risk of hyperkalemia leading to cardiac arrest
___________ is the enzyme responsible for rapid hydrolysis of released ACh
Acetylcholinesterase (AChASe)
________% of released ACh is hydrolyzed during its diffusion across the synaptic cleft before reaching the nicotinic receptor.
50%
AChASe can catalyze ACh at __________ molecules per active site per second
4,000
Anticholinesterase/Acetylcholinesterase Inhibitors (3):
Neostigmine
Edrophonium
Pyridostigmine
Selective Relaxant Binding Agent
Sugammadex
How can NMBAs be reversed? (5)
-Diffuse away
-Reversed with an anticholinesterase.
-Excreted
-Encapsulated
-Metabolized
Acetylcholinesterase Inhibiting Agents (___________)
Anticholinesterase
Anticholinesterase Block the breakdown of ACh by __________ whichCauses an increase in ACh at the ___________.
Acetylcholinesterase ;
Synaptic cleft
Anticholinesterase increase the amount of ________ to compete with NMBA remaining in the _______, causing normal muscle contraction.
ACh ;
NMJ
Possible side effects of Anticholinesterases: (4)
- Significant parasympathetic effects.
- Bronchoconstriction
- Increased salivation
- Increased bowel motility (will make you poop :) )
Significant parasympathetic effects caused by Anticholinesterase are due to stimulation of muscarinic Ach receptors in the _______, ________, ________.
heart, lungs, and GI tract.
Anticholinesterases are usually given in combination with an ______________.
Anticholinergic (Antimuscarinic)
(Ex. glycopyrrolate).
Anticholinesterases have a ceiling effect meaning there is maximal inhibition - when _____% of acetylcholinesterase has been inhibited.
100
Ceiling effect
At maximal inhibition, additional doses of of Anticholinesterases (ex. Neostigmine) will NOT improve recovery and can actually lead to ________________.
paradoxical muscle weakness.
**Resultant weakness may be due to desensitization of Ach receptors leading to transmission failure and depolarization block
***occurs with high doses of Neostigmine
Neostigmine (_______)
Prostigmin
Neostigmine inhibits hydrolysis of ACh by AChAsE and blocks AChAse at all cholinergic synapses causing parasympathetic effects such as (3):
*Bradycardia
*increased salivation
GI effects
Used with _____________ (anticholinergic/antimuscarinic) to decrease muscarinic side effects of Neostigmine
glycopyrrolate
Neostigmine is a ____________ compound therefore does not penetrate the blood-brain barrier (BBB) very well.
Quaternary ammonium
Neostigmine has a _________effect and a big dose can cause post - op __________.
ceiling;
PONV
When to reverse with Neostigmine?
Used in deep blocks.
** most effective in moderate blocks but SLOW acting!
Neostigmine shouldn’t be given until _________ recovery is evident (TOF).
spontaneous (at least one twitch).
Neostigmine is more effective with moderate blocks but rapid acting (T/F)
False: SLOWWWW acting.
Current recommendations for Neostigmine include waiting until 4 tactile TOF counts are visible at the __________ before administering.
adductor pollicis
T/F: you always have to give a full dose of neostigmine for it to work.
False;
ex. pt. who received dose of Roc 4 hours ago does not need a full dose of neostigmine because it is not all there. maybe give half?
Neostigmine dose and max dose:
0.04-0.08 mg/kg
(max 5mg)
For every 1 mg of Neostigmine mix with _______ mg Glycopyrolate.
0.2mg/ 1 cc
**sometimes less….. Give glyco first or mixed.
Neostigmine onset:
starting at 15 minutes (dependent on twitches).
*no twitches takes longeerr.
Neostigmine duration:
1-2 hours.
Neostigmine metabolism and excretion
Hepatic and renal excretion.
Edrophonium (_________)
Enlon
Edrophonium is used with ________ (crosses the BBB) due to rapid onset.
atropine
***is faster than glyco
what is Enlon- Plus?
a mixture of Edrophonium and atropine together in the same vial.
Edrophonium (Enlon) is mostly INEFFECTIVE when given for DEEP blocks (T/F)
TRUE :)
*You are doing great Mik!! haha
Edrophonium (Enlon) has a ______onset of _______, and a ________ duration.
Rapid; 1-2 mins
Short
Edrophonium (Enlon) is a ___________. which crosses or does not cross BBB?
Quartenary ammonium ; does NOT cross BBB.
Edrophonium (Enlon) dose with atropine dose:
0.5-1 mg/kg mixed with atropine 7-10 mcg/kg (0.014 mg/mg of edrophonium)
Enlon-plus dose:
0.05 - 0.1mg/kg slowly over a minute
Sugammadex (__________)
Bridion
Sugammadex is a __________ that has been developed as an selective relaxant binding agent (SRBA).
gamma (y) - cyclodextrin.
Sugammadex is an eight sugars arranged in a ring specifically designed to:
ENCAPSULATE.
** it does NOT breakdown***
Sugammadex is highly water soluble with a hydrophobic cavity large enough to encapsulate _________________ drugs, especially ___________.
steroidal intermediate-acting neuromuscular blocking.
**rocuronium > vecuronium
This reversal has no real undesirable effects like anticholinesterases.
Sugammadex
Sugammadex is __________ of depth of neuromuscular blockade.
Independent
Sugammadex has no effect on ___________ or __________ receptors.
Acetylcholinesterase or cholinergic receptors.
Sugammadex when injected (over 10 seconds) it immediately captures free molecules of _______ or __________.
rocuronium or vecuronium.
Sugammadex removes the relaxant from the ______ and moves it into the plasma
NMJ
The sugammadex-drug complex is filtered out by the:
Glomerulus
**not affected by liver disease
Sugammadex is eliminated unchanged by the kidneys which is why you should avoid in pt’s with decreased _____________.
Createnine clearance.
**can still be used.
Sugammadex is not recommended for patients with:
End-stage renal disease.
Sugammadex vials are available in ______ or _______ .
2 mL or 5 mL vials (100mg/ml).
Sugammadex elimination:
24hr clearance unchaged via kidneys.
Dose of sugammadex for routine reversal of moderate block (T2 appearance or 3,4, twitches):
&
Mean recovery time to TOF 0.9:
2mg/kg
&
2 minutes
Dose of sugammadex for routine reversal of deep neuromuscular block (PTC 1-2):
&
Mean recovery time to TOF 0.9:
4mg/kg
&
3 minutes
Dose of sugammadex for IMMEDIATE reversal after 1.2mg/kg rocuronium:
&
Mean recovery time to TOF 0.9:
16mg/kg
&
1.5 minutes
sugammadex has no interaction with succinylcholine or benzylisoquinolines; it only cares about:
aminosteroids NMBAs.
High does of Sugammadex (16 mg/kg) can possibly cause:
- Bradycardia ( or cardiac arrest).
- headache
- hypotension
- N/V
- Anaphylaxis
- Hypersensitivity (pruritus and uticaria).
Sugammadex may affect hormonal contraceptives ( for ______ Days) and some antibiotics.
7
** tell patient and bracelet is placed on patient to help them remember.
Use the lowest dose possible of sugammadex : (requires 4 mg to encapsulate _______mg of rocuronium… usually _____ mg is adequate).
1mg;
200 mg.
T/F : with Sugammadex most IV infusion solutions are compatible.
True :) - (LR,D5,NS) okay!
Sugammadex is physically incompatible with what 3 meds?
- Verapamil
- Ondasetron (Zofran)**
- Ranitidine (Zantac)
Recommended wait time of _______ hours for readmission of Roc/Vec after reversal.
24
It is recommended to use a ________ or __________ for NMBA redose after reversal with sugammadex.
Benzylisoquinolinium ( Nonsteroidal ) or Succinylcholine.
If there is nothing else available and you have to redose (< 24 hours ) after giving sugammadex. How much Roc or Vec can you give after:
5-minutes:
4-hours:
5 minutes:
1.2mg/kg rocuronium.
4 hours:
0.6 mg/kg rocuronium or
0.1 mg/kg vecuronium.
High dose Sugammadex is …..
16 mg/kg
High dose Sugammadex (16 mg/kg) is associated with increases in ______,______, and _______.
aPTT, PT, INR
Becareful giving high dose of Sugammadex in patients with (3):
- Coagulopathies
- treated with therapeutic anticoagulation.
- Receiving thromboprophylaxis other than heparin and LMWH.
High dose Sugammadex can also cause ___________ & __________.
Hypersensitivity:
Sneezing, nausea, rash and urticaria
Anaphylaxis.
Anaphylaxis with sugammadex is seen more often in higher dosing within ______ minutes of administration. It involves ________,_________, and ___________.
5- minutes;
Airway edema, bronchospasm and CV collapse.
Treatment for anaphylaxis w/ sugammadex includes small boluses of ______ (10-20 mcg) titrated to response,________, ________ and _________.
epinephrine (10-20mcg)
Benadryl
Dexamethasone
Famotidine
Physostigmine is a _____________. The ONLY anticholinesterase to do what?
tertiary amine;
cross the blood brain barrier.
Not used for reversal of muscle relaxants but used to treat anticholinergic toxicity.
Physostigmine
flushing, dry skin and mucous membranes, mydriasis with loss of accommodation, altered mental status, fever and urinary retention are signs of:
anticholinergic toxicity
- Hot as a hare
- Dry as a bone
- Blind as a bat
- Red as a beat
- Mad as a hatter
Since Physostigmine crosses the BBB it can cause
Agitation
Restlessness
Disoriented
Shivers
Types of anticholinergics (5):
Atropine
Cyclic antidepressants
Antihistamines
Scopolamine
Antipsychotic
Excessive use/overdose of cholinesterase inhibitors or organic pesticides.
Cholinergic Crisis/Syndrome
In Cholinergic Crisis/Syndrome there is excessive _______ peripherally and centrally
ACh response
S/S: miosis, salivation, bronchoconstriction, bradycardia, abdominal cramping, weakness, lacrimation. CNS: dysphoria, confusion, seizures, coma
Cholinergic Crisis/Syndrome
Treatment of Cholinergic Crisis/Syndrome
Doses
Atropine:
Pralidoxime:
Atropine 35-70 mcg/kg
Pralidoxime 15 mcg/kg every 20 min
- also Benzos
Cholinergic Crisis
Muscarinic Symptoms:
Nicotinic SymptomS:
Salivation
Lacrimation
Urination
Defecation
GI cramping
Emesis
Muscle cramps
Tachycardia (Bradycardia in Muscarinic)
Weakness
Twitching
Fasciculations
decrease in Ach activity due to auto-reactive antibodies that attack the nicotinic Ach receptors on postsynaptic membranes
Myasthenic Crisis
How do your differentiate Cholinergic vs Myasthenic Crisis?
Give edrophonium - muscle strength will improve if myasthenia gravis.
** if it gets worse it could be cholinergic crisis
Cholinergic Crisis S/S (6)
Increased cholinergic activity
Increased secretions
Bradycardia
Pupils constricted
Weak or fasiculating muscles
Tensilon test exaggerates symptoms..makes it worse ( edrophonium)
Myasthenic Crisis (6) s/s
Decreased receptors
Normal secretions
Tachycardia
Pupil normal or dilated
Muscles are weak
Tensilon test relieves symptoms (edrophonium injection)
Clinical signs of muscle weakness
Blurry vision,
Double vision
Facial weakness,
Facial numbness,
and general weakness
Most common signs of Muscle Weakness in the PACU:
- Generalized weakness
- Patient reported difficulty completing 5-second eye opening
- Difficulty visually tracking or speaking.
***Indicative of ocular and pharyngeal muscle sensitivity
Complications of residual neuromuscular blockade
- Pharyngeal dysfunction
- Increased risk of aspiration and pneumonia.
- Need for tracheal reintubation
- Impaired oxygenation and ventilation (may be blamed on Opioids).
- Delayed discharge from the PACU
- Impaired pulmonary function
Clinical Signs of Neuromuscular Recovery
Tidal volume
Negative inspiratory force
Grip strength
5-second head lift (not a sensitive test for residual block)
Ability to protrude the tongue
**these are unreliable signs of return of muscle strength
