Lecture 13 (Exam 3 NMBD Intro/Depolarizing NMBD) Flashcards
Which of the following is the newest NMBD?
A. Atracurium
B. Vecuronium
C. Pancuronium
D. Cistracurium
A. Atracurium (1980)
B. Vecuronium (1980)
C. Pancuronium (1960)
D. Cistracurium (1995)
Why was Rapacurium (Raplon) discontinued in 2001?
Massive laryngospasm and bronchospasm leading to death.
The effect of NMBD is to interrupt the transmission of nerve impulses at the _____.
Neuromuscular Junction (NMJ)
The MOA of NMBD is either depolarizing or non-depolarizing.
Deploarizing NMBD will _________ the action of ACh.
Non-depolarizing NMBD will ______ the action of ACh.
Deploarizing NMBD will mimic the action of ACh.
Non-depolarizing NMBD will interfere with the action of ACh.
Purpose of NMBD for anesthesia.
- Decrease airway trauma
- Facilitate surgical exposure
- Minimize injury from patient movement
What classification of NMBD is Succinylcholine (Anectine)?
Depolarizing NMBD
Only depolarizing agent used in anesthesia.
Name a long-acting non-depolarizing NMBD.
Pancuronium (Pavulon)
Name a short-acting non-depolarizing NMBD.
Mivacurium (Mivacron)
Move a lot, short-acting
What is the chemical classification of Pancuronium?
Aminosteroid
What is the chemical classification of Mivacurium?
Benzylisoquinoline
(Ben-zo-lie-so-kwen-no-lynn)
What is the chemical classification of Pancuronium (Pavulon)?
Aminosteroid
Which intermediate-acting NMBDs are Benzylisoquinoline?
Atracurium (Tracrium)
Cisatracurium (Nimbex)
Which intermediate-acting NMBD are Aminosteroids?
Vecuronium (Nocuron)
Rocuronium (Zemuron)
What is ED95?
The potency of NMBD. The dose that is necessary to produce a 95% supression of a single twitch in the presence of nitrous/ barbiturate/ opioid anesthesia.
What nerve is stimulated so that the adductor pollicis muscle will produce a single twitch at 1 Hz (thumb adduction)?
Ulnar nerve
The order of block for NMBD is dependent on:
The number of presynaptic ACh-containing vesicles released.
The number of ACh receptors.
Blood Flow to the area.
Drug potency
Low potency NMBD will onset _________ than higher potency NMBD.
Faster
Lower potency NMBD will have more molecules than higher potency NMBD. This will create a higher concentration gradient and result in a faster onset.
Small, rapidly moving muscles will be blocked ________ than large muscles.
Faster
Eyes will be paralyzed first before diaphragm.
What does this graph show?
Both Larynx and Adductor Pollicis muscle received 0.5 mg/kg of Rocuronium.
Both Muscles experience a dramatic decrease in twitch percent height, but the adductor pollicis is completley blocked while the larynx got down to a twitch height of 20%.
Both muscles recovered at the same rate. Almost 100% twitch response returned by minute 40.
Checking a twitch in which muscle will assess the diaphragm and laryngeal muscle blockade.
Orbicularis Oculi
If there are no twitches to the facial nerve, the diaphragm and laryngeal muscles are adequately blocked. Best indicator of intubating conditions.
The orbicularis oculi underestimates _____________.
residual paralysis.
Is checking a twitch in the adductor pollicis a good indictor for laryngeal relaxation?
No, it is not a good indicator of laryngeal relaxation.
Checking a twitch of the adductor pollicis is a good indicator or peripheral recovery.
Which muscle is the gold standard to check a twitch on for recovery?
Adductor pollicis (Ulnar Nerve)
What is the placement of electrodes on ulnar nerve?
What will the response be?
What is a defasciculating dose of NMBD?
What symptoms will the patient experience with a defasciculating dose?
Where 20% of intubating dose is given early (primer) to prevent fasciculation.
Blurred Vision
Mandibular weakness
Ptosis (droopy eyes)
Diplopia (double vision)
Dysphagia
Increased hearing acuity - people need to be quiet
Let patient know they might start to feel week and get blurry vision. Encourage them to close their eyes.
A single twitch nerve stimulator starts at _____ Hz/second decreasing to ______ Hz/10 secs.
1 Hz/sec to 0.1 Hz/10 secs
With an onset of a block a single twitch will ______ with each stimulus.
fade
Double burst stimulator is _____ short burst followed by ______ short burst.
The double bust stimulator use ________ Hz
3, 3
50 Hz (supramaximal current)
Why was the double burst stimulator developed?
Developed to improve detection of residual block (fade).
Fade in 2nd response vs 1st response.
Qualitatively better than TOF.
Train of Four is ________ stimuli at _______ Hz with ______ seconds between each burst.
4 stimuli at 2 Hz w/ 0.5 seconds between each burst
TOF reflects events at _________ membrane.
Presynaptic
Prior to NMBD what will be your twitches on the TOF?
What will be the TOF ratio (Twitch 4 : Twitch 1)?
4/4 twitches
Ratio 1
Experience anesthetist are unable to qualitatively detect the fade of a TOF > ______.
0.4
The twitch will have to go from unblocked to completely blocked in order to tell a difference
There will be significant residual block with a TOF of ______ to _____.
0.7 to 0.9
You will not fill a fade, but there will still be blockade at the NMJ. Patient will still need reversal agent.
Tetanic stimulation is very rapid, it will be ________ Hz for _____ seconds.
50 Hz for 5 seconds
If a _____ NMBD is given, a tetanic stimulation will result in a sustained muscle response.
Depolarizing NMBD (Succinylcholine)
If a _____ NMBD is given, a tetanic stimulation will result in a a non-sustained muscle response (fade).
Nondepolarizing NMBD (Roc/Vec)
The fade is a result of presynaptic depletion of ACh or inhibition of release
What is post-tetanic stimulation?
Single twitch 3 seconds after tetanic stimulation.
The post-tetanic stimulation will occur d/t accumulation of calcium during tetany, the excess calcium will stimulate ACh release.
No response in post-tetanic stimulation will mean ______.
intense blockade
What kind of blocks are in column A, B, and C?
What kind of nerve stimulation is performed in row 1 through 4?
A study performed showed that _____ % of patients that were not given anticholinesterase drugs for NMBD reversal and no use of nerve stimulator had post-op blockade once extubated.
42%
A study performed showed that less ____ % of patients that were given anticholinesterase drugs for NMBD reversal and use of nerve stimulator had post-op blockade once extubated.
<4%
The presynaptic motor neuron is large and _________ which helps with transmission of nerve impulses.
myelinated
The motor nerve ending is ________ and innervates single muscle fibers.
unmyelinated
The presynaptic motor neuron is responsible for what three things involving ACh?
Ach synthesis
Ach uptake and storage in vesicles
ACh release and uptake of choline
The synaptic cleft is _______ nm (range) wide with fluid that contains ________ and _________.
20-50 nm
Collagen and acetylcholinesterase (plasma cholinesterase, butyrylcholinesterase)
ACh release is dependent on what electrolyte?
Calcium
What does Acetylcholinesterase do to ACh?
Hydrolyze ACh to acetic acid and choline
Post-synaptically, the membrane has multiple _______.
Post-synaptically, the resting membrane potential is _______.
Membrane potential is largely maintained by what two electrolytes?
folds
-90 mV
Na+ and K+
How many subunits are on a transmembrane nicotinic acetylcholine receptor (nAChR)?
Name them.
Five subunits. (Pentameric unit)
2 alphas, beta, delta, gamma
If ACh binds to nAChR, there will be a _______ change and the pores will allow ______, _______, and _______ to flow.
conformational change
Na+ (influx), Ca2+ (influx), and K+ (efflux)
If NMBD (non-depolarizer) binds to nACh, there will be no __________ change and no ion flow.
conformational change
Succinylcholine only requires binding at one ________ subunit. It is postulated that this will cause ________ before total blockade.
one alpha subunit
fasciculation
_________ is the only depolarizing NMBD in clinical practice.
What are two unique characteristics of this drug?
What is this NMBD most useful for?
What is the downside of this NMBD?
Succinylcholine
Provides very intense and rapid paralysis
Offsets of effects prior to hypoxia
Rapid Sequence Induction
Histamine Release (tachycardia, rash, welps)
What is the dose of Succinylcholine?
Onset:
Duration:
Dose: 1 mg/kg IV
Onset: 30-60 seconds
Duration: 3-5 minutes
What is the MOA of succinylcholine (Sch)?
Attaches to one or both alpha subunit of the nAChR.
Mimics the effect of ACh, but has a sustained opening of the receptor channel (hydrolysis is slower than ACh).
SCh will cause how much increase in serum K+?
0.5 mEq/L
What are characteristics of a phase I block?
Decrease contraction to single twitch stimulation.
Decrease amplitude to continuous stimulation.
TOF ratio > 0.7 (no fade)
Absence of post-tetanic facilitation
Skeletal muscle fasciculation
Phase II Block are typical of ___________ NMBD.
non-depolarizing
How can a Phase I block transition to a Phase II block?
Large dose of SCh (2-4 mg/kg)
Lack of/ poorly functioning pseudocholinesterase
Relative “overdose”
Succinylcholine is hydrolyzed by __________.
Butyrylcholinesterase (plasma cholinesterase)
What factors can affect pseudocholinesterase activity?
75% decrease in hepatic production
Drug-induced decrease (neostigmine, reglan, chemo)
Genetically Atypical
Chronic Renal disease
Pregnancy (estrogen cause decrease)
Obesity (increase pseudocholinesterase activity)
What does dibucaine number mean?
Dibucaine number reflects the quality of the enzyme to inhibit breakdown of butyrylcholinesterase.
What is normal dibucaine number?
80
More butyrylcholinesterase will stick around and break down Sch
What will a dibucaine number of 20 mean for Sch?
1 mg/kg of SCh will last 3 hours
Less butyrylcholinesterase will stick around
Side effects of SCh
Cardiac Dysrhythmias
Hyperkalemia
Myalgia
Myoglobinuria
Increase Intragastric Pressure
Increase Intraocular Pressure
Increase ICP
Masseter Spasm
What is the pre-treatment to the side effects of SCh?
Pre-treatment with a small dose (20%) of non-depolarizing NMBD.
The defasciculating dose either decreases, prevents, or mask the side effects of SCh.
What are the cardiac dysrhythmia of SCh?
Sinus Brady
Junctional Rhythm
Sinus Arrest
Sch’s action at the cardiac muscarinic, cholinergic receptors mimic actions of ACh. Cardiac dysrhythmia is usually presented on the ______ dose of Sch
2nd dose
What is Sch action at the ANS ganglia?
Increase HR and and mimics action of ACh. This usually occurs with large doses.
Patient’s with _________ sites will have true hyperkalemia when given SCh.
What group of people will have these sites?
extrajunctional sites (more ion channels)
Individuals with unrecognized muscular dystrophy (Duchenne’s)
Unhealed 3rd degree burns
Denervation of Skeletal Muscles (bed-ridden patients)
Upper motor lesions
Who will experience myalgia with Sch?
Where will the myalgia be located?
Young adults
Neck, back, abdomen
More pediatrics will experience this with SCh.
Myoglobinuria (damaged to skeletal muscles), usually found later to have MH or muscular dystrophy.
We don’t give Sch to children.
Sch will increase intragastric pressure and LES pressure, this will increase the risk of _______.
Aspiration
This is related to the intensity of the fasciculation and the direct increase in vagal tone.
Sch will increase intraocular pressure _______ minutes (range) after administration and last _________ minutes (range).
2-4 minutes after admin
last 5-10 minutes
Sch will be contraindicated in ______________ chamber injury.
open anterior
Sch will increase ICP transiently, how will you attenuate this effect?
By hyperventilating the patient, the PaCO2 will decrease leading to cerebral vasoconstriction. This will decrease CBF and decrease ICP before Succinylcholine administration.
Sustained skeletal muscle contraction, incomplete jaw relaxation, and/or masseter muscle spasm d/t Sch could be an indication of what conditions?
Early indicator of Malignant Hyperthermia
Inadequate dosage given in children
What is the hereditary rhabdomyolysis associated with all volatile anesthetics and SCh?
Malignant Hyperthermia (MH)
If MH is untreated what can it lead to?
Muscle destruction
Hyperkalemia
Acidosis
Dysrhythmia
Renal Failure
DIC
MH causes mutations in what receptor to have excessive calcium release from the SR?
Ryanodine Receptor (RyR1)
What group of patients are susceptible to MH?
Native Americans
What are the symptoms of MH?
An acute increase in skeletal muscle metabolism
Increase O2 consumption
Lactate formation
Heat Production
Rhabdomyolysis (Spiked increase ETCO2, Increase temp 1C/5mins, arrhythmias, rigidity.)
Emergency ABCD’s of MH
Dantrolene has decreased the mortality of MH from 80% to ________%.
10%
What is the dose of dantrolene?
2mg/kg IV
Repeat doses until symptoms subside or 10mg/kg IV
How does dantrolene work?
How is dantrolene metabolized?
Inhibits the Ca2+ release from the SR and produces a muscle relaxant effect.
Dantrolene is metabolized in the liver to 5-hydroxydandrolene
Patients on calcium channel blockers (verapamil, Cardizem) that receive dantrolene as a treatment can result in __________
Cardiovascular Collapse (d/t synergistic effects)
What are the most common side effects of dantrolene?
What are less common S/Es?
Most Common: Weakness, Phlebitis, Respiratory Failure, GI upset
Less Common: Confusion, Dizziness, Drowsiness
What autoimmune disease develops Antibodies against the ACh receptor?
Symptoms (Sx)
Treatment (Sx)
Myasthenia Gravis (MG)
Sx:
Increasing weakness and fatigue throughout the day
Diplopia
Ptosis
Extremity and Resp muscle weakness
Tx: Cholinesterase Inhibitor
What part of the day would a Myasthenia Gravis patient be scheduled for surgery?
Should be the first case of the day. When they have the most ACh and their ACh receptors are not worn out.
Myasthenia Gravis patients are _________ to Succinylcholine? Why?
What is the dose of SCh for MG patients?
Resistant to SCh. More SCh is needed because the ACh receptors that are left do not function as well.
1.5-2.0 mg/kg
What is Lambert-Eton (LE) disease?
LE has an increased sensitivity to which type of NMBD?
An autoimmune disease that can result from small-cell lung cancers. LE can produce antibodies against calcium channels and decrease the release of ACh pre-junctionally.
LE has a sensitivity to both depolarizing and nondepolarizing NMBD.
