Neuromuscular Blocking Agents
description
Transcript of Neuromuscular Blocking Agents
![Page 1: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/1.jpg)
Neuromuscular Blocking AgentsDavid Hirsch MD
CA-1
![Page 2: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/2.jpg)
Disclosures
![Page 3: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/3.jpg)
Key Concepts
• 1) – PARALYTICS DO NOT CAUSE AMNESIA, ANALGESIA
OR UNCONSCIOUSNESS• 2)– Depolarizing = Ach receptor agonists– Non-depolarizing=competitive antagonists
![Page 4: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/4.jpg)
History
• 1942– Harold Griffith• Studied a refined extract of curare
– “South American Arrow Poison”• Noted that they produced paralysis not anesthesia
![Page 5: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/5.jpg)
Introduction
• Skeletal muscle relaxation can be caused by– Deep inhalational anesthesia– Regional nerve block– Neuromuscular blocking agents
![Page 6: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/6.jpg)
Neuromuscular Transmission
• Neuromuscular Junction– Between motor neuron and muscle cell– AP depolarizes terminal, influx of calcium
ions through voltage gated Ca channels =release of ach
– Diffuse along synaptic cleft– Bind with nicotinic cholinergic receptors on
motor end plate– Each NM junction = 5 million receptors– Activation requires around 500k
![Page 7: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/7.jpg)
Neuromuscular Transmission
![Page 8: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/8.jpg)
Structure
• Ach receptor– 5 protein subunits• 2 alpha, 1 beta, 1 delta, 1 epsilon• Only alpha bind ach• If both binding sites occupied byAch, conformational change occurs
– Fetal muscle • Gamma subunit instead of epsilon
![Page 9: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/9.jpg)
![Page 10: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/10.jpg)
Neuromuscular Transmission
• Cations flow through open ach– Na/Ca in; K out– Generates end plate potential– 1 vesicle = quanta of ach (104)
• usually 200 per nerve impulse released• Depend on extracellular ionized calcium (higher calcium
concentration = increased quanta release– When enough receptors occupied by ach, end plate potential
strong enough to depolarize peri-junctional membrane– Sodium channels open when threshold voltage reached, as
opposed to end-plate receptors that open to Ach.
![Page 11: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/11.jpg)
Sodium Channel
• Trans-membrane protein with two functional gates– Sodium ions pass only when both gates are
open• At rest, lower gate open, upper gate closed• Muscle membrane reaches voltage
depolarization, upper gate opens and sodium can pass• Shortly after upper gate opens, time dependent
lower gate closes• When membrane repolarizes to its resting
voltage , upper gate closes and lower gate opens
![Page 12: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/12.jpg)
Action Potential
– The resulting action propagates down muscle membrane and T tubule system.• Opens sodium channels• Releases calcium into sarcoplasmic reticulum• Allows contractile proteins myosin and actin to
interact• Amount of ach released and number of receptors far
exceed minimum required– Except for
• Lambert-Eaton Syndrome (decreased release of ach)• Myasthenia gravis (decreased number of receptors
![Page 13: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/13.jpg)
Neuromuscular Blockade: Mechanism
• Depolarizing Muscle Relaxants– Closely resemble Ach– Bind to receptors– NOT metabolized by acetylcholinesterase
therefore concentration in synaptic cleft does not fall as rapidly
– Results in prolonged depolarization of muscle-end plate
![Page 14: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/14.jpg)
Neuromuscular Blockade: Mechanism
• Depolarizing Muscle relaxant– Prolonged depolarization causes relaxation due to
the time limited lower gate on the sodium channel.– Gate cannot reopen until end plate repolarization– End plate cannot repolarize as long as muscle
relaxant bind to ach receptor (Phase 1 block)– Prolonged end-plate depolarization can cause ionic
and conformational changes in ach receptor that result in phase II block • similar to non depolarizing muscle relaxants
![Page 15: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/15.jpg)
Neuromuscular Blockade: Mechanism
• Non-depolarizing muscle relaxants– Bind to ach receptors– Incapable of inducing conformational changes– Ach prevented from binding to receptors – No end-plate potential• NM blockade even if only one alpha subunit blocked
• *Depolarizing=agonist• *Non-depolarizing = competitive antagonists
![Page 16: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/16.jpg)
Acetylcholinesterase
• Substrate-specific enzyme• Rapidly hydrolyzes acetylcholine into acetate
and choline• Embedded into motor end-plate immediately
adjacent to ach receptors
![Page 17: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/17.jpg)
Depolarizing and non-depolarizing Muscle Relaxants
Depolarizing Non-depolarizing
Short-acting Succinylcholine
Short-acting MivacuriumIntermediate-acting
Atracurium; Cisatracurium
Rocuronium; Vecuronium
Long-Acting
Doxacurium
Pancuronium; Pipecuronium
![Page 18: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/18.jpg)
Non-classical Blockade
• Some drugs interfere without agonist or antagonist properties– Include inhaled anesthetic, local anesthetic or ketamine– Interfere with normal functioning of ach binding site
and/or opening and closing of receptor channel– Closed channel blockade– Open channel blockade
• Drug enters and obstructs ach receptor channel after opened– Use dependent– Occurs with antibiotics, cocaine and quinidine– Interferes with blockade reversal
![Page 19: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/19.jpg)
Reversal
• Jake Hummel’s wonderful lecture to follow
![Page 20: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/20.jpg)
Succinylcholine
• Only depolarizing in clinical use• Copycat Ach structure• Rapid onset (30-60s)– Low lipid solubility as well as relative overdose given
• Short duration of action (< 10 min)• As it enters the system, most is metabolized by
pseudocholinesterase– Only small fraction of injected dose reach NMJ
![Page 21: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/21.jpg)
Duration of Action: Succinylcholine
• Prolonged by high dose or abnormal metabolism– Hypothermia
• Decreased rate of hydrolysis– Low pseudo-cholinesterase levels
• Pregnancy, liver disease, renal failure and drugs– Esmolol, metoclopramide, OCP among others
– Genetically variable enzyme• 1 in 50 = one normal and one abnormal gene
– Slightly prolonged block (20-30 min)• 1 in 3000
– 2 abnormal genes, up to 4-8 hour blockade – Dibucaine resistant –most common abnormal pseudocholinesterase
![Page 22: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/22.jpg)
Q
• How should prolonged paralysis from succinylcholine caused by abnormal pseudo cholinesterase be treated?– A. Page Dr Friedman and ask for help– B. Give Neostigimine– C. Mechanical ventilate until muscle function
returns to normal– D. Give cholinesterase substitute
![Page 23: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/23.jpg)
• C
![Page 24: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/24.jpg)
Drug Interactions: Succinylcholine
• Cholinesterase inhibitors– Prolong phase 1 block• Inhibit acetylcholinesterase=higher ach concentration
which increase depolarization• Reduce hydrolysis of succinylcholine
– Inhibit pseudocholinestrase
![Page 25: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/25.jpg)
Drug Interactions: Succinylcholine
• Non-depolarizing muscle relaxant– Small dose
• Occupy some ach receptors, blocking succinylcholine depolarization– Exception: Pancuronium: augments by inhibiting
pseudocholinestrase
– Intubating dose• Reduced dose needed
– Atracurium and rocuronium• No effect
– Mivacurium, pancuronium, pipercuronium
![Page 26: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/26.jpg)
Dosage: Succinylcholine
• Adult– Intubation
• 1-1.5 mg/kg IV *(possibly excessive)• .5 mg/kg acceptable if defasciculating dose of non-depolarizer is not
used– Maintenance
• Repeated small bolus (10mg) or drip (1g in 500-1000ml titrated to effect)
• Children– Intubation
• Infants/Small kids: 2mg/kg• Older children and Adolescents 1mg/kg
![Page 27: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/27.jpg)
Side Effects• Cardiovascular– Variable
• Secondary to possible stimulation of nicotinic receptors in parasympathetic and sympathetic ganglia, as well as muscarinic receptors in SA node
– Low doses• Can produce negative chronotropic/inotropic effects
– Higher doses• Tend to increase heart rate and contractility as well as elevate circulating
catecholamine– Children
• Particularly susceptible to bradycardia• Often treated prophylactically with atropine
![Page 28: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/28.jpg)
Side effects cont.
• Fasciculation– Signals onset of paralysis• Prevented by non-depolarizing relaxant
• Muscle Pains– Increased post-op myalgia• Possibly from unsynchronized contraction of muscle
groups– Increased CK and myoglobinemia can be found after
succinylcholine given– Reduced by NSAID preoperatively
![Page 29: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/29.jpg)
Side Effects
• Hyperkalemia– Intubating dose
• Normal muscle releases enough potassium to raise serum .5 meq– Concerning in cases of
• Preexisting hyperkalemia (renal failure)• Burn Injury• Massive Trauma• Neurological disorders• Many more
– Cardiac arrest can prove to be quite refractory to routine cardiopulmonary resuscitation
![Page 30: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/30.jpg)
Side effects
• Malignant Hyperthermia– Potent triggering agent in patients susceptible to
MH• Intracranial pressure– May lead to increase in cerebral blood flow and
ICP• Attenuated with hyperventilation/good airway control• Pre-treat with non-depolarizing muscle relaxant and IV
lidocaine 2-3 minutes prior to intubation
![Page 31: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/31.jpg)
Side effects
• Intragastric pressure elevation– Abdominal wall fasciculations increase pressure
• Offset by increase LES tone• No increase reflux/aspiration• Abolished by pretreatment
• Intraocular pressure elevation– Extra-ocular muscle
• multiple motor-end plates each cell– Prolonged depolarization and contraction of muscle
transiently raise IOP• Worrisome in patient’s with injured eye
![Page 32: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/32.jpg)
Which non-depolarizer has the slowest onset (at proper intubating dose)?
• A. Rocuronium• B. Pancuronium• C. Vecuronium• D. Doxacurium• E. Atracurium
![Page 33: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/33.jpg)
• D
![Page 34: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/34.jpg)
Which non-depolarizer causes the most vagal blockade?
• A. Rocuronium• B. Pancuronium• C. Vecuronium• D. Doxacurium• E. Atracurium
![Page 35: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/35.jpg)
• B
![Page 36: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/36.jpg)
Non-DepolarizersDrug Structure Metabolism Primary
ExcretionOnset Duration Hist.
ReleaseVagal Blockade
Atracurium B +++ x ++ ++ + 0
Cisatracurium B +++ x ++ ++ 0 0
Mivacurium B +++ x ++ + + 0
Doxacurium B Insignificant Renal + +++ 0 0
Pancuronium S + Renal ++ +++ 0 ++
Pipercuronium S + Renal ++ +++ 0 0
Vecuronium S + Biliary ++ ++ 0 0
Rocuronium S insignificant Biliary +++ ++ 0 +
![Page 37: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/37.jpg)
Drug Intubation dose(mg/kg)
Onset of action for Intubating dose(mg/kg)
Duration of Intubating dose(min)
Maintenance dosing by boluses(mg/kg)
Maintenance dosing by infusion (ug/kg/min)
Succinylcholine 1 .5 5-10 .15 2-15 mg/min
Rocuronium .8 1.5 35-75 .15 9-12
Mivacurium .2 2.5-3.0 15-20 .05 4-15
Atracurium .5 2.5-3.0 30-45 ,1 5-12
Cisatracurium .2 2-3 40-75 .02 1-2
Vecuronium .12 2-3 45-90 .01 1-2
Pancuronium .12 2-3 60-120 .01 x
Pipercuronium .1 2-3 80-120 .01 x
Doxacurium .07 4-5 90-150 .05 x
![Page 38: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/38.jpg)
Non-depolarizers
• Two types– Benzylisoquinolines• Release histamine
– Steroids• Vagolytic
– Related allergic history
![Page 39: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/39.jpg)
Non-depolarizers
• Intubation– None as rapid onset as succinylcholine– Quickened by larger dose or priming dose
• Prolongs duration of blockade and exacerbates SE– Priming dose
• 10-15 % of intubating dose 5 minutes before induction will occupy enough receptors so that paralysis quickly follows full dose– Intubation conditions at 60s (Rocuronium)
» 90s with other intermediate-acting depolarizers• Does not usually lead to clinically significant paralysis
– (75-80% of receptors blocked)• Can cause dyspnea, dysphagia and diplopia
![Page 40: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/40.jpg)
Non-depolarizers
• Maintenance relaxation– LARGE VARIABLE IN DOSE RESPONSES– Requires Close monitoring with Neuro-stimulator– Bolus or infusion should be guided by stimulator as well as
clinical signs• Movement• Spontaneous ventilation
– Some return of neuromuscular transmission should be evident prior to bolus dose
– Infusion should be titrated at or just above rate that allows return of neuromuscular transmission
![Page 41: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/41.jpg)
Non-depolarizers
• Potentiated by inhalational anesthetics– Volatile agents decrease dosage requirements by
at least 15 %– Depends on agent• Des> Sevo > Iso and Enflurane > Halothane > N202
– Muscle relaxant• Pancuronium > vecuronium and atracurium• Hypothetically due to volatile induced enhanced affinity
for non-depolarizing muscle relaxants
![Page 42: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/42.jpg)
Autonomic side Effects
• Older agents (tubocurarine/metocurine)– Blocked autonomic ganglia• Decreased contractility/response to hypotension
• Pancuronium– Blocks vagal muscarinic receptors• Tachycardia
• Newer agents – Devoid of significant autonomic effects
![Page 43: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/43.jpg)
Excretion
• Hepatic– Pancuronium\Vecuronium metabolized mostly by liver– Liver failure
• Prolongs pancuronium as well as rocuronium blockade• Less effect on vecuronium• No effect on Cisatracurium or atracurium
• Renal– Doxacurium/Pancuronium/Vecuronium and
pipecuronium excreted by kidneys• Prolonged action in patients with renal failure
![Page 44: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/44.jpg)
Characteristics
• Greater Potency=slower onset• Temperature
– Hypothermia prolongs blockade• Decreased metabolism and excretion
• Acid-Base– Respiratory acidosis
• Potentiates blockade
• Hypokalemia/Hypocalcemia– Prolong blockade
• Hypermagesemia– Prolongs blockade by competing with Ca++ at motor-end plate
• Seen in preeclampsia
![Page 45: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/45.jpg)
Atracurium• Benzylisoquinoline– Metabolized independent of renal and biliary routes
• Hoffman elimination– Triggers dose –dependent histamine release above .5mg/kg
(intubating dose)• Hypotension/reflex tachycardia/cutaneous flush
– Laudanosine toxicity• Product of breakdown of atracurium• CNS excitation: possibly seizures• Only relevant at extremely high doses or hepatic failure
– Precipitate as free acid if placed in IV line with alkaline solution (thiopental)
![Page 46: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/46.jpg)
Cisatracurium
• Stereoisomer of atracurium• 4 times more potent• Hoffman elimination• *Does not produce a dose-dependent increase in
histamine– Also lower laudaonsine toxicity
• PH/Temperature sensitive– Secondary to unique metabolism– Prolonged action by hypothermia/acidosis
![Page 47: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/47.jpg)
Mivacurium
• Metabolized by pseudocholinesterase– Also prolonged by low pseudocholinesterase levels
• Also causes histamine release• Brief duration of action– About half of atracurium/vec/rocuronium
• Markedly prolonged by prior administration of pancuronium
![Page 48: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/48.jpg)
Doxacuronium
• Benzylisoquinoline• Renal excretion– Similar to other long acting non-depolarizers
• Slow onset (4-6 minutes)– .05mg/kg for tracheal intubation within 5 min
• No cardiac or histamine-release side effects• Duration:60-90 minutes
![Page 49: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/49.jpg)
Pancuronium• Steroid base• Primarily renal excretion
– Slowed by renal failure• Some excretion by bile
– Cirrhotic patients require higher initial dose• Side Effects:
– HTN and tachycardia• Combination of vagal blockade and sympathetic stimulation
– Caution with CAD, aortic stenosis
– Arrhythmias• Increases AV conduction and catecholamine release• Worsened in patients using TCA and halothane
– Allergic reaction possible in patients hypersensitive to bromide
![Page 50: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/50.jpg)
Pipecuronium
• Steroid base (similar to Pancuronium)• Renal excretion• No cardiovascular side effects– Advantage over pancuronium
![Page 51: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/51.jpg)
Vecuronium
• Biliary and renal excretion• Satisfactory in renal failure however some prolongation
occurs
• Side effects– No significant CV effects• Can cause potentiation of opioid-induced bradycardia
– *Long term administration causes buildup of active 3-hydroxy metabolite: elongates drug clearance and can cause polyneuropathy
![Page 52: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/52.jpg)
Rocuronium
• Analogue of vecuronium designed for rapid onset• No active metabolite– Better choice for long term infusion
• Can cause prolonged duration of action in elderly• Primary hepatic and renal elimination– Duration of action prolonged by hepatic disease and
pregnancy– Not Significantly affected by renal failure
![Page 53: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/53.jpg)
Rocuronium
• Useful for quick onset of action– Closest non-depolarizer to succinylcholine
• .1 mg/kg shown to be rapid and effective agent (decreased fasciculations and post-op myalgias for precurarization administration of succinylcholine
• Slight vagolytic tendencies
![Page 54: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/54.jpg)
The Future?
• Want better control over onset/duration/off• Replacement for succinylcholine– 430a• Supposedly coming soon• Similar onset, duration and offset to succinylcholine• First non-depolarizer with these futures
• Quicker/more efficient reversal– Cysteine?• Reversal of still-developing drugs in 1-2 minutes at 100%
![Page 55: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/55.jpg)
Key Concepts
• 1) – PARALYTICS DO NOT CAUSE AMNESIA, ANALGESIA
OR UNCONSCIOUSNESS• 2)– Depolarizing = Ach receptor agonists– Non-depolarizing=competitive antagonists
![Page 56: Neuromuscular Blocking Agents](https://reader036.fdocuments.us/reader036/viewer/2022081421/568164a0550346895dd68e12/html5/thumbnails/56.jpg)
Sources• Feldman S: Neuromuscular Blockade. Butterworth-Heinemann, 1996.
Excellent chapters on neuromuscular transmission, acetylcholine pharmacology, and mechanisms of muscle relaxant actions.
• Miller, Ronald D, Pardojr, Manuel C. Chapter 12. Neuromuscular Blocking Agents, IN: Miller: Basics of Anesthesia. 6th ed. Philadelphia, PA: Elsevier Saunders; 2011.
• Morgan, Jr. GE, Mikhail MS, Murray MJ. Chapter 9. Neuromuscular Blocking Agents. In: Morgan, Jr. GE, Mikhail MS, Murray MJ, eds. Clinical Anesthesiology. 4th ed. New York: McGraw-Hill; 2006.
• Naguib M, Flood P, McArdle JJ, Brenner HR: Advances in the neurobiology of the neuromuscular junction. Anesthesiology 2002;96:202.
• Naguib M, Samarkandi A, Riad W, Alharby SW: Optimal dose of succinylcholine revisited. Anesthesiology 2003;99:1045.