Muscle Relaxants DMR & NDMR

1. Depolarising Muscle Relaxants
Quaternary Amines
( Suxamethonium )
2. Non Depolarising Muscle Relaxants
Amino Steroids
( Pancuronium, Vecuronium, Rocuronium )
Benzylisoquinolium Diesters
( Atracurium, Cisatracurium, Mivacurium )

1. Muscle Relaxants
Mr. Harshad Khade
MSc. Medical Technology (OTA)
Symbiosis International University, Pune.

2. Classification
1. Depolarising Muscle Relaxants
•Quaternary Amines
( Suxamethonium)
2. Non Depolarising Muscle Relaxants
•Amino Steroids
( Pancuronium, Vecuronium, Rocuronium)
•BenzylisoquinoliumDiesters
( Atracurium, Cisatracurium, Mivacurium)

3. Suxamethonium
Class
•Depolarizing muscle relaxant; ultra short-acting
Uses
1. wherever rapid and profound neuromuscular blockade is required,
e.g. to facilitate tracheal intubation and
2. for the modification of fits after electroconvulsive therapy.
Main actionsNeuromuscular blockade of brief duration in skeletal muscle.

4. Presentation
•As a clear aqueous solution containing 50 mg/ml of suxamethonium
chloride; the preparation should be stored at 4°C.
Mode ofaction
•Suxamethoniumcauses prolonged depolarization of skeletal muscle fibers
to a membrane potential above which an action potential can be triggered.
Routes ofadministration/doses
•The intravenous dose is 0.5–2.0 mg/kg; the onset of action occurs within 30
seconds, and the duration of action is 3–5 minutes.
•Infusion of a 0.1% solution at 2–15 mg/kg/hour will yield 90% twitch
depression.
•The intramuscular dose is up to 2.5 mg/kg.
•Equal doses on a mg/kg basis have a shorter duration of action in infants.
•The drug may also be administered sublingually at a dose of 2 mg/kg.

5. •Dose
•Intubaton: 1-1.5 mg/kg IV or 2.5-4 mg/kg IM
•Onset
•30-60 seconds after IV administration 2-3 minutes after IM dose
•Duration
•Duration is 4-6 minutes after IV dose 10-30 minutes after IM dose
•Elimination
•Hydrolysis by plasma pseudocholinesterase

6. Effects
•CNS
•Raised intracranial pressure and raised intraocular pressure.
•CVS
•Because of cross-reactivity at the muscarinic acetylcholine receptors, Sch
causes vagal cardiac dysrhythmias.
•Bradycardia, junctional rhythm and sinus arrest can occur particularly if a
second dose is administered and particularly in children.
•Respiratory
•Occasionally leads to bronchospasm and excessive salivation due to
muscarinic effects.
•Intragastricpressure is increased thereby theoretically increasing the risk
of regurgitation.

7. •Misc.
•Most of the other effects are secondary to the depolarization and
subsequent contraction of skeletal muscle.
•Schelevates serum potassium 0.3-0.5 mEq/L in normal patients It can
cause an exaggerated release of potassium (leading to fatal
hyperkalemia) in those with neuromuscular or muscle disease.
•Post-operative myalgia is common particularly in young adults.
•Succinylcholine is a potent trigger of malignant hyperther
Contraindications
There is a long list of absolute and relative contraindications which can be
found in any Anesthesia text. A brief summary follows:
Malignant Hyperthermia (MH) or presence of conditions associated with
MH.

8. Pseudocholinesterasedeficiency. Deficiency can result as a genetic defect, as a
consequence of various medications or a result of liver disease.
The latter two causes are usually relative while the genetic defect can produce a
complete lack of pseudocholinesteraseactivity in homozygous individuals. The
use of succinylcholine in a patient with pseudocholinestersasedeficiency leads
to prolonged paralysis.
Hyperkalemia.
Presence of neurologic or muscular condition which would predispose to
hyperkalemia after Sch-induced muscle contraction. Examples include recent
paralysis (spinal cord injury or stroke), amyotrophic lateral sclerosis (ALS),
Duchenne’smuscular dystrophy and recent burn or crush injury. Myotonia
congenitaor myotoniadystrophicacan manifest sustained contractionwith Sch.

9. Atracurium
Class
•Nondepolarizingskeletal muscle relaxant (NDMR); short-acting.
Uses
•Atracuriumis used to facilitate intubation and controlled ventilation
Main action
•Competitive, non-depolarizing neuromuscular blockade.
Mode ofaction
•Atracuriumacts by competitive antagonism of acetylcholine at nicotinic
(n2) receptors in the post-synaptic membrane of the neuromuscular
junction.

10. Presentation
•As a clear, colourlessor pale yellow solution for injection available in 2.5
ml, 5 ml, and 25 ml vials, containing 10 mg/ml of atracuriumbesilate
(equivalent to atracurium7.5 mg/ml),
•Needing to be stored at 2–8°C.
•It has a phof between 3.25 and 3.65.
Routes ofadministration/doses
•The drug is administered intravenously.
•The ED95 of atracuriumis estimated to be 0.23 mg/kg.
•An initial dose of 0.3–0.6 mg/kg is recommended, providing muscle
relaxation for between 15 and 35 minutes.
•Endotracheal intubation can be achieved within 90–120 seconds of an
intravenous dose of 0.5–0.6 mg/kg, with maximal resultant neuromuscular
blockade achieved within 3–5 minutes following administration.

11. •Ninety-five percent recovery of the twitch height occurs within
approximately 35 minutes.
•Maintenance of neuromuscular blockade may be achieved with bolus doses
of 0.1–0.2 mg/kg.
•Atracuriummay be administered by intravenous infusion at a rate of 0.3–0.6
mg/kg/hour, although there is wide inter-patient variability in dosage
requirements, particularly in patients on ventilation in intensive care.
•Induced hypothermia to a temperature of approximately 25°C reduces the
rate of metabolism of atracurium.
•Consequently, neuromuscular block can be maintained with approximately
half the original infusion rate.
•The drug is non-cumulative with repeated or continuous administration.
•Ninety-five percent recovery of twitch height, following a single dose of
atracurium, occurs within 35 minutes.

12. Dose
•Intubation : 0.5-0.6 mg/kg IV
•Maintenance bolus: 0.1-0.3 mg/kg IV
Onset
•3-4 minutes
•Duration
•20-35 minutes
Elimination
•Hoffman elimination, ester hydrolysis

13. Effects
•MSK
•The neuromuscular blockade effects of non-depolarizing muscle relaxants are
potentiated by succinylcholine, volatile anesthetics, aminoglycosides, lithium, loop
diuretics, lidocaine, magnesium, lithium, ganglionic blockers, hypothermia,
hypokalemiaand respiratory acidosis.
•Enhanced neuromuscular blockade is seen in patients with myasthenia gravis or
myopathies
•The effects of ndmrare antagonized by cholinesterase inhibitors.
•Increased resistance to ndmris seen in patients on theophylline, burn patients and
those with paresis or paralysis.
•Misc.
•Histamine release may occur with rapid administration or higher dosages. Produces an
excitatory metabolite called laudanosine.
•Muscle relaxants are the most common cause of anaphylactoidreactions under general
anesthesia.

14. Cis-atracurium
Class
•Non-depolarizing skeletal muscle relaxant (NDMR); intermediate-acting
Uses
•Cisatracuriumis used to facilitate intubation and controlled ventilation.
Main action
•Competitive, non-depolarizing neuromuscular blockade.
Mode ofaction
•Cisatracuriumacts by competitive antagonism of acetylcholineat
nicotinic (N2) receptors at the post-synaptic membrane of the
neuromuscular junction.

15. Presentation
•As a clear, colourlessor pale yellow solution for injection available in 5,
10, and 20 ml vials containing 6.7 mg/ml of cisatracuriumbesilate
(equivalent to cisatracurium5 mg/ml), needing to be stored at 2–8°C.
•It contains no antimicrobial preservative.
•It has a pH of between 3.25 and 3.65.
Routes ofadministration/doses
•The drug is administered intravenously.
•The ED95 of cisatracuriumis estimated to be 0.05 mg/kg during opioid
anaesthesia.
•An initial dose of 0.15 mg/kg is recommended, providing good to
excellent intubating conditions in 120 seconds.
•The time to 90% T1 suppression following this dose is 2.6 minutes;
•the time to maximal T1 suppression is 3.5 minutes, and the time to 25%
spontaneous T1 recovery is 55 minutes.

16. •Maintenance of neuromuscular blockade may be achieved with bolus doses of
0.03 mg/kg (0.02 mg/kg in paediatricpatients) which will provide approximately
20 minutes of additional neuromuscular blockade (approximately 9 minutes in
paediatricpatients).
•Once recovery from neuromuscular blockade has started, the rate of recovery is
independent of the dose of cisatracuriumadministered.
•Cisatracuriummay be administered by intravenous infusion at an initial rate of 3
micrograms/kg/min (0.
•18 mg/ kg/hour), although there is wide inter-patient variability in dosage
requirements, particularly in patients ventilated on intensive care.
•This infusion rate should result in T1 suppression of between 89 and 99%. After an
initial period of stabilization of neuromuscular block, a rate of 1–2 micrograms/
kg/min (0.06–0.12 mg/kg/min) is recommended to maintain adequate blockade
(0.03–0.06 mg/kg/min in patients ventilated on intensive care).

17. Dose
•Intubation: 0.15-0.2 mg/kg
•Maintenance bolus: 0.03 mg/kg
•Maintenance infusion: 1-2 $g/kg/minute
Onset
•Dose-dependent:
•2 minutes (0.15 mg/kg)
•1.5 minutes (0.2 mg/kg)
Duration
•Dose dependent:
•55 minutes (0.15 mg/kg)
•65 minutes (0.2 mg/kg)
•20 minutes (maintenance bolus 0.03 mg/kg)

18. Effects
•MSK
•The neuromuscular blockade effects of non-depolarizing muscle relaxants are
potentiated by succinylcholine, volatile anesthetics, aminoglycosides, lithium,
loop diuretics, lidocaine, magnesium, lithium, ganglionic blockers, hypothermia,
hypokalemiaand respiratory acidosis.
•Enhanced neuromuscular blockade is seen in patients with myasthenia gravis or
myopathies.
•The effects of NDMR are antagonized by cholinesterase inhibitors. Increased
resistance to NDMR is seen in patients on theophylline, burn patients and those
with paresis or paralysis.
•Misc.
•Histamine release may occur with rapid administration or higher dosages.
Produces 5-10x less laudanosinemetabolite than atracurium.
•Muscle relaxants are the most common cause of anaphylactoidreactions under
general anesthesia.

19. Vecuronium
Uses
•Vecuroniumis used to facilitate intubationnand controlled ventilation.
Main action
•Competitive non-depolarizing neuromuscular blockade.
Mode ofaction
•Vecuroniumacts by competitive antagonism of acetylcholine at nicotinic (N2)
receptors at the post-synaptic membrane of the neuromuscular junction.
•The drug also has some pre-junctional action.

20. Routes ofadministration/doses
•The drug is administered intravenously.
•The ed90 of vecuroniumis estimated to be 0.057 mg/kg.
•An initial dose of 0.08–0.1 mg/kg is recommended, providing muscle
relaxation for between 25 and 40 minutes.
•Endotracheal intubation can be achieved within 90–120 seconds of an
intravenous dose, with maximal resultant neuromuscular blockade
achieved within 3–5 minutes following administration.
•Ninety-five percent recovery of the twitch height occurs within
approximately 45 minutes.
•Maintenance of neuromuscular blockade may be achieved with bolus
doses of 0.02–0.03 mg/kg.
•Vecuroniummay be administered by intravenous infusion at a rate of
0.8–1.4 micrograms/kg/min.
•The drug is non-cumulative with repeated administration.

21. Effects
•CVS
•Vecuroniumhas minimal cardiovascular effects; with large doses, a slight
(9%) increase in the cardiac output and 12% decrease in the systemic
vascular resistance may occur.
•Unlike pancuronium, the drug will not antagonize the haemodynamic
changes or known side effects produced by other pharmaceutical agents
or surgical factors.
•RS
•Neuromuscular blockade leads to apnoea. Vecuroniumhas a very low
potential for histamine release; bronchospasm is extremely uncommon.
•CNS
•The drug has no effect on intracranial or intraocular pressure.

22. Mivacurium
Uses
•Mivacuriumis used to facilitate intubation and controlled ventilation.
Presentation
•As a clear, pale yellow aqueous solution in 5 and 10 ml ampoules
containing 2.14 mg/ml of mivacuriumhydrochloride.
•It has a pH of approximately 4.5.
Main action
•Competitive, non-depolarizing neuromuscular blockade.

23. Mode ofaction
•Mivacuriumacts by competitive antagonism of acetylcholine at
nicotinic (N2) receptors at the post-synaptic membrane of the
neuromuscular junction.
Routes ofadministration/doses
•Mivacuriumis administered by intravenous injection; in adults, the
mean dose to reach the ED95 is 0.07 mg/kg.
•The recommended intubating dose in adults is 0.2 mg/kg
administered over 30 seconds or a dose of 0.25 mg/kg
administered as a divided dose (0.15 mg/kg, followed 30 seconds
later by 0.1 mg/kg), which provides good to excellent intubating
conditions within 2–2.5 minutes and 1.5–2 minutes (following
completion of the first divided dose), respectively.

24. •Maintenance doses of 0.1 mg/kg are required at approximately 15-
minute intervals in adults and children.
•Continuous infusion of mivacuriumin adults may also be administered
at a rate of 8–10 micrograms/kg/min (0.5–0.6 mg/kg/hour).
•The ED95 in infants and children is 0.07 mg/kg and 0.1 mg/kg,
respectively.
•The corresponding recommended doses for tracheal intubation are
0.15 mg/kg for infants and 0.2 mg/kg for children, with times to
maximal neuromuscular block of 1.4 and 1.7 minutes, respectively.
•Average infusion rates to maintain 89–99% neuromuscular block are
11–14 micrograms/kg/min for children aged 2months to 12years
old (0.7–0.9 mg/kg/hour).

25. •The duration of neuromuscular blockade is related to the bolus dose;
doses in adults of 0.07, 0.15, 0.2, and 0.25 mg/kg produce clinically
effective block for approximately 13, 16, 20, and 25 minutes,
respectively.
•Spontaneous recovery after a continuous infusion is independent of the
duration of infusion and is similar to recovery reported for single
doses.
•Tachyphylaxisor cumulative neuromuscular blockade is not associated
with continuous infusion of mivacurium.
•Significant train-of-four fade is not seen during the onset of block with
mivacurium, and intubation of the trachea may be possible before the
train-of-four count has been abolished.

26. Effects
•CVS
•Mivacuriumhas minimal CVS effects; a slight (7%) transient decrease in
the blood pressure and a slight (7%) increase in the heart rate may occur
after rapid intravenous injection.
•The drug has no significant vagal or ganglion-blocking properties in the
normal dosage range.
•RS
•Neuromuscular blockade leads to apnoea; bronchospasm may occur,
secondary to histamine release

27. ROCURONIUM
Class
•Non-depolarizing muscle relaxant (NDMR); shortacting
Uses
1. To facilitate tracheal intubation during routine and modified rapid
sequence induction
2. For controlled ventilation.
Main action
Competitive neuromuscular blockade

28. Presentation
•As a clear, colourlesssolution containing 10 mg/ml of rocuroniumbromide.
•The drug is available in 5 and 10 mg ampoules.
Mode ofaction
•Rocuroniumacts by competitive antagonism of acetylcholine at nicotinic (n2)
receptors at the post-synaptic membrane of the neuromuscular junction;
•It also has some pre-junctional activity.
Routes ofadministration/doses
•Rocuroniumis administered intravenously;
•The normal intubating dose is 0.6 mg/kg, with subsequent doses of 0.15 mg/kg.
•This intubating dose equates to twice the ed90 for rocuronium(ed90 0.3
mg/kg) and results in ‘excellent’ intubating conditions in 80% of cases within 60
seconds.

29. •Adose of 1 mg/kg is recommended when rocuroniumis used during
modified rapid sequence induction, resulting in intubating conditions
within 60 seconds in 93–96%.
•The increased speed of onset relates to the low potency of rocuronium.
•As a result of giving an increased dose (increased number of drug
molecules), the concentration gradient at the neuromuscular junction is
increased, leading to a faster diffusion of drug molecules and a reduction
in drug onset time.
•The duration of action relates to the dose given, and, as a result, the usual
recovery index of 8–17 minutes with a normal intubating dose is increased
to nearly an hour when 1.0 mg/kg is used.
•The drug may also be infused at a rate of 300–600 micrograms/kg/hour.
•The drug is non-cumulative with repeated administration.

30. Dose
•Intubation: 0.45-.9 mg/kg
•Maintenance bolus 0.1-0.2 mg/kg
•Not usually administered by infusion
Onset
•Dose-dependent:
•1-1.5 minutes (0.6 mg/kg)
•0.5-1.0 minutes (0.9 mg/kg)
•Higher dose is therefore suitable for rapid sequence induction.
Duration
•Dose-dependent: 31 minutes (0.6 mg/kg) 60 minutes (0.9 mg/kg)
EliminationHepato-biliary (70%); renal (10%)

31. Effects
•CVSVery weak vagolyticeffect.
•MSK
•The neuromuscular blockade effects of non-depolarizing muscle
relaxants are potentiated by succinylcholine, volatile anesthetics,
aminoglycosides, lithium, loop diuretics, lidocaine, magnesium, lithium,
ganglionic blockers, hypothermia, hypokalemiaand respiratory acidosis.
•Enhanced neuromuscular blockade is seen in patients with myasthenia
gravis or myopathies.
•The effects of NDMR are antagonized by cholinesterase inhibitors.
•Increased resistance to NDMRs is seen in patients on theophylline, burn
patients and those with paresis or paralysis.
•Misc.
•Muscle relaxants are the most common cause of anaphylactoidreactions
under general anesthesia.

32. PancuroniumBromide
Class
•Nondepolarizingskeletal muscle relaxant (NDMR); long-acting
Presentation
•As a clear colourlesssolution for injection containing 2 mg/ml of
pancuroniumbromide.
•The solution has a pH of 4.
Main action
•Pancuroniumacts by competitive antagonism of acetylcholine at nicotinic
(N2) receptors at the post-synaptic membrane of the neuromuscular junction.
•The drug also has some pre-junctional action.

33. Routes ofadministration/doses
•The drug is administered intravenously.
•The ED95 of pancuroniumis estimated to be 0.05 mg/kg.
•An initial dose of 0.05–0.1 mg/kg is recommended in adults, providing
muscle relaxation for between 65 and 100 minutes.
•Endotracheal intubation can be achieved within 90–150 seconds of an
intravenous dose, with maximal resultant neuromuscular blockade achieved
within 4 minutes following administration.
•Maintenance of neuromuscular blockade may be achieved with bolus doses
of 0.01–0.02 mg/kg.
•An initial dose of 0.06–0.1 mg/kg is recommended in children.
•If pancuroniumis administered after suxamethonium, then the initial
intravenous dose of the former should be reduced to 0.02–0.06 mg/kg in
both adults and children.

34. Effects
•CVS
•Pancuroniumcauses an increase in the heart rate, blood pressure, and
cardiac output, secondary to a vagolyticaction.
•The systemic vascular resistance remains unchanged after the
administration of the drug. Aslight fall in central venous pressure may
occur.
•RS
•Neuromuscular blockade results in apnoea.
•Pancuroniumhas a very low potential for histamine release;
•bronchospasm is extremely uncommon.

35. “
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