Download NEUROMUSCULAR BLOCKING AGENTS

MUSCLE RELAXANTS
Mr. D.Raju, M.pharm,
Lecturer
Muscle Relaxants are classified as:
I)Peripherally acting
A.Neuromuscular blocking agents:1)
2)
Depolarizing muscle relaxants.
Non-depolarizing muscle relaxants
B.) Directly acting: Dantrolene, Quinine
II)Centrally acting
o
Chlorzoxazone,Chlormezanone, Diazepam, Baclofen,
Tizanidine, Metaxalone.
Depolarizing Muscle relaxants:
y
Succinylcholine (short acting)
Non-depolarizing Muscle relaxants:
Short acting:
y
Mivacurium
Intermediate –acting:
y
y
y
y
Atracurium,
Cisatracurium,
Vecuronium,
Rocuronium
Long acting :
y
y
y
Doxacurium
Pancuronium
Pipecuronium
MECHANISM OF ACTION
SUXAMETHONIUM:
• Block transmission by causing prolonged
depolarization of endplate at neuromuscular
junction.
• Manifestation by initial series of muscle
twitches (fasciculation) followed by flaccid
paralysis.
• It immediately metabolize in plasma by Pseudocholinesterase which is synthesized by liver so
to prevent its metabolism in plasma it should
be given at faster rate.
SYSTEMIC EFFECTS
Cardiovascular: Produces muscarinic effects as
acetylcholine , therefore causes bradycardia (
but when given high doses causes tachycardia
because of stimulation of nicotinic receptors at
sympathetic ganglions.)
´ Hyperkalemia: Occurs due to excessive muscle
fasciculations. Ventricular fibrillation can occur
due to hyperkalemia.
´ CNS: Increases intracranial tension ( due to
contraction of neck vessels)
´ Eye: Increases intraocular pressure.
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GIT: Increases intra-gastric pressure , salivation,
peristalsis.
´ Muscle pains ( myalgia): This is a very common
problem in post operative period. These are due
to excessive muscle contractions.
´ Malignant hyperthermia
´ Severe Anaphylaxis
´ Masseter Spasm : Sch can cause masseter spasm
especially in children & patients susceptible for
malignant hyperthermia.
Doesnot require reversal rather cholinesterase
inhibitors (neostigmine) can prolong the
depolarizing block (because these agents also
inhibits the pseudocholinesterase)
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CONTRAINDICATIONS
Hyperkalemia: Serum K > 5.5 is an absolute
contraindication for use of Sch.
´ Head Injury : It increase ICP
´ Newborns and infants: These have
extrajunctional receptors which are sensitive
to depolarizing agents & Sch can produce
severe hyperkalemia by interacting with these
receptors.
´ Glaucoma & eye injuries.
´ Up to 2-3 months after trauma, Up to 6
months after hemiplegia/paraplegia, Up to 1
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Renal Failure : If associated with hyperkalemia.
Prolonged intra abdominal infection can be associated with
hyperkalemia.
Diagnosed case of atypical pseudocholinesterase & low
pseudocholinesterase.
Duchene muscular dystrophy
Dystrophia myotonica: Permanent contractures may develop if
SCh is given in these patients.
Tetanus.
Gullian Barre Syndrome
Metabolic Acidosis :Acidosis is associated with hyperkalemia.
Shock : It is associated with acidosis which in turn is associated
with hyperkalemia.
Spinal cord injury.
NON-DEPOLARIZING MUSCLE
RELAXANTS:
Mechanism
of action:
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It blocks nicotinic receptors competitively
resulting in inhibition of sodium channels and
excitatory post-synaptic potential.
It binds at the same site at which acetylcholine
binds.
All NDMR are quarternary ammonium
compounds & highly water soluble i.e.
hydrophilic. So, they do not cross blood brain
barrier & placenta except Gallamine.
BROAD CLASSIFICATION
These are broadly divided into steroidal
compounds and benzylisoquinoline (BZIQ)
compunds.
´ STEROIDAL COMPOUNS: (vagolytic properties)
It includes PANCURONIUM,VECURONIUM ,
PIPECURONIUM,ROCURONIUM,
RAPACURONIUM.
´ BZIQ(Benzylisoquinoline): (hystamine realease)
It includes d-Tubocurare, Metocurine,
Doxacurium, Atracurium, Mivacurium,
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STEROIDAL COMPOUNDS
Pancuronium(PAVULON)
´ Very commonly used as it is inexpensive.
´ It releases noradrenaline & can cause tachycardia & hypertension. Because
of this there are increased chances of arrhythmia with halothane
Pipercuronium
´ It is a pancuronium derivative with no vagolytic activity, so cardiovascular
stable, slightly more potent
Vercuronium (Norcuron)
´ It is very commonly used now a days. It is cardiovascular stable. Shorter
duration of action.
´ It is the muscle relaxant of choice in cardiac patient.
Rocuronium
´ 8 times more potent than vecuronium and it also has earlier onset of action
´ Because of onset comparable to succinylcholine it is suitable for rapid
sequence intubation as an alternative to succinylcholine.
BENZYLISOQUINOLINE COMPOUNDS
D- Tubocurare
´ It is named so because it was carried in
bamboo tubes & used as arrow poison for
hunting by Amazon people.
´ It has highest propensity to release
histamine
´ It causes maximum ganglion blockade.
Because of ganglion blocking & histamine
releasing property it can produce severe
hypotension.
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CENTRALLY ACTING MUSCLE RELAXANTS
These are drugs which produce muscle
relaxation through central mechanism both at
supraspinal & spinal level
´ Polysynaptic reflexes involved in maintenance
of muscle tone are inhibited at both spinal &
supraspinal level. It also produces sedation
Uses
´ Muscle spasms.
´ Tetanus : IV diazepam is most effective.
´ Spastic neurological diseases like cerebral
palsy,Spinal injuries.
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REVERSAL OF BLOCK
Drugs used for reversal of block are cholinesterase inhibitors
(anticholinesterases).
´ Reversal should be given only after some evidence of spontaneous
recovery appear.
Mechanism of Action
´ It inactivate the enzyme acetylcholinesterase which is responsible
for break down of actetylcholine, thus increasing the amount of
acetylcholine available for competition with non depolarizing agent
thereby re-establishing neuromuscular transmission.
´ Anticholinesterases used for reversal are:
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Neostigmine
Pyridostigmine
Edrophonium
Physostigmine
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These agents except physostigmine are quarternary ammonium
compounds so they do not cross blood brain barrier.
The biggest disadvantage is that these agents also increase the
acetylcholine level at muscarinic receptors producing muscarinic
side effects like bradycardia, bronchospasm.
So, to prevent these muscarinic effects some anti cholinergic like
atropine or glycopyrrolate is to be given with cholinesterase
inhibitors.
Neostigmine : Anticholinergic preferred with it is glycopyrrolate
because both have same onset of action (both are slow acting).
Edrophonium : Anticholinergic preferred with it is atropine (both
fast acting).
Pyridostigmine: It is preferred drug for renal failure patients in
whom a prolonged stay of muscle relaxant is expected.
DRUGS WHICH ANTAGONISE
NEUROMUSCULAR BLOCKADE
They reverse the block by NDMR only
´ Phenytoin
´ Carbamazepine
´ Calcium
´ Cholinesterase inhibitors
´ Azathioprine
´ Steroids.
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