MUSCLE RELAXANTS

Mr. D.Raju, M.pharm,

Lecturer
Muscle Relaxants are classified as:
I)Peripherally acting
A.Neuromuscular blocking agents:-
1) Depolarizing muscle relaxants.
2) 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 Atracurium,
y Cisatracurium,
y Vecuronium,
y Rocuronium
Long acting :
y Doxacurium
y Pancuronium
y 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 Pseudo-
cholinesterase 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.
´ 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)
 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
´ 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:
• 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,
 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.
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.
 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:
² Neostigmine
² Pyridostigmine
² Edrophonium
² Physostigmine
´ 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.