Indian Dental Academy's Guide to Skeletal Muscle Relaxants

INDIAN DENTAL ACADEMY
Leader in continuing Dental Education
www.indiandentalacademy.com

INTRODUCTION
 Skeletal muscle relaxants are drugs that act peripherally at
neuromuscular junction/ muscle fibre itself or centrally in the
cerebrospinal axis to reduce muscle tone and / or cause paralysis
 The neuromuscular blocking agents are used in conjunction with
general anaesthetics to provide muscle relaxation for surgery,
 while centrally acting muscle relaxants are used primarily for painful
muscle spasms and spastic neurological diseases.

According to the mode of action
 Peripherally acting muscle relaxants
 Centrally acting muscle relaxants
Peripherally acing muscle relaxants
I. Neuromuscular blocking agents
A. Nondepolarizing (competitive ) blockers
a) Long acting : d-Tubocurarine, Pancuronium, Doxacurium,
Pipecuronium
b) Intermediate acting : Vecuronium,Atracurium,Rocuronium
c) Short acting : Mivacurium
2. Depolarizing blockers
Succinylcholine(SCh., Suxamethonium),
Directly acting agents
Dantrolene sodium,Quinine

Neuromuscular blocking agents
 Curare – it is generic name for certain plant extracts used by south
American tribal's as arrow poison for game hunting. The animals got
paralysed even if not killed by the arrow.
 Natural source of curare are Stychnos toxifera,
Chondrodendron tomentosum and related plants.

Mechanism of action
The site to action of both competitve and depolarizing blockers is the
endplateof sketal muscle fibers.
Competitive block ( nondepolarizing bock)
This is produced by curare & related drugs. The competitive blockers
have affinity for nicotinic (Nм) cholinergic receptors at muscle
endplate but have no intrinsic activity.
 Nм receptor is a protein with 5 subunits (α2 β € or γ & δ ) which are
arranged like rosette surrounding the sodium channel .
 The two α subunits carry 2Ach binding sites; these have negatively charged
groups which combine with cationic head of Ach-→opening of sodium
channel.
 Most of the competitive blockers have two or more quaternary sodium
atoms which provide the necessary attraction to the same site, but the bulk
of the antagonist molecule does not allow conformational changesin the
subunits needed for opening the channel.
 Ach released from the motor nerve endings is not able to combine with its
receptors to generate endplate potential.(EPP) and muscle fails to contract
in response to nerve impulse

Depolarizing block
 Decamethonium and SCh have affinity as well as
submaximal intrinsic activity at the Nм cholinoreceptors.
 They depolarize muscle endplates by opening sodium
channels and initially produce twitching and
fasciculations.
 These drugs do not dissociate rapidly from the receptor →
induce prolonged partial depolarization of the region
around muscle endplate →Na ⁺ channels get
inactivated→Ach released from motor nerve endingsis
unable to generate propagated muscle action potential
(MAP )→flaccid paralysis in mammals.

Actions
 Skeletal muscles- intravenous injection of
Nondepolarizing blockers rapidly produces muscle
weakness followed by flaccid paralysis.
 Small fast response muscles are affected first . and spreads
to hands, feet, arm, legs, neck, face, trunk—finally
intercostals muscles-diaphram, and then respiration stops.
 Recovery occurs in the reverse sequence, diaphramatic
contractions reduce first.
 Depolarizing blockers typically produce fasciculations
lasting for few seconds before inducing flaccid paralysis.

 2.Autonomic ganglia- because the cholinergic receptors in
autonomic ganglia are nicotinic, competitive neuromuscular
blockers produce some degree of ganglionic blockade.SCh
may cause ganglionic stimulation.
3.Histamine release- d-TC releases histamine from mast
cells resulting in hypotension, flushing, bronchospasm and
increased respiratory secretions.
4. CVS
d-tubocurarine produces significant fall in the BP.
This is due to
 Ganglionic blockade,
 Histamine release &
 Reduced venous return – a result of paralysis of limb and
respiratory muscles.

5.GIT
 The ganglionic blocking activity of competitive blockers may
enhance postoperative paralytic ileus after abdominal
operations.
6. CNS
 All neuromuscular blockers are quaternary compounds- do
not cross blood- brain barrier, and no side effects.

Comparative properties of neuromuscular blocking
drugs.
Drug Dose (mg/kg) Onset (min) Duration (min) Histamine
release
Ganglionic block Vagal block
Long acting
d-Tubocurarine 0.2-0.4 4-6 30-60 +++ ++ ±
pancuronium 0.04-0.1 4-6 40-80 ± ±,st. +
Doxacurium 0.03-0.08 4-8 60-120 + - -
Pipecuronium 0.05-0.08 2-4 50-100 ± - -
INTERMEDIATE
ACTING
Vecuronium 0.08-0.1 2-4 30-60 ± ±
Atracurium 0.3-0.6 2-4 20-35 + - -
Rocurorium 0.6-0.9 1-2 25-40 - - ±
Short acting
Mivacurium 0.07-0.15 2-4 12-20 + - -
Succinylcholine 0.5-0.8 1-1.5 3-6 ++ st st

Pharmacokinetics
 All neuromuscular blockers are quaternary compounds -
not absorbed orally.
 So given by i.v
 SCh is rapidly hydrolysed by plasma pseudocholinesterase
 Some patients have genetically determined abnormality or
deficiency of pseudocholinesterase. in them, SCh causes
muscle paralysis and apnoea lasting for hours.

TOXICITY
 Respiratory paralysis and prolonged apnoea is the most important
problem
 Flushing can occasionally occur with attracurium and mivaruim.
 Fall in BP and cardiovascular collapse can occur , specially in
hypovolemic patients.
 Cardiac arrhythmias and even arrest have occurred, especially with SCh..
 Precipitation of asthma with histamine releasing neuromuscular
blockers.
 Postoperative muscle soreness after SCh

USES
 Most important use of neuromuscular blockers is as adjuvants to general
anaesthesia; adequate muscle relaxation can be achieved at lighter planes.
 They are specially valuable in abdominal and thorasic surgery. In
dentistry they may be needed for setting of mandibular fractures.
 Succinylcholine is employed for brief procedures, e.g. endotracheal
intubation, laryngoscopy, reduction of fractures and to treat
laryngospasm.
 Convulsions and trauma from electroconvulsive therapy can be avoided
by the use of muscle relaxants.
 Severe cases of tetanus and status epilepticus, may be paralysed by a
neuromuscular blocker.

DIRECTLY ACTING MUSCLE RELAXANTS
Dantrolene
 This different from neuromuscular blockers both in chemical &
pharmacologically.
 It does not affect neuromuscular transmission or MAP, depolarization
triggered release of Ca ²⁺ from sarcoplasmic reticulum is reduced.
 Orally it reduces spasticity in upper motor neurone disorders, hemiplegia,
paraplegia, cerebral palsy and multiple sclerosis.
 IntraVenously it is the drug of choice for malignant hyperthermia which is
due to persistant release of Ca ²⁺ from sarcoplasmic reticulum
Side effects
 Muscular weakness
 Troublesome diarrhoea
 Liver toxicity in long term usage

Quinines
 This antimalarial drug increases refractory period & decreases motor
endplates exitibility
 Abolishes nocturnal leg cramps in some patients when taken during
bed time
 Muscle tone in myotonia is reduced.

CENTRALLY ACTING MUSCLE RELAXANTS
 These drugs which reduce skeletal muscle tone by a selective action in the
cerebrospinal axis, with out altering consciousness.
 They selectively depress spinal and supraspinal polysynaptic reflexes
involved in the regulation of muscle tone with out significantly affecting
monosynaptically mediated stretch reflex.
 Polysynaptic pathways in the ascending reticular formation which are
involved in the maintenance of wakefulness are also depressed to a lesser
extent.
 All centrally acting muscle relaxants do have some sedative properity and
they overlap with antianxiety drugs.
 They have no effect on neuromuscular transmission and on muscle fibres

CLASSIFICATION
Mephenesin group;
 Mephenesin
 Carisoprodol
 Chlorzoxazone
 Methocarbamol
Benzodiazepines
 Diazepam & other
GABA derivatives
 Balcofen
Central α₂ agonist
 Tizanidine

MEPHENESIN
 It was the first drug found to reduce muscle tone by depressing spinal
internuncial neurons, which modulate polysynaptic reflexes that
maintain muscle tone.
 It is not used clinically due to its toxicity.
 Its congeners like carisoprodol, chlorzoxaxone, chlormezanone &
methocarbamol have low toxicity and are used for musculoskeletal
disorders associated with spasm.
 They are often combined with NSAIDs.
Side effects
 Gastric irritation
 Sedation

DIAZEPAM
 It is the prototype of benzodiazepins which act in the brain on specific
receptors enhancing GABAergic transmission.
 It reduces muscle tone by supraspinal than spinal action
 It is valuable particularly in spinal injuries & in tetanus,& is popular for
rheumatic diseases associated with muscle spasm
Side effect
 Sedation

BACLOFEN
 It is an analogue of the inhibitory transmitter GABA
 Act as selective GABA receptor agonist.
 The primary site of action is in spinal cord where it depresses both
polysynaptic & monosynaptic reflexes.
 It produces muscle weakness.
 Reduces spasticity in many neurologic disorders like multiple sclerosis.
Amyotrophic lateral sclerosis, spinal injuries & in flexar problems.
 Inefective in stroke, cerebral palsy, rheumatic and traumatic muscle
spasms & parkinsonism.

TIZANIDINE
 Recently introduced clonidine congener is a central α₂
adrenergic agonist- inhibits release of excitatory amino
acids in spinal interneurons
 Inhibits polysynaptic reflexes
 Reduces muscle tone & frequency of muscle spasms
without reducing muscle strength.
 Indicated in spasticity due to neurological disorders, & in
painful muscle spasms of spinal origin.
 Side effects
 Dry mouth
 Drowsiness
 Night time insomnia & hallucinations
 Dose dependent elevation of liver test values have been
noted

USE OF CENTRALLY ACTING MUSCLE RELAXANTS
 ACUTE MUSCLE SPASMS
 Overstreching of a muscle, tearing of ligaments and tendons,
dislocation,fibrisitis, bursitis etc cause painful spasm of muscles.
 The mephenesin like & BZD muscle relaxants are often combined with
analgesics.
 They may help to relieve trismus after dental procedures.
 Torticollis , lumbago, backache, neuralgias in the same way as acute
muscle spasm.
 Anxiety & tension associated with increased tone of muscles.

 Spastic neurological diseases like hemiplegia, paraplegia, spinal
injuries,multiple sclerosis are little bit benefited by baclofen, diazepam,
tizanidine& dantrolene.
 Tetanus
Diazepam is most commonly infused.
Methocarbamol is alternative.
 Electroconvulsive therapy
Diazepam may be used to suppress convulsions
 Orthopaedic manipulations may be performed under influence of
diazepam or methocarbamol given i.v

Comparative features of centrally acting and
peripherally acting muscle relaxants
Centrally acting Peripherally acting
 Decrease muscle tone
without reducing voluntary
power
 Selectively inhibit
polysynaptic reflexes in CNS.
 Cause some CNS depression
 Given orally and sometimes
parenterally
 Used in chronic spastic
conditions,acute muscle
spasms, tetanus
 Cause muscle paralysis,
voluntary movements lost.
 Block neuromuscular
transmission
 No effect on CNS
 Practically always given i.v
 Used for short term
purposes(surgical operation)

Thank you

Indian Dental Academy's Guide to Skeletal Muscle Relaxants

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