SKELETAL MUSCLES

RELAXANTS
Dr. Gita Paudel
Associate Professor
Department of Pharmacology
 INTRODUCTION
•Drugs which are used to reduce unwanted
spasm and, spasticity, or to cause paralysis of the
skeletal muscle without interfering with
consciousness and normal voluntary
movements SKELETAL MUSCLE RELAXANTS
•Act at
* Neuromuscular junction
* Muscle fibre
* Centrally at cerebrospinal axis
 INTRODUCTION
SPASM SPASTICITY
An involuntary Due to increase in
contraction of muscle skeletal muscle tone
or group of muscles associated with
usually accompanied by decrease in skeletal
pain and limited muscle power due to
function. damage to the cortico
motoneuronic
pathways.
 Skeletal Muscle Relaxants

• Drugs acts peripherally at neuromuscular

junction/muscle fiber itself or
• centrally in the cerebrospinal axis to reduce
muscle tone/or cause paralysis
• The neuromuscular blocking agents are used
primarily in conjunction with GA to provide muscle
relaxation for surgery, while centrally acting muscle
relaxants are used mainly for painful muscle
spasms and spastic neurological conditions.
INTRODUCTION
CLASSIFICATION
 CLASSIFICATION:
PERIPHERALLY ACTING SMR
NEUROMUSCULAR DIRECTLY ACTING
BLOCKING AGENTS AGENTS

NON
DEPOLARIZING DEPOLARIZING
BLOCKERS BLOCKERS •Dantrolene
sodium
•Quinine
• Succinylcholine
• Decamethonium
 CLASSIFICATION:
PERIPHERALLY ACTING SMR
 CLASSIFICATION:
CENTRALLY ACTING SMR
PHYSIOLOGY OF SKELETAL MUSCLE
CONTRACTION

NMJ
 PHYSIOLOGY OF SKELETAL MUSCLE
CONTRACTION
Motor nerve impulse
↓
Release of Acetylcholine
↓
Binds with Nm receptors in NMJ
↓
Depolarization & development of end plate potential (EPP) at motor end
plate (mainly due to influx of Na+)
↓
Contraction of skeletal muscle
↓
Ach is rapidly inactivated by cholinesterase leading to repolarization
↓
Muscle is ready for fresh nerve impulse
Neuromuscular Junction (NMJ)

Na+

a
ab
ACH

ACH ACH
ACH ACH
ACH

a
ACH

b
ACH
ACH

a
ACH
Motor neuron ACH
ACH
ACH
a
ba ACHEsterase

Skeletal
Muscle
HISTORY OF SKELETAL MUSCLE RELAXANTS
 PERIPHERALLY ACTING SMR

NON-
DEPOLARIZING
DEPOLARIZING
BLOCKERS
BLOCKERS
NON-DEPOLARIZING NEUROMUSCULAR
BLOCKERS
 Neuromuscular blocking agents
• Block cholinergic transmission between motor nerve
endings and nicotinic receptors on the neuromuscular end
plate
• Acts as agonist and antagonist
• A. Non-depolarizing blockers (Competitive blockers):
prevent the access of Ach to Nm receptor of motor end
plate and prevents depolarization.
• Depolarising blockers (Persistent depolarisers): produce an
excessive depolarization which persists for longer duration
at NMJ primarily because they are resistant to hydrolysis by
true AChE present in synaptic cleft.
 NON-DEPOLARIZING NEUROMUSCULAR
BLOCKERS: MOA
D- TUBOCURARINE (Competitive
blockers)
AT LOW DOSE
Competitively binds with nicotinic
NM receptor
↓
Prevent binding of Acetylcholine
↓
Prevent depolarization
↓
Muscle relaxation
 NON-DEPOLARIZING NEUROMUSCULAR
BLOCKERS: MOA
D- TUBOCURARINE (Competitive blockers)
AT HIGH DOSE
d-tc
↓
Enter the Na+ channel & blocks them
↓
More intense motor blockade
↓
Weakens the neuromuscular transmission
 NON-DEPOLARIZING NEUROMUSCULAR
BLOCKERS: MOA
D- TUBOCURARINE
• Because these agents
compete with Ach at the
receptor without
stimulating it , they are
called competitive
blockers
 REVERSAL OF NON-DEPOLARIZING
NEUROMUSCULAR BLOCKERS
• This blockade can be reversed by : Neostigmine,
pyridostigmine (anticholinesterase)
• They antagonize or reverse the non-depolarizing
neuromuscular blockade by increasing the availability of
Ach, by inhibiting true AChE present in the synaptic cleft.
• USES:
1. To reverse the NM blockade after the surgical
procedure is completed
2. Neostigmine reverse the skeletal muscle paralysis and
is the antidote in curare poisoning (neostigmine)
 D- TUBOCURARINE

Order of muscle relaxation/ paralysis

• Extrinsic eye muscles- neck (muscles of
phonation & swallowing) – face –hands- feet-
limbs- trunk & finally respiratory muscles
(intercostal muscles & diaphragm) are
paralysed
• But recovery occurs in reverse order. The
respiratory muscles are the first to recover.
 D- TUBOCURARINE : ADR

1. Hypotension (due to ganglion blockade & histamine

release)
2. Hypoxia, Respiratory paralysis & prolonged apnea
(treated by artificial respiration and neostigmine may
be used to reverse the skeletal muscle paralysis).
3. Bronchospasm or precipitation of asthma (due to
histamine release)
4. Flushing (due to histamine release)
5. Constipation (due to decrease in the tone and
motility of GIT).
DEPOLARIZING BLOCKERS

SUCCINYLCHOLINE
(SUXAMETHONIUM)
 Succinylcholine
• Ach analogue which is hydrolysed by
pseudocholinesterase but not by true AchE
• On IV dose only a small fraction reaches the
NMJ after being hydrolysed by
pseudocholinesterase. At NMJ it acts like an
excess of Ach and its action persist for longer
duration primarily as it is not degraded by true
AchE.
 SUCCINYLCHOLINE: MOA
• Non-competitive blockers
• Succinylcholine binds to the nicotinic receptor
(Nm) & acts like Ach to depolarize the skeletal
muscle
• Occurs in 2 phases
1. Phase I block
2. Phase II block
 SUCCINYLCHOLINE: MOA
PHASE I inactivation of Na+
SCh bind to the Nm receptor channel
↓
opens Na+ channel ↓
↓ ACH unable to generate
doesn’t dissociate rapidly AP
↓
prolonged persistent depolarization ↓
↓ flaccid paralysis
Twitching of muscle (transient muscle
Fasciculation)

↓
SUCCINYLCHOLINE: MOA
 SUCCINYLCHOLINE: MOA
PHASE II
With continuous binding
of Succinylcholine

membrane repolarizes
but receptor become
desensitized to the
effect of ACh
 Phase I block is rather augmented, not reversed, by AChE
inhibitors like neostigmine.
Phase-II block resembles that of non-depolarizing block and can
be reversed by neostigmine.
 SUCCINYLCHOLINE: MOA
• In man, normally only phase I block occurs.
• Phase II block may be seen when SCh is
injected in high dose or infused continuously
particularly if fluorinated anesthesia have
been used.
• SCh produces phase II in patients with atypical
pseudocholinesterase.
 SUCCINYLCHOLINE
• It is the blocker with rapid onset of action &
shortest duration of action (5-10 mins)
• It is rapidly hydrolysed by plasma
pseudocholinesterase present in the liver and
plasma.
 SUCCINYLCHOLINE: ADR
1. Hyperkalemia
• SCh: efflux of intracellular K+ occurs during
depolarising blockade ↑ plasma K+ level
(hyperkalemia)
• In case of extensive burns, nerve damage, soft
tissue injury: precipitate arrhythmias and even
cardiac arrest
• These cases have freshly denervated muscles & the
Nm receptors show hyper-responsiveness.
 SUCCINYLCHOLINE: ADR
2. Malignant Hyperthermia
• Genetic condition
• Mutation of Ca2+ release channel of
sarcoplasmic reticulum persistent release
persistent contraction ↑ heat production
(hyperthermia)
• Sch will trigger this condition
• t/t : Dantrolene
 SUCCINYLCHOLINE: ADR
3. Prolonged apnoea ( succinylcholine apnoea)
• Persons having atypical pseudocholinesterase
(genetic defect) metabolism of SCh becomes
slow  severe neuromuscular blockade 
respiratory paralysis & prolonged apnea (referred
as succinylcholine apnea)
• No antidote available.
TREATMENT:
• Fresh frozen plasma is infused
• Artificial ventilation till recovery
 SUCCINYLCHOLINE: ADR
4. Increased Intragastric pressure
5. Rise in IOP
6. Postoperative muscle soreness and muscle
pain (myalgia) due to initial fasciculations.
 PERIPHERALLY ACTING DRUGS: USES

1. As an adjuvant to General anesthesia

• To provide skeletal muscle relaxation during
abdominal surgery or thoracic surgery
• To counteract laryngospasm during barbiturate
anesthesia
• To prevent reflex muscle
contractions during surgery
 PERIPHERALLY ACTING DRUGS: USES

2. Succinylcholine: preferred for brief procedures e.g.

endotracheal intubation,
laryngoscopy, bronchoscopy,
reduction of fractures,
dislocations
3. Assisted ventilation: critically ill patients in ICU
often needs ventilatory support which can be
facilitated by continuous infusion of neuromuscular
blockers
 PERIPHERALLY ACTING DRUGS: USES

4. To prevent trauma during Electroconvulsive

Therapy : SCh with diazepam

5. Severe cases of tetanus & status

epilepticus ( not controlled by
diazepam)
 Interaction
• Antibiotics: Aminoglycoside group of
antibiotics themselves produce NMB by
decreasing Ach release. Tetracyclines (by
chelating Ca), polypeptide antibiotics,
clindamycin and lincomycin also synergise
with competitive blockers.
• CCBs potentiate both competitive and
depolarizing neuromuscular blockers.