Skeletal muscle relaxants

WHERE?
• Neuromuscular blocking agents
INTRODUCTION - used in conjunction with
Drugs that act peripherally at
general anaesthetics - muscle
n e u ro m u s c u l a r j u n c t i o n o r
relaxation for surgery
muscle fibre itself or centrally in
cerebrospinal axis to reduce
• Centrally acting MR - for
muscle tone
pa i n f u l m u s c l e s p a s m s a n d
spastic neurological conditions
Centrally Acting Skeletal Muscle Relaxants:
Most of the centrally acting skeletal muscle relaxants are available with NSAIDS. All of them cause certain degree
of sedation. They act by depressing polysynaptic pathways in spinal and supra-spinal sites. They are used to
reduce spasm associated with cerebral palsy, trauma, sprain, tetanus, multiple sclerosis, etc

1.Thiocolchicoside:
• derived from colchicoside.
• Has anti-inflammatory & analgesic action also.
• Used for painful muscle spasm like torticollis and
sprains
• Has GABA-A & glycine antagonist action.
• A/E-Photosensitivity
2.BACLOFEN
• Selective GABA-B receptor agonist
• depresses both polysynaptic and monosynaptic reflexes
• Sedation is minimal
• Decrease spasticity in many neurological disorders like
multiple sclerosis, amyotropic lateral sclerosis, spinal
injuries and flexor spasm
• A/E - drowsiness, mental confusion, weakness and ataxia
3.Central a2 agonist -Tizanidine
Tizanidine

• clonidine congener, with no effect on BP.

• Central a2 agonist 6.CHLORZOXAZONE
• Inhibits spinal interneurons. • Pharmacologically similar to mephenesin
• Used in spasticity due to multiple sclerosis, ALS, • Better tolerated orally
spinal injuries
7.CHLORMEZANONE
4.MEPHENESIN
• Has antianxiety and hypnotic
• Not used clinically - because orally it causes marked gastric
• Used for tension states associated with increased muscle tone
irritation, and injected i.v., it causes thrombophlebitis,
haemolysis and fall in BP
• Included in counterirritant ointments 8.METHOCARBAMOL
• Less sedative
• Orally used in reflex muscle spasms
5.CARISOPRODOL • Injected i.v. for orthopedic procedures and tetanus
• Favourable muscle relaxant:weak analgesic, antipyretic and
anticholinergic properties 9.DIAZEPAM
• Used in musculoskeletal disorders associated with muscle • Muscle relaxant:sedative activity ratio is low
spasm • No gastric irritation occurs
• Uses - spinal injuries, tetanus, rheumatic disorders
with spasm
Neuromuscular Blockers:
SKELETAL MUSCLE:
Nondepolarising blockers - rapid muscle weakness followed by flaccid paralysis;
smaller to larger muscles
Depolarising blockers - fasciculations before flaccid paralysis
AUTONOMIC GANGLIA:
• Competitive blockers produce some degree of ganglionic
blockade through N~ receptors
• d-Tc - maximum blockade
• SCh - ganglionic stimulation by agonistic action
CVS:
• d - TC produces fall in BP by ganglionic block
Histamine release
• Sch - Bradycardia; prolonged administration;
arrhythmias and arrest
CNS:
• quaternary compounds - do not cross BBB
• no central effects on i.v. administration
 DEPOLARISING BLOCKERS:
SUCCINYLCHOLINE:
• SCh is rapidly hydrolysed by plasma pseudocholinesterase
• Some patients have genetically determined abnormality (low affinity
for SCh) or deficiency of pseudocholinesterase → prolonged phase II
blockade resulting in muscle paralysis and apnoea lasting 4-6 hrs
• Prolonged apnoea treated only by mechanical ventilation
• Succinylcholine produces spastic paralysis in birds:

Directly Acting Skeletal Muscle Relaxant:

Dantrolene:
Inhibits release of Ca2+ from sarcoplasmic reticulum by binding to ryanodine receptors(RYR1)
DOC for malignant hyperthermia
Can also be used for neuroleptic malignant syndrome
ADRs - hepatitis, muscle weakness

Quinine:
Decreased xcitability of motor end plate
Uses -rarely - nocturnal leg cramps, myotonia congenita

Botulinum Toxin A:
Source: Produced by Clostridium botulinum
Uses: Injected intradermally for anti-wrinkle treatments and into muscles for spasticity or dystonia.Also injected into salivary
glands for sialorrhea under ultrasound guidance.
 Competitive Blockers (Nondepolarizing Blockers):
Steroidal derivatives: Benzylisoquinoline derivatives:
Vecuronium ORDER OF RELAXATION:
Mivacurium,
Rocuronium 1st - small muscles - face, eye
Atracurium,
Rapacuronium 2nd - medium - trunk, limbs, neck
Cisatracurium,
Pancuronium 3rd - large - intercostals,diaphram
Doxacurium
Pipecuronium

PHARMACOKINETICS:
• Only given IV – not absorbed orally
• Do not cross BBB
• Duration of action much shorter in
ADVERSE EFFECTS:
respiratory alkalosis ← hyperventilation Benzylisoquinoline derivatives
• Atracurium & Cisatracurium – Ho man’s (1)release histamine
elimination (2) ganglion block - C/I
• Mivacurium hydroylsed by in asthma/ COPD
pseudocholinesterase – similar to SCh (3) Atracurium metabolized to laudanosine
• Muscles with higher blood flow receive (glycine antagonist) seizures
more drug and are affected earlier (4)Pancuronium – ↑ BP (vagolytic) & ↑ HR,
↑ arrhythmogenic action of halothane
 SHORT ACTING:
Gantacurium - shortest acting & fastest
onset of action – inactivated by addition of LONG ACTING:
cysteine – less histamine release
Mivacurium - metabolized by Doxacurium – longest acting & most potent
pseudocholinesterase & is shortest acting Pancuronium – 2nd longest acting, ↑BP
(after Rapacuronium) (vagolytic) & ↑HR, ↑arrhythmogenic action
Dose and speed of injection related transient of halothane restricted to prolonged surgeries
cutaneous flushing. Pipecuronium – derivative of Pancuronium
Rapacuronium – shortest acting – severe w/o vagolytic
bronchoconstriction – withdrawn action
D-TUBOCURARINE (CURARE)
INTERMEDIATE ACTING: • drug known to block the NMJ
Vecuronium – preferred for cardiovascular • 1st known as South American arrow
surgery. C/I liver disease poison used for
Atracurium & Cisatracurium – Ho hunting
man’s elimination • ACh is the agonist, whereas d-TC is the
Atracurium - metabolized to laudanosine antagonist at Nm receptors.
(glycine antagonist) seizures • Curariform drugs competitively
• Preferred muscle relaxant for liver/kidney antagonize the actions of ACh at the Nm
disease patients as well as for neonates and • Anticholinesterases (neostigmine or
the elderly. edrophonium) are used to reverse the
Rocuronium – fastest onset of action & effects of competitive blockers by
least potent.Preferred for intubation as increasing the concentration.
alternative to SCh.Used to facilitate
mechanical ventilation in ICUs
SUGAMMADEX:
• Novel reversing agent developed for terminating the action of
nondepolarizing muscle relaxants.
• Sugamadex- i.v. reverses rocuronium block within 3 min
• A/E - mild precordial pain, nausea, alteration of taste and rarely
allergy

Toxicity of Neuromuscular Blockers:

- Respiratory paralysis & prolonged apnoea

- Flushing (common with d-TC, occasional with
atracurium/mivacurium)
- Fall in BP & cardiovascular collapse (especially in
hypovolemic patients, less likely with newer drugs)
- Cardiac arrhythmias & arrest (especially with SCh, risk in
digitalized patients due to K+ release)
- Hyperkalemia (especially in burn/soft tissue injury patients
with SCh)
- Asthma precipitation (due to histamine release)
- Postoperative muscle soreness & myalgia (after SCh)
- Malignant hyperthermia (triggered by SCh with fluorinated
anaesthetics)
QUESTIONS:
1.The site of action of d-tubocurarine is: 4.Which of the following drugs undergoes 'Hofmann' elimination
A. Spinal internuncial neurone A. Succinylcholine
B. Motor nerve ending B. Pancuronium
C. Muscle end-plate C. Vecuronium
D. Sodium channels in the muscle fibre D. Atracurium

2.Select the skeletal muscle relaxant that is commonly used for 5.The neuromuscular blocker that does not need reversal of
endotracheal intubation despite causing histamine release, Kt action by neostigmine at the end of the operation is:
efflux from muscles and cardiovascular changes: A. d-Tubocurarine
A. Pipecuroniun B. Doxacurium
B. Succinylcholine C. Pipecuronium
C. Pancuronium D. Mivacurium
D. Cisatracurium
6.The most rapidly acting nondepolarizing neuromuscular
3.Neuromuscular blocking drugs do not produce central actions blocking agent which can be used as an alternative to
because: succinylcholine for tracheal intubation is:
A. They do not cross the blood-brain barrier A. Rocuronium
B. Nicotinic receptors are not present in the brain B. Pancuronium
C. They are sequestrated in the periphery by tight binding to the C. Doxacurium
skeletal muscles D. Pipecuronium
D. They do not ionise at the brain pH
7.Diazepam is used as a muscle relaxant for:
A. Deep intra-abdominal operation
B. Tracheal intubation
C. Tetanus
D. Diagnosis of myasthenia gravis

8.Dantrolene sodium reduces skeletal muscle tone by:

A. Reducing acetylcholine release from motor nerve endings
B. Suppressing spinal polysynaptic reflexes
C. Inhibiting the generation of muscle action potential
D. Reducing Cal release from sarcoplasmic reticulum in the
muscle fibre

9.Which of the following is a centrally acting skeletal muscle

relaxant:
A. Carisoprodol
B. Dantrolene sodium
C. Quinine
D. Decamethonium
THANK YOU！