This document discusses neuromuscular blockers (muscle relaxants) including their physiology, classification, and role in surgery. It describes how muscle relaxants work by blocking acetylcholine receptors at the neuromuscular junction, classifying them as depolarizing or non-depolarizing. Specific muscle relaxants are outlined, their mechanisms of action, durations, and side effect profiles. The document also briefly discusses centrally-acting muscle relaxants and direct acting drugs like dantrolene. Choice of muscle relaxant depends on factors like required duration, excretion route, and side effect risks.

1. Neuromuscular blocker
(Muscle Relaxants)
Objectives
1. Physiology of neuromuscular junction
2. Muscle relaxants definition
3. Classification of Muscle Relaxants
4. Role of MR
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2. October 13
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3. Skeletal muscle fibre
Motor unit =
Motor neurone
Motor axon
+ branches
+ terminals
All muscle fibres to which it connects
Motor
neurone
One motor neurone has exclusive
Control of many muscle fibres
eg 10 oculomotor,
1000 biceps
One muscle fibre innervated by
one motor nerve terminal
Next slide

4. Muscle Relaxants: Definition :
Drugs that decrease muscle tone
• Spasmolytics :
• Neuromuscular
blockers (NMB’s) :
Drugs that used to relieve
muscle spasm & bring
them from hypertonic
state to normal muscle
tone.
Drugs that completely
paralyze skeletal muscles
(from normal tone to zero)
by interfering with
acetylcholine at
neuromuscular jnx.
NOT DISCUSSED
antispasmodics, vasodilators, Bronchodilators
 IMPORTANT IN SURGERIES
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5. Role of NMB ‘s in surgery:
 NMB’s are co-administrated with anesthetics in the induction
phase to induce muscle paralysis (Abdominal wall & lower
limbs)
 facilitate the surgery, especially intra-abdominal and intrathoracic surgeries
 facilitate endotracheal intubation.
 Control convulsion Electroshock therapy in psychotic patient
 Relieve of tetanus and epileptic convulsion
• BUT bcz NMB may paralyze muscles required for breathing,
mechanical ventilation should be available to maintain
adequate respiration.
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6. Sequence of skeletal muscle paralysis
Paralyzed as follow:
– Small rapidly contracting muscles of face, eye, Jae,
toes and larynx
– Larger muscles like Limbs, Neck, Trunk,
– Finally Intercostals and lastly diaphragm.
Recovery is in reverse.
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7. Skeletal muscle relaxants
A. Nicotinic (Muscle) receptor blockers – Peripherally
B. Centrally acting muscle relaxants
C. Directly acting muscle relaxants

8. Skeletal muscle relaxants
• Skeletal muscle relaxants block peripherally at the
neuromuscular junction (NM receptor of Ach – Muscle).
• Types of Skeletal muscle relaxants:
Competitive (Non-depolarizing)
Non-competitive (Depolarizing)

9. A. Non-depolarizing agents (Competitive blockers).
Mechanism of action :
• These have an affinity for the Nicotinic (NM) receptors at the
muscle end plates but have no intrinsic activity.
• The antagonism is surmountable by increasing the conc. of
Ach.

10. Characteristic series of potential changes due to a conducted
stimulus when an axon is stimulated.
Action Potential

11. Depolarizing block ( Non-competitive ) :
 Succinylcholine have affinity and sub maximal intrinsic
activity at NM receptors.
 They open Na channels which cause initial twitching and
fasciculation. (fasciculation or "muscle twitch)
 It does not dissociate rapidly from the receptors resulting in
prolonged depolarization and inactivation of the Na +
channels

12. • Phase –I Block
• Phase –II Block

14. Skeletal muscle relaxants
• Neuromuscular blockers
– Non - depolarizing ( competitive )
• Long acting : d-TC,Pancuronium, Pipecuronium, Gallamine
(Kidney Excretion)
• Intermediate : Vecuronium, Rocuronium, Atracurium
(eliminated by liver)
• Short acting : Mivacurium, Ropcacuronium
(Inactivated by plasma cholinesterase)
• Depolarizing blockers : (Non-competitive)
• Succinylcholine (Suxamethonium)

15. Skeletal muscle relaxants
Pharmacokinetics :
• Most peripheral NM blockers are quaternary
compounds
• Not absorbed orally.
• Administered intravenously.
• Do not cross blood brain barrier or placenta (Except
Gallamine)
• SCh is metabolized by Pseudocholinesterase.

16. d – Tubocurarine
•
•
•
•
More potent than gallamine
Long duration of action ( 1 - 2 hr. )
Eliminated by kidney 60% - liver 40%.
Histamine releaser
• Bronchospasm
• Hypotension
• Blocks autonomic ganglia (Hypotension)

17. Atracurium
• As potent as curare (1.5)
• Has intermediate duration of action (30 min).
• Eliminated by non enzymatic chemical
degradation in plasma
• used in liver failure & kidney failure, neonate (
drug of choice ).
• Liberate histamine (Hypotension ).

18. Pancuronium
•
•
•
•
More potent than curare ( 6 times ).
Excreted by the kidney ( 80 % ).
Long duration of action.
Tachycardia
– Antimuscarinic action

19. Gallamine (Flaxedil)
• Less potent than curare ( 1/5 ).
• Metabolized mainly by kidney 100% # in
renal failure
• Long duration of action.
Tachycardia due to :
• Atropine like action.
• Release of NA from adrenergic nerve
endings

20. Reversal of Blockade (N.D)
• Neostigmine and Pyriodostigmine antagonise
• Inc. availability of Ach by Inhibiting AChE
• Direct N action at motor end plate
• Use: If longer acting or intermediate acting

21. Autonomic effects
• Autonomic ganglia (nicotinic) & post
ganglionic parasympathetic (muscarinic)
receptors
• Succinylcholine: salivary secretions,
bradycardia
• d-Tubocurarine - ganglionic blockade
• Pancuronium - vagolysis

22. Histamine Release
Hypotension (Histamine release)
• d.Tubocurarine
• Mivacurium
• Atracuronium
H.R
• Pancuronium
• Gallamine

23. Skeletal muscle relaxants
Duration (mins.)
Pancuronium
40-80
Pipecuronium
50-100
Vecuronium
20-40
Atracurium
20-40
Rocuronium
20-40
Mivacuronium,
Rapacuronium
Succinyl choline
10-20
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24. Synergists & Antagonist
• Anti AChE antagonise
• Inhalational G.A  stabilize post junctional
membarane Synergetic
• Aminoglycoside syner
• Ca++ channel blockers  Syner

25. Deploarizing PK
•
•
•
•
•
Quaternary ammonium groups
IV
Doesn’t cross BBB, Palcental B.
Sch 5-10min (ChE)
Stimulates ganglion agonist action on NN

26. Skeletal muscle relaxants
Depolarizing block (Non-competitive) :
Succinylcholine
•
•
•
•
•
•
•
It causes muscle pain.
It causes hyperkalemia. (inc. k efflux depolarizing)
Malignant Hyperthermia.
Prolong apnoea
Inc. Intra gastric pressure
CVS arrhythmia
IOP # glaucoma

27. Centrally acting
• Cerebrospinal axis without altering
consciousness.
• Mode of action is non specific
• Depressants of poly synaptic reflexes ( Spinal
& Supra spinal  regn of muscle tone)
• Mephensin group: Carisoprodol, Chlorozoxazone,
Chlormezanone
• Benzodiazepine group: Diazepam & Clonazepam
• GABA derivative: Baclofen

29. • Chlorzoxazone: Long acting (8-12hr)Slow onset
• Carisoprodol: Intermediate action + analgesic,
antipyretic, anti muscarinic action
• BZD
• GABA derivative: GABAB – G protein
• Inc. K+ conductance, dec. Ca++ conductance

30. Skeletal muscle relaxants
Directly acting muscle relaxants :
Dantrolene :
Depolarization triggered release of calcium from the
sarcoplasmic contraction is blocked / reduced.
• Dantrolene is used orally/ i.v to reduces spasticity in
hemiplegia and cerebral palsy.
• It is the drug of choice – malignant hyperthermia

31. Active Zones

32. • Miscellaneous group:
• Quinine: Dec. excitability of motor end plate
• Botulinum: Prevents Ca dependent release of
Ach ( Inhibits Ach release)

33. Choice of muscle relaxants:
Consideration for choosing a muscle relaxant
include:
* Duration of action required
* Route of excretion
* Tendency to release histamine
* Cardiopulmonary side effects
* The ability to reverse the blockage
* Contraindication to any specific muscle relaxant.
* Cost
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