1. BY
Dr Oyedepo O. O. (B.Sc.; MBBS; FMCA)
Dept. of Anaesthesia,
College of Health Sciences,
University of Ilorin. Ilorin.
Nigeria.

45. OUTLINE
ANATOMY OF NEUROMUSCULAR JUNCTION
 PHYSIOLOGY OF NEUROMUSCULAR
TRANSMISSION
 FACTORS THAT MAY AFFECT NMT&NMB
 CHARACTERISTICS OF IDEAL MUSCLE
RELAXANT
 CLASSIFICATION OF NMB & DISTINCTION
BTW DMR&NDMR
 INDIVIDUAL AGENT
 REVERSAL OF NMB


46. ANATOMY OF NMJ
Each motor nerve sends processes to each
muscle fiber in the motor unit
 Forming a highly organized and specialized
structure neuromuscular junction, or
motor endplate
 The invagination of the muscle fiber
sarcolemma forms the synaptic trough
 The space between the axon terminal and
invaginated sarcolemma is called the
synaptic cleft


48. THE NEUROMUSCULAR JUNCTION

49. PHYSIOLOGY OF NEUROMUSCULAR
TRANSMISSION

50. FACTORS AFFECTING NMT
Muscle relaxants are potentiated by various factors: Drugs Most of the inhalational anaesthetic agents.
Aminoglycoside antibiotics esp. Gentamycin,
Kanamycin.
β-Blockers
Ca-channel blockers

Electrolytes Depressed Ca++
Raised Mg++
Raised K+
 Acidosis
 Temperature -If T° depressed then Suxamethonium is
potentiated.
-If T° raised then Non-depolarisers are
potentiated

Myasthenia gravis and other inherited muscle
abnormalities e.g. dystrophies, dystonias

51. Muscle contraction is controlled by motor
neurons that release the neurotransmitter
acetylcholine at neuromuscular junctions.
 Acetylcholine then diffuses across the narrow
synaptic cleft and binds to acetylcholine
receptors on the membrane of the muscle cell.
 Opening of ion channels within the receptor
molecules, in such a way that a
depolarizing, synaptic ion current can flow. This
current triggers an all-or-nothing response in the
form of an action potential across the plasma
membrane of the muscle cells.
 The action potential moves out in all directions
from the neuromuscular junctions, resulting in
stimulation of the entire muscle fiber within a few
milliseconds, the contractile mechanism
responds and the fiber contracts


52. DEPOLARIZING NEUROMUSCULAR
BLOCKADE
ACETYLCHOLINE ANALOGUES INTERACT
WITH POSTJXNAL CHOLINERGIC-NICOTINIC
RECEPTOR
 DEPOLARIZATION OF ENDPLATE AND
MUSCLE FIBRE THEN MUSCLE CONTRACTS
 CONTRACTION IS NOT SUSTAINED
 PERSISTENT OCCUPATION OF RECEPTORS,
DEPOLARIZATION, INTERUPTION OF
NEUROMUSCULAR TRANSMISSION
 END RESULT IS MUSCLE PARALYSIS


53. NON-DEPOLARIZING
NEUROMUSCULAR BLOCKADE
COMBINE REVERSIBLY WITH PJXNAL
CHOLINERGIC-NICOTINIC RECEPTORS
WITHOUT OPENING SODIUM CHANNELS
 COMPETING WITH ACETYLCHOLINE
REDUCING THE RECEPTORS AVAILABLE FOR
ACH
 70% OCCUPANCY BLOCK RESPONSE OF
END-PLATE POTENTIAL IN RESPONSE TO A
SINGLE NV IMPULSE -MSC REMAIN INERT
 90-95% OCCUPANCY RESULTS IN COMPLETE


54. CHARACTERISTICS OF IDEAL
MUSCLE RELAXANT
NON DEPOLARZING
 FAST ONSET
 FREE OF CVS SIDE EFFECT
 EASILY ANTAGONISED
 STABLE PHARMACOKINETIC &
PHARCODYNAMIC IN PRESENCE HEPATIC
AND RENAL DISEASES

NO SUCH DRUG YET

55. CLASIFICATIONS
DEPOLARIZING-SUCCINYLCHOLINE,
DECAMETHONIUM(SHORT ACTING)
 NON DEPOLARIZING
-AMINOSTEROIDS(VAGOLYSIS)
.PANCURONIUM
.VECURONIUM
.PIPECURONIUM
.ROCURONIUM
.RAPACURONIUM
-BENZYLISOQUINOLINIUM
.D-TUBOCURARINE
.ATRACURIUM
.DOXACURIUM
.MIVACURIUM
.CIS-ATRACURIUM
.METOCURINE
.GALLAMINE


56. CLASSIFICATION OF NON-DEPOLARIZERS

LONG ACTING
D-TUBOCURARINE
METOCURINE
DOXACURIUM
PANCURONIUM
GALLAMINE
PIPECURONIUM

INTERMEDIATE ACTING
ATRACURIUM
CIS-ATRACURIUM
VECURONIUM
ROCURONIUM

SHORT ACTING
MIVACURIUM
RAPACURONIUM

57. DIFFERENCES BTW DEPOLARISERS AND NON
DEPOLARIZERS
EVOKE STIMULUS
DEPOLARIZING
NON-DEPOLARIZING
TRAIN OF FOUR
CONSTANT BUT
DIMINISHED
FADE
TETANY
CONSTANT BUT
DIMINISHED
FADE
DOUBLE BURST
STIMULATION
CONSTANT BUT
DIMINISHED
FADE
POSTTETANIC
POTENTIATION
ABSENT
PRESENT
NEED NO REVERSAL OF
BLOCK
NEED REVERSAL OF
BLOCK
FASCULATION PRESENT
FASCULATION ABSENT

58. SUXAMETHONIUM
Chemical structure:- 2 molecules of Acetyl Choline
linked together with 2 quaternary amine groups.
 Physical properties:- It is available in 2 forms:
Succinylcholine chloride-Aqeous-Temperate
Succinylcholine bromide-Powder-Tropic

Rapid onset, short duration(3-5mins)
 Indications-To facilitate ETT placement
 Dose-Intubating dose in adult is 1mg/kg
-Xren esp infants is 1.5-2.0mg/kg
 Rapidly hydrolysed by plasma cholinesterase


59. SIDE-EFFECTS
Cardiac arrhythmias-sinus bradycardia, ventricular
premature beats
 Hyperkalaemia esp-massive burns, muscle
trauma, UMNL&LMNL, renal dx and severe abd
infx
 Raised IOP
 Raised ICP
 Raised IGP
 Scoline pain-ambulant and muscular pts
 Anaphylactoid rxn
 Masseter spasm-could erald MH


60. CAUSES OF PROLONGATION OF ACTION IN
PLASMACHOLINESTERASE DEFFICIENCY

PHYSIOLOGICAL

PREGNANCY

CONTRACEPTIVE PILLS

MALNUTRITION

LIVER DX CIRRHOSIS

HEMODIALYSIS

ECHOTHIOPATE (AN EYE DROP)

61. D- TUBOCURARINE
FIRST NMB AGENT USEDD IN ANESTHESIA
 IT CAUSES MS PARALYSIS WITHIN 3 MINS
 DURATION= 30-40 MINS (LONG ACTING)
 CAUSES HYPOTENSION BY 2 MECH
1.SYMPATHETIC GANGLIONIC BLOKAGE
2.HISTAMINE RELEASE
 METABOLISED IN LIVER & EXCRETED BY
KIDNEY


62. PANCURONIUM








IS AN AMINOSTEROID MS RELAXATION WITHIN 2
MIN
RECOMMENDED LOADING DOSE WITHING 0.060.08 MG/KG
INCREMENT OF 0.01-0.02 MG/KG
LARGE AMOUNT BOUND TO PLASMA PROTEIN
DEPENDENT ON RENAL EXCRETION 80%
METABOLISED AND EXCRETED BY THE LIVER
DOES NOT RELEASE HISTAMINE
CVS- INCR BP DUE TO NOR ADRENALINE
RELEASE
- SINUS TACHYCARDA DUE TO ITS

63. GALLAMINE

SOLELY EXCRETED BY THE KIDNEY HENCE
ABSOLATELYCONTRAINDICATED IN RENAL
DISEASE

CROSSES THE PLACENTA HENCE
CONTRAINDICATED IN OBST

Vagolytic, causing early, severe tachycardias

64. ATRACURIUM






Dose
0.3-0.4 mg kg-1 or 30 mg increment 0.080.1mg kg-1
Amps 2.5 ml = 25 mg
Cardiovascularly stable, but larger doses release
histamine with mild hypotension
Breakdown occurs spontaneously and is dependent
on pH and T° (Hoffman degradation).
Hepatic degradation also occurs resulting in the
formation of Laudanosine
Laudanosine is a convulsant in high doses, but
clinically has not been a problem
It is safe in hepatic & renal failure
Non-cumulative, even after prolonged infusions
Similar duration of action to Vecuronium
Expensive

65. CIS-ATRACURIUM

Dose
0,15 mg kg-1 or 10 mg
Amps

5 ml = 10 mg
Features Similar to Atracurium without the
histamine release.

66. MIVACURIUM
Dose 0.15 mg kg-1 or 10 mg
Amps 5 ml = 10 mg and 10 ml = 20 mg
 New on the market
 Much shorter acting than the previous 2 agents (±
10 minutes), with rapid recovery
It will not replace Suxamethonium
 Degraded by plasma cholinesterase (competing
with Suxamethonium) and thus contraindicated
in patients with “Scoline Apnoea”.
 May be used as an infusion
 Expensive


67. VECURONIUM
Dose 0.1 mg kg-1 or 6 mg
Amps 2 ml = 4 mg and 10 ml = 20 mg as a dry
powder needing reconstituting with sterile water
 Cardiovascularly very stable, with occasional
bradycardia
 No histamine release
 Shorter acting (± ½ the duration of the preceding
drugs)
 Hepato-biliary excretion and can thus be used in
renal failure
 Expensive


68. ROCURONIUM







Dose
0,3 - 0,9 mg kg-1 or 20 - 50 mg
Amps 5 ml = 50 mg and 10 ml = 100 mg
New on the market
Low dose provides slow intubation and short duration
(± 15 min)
High dose provides very fast intubation (± 60 - 90 sec)
and long duration
Cardiovascularly stable with a mild increases in heart
rate and blood pressure
Very rapid onset (similar to, but not as predictable as
Suxamethonium), but has an intermediate to long
duration of action.
Undergoes no metabolism and 10ly eliminated by d
liver & slightly by d kidney
Expensive.

69. ALCURONIUM
0,25 mg kg-1 or 15 mg
Amps 2 ml = 10 mg
 Cardiovascularly more stable, with
occasional tachycardia
 Histamine release with possible mild
hypotension.
 Dose

70. DOXACURIUM
Benzylisoquinoline compound closely related to
mivacurium and atracurium
 MOST POTENT CURRENTLY


ONSET-10MIN

DURATION 3HOURS

ELIMINATED UNCHANGED BY THE KIDNEY

SLIGHTLY METABOLISED BY PLASMA
CHOLINESTERASE

71. METOCURINE
BIS-QUARTERNARY AMINE
DERVATIVE OF DTC
PHARMACOLOGY SIMILAR
TO DTC

72. PIPECURONIUM
Elimination depends on renal (70%)
and secondarily biliary (20%).
principal advantage over
pancuronium is its lack of
cardiovascular side effects due to a
decreased binding to cardiac
muscarinic receptors

73. REVERSAL OF NMB




Acetyl Choline is normally degraded in milliseconds by Cholinesterases.
The degradation of Acetyl Choline may be inhibited by the use of an Acetyl
Cholinesterase inhibitors e.g
Edrophonium
Pyridostigmine
Neostigmine
Physiostigmine
Acetyl Choline is the neuro-transmitter at numerous receptors and the use
of an Acetyl Cholinesterase inhibitor will result in an increase in Acetyl
Choline at all cholinergic receptors (pre- and post-ganglionic
Parasympathetic nerves, as well as pre-ganglionic Sympathetic nerves).
The effects of relative overactivity of Acetyl Choline that would result if a
Muscarinic blocker were not given at the same time, includes the following
severe bradycardia
bronchospasm
copious secretions
other parasympathetic effects e.g. increased gut motility, pupil
constriction, etc.
The standard reversal "cocktail" for an adult is therefore a mixture of:Neostigmine 2,5 mg plus Atropine 1,0 - 1,2 mg
or
Neostigmine 2,5 mg plus Glycopyrrolate 0,4 - 0,6 mg
mixed in the same syringe.