Neuro Muscular Blocker

ACETYLCHOLINE

NERVE IMPULSE
ACETYLCHOLINE

MYONEURAL JUNCTION

JUNCTIONAL CLEFT

FIXED AT LIPOPROTEIN RECEPTORS

ON THE JUNCTIONAL FOLD AT THE
END PLATE MEMBRANE

PERMITS ENTRY OF SODIUM

EXIT OF POTASSIUM

DEPOLARIZATION
Ca++ enters nerve terminal

Increased permiability of special

sodium channels in the neuro muscular
Junction is the trigger which leads to
The propagating of action potential

Na enters fibers K + leaves

Action potential proceeds
A change in 20 MV is adequate to
Initiate this process

Synthesis

Acetylcholine is synthezised in
Axoplasm of nerve terminal from
Choline obtained from E.C.F
And transferred to vesicles ready
For use

Hydrolysis

By cholin esterase in the region of

The motor end plate, so that when the
Exited muscle fibre has come out of
Its refractory state, it will not become
Excited again by the depolarized end
Plate, unless a new nerve impulse has
arrived and released a new supply of
acetylcholine

Receptors at neuro muscular

junction

Post junctional receptors

Size 8-9 nm
The mouth is surrounded by 5 proteins
2 alpha proteins are cholinoceptors which
respond to depolarizing relaxants, causing
the other 3 sub units to rotate to a new
conformation with opening of the channels
Na++ and Ca++ moves in
K+
moves out

 Non Depolarizer blocks the Alpha units

Preventing Acess of Acetyl Choline
Blocked the channels closed
Depolarizers blocked the channel open
Initial Stimulation muscle fasciculation

Pre junctional receptors

Control ion channel spesific for Na++
which is responsible for synthesis and
mobilization of transmitter

Extra junctional receptors

Appear all over the surface of muscle fibre when
the muscle is denervated or deprived of nerve
stimulation by injury, stroke, disuse
Similar but more responsive than junctional
receptors to depolarizing agents and less
responsive to non depolarizing agents
Suxamethonium causes substantial flows of ions
across the membrane, producing Hypercalemia
which is difficult to supress by prior non
depolarizing drugs

Pharmacokinetics
Non depolarizers
Poorly bound to plasma protein
Eliminated unchanged by the liver excepting atracurium,
and to a smaller extent by gall bladder
Biliary excretion increase in renal failure
The drugs are concentrated in the liver, kidney, cartilage
Early hepatic uptake lowers plasma concentratic of these
drugs except gallamin & atracurium
These pharmacokinetics are altered in liver disease,
increasing terminal elimination half time by about 50%

Pharmacodynamics
Effects on motor end plate
Preventing absorbsion of acetylcholine to
cholinergic receptors prevent the changes
in the end plate which cause muscular tone
and contraction

Effects on respiration
Cause paralysis of muscle of respiration
Causing square wave respiration
The diaphragm being less sensitive than other
is the last one to be paralysed

 Effects on circulation

Turbocurarine
Pancuronium
Tachycardia
Skin flushing

:Hypotension
:Hypertension
:Gallamine
: Atracurium

Allergic effect
Any of these drugs may cause histamine release at the first
injection
Turbocurarine
:The most likely
Vercuronium
:The least likely
A second injection in the same day will not do so (owing to the
great rapidity which histamine release develops tachyphylaxis)

 Gastro Intestinal System

The cardiac sphincter is probably not relaxed
completely and still has an opening pressure

Choice of non depolarizers

1. Renal failure

Vercuronium
Atracurium

2. Hepatic failure

Atracurium

3. Mysthenia Gravis

1/10th dose of atracurium

4. Arterial surgery to maintain arterial

pressure

Pancuronium

5. Reduced blood pressure

Turbocurarine

6. Obstetrics

Any relaxant except gallamine

7. Short cases

Atracurium

8. Crash induction

Alcuronium
Vercuronium

Sign of incomplete reversal

Shallow respiration
Jerky respiration
Tracheal tug and see saw respiration as the
abdomen moves out, the chest moves in
Cyanosis
Restless, frightened, struglling patient who says
that he cannot breathe
Diplopia
Inability to raise head/extrude tongue

Management of incomplete
reversal
IPPV is given with a mask an oxygen while the
degree of incomplete reversal is assesed
If mild (T4/T1 ratio >50%, respiration is almost
adequate, more neostigmine or other
anticholinesterase is given
If severe (T4/T1 ratio <50%, respiration is
obviously in adequate) the patient is sedated
(e.g with diazepam), intubated and IPPV
continued with a ventilator for at least an hour,
acid base balance determined and corrected
serum electrolyte estimated and normalized re
assesment using nerve stimulators

 A Diuresis is promotes to reduce plasma

concentration of the drugs
Alternative diagnosis are considered

Overdose of inhalation agents opioid, barbiturate

Renal failure
Botulism
Myasthenia gravis
Myasthenic syndrome
Adrenal failure
Hypothermia

The ideal muscle relaxants

Non depolarizers
Rapid onset
Short duration of action
Rapid recovery
Non cummulative
No cardiovascular side effects
No histamine release
Reversible
High potency
Pharmacological inactive metabolites

Side effects of depolarizing neuro

muscular blocking agents

Muscle facilitation
Post operative muscle pain
Hyperkalemia
Increased intra ocular pressure
Increased intra gastric pressure
Increased intra cranial pressure
Cardiovascular effects

Disadvantages of non depolarizers

Slow onset of action

Long duration of action
Slow recovery
Cummulation
Cardiovascular side effects
Histamine release

Hyperkalemia in succynylcholin
Massive burns especially in children
Massive muscle trauma
Lower motor neuron disease &
denervation of motor nerves
E.G : Guillain Barre Syndrome
Acute spinal cord comression
Rapid onset of demyelinating disease of
the motor nerves and other neuropathies

 Upper motor neurone lesions

E.G : Cerebro Vascular Accidents
Encephalities
Brain injury
Abdominal infection
Renal disease

 Atypical serum cholin esterase

Homozygote
Need heparinized, blood sample & full clinical history

Dehydration & electrolyte imbalance

Leading ti development of dual block at a very early stage

Over dose
More than 1 G in an infusion
Tachyphylaxis may occur

Low serum cholinesterase in blood

Seldom causes prolonged apnoe if 50 MG is not exceeded
Not happened when serum cholinesterase level > 25 units
May be reversed by blood transfusion containing 30 MG
cholinesterase

Excessive formation of succynyl mono choline

Phase II (Dual block)

Central depression of respiratory centre

Narcotic analgesic
Thiopentone
Volatile anesthetics

Hypocapnia
Respiration will reccomence if blood level is allowed to rise
Unlikely in practice can cause ventricular fibrillation

Hypercapnia
Unlikely in practice can cause ventricular fibrillation

Depression of Hering Breuer mechanism

During controlled respiration

Reflex laryngeal apnoa

Presence of tracheal tube

Head injury & acute rise of intra cranial pressure

Moribundity
Gravely ill patients it is wise not to about voluntary respiration

Metabolic acidosis
Mechanism not understood

Cardiocaskular effects of neuro

muscular blocking agent

Ganglionic blockade
Blockade of cardiac muscarinic receptors
Nor adrenalin
Stimulation of nor adrenalin release
Histamin release

Characteristic of muscle relaxants

Non depolarizers

Depolarizers

Do not cause muscle fasciculation

Cause muscle fasciculation

Relatively slow onset (1-5)

Rapid onset

Reversed by neostigmin and other anti cholin

esterase

The depolarized muscle fibers are unresponsive

to other stimuli

The sodium channel are blocked closed

The sodium channels are blocked open

Potentiated by volatile agents ang Mg++

Potentiated by Isoflurane, enflurane,

acetylcholine, respiratory alkalosis, hypothermia
and Mg++

In partial paralysis neuro muscular monitoring

shows: a. fade; b. post tetanic fascilitation; c.
depression of muscle twitch

In partial paralysis neuro muscular monitoring

shows: a. no fade; b. deoression of muscle
twitch; c. no post tetanic fascilitation

Acidosis increase duration and degree of non

depolarizing block

Antagonized by ether, halothane, acidosis and

non depolarizing relaxants

Slow dissociation constant at receptors

Fast dissociation constant at receptors there is

little or no bond between drug and receptors

Patient who is sufficiently

recovered not totally recovered
Ability to sustain 5 second head lift & hand
grasp & tongue protrusion
Ability to cough and clear secretions
Vital capacity 10-20 )L/KG BW
Inspiratory force at least 25 cm H2O
Respiratory rate less than 30 /min

Clinical sign related to receptors

occupied
Clinically
normal

% receptor still
occupied

Nerve
stimulator

Tidal volume

75-80

Sustain T 30

Efr & vital

capacity

70-75

Normal TOF

Inspiratory force 50

Sustain T 100

Head lift & hand 33

grip 5 second

Sustain T 200