Neuro Muscular Blocker

8/8/2019 Neuro Muscular Blocker

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Neuro Muscular Blocker


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ACETYLCHOLINE

NERVEIMPULSE

ACETYLCHOLINE

MYONEURAL JUNCTION

JUNCTIONALCLEFT

FIXEDATLIPOPROTEIN RECEPTORS

ON THE JUNCTIONALFOLDATTHE

END PLATE MEMBRANE


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PERMITSENTRYOFSODIUM

EXITOF

POTASSI

UM

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

I

nitiate this process


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Synthesis Acetylcholine is synthezised in

Axoplasm of nerve terminal from

Choline obtained from E.C.F

And transferred to vesicles readyFor use

Hydrolysis By cholin esterase in the region of

The motor end plate, so that when the

Exited muscle fibre has come out ofIts 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


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Receptors at neuro muscular

junction


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Post junctional receptors

Size 8-9 nm

The mouth is surrounded by 5 proteins

2 alpha proteins are cholinoceptors whichrespond 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


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Non Depolarizer blocks the Alpha units

Preventing Acess ofAcetyl Choline

Blocked the channels closed Depolarizers blocked the channel open

Initial Stimulation muscle fasciculation


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Pre junctional receptors

Control ion channel spesific for Na++

which is responsible for synthesis and

mobilization of transmitter


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Extra junctional receptors

Appear all over the surface of muscle fibre whenthe muscle is denervated or deprived of nervestimulation by injury, stroke, disuse

Similar but more responsive than junctionalreceptors to depolarizing agents and lessresponsive to non depolarizing agents

Suxamethonium causes substantial flows of ions

across the membrane, producing Hypercalemiawhich is difficult to supress by prior nondepolarizing drugs


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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 thesedrugs except gallamin & atracurium

These pharmacokinetics are altered in liver disease,

increasing terminal elimination half time by about 50%


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Pharmacodynamics

Effects on motor end plate

Preventing absorbsion of acetylcholine tocholinergic receptors prevent the changes in

the end plate which cause muscular tone andcontraction

Effects on respiration

Cause paralysis of muscle of respiration

Causing square wave respiration

The diaphragm being less sensitive than otheris the last one to be paralysed


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Effects on circulation Turbocurarine :Hypotension

Pancuronium :Hypertension

Tachycardia :Gallamine

Skin flushing : 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)


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Gastro Intestinal System

The cardiac sphincter is probably not relaxed

completely and still has an opening pressure


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Choice of non depolarizers1.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


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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


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Management of incomplete

reversal IPPV is given with a mask an oxygen while thedegree of incomplete reversal is assesed

If mild (T4/T1 ratio >50%, respiration is almostadequate, more neostigmine or otheranticholinesterase is given

If severe (T4/T1 ratio


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ADiuresis 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


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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


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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


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Disadvantages of non depolarizers

Slow onset of action

Long duration of action

Slow recovery Cummulation

Cardiovascular side effects

Histamine release


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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


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Upper motor neurone lesions

E.G : Cerebro VascularAccidents

EncephalitiesBrain injury

Abdominal infection

Renal disease


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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 MGcholinesterase

Excessive formation of succynyl mono choline

Phase II (Dual block)


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Central depression of respiratory centre Narcotic analgesic

T

hiopentone 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 ofHering 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


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Cardiocaskular effects of neuro

muscular blocking agent

Ganglionic blockade

Blockade of cardiac muscarinic receptors

Nor adrenalin Stimulation of nor adrenalin release

Histamin release


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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


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Patient who is sufficiently

recovered not totally recovered

Ability to sustain 5 second head lift & hand

grasp & tongue protrusion

A

bility 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


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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

grip 5 second

33 Sustain T 200

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Neuro Muscular Blocker