NMB MY COPY

7/31/2019 NMB MY COPY

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NMBSANKAR


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1. Precurarization?

2. Ed95?

3. Suxa why brady?

4. Reversal needed for suxa?why not?

5. Cardiac stable relaxant?

6. How ll be effect of mr in myasthenia gravis?7. Why cardiac muscle not affected?

8. END PRODUCT OF ATRACURIUM

AMETABOLISM?

9. BILIARY MECH OF elimation for whichrelaxants?


3/91

Pithed frog

Isolated one limb & Injected curare in blood

Findings:

1. Paralysis

No response to nerve stimulus

Response to direct muscle stimulation

2. Isolated limb responded to both

3. Stimulating nerves in paralyzed limb gave

some movement in the isolated (circulation

deprived) limb

Claude Bernards experiments


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Class of

Blocker

Clinical Duration

Long-Acting

(>50 min)

Intermediate-

Acting (20-50

min)

Short-Acting

(15-20 min)

Ultrashort-

acting (


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MECHANISM OF ACTION


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ACh

AChEpsilon / Gamma Alpha

Ion Channel

Beta

Delta

Alpha

Nicotinic Receptor at adult NMJ

Each of the two -subunits has an

acetylcholine binding site.


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The pulse stops when the channel closes and one or

both agonist molecules detach from the receptor.


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Potent

Very Short Lived

Destroyed in Less than One m.sec

RELEASED Ach


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agonistic and

antagonistic actions atpostjunctional

receptors for

depolarizing andnondepolarizing

relaxants.


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the depolarizing relaxants characteristically have a biphasic

action on musclean initial contraction, followed by

relaxation lasting minutes to hours. Because they are notsusceptible to hydrolysis by acetylcholinesterase, the

depolarizing relaxants are not eliminated from the junctional

cleft until after they are eliminated from plasma. The time

required to clear the drug from the body is the principal

determinant of how long the drug effect lasts. Whole-body

clearance of the relaxant is very slow in comparison to

acetylcholine, even when plasma cholinesterase is normal.

Because relaxant molecules are not cleared from the cleft

quickly, they react repeatedly with receptors, attaching to onealmost immediately after separating from another, thereby

repeatedly depolarizing the end plate and opening channels.


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Suxa always binding then why

not continuous contraction?

Time gated channel close ..

Channel has to come to resting

stage .. But it is not happening

because suxa is binding to it


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PHASE II BLOCKSeveral factors are involved. The repeated

opening of channels allows a continuous efflux of potassium andinflux of sodium, and the resulting abnormal electrolyte balance

distorts the function of the junctional membrane. Calcium

entering the muscle through the opened channels can cause

disruption of receptors and the subend-plate elements

themselves. The activity of the sodium-potassium adenosinetriphosphatase pump in the membrane increases with

increasing intracellular sodium and, by pumping sodium out of

the cell and potassium into it, works to restore the ionic balance

and membrane potential toward normal. As long as thedepolarizing drug is present, the receptor channels remain open

and ion flux through them remains high.[78]


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Some receptors that bind to agonists, however,

do not undergo the conformational change toopen the channel. Receptors in these states are

called desensitized (i.e., they are not sensitive

to the channel-opening actions of agonists).


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Depolarizing neuromuscular blockers such as succinylcholine

produce prolonged depolarization of the end-plate region,

which results in (1) desensitization of the nAChR, (2)

inactivation of voltage-gated sodium channels at the

neuromuscular junction, and (3) increases in potassium

permeability in the surrounding membrane. The end result is

failure of action potential generation, and blockade ensues. It

should be noted that although acetylcholine produces

depolarization, it results in muscle contraction underphysiologic conditions because it has a very short duration of

action (a few milliseconds). Acetylcholine is rapidly hydrolyzed

by acetylcholinesterase to acetic acid and choline.

Administration of large doses of acetylcholine to experimentalanimals, however, produces neuromuscular blockade.


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Repeated boluses (infusion) of SCh May occur with single dose in E1

a

Fade, post tetanic facilitation

Memb. potential returns to resting statedespite presence of the drug and the

transmission is blocked

Possibly due to pre synaptic block, aggravatedby inhalational agents

PHASE II BLOCK


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If agonist present for longer time (> 1 sec.)

Different conformation

Receptor no longer activatable No role in normal transmission

Safety mechanism

Receptor desensitization


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Immature,fetal,EJ

Spread

Unstable

life 24 hrs

Longer burst duration

Smaller conductance

2-10 times longer channel

opening (slow closing)

(reason for hyperkalaemia )

Mature

Localized

Stable

life 2 weeks

Burst activity

Normal conductance

Channel opens for 0.5millisecond

Ach Receptors


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The fetal nAChR contains a -

subunit instead of an adult -

subunit. The mature nAChR

has a shorter burst duration

and higher conductance for

Na+, K+, and Ca2+ than the fetal

nAChR does.[14]


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Normally suppressed by neural activity

When nerve activity is reduced (trauma, skeletal

muscle denervation), they proliferate rapidly &

spread over entire post junctional membrane Highly sensitive to agonists (Ach & SCh)

Degraded soon after neural influence returns

Mixture of junctional & extra junctional receptors indifferent clinical situations

Extra junctional AChRs(immature)


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Why resistant to non depolarising muscle

relaxant?fetal receptors have long opening of

ion channels so when normal ach

molecules are present it ll cause

prolonged influx of Na,Ca so some

contraction ll be present,,, it is called

resistant to NDMR or higher doses are

needed


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UMN lesions

LMN lesions

Muscle trauma

Burn injury

ImmobilizationSepsis

CHRONIC RELAXANTS

Normal

Myasthenia

Organophosphates

Cholinesterase inhibition

Up-regulation

Increased requirement

for non-depolarizing

Agents (resistance)Hyperkalemia after SCh

Receptor unaltered

Down-regulationReduced requirements

For non-depolarizers

Up & Down-regulation of AChRs


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The fetal nAChR is a low-conductance channel, incontrast to the high-conductance channel of the adult

nAChR. Thus, release of acetylcholine causes brief

activation and a reduced probability ofopening of the

channel.[14] The upregulation of nAChRs found in states

of functional or surgical denervation is characterized by

the spreading ofpredominantly fetal-type nAChRs. These

receptors are resistant to nondepolarizing

neuromuscular blockers and more sensitive to

succinylcholine.[18] When depolarized, the immatureisoform has a prolonged open channel time that

exaggerates the efflux ofK+.[19]


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Pre-synaptic AChRs

Different strains of only alpha andbeta units

Non depolarizing NMB agents (fade)block prejunctional Na+ channel butnot Ca2+ channels

Mobilisation of Ach from synthesissite to release sites depend on Na+

channel

Release of Ach s calcium dependent


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Reason for Fasiculation due to Suxa &

Prevention of Fasiculation by NDP ( inhibit

mobilisation)

Regulate Ach Release- Positive Feedback-MoreMobilisation of Vesicles

BlockInhibit Mobilisation of Vesicles

Pre-Jn Ach Receptors


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Inhibition of

postjunctionalacetylcholinesterase by

anticholinesterases

increases theconcentration of

acetylcholine, which can

compete with and

displace the

nondepolarizer and thus

reverse the paralysis


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Non competitive Local anesthetics,

depolarizing agents,

Acetylcholine

Plug the channel &

prevent ion movement

Competitive Non-depolarizing

agents

Block of one or both

Ach binding sites

Affinity more at alpha-

epsilon site

AChR blocking agents

N i i h i f


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Depolarizing agentsAcetylcholine, Succinylcholine

Desensitization block

Inhalational, Thiopentone, Local anesthetics

Ion-channel block

1. Closed: TCA, Naltrexone, Naloxone2. Open: High conc. of NMB

Non-competitive mechanisms of

neuromuscular block


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Contain at least one +ve chargedquaternary amine (4 C atoms attached to

nitrogen) like Ach

N+ attracted to Alpha sub unit of AChR (-

ve charge)

Structure / Activity Relationship


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Oral

not absorbed

IV

rapid onset, fast distribution & predictableelimination

S/C or IM

unpredictable absorption, high dose required, only inlaryngospasm without iv line

Succinylcholine rapid & effective absorption

Absorption & distribution


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Potency Low affinity high dose

High affinity small dose

Speed of onset Fast injection high gradient quick onset

Perfusion Delayed onset with reduced cardiac output

Regional blood flow.

Pharmacokinetics


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More receptors in fast (glottis) than slow (adductorpollicis) muscle fibres

Rapid onset at glottis muscles is due to rapidequilibrium (more blood flow)

Dose required for diaphragmatic block is twice thedose required for similar block @ adductor pollicis

Sequence of onset: small muscles (eyes, digits)

larynx trunk & abdomen

diaphragm

Muscle responses

Ph ki ti


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Children: Larger Vd (more dose required)

Sensitive NMJ (prolonged action)

Higher HR & CI (faster onset)Aged:

Widening of NMJ & reduced no. of receptors

Delayed distribution & elimination

Organ-dependent metabolism & elimination ofsteroid relaxants are affected

PharmacokineticsAge


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Obesity

+ve charge prevents fat absorption

Vd / kg and clearance markedly reduced

Unaltered elimination half life

Temperature

Prolonged action with hypothermia

Slowed Hoffman elimination

Temp. independent degradation of Mivacr.


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Pregnancy

Unaltered

Magnesium increased potency & duration of

action Ionized state minimal placental transfer

(except prolonged use in ICU)

May have reduced plasma cholinesteraseactivity


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Burns

Up-regulation of receptors (at least 30% burns)

Resistance to non-depolarizers (starts at10 peaks at40 declines at 60 days.)

Sensitive to Succinylcholine (hyperkalemia)

Reduced plasma cholinesterase


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The ED95 is the effective dose of a drug in 95% of

individuals. One to two times the ED95is usually used

for intubation. Although a larger intubating dosespeeds onset, it exacerbates side effects and prolongs

the duration of blockade. For example, a dose of 0.15

mg/kg of pancuronium may produce intubating

conditions in 90 s, but at the cost of more pronounced

hypertension and tachycardiaand a block that may

be irreversible for more than 60 min.

S i l h li


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Only NMBA with short onset (< 1 min) & shortduration (5 10 min)

Both N2 atoms are quaternary (+ ve)

Almost exclusively used for RSI or to counteract

laryngospasm (0.1 mg/kg)

IV injection small fraction reaches NMJ

Depolarizing effect within 20-40 sec (fasciculations)followed by relaxation (< 60 sec)

Succinylcholine

1951

Manifestation by initial series of muscle twitches

(fasciculation) followed by flaccid paralysis.


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Stimulation of muscarinic AChR

Sinus bradycardia, even sinus arrest

AV node dysrhythmia, nodal rhythm

Ventricular arrhythmia

Usually with 2nd dose

Ganglionic stimulation

, hypertensionAllergic Reactions

Succinylcholine

Side effects


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Depolarization of the endplate

Trigger for MHMasseter spasm

Raised potassium

(0.5 - 1 meq/L)

Muscular destrophy, myopathy, denervation, UMN, muscletrauma, burns, severe abdominal sepsis

No benefit with precurarization

Myalgia Prevented by precurarization, Benzo, Lido, Ca, Mg, repeated

Thio)


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Depolarization of the endplate

Raised Intra Cranial Pressure

Due to increased cerebral perfusion. Prior hyperventilation

can attenuate

Raised Intra Ocular Pressure4-8 mm, peaks 1-2 min. Due to Increase in choroid blood

vol., extra ocular muscle tone & aqueous outflow resistance

Raised Intra Gastric Pressure

Due to fasciculations & increased vagal tone. Unalteredbarrier pressure). Prevented by precurarization


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Doesnot require reversal rather

cholinesterase inhibitors

(neostigmine) can prolong thedepolarizing block (because these

agents also inhibits the

pseudocholinesterase)


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PRECURARISATION

TO PREVENT

FASCICULATIONS,myalgia,10-15% OFNDMR INTUBATING DOSE GIVEN 5 MIN

BEFORE SUXA..ROCURONIUM AND

TUBOCURARIUM IS EFFICACIOUS..

SUXA DOSE TO BE 1.5 mg/kg

Not prevent hyperkalaemia and

elevation in intraocular pressure

Synchronous contraction of the cells in a

motor unit is calledfasciculation

PRIMING DOSE


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Since the introduction of rocuronium, the use of priming

has decreased considerably. Several groups of

investigators have recommended that a smallsubparalyzing dose of the nondepolarizer (about 20% of

the ED95 or about 10% of the intubating dose) be given 2

to 4 minutes before a large second dose for tracheal

intubation.[ This procedure, termed priming, has been

shown to accelerate the onset of blockade for most

nondepolarizing neuromuscular blockers by 30 to 60

seconds, which means that intubation can be performed

within approximately 90 seconds of the second dose.

However, the intubating conditions that occur afterpriming do not match those that occur after

succinylcholine. Moreover, priming carries the risks of

aspiration and difficulty swallowing, and the visual

disturbances associated with subtle degrees of blockadeare uncomfortable for the atient.[167]

PRIMING DOSE

Succinylcholine


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Neuromuscular disease

Denervation (after 2 days)

Immobilization (after 3 days)

Burns (after 2 days) MH susceptibility

Homozygous for E1a

Basal sr. K > 5.5

Sepsis / infection

Allergy to SCh

Succinylcholinecontraindications


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Hyperkalemia: Serum K > 5.5 is an absolute

contraindication for use of Sch.

Head Injury : It increase ICP

Newborns and infants: These have extrajunctional

receptors which are sensitive to depolarizing agents & Sch

can produce severe hyperkalemia by interacting with these

receptors.

Glaucoma & eye injuries.

Up to 2-3 months after trauma, Up to 6 months after

hemiplegia/paraplegia, Up to 1 year after burns. In theseconditions the denervated/regenerating nerve develops

extra junctional receptors which can produce

hyperkalemia.


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Renal Failure : If associated with hyperkalemia.

Prolonged intra abdominal infection can be associated with

hyperkalemia.

Diagnosed case of atypical pseudocholinesterase & low

pseudocholinesterase.

Duchene muscular dystrophy

Dystrophia myotonica: Permanent contractures may develop if

SCh is given in these patients.

Tetanus.

Gullian Barre Syndrome

Metabolic Acidosis :Acidosis is associated with hyperkalemia. Shock : It is associated with acidosis which in turn is associated

with hyperkalemia.

Spinal cord injury.

d l i i


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Bind to one or both Alpha units of AChRs

Competitive antagonism of Ach

No conformational change in AChR

Dynamic binding (repeated association &

dissociation) competition

Presynaptic receptors also blocked

70 80 % receptor occupancy - twitch depression

92 % receptor block: complete block

Non-depolarizing agents


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Depolarizing Nondepolarizing

Also called Phase I block -

Block preceded by muscle fasciculations No fasciculations

Depolarizing blocking drugs are called

Leptocurare

Called pachycurare

Does not require reversal rather

cholinesterase inhibitors (Neostigmine) can

prolong the depolarizing block ( because

these agents also inhibit the

pseudocholinesterase).

Reversed by cholinesterase inhibitors

like Neostigmine.


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Antibiotics

Aminoglycosides: pre junctional effects like

magnesium (decreased release of Ach)

Stabilize post junctional memb. Calcium improves Ach release but stabilize pos

tjunctional memb, so unpredictable effect


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Local Anesthetics

Enhance the block by interfering Ach release,

stabilizing memb & depressing skeletal muscle

fibres.

Esters compete with SCh for plasma

cholinesterase activity


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Magnesium

Enhanced block by reduced Ach release and

stabilizing the memb.

SCh effect also enhanced (? Phase II block)

Lithium

Enhanced block

Phenytoin

Resistance to non-depolarizing NMBA


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Steroids

IV steroids -- no effect

In myasthenia, ACTH or cortisol improve NM

functionHypothermia

Prolonged duration of action (Panc, Vec)

Reduced hepatic, renal & Hoffman clearance

Atracurium


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Non-organ dependent elimination

Used in liver and renal failure patients Histamine release in 30% of patients

Dosage: 0.3-0.6mg/kg (within 2 min)

Metabolism

Ester hydrolysis: 60% of elimination

Hofmann elimination

Side-effects : Hypotension and tachycardia

Bronchospasm

Laudanosine toxicity-breakdown product from Hoffmann elimination, mayprecipitate seizures.

Cis-atracurium Minimal histamine release

Rest similar like atracurium

Atracurium

V i


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commonly used nowadays Non cummulative

No histamine release

Cardiovascular stability Easy reversibility

Action depends primarily on biliary excretion

and secondarily on renal excretion Intermediate acting

Dosage : 0.08-0.12mg/kg

Vecuronium

P i


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Long acting

60-80% excreted in urine,

Dosage : 0.08-0.12 mg/kg (2-3 min)

Minimal histamine release Sympathomimetic and anticholinergic effects- vagal

blockade and catecholamine release.

Hypertension,

Tachycardia dysrhythmias

and pulmonary vasoconstriction

Pancuronium

Rocuronium


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onset = 1 - 2 min and

duration 60 - 90 min Resembles Vec but less potent (fast onset)

Largely excreted unchanged (upto 50%) in bile in 2

hrs (>30% renal excretion in 24 hrs) Prolonged action in renal, hepatic diseases and old

age

Absence of histamine release

Slight vagolytic action

RocuroniumMono quaternary aminosteroid


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Derivative of vecuronium

Dosage : 0. 5 -1.2 mg/kg

Less potent : 7-10x < vecuronium

Faster onset ( 60-90 sec),

intermediate acting

No metabolism, eliminated primarily by liver.

Duration prolonged by severe hepatic failure andpregnancy.

Free from histamine release and CVS effects

Cis-atracurium


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Purified form of one of 10 steroisomers of

atracurium, 5 times more potent Similar to atracurium except slow onset, very little

histamine & 1/5th less laudanosine (cerebralexcitatory)

onset 3 - 5 min & duration 20 35 min

77% Hoffman degradation at normal pH to inactivelaudanosine + alcohol (again Hoffman)

17% renal clearance (non specific esterases notinvolved)

Stable hemodynamics, organ independent clearance

Cis atracuriumbenzylisoquinolinium

Mivacurium


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MivacuriumBenzylisoquinoline

Only non-depolarizer with short duration onset 2 3 min, duration 12 20 min

histamine release and hypotension

Hydrolyzed by plasma cholinesterase (88 % rate ofSCh) 7% unchanged in urine

Inactive metabolites


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BILIARY EXCRETION- VEC,RO

RENAL EXCRETION-PAN,PIPE,DOXA

HOFFMAN- ATRACU,CIS-ATRAESTER HYDROLYSIS-ATRA

PSEUDOCHOLINEESTERASE-SUXA ,MIVA

METABOLISM


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ib i l d d l i i l l k d


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Drugs

Inhaled anesthetic drugs

Local anesthetics (lidocaine)

Cardiac antidysrhythmics (procainamide)

Antibiotics (polymyxins, aminoglycosides, lincosamines [clindamycin], metronidazole

[Flagyl], tetracyclines)

Corticosteroids

Calcium channel blockers

Dantrolene

Metabolic and Physiologic States

Hypermagnesemia

Hypocalcemia

Hypothermia

Respiratory acidosis

Hepatic/renal failure

Myasthenia syndromes

Factors Contributing to Prolonged Nondepolarizing Neuromuscular Blockade


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Factors Contributing to Prolonged Depolarizing Blockade

Excessive dose of succinylcholine

Reduced plasma cholinesterase activity

Decreased levels

Extremes of age (newborn, old age)

Disease states (hepatic disease, uremia, malnutrition, plasmapheresis)

Hormonal changes

Pregnancy

Contraceptives

Glucocorticoids

Inhibited activity

Irreversible (echothiophate)

Reversible (edrophonium, neostigmine, pyridostigmine)

Genetic variant (atypical plasma cholinesterase)


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Clinical characteristics of phase 1 and phase 2 neuromuscular blockade


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Characteristic Phase 1 Transition Phase 2

Tetanic stimulation No fade Slight fade Fade

Post-tetanic

facilitationNone Slight Yes

Train-of-four fade No Moderate fade Marked fade

Train-of-four ratio >0.7 0.4-0.7 6

Tachyphylaxis No Yes Yes

Clinical characteristics of phase 1 and phase 2 neuromuscular blockadeduring succinylcholine infusion


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Type of

Butyrylcholinest

erase

Genotype IncidenceDibucaine

Number *

Response to

Succinylcholine

or MivacuriumHomozygous

typicalE1

uE1u Normal 70-80 Normal

Heterozygous

atypicalE1

uE1a 1/480 50-60

Lengthened by

50%-100%

Homozygous

atypical E1a

E1a

1/3200 20-30

Prolonged to 4-8

hr

* The dibucaine number indicates the

percentage of enzyme inhibited.

Histamine Release


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True anaphylaxis: Antigen / Antibody (IgE)

Complement activation (IgG or IgM)

Direct action on mast cell surfacetachyphylaxis

Prophylactic H1 & H2 receptor blockers

suppress

Histamine Release


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More receptors in fast (glottis) than slow (adductorpollicis) muscle fibres

Rapid onset at glottis muscles is due to rapidequilibrium (more blood flow)

Dose required for diaphragmatic block is twice thedose required for similar block @ adductor pollicis

Sequence of onset: small muscles (eyes, digits)larynx trunk & abdomen diaphragm

Muscle responses

Monitoring


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Increased safety

Cost effective

Easy documentation

Techniques

Peripheral nerve stimulation (PNS)

Mechanomyograph (MMG)

Electromyograph (EMG)

Acceleromyography (AMG)

Features


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Choice of muscle

Diaphragm (most resistant) > other resp, upperairway & facial muscles > peripheral & abdominal(least resistant)

Adductor pollicis (hand) & Flexor hallucis brevis (leg):

sensitive (may be unreliable for intubation), lesschance of overdosing,

Orbicularis oculi: Onset, duration & sensitivity sameas resp. muscles

Other: Laryngeal, masseter, other facial muscles(research purposes only)


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T i f f (TOF)


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Train of four (TOF)ratio of 1st to 4th response


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1. Progressively fade as relaxation increases

2. Clinical relaxation requires 75 to 95% blockade

3. DBS is more sensitive TOF for clinical evaluation offade(visual)

4. recent international guideline a TOF ratio of 0.9 was

recommended as an end point for recovery from a

nondepolarizing neuromuscular block

5. they could oppose their incisors to retain a tongue

depressor, their TOF ratio was, on average, 0.8 and at

least 0.68.

6. maximum antagonistic effect of neostigmine occurs in

10 minutes or less7. For neostigmine, this maximum effective dose is in the

60- to 80-g/kg range,[327] and for edrophonium, it is in

the 1.0- to 1.5-mg/kg range. [339] [340]

SIGNS OF ADEQUATE REVERSAL


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Regular respiration with adequate tidal volume i.e. patient

is able to maintain oxygen saturation on room air.

Spontaneous eye opening

Spontaneous limb movement

Able to protrude tongue

Upper airway reflexes returns like patient is able to cough& spit.Gag reflex present.

Able to lift head for more than 5 seconds. This is the best

clinical sign.

Forceful hand grip

Able to generate ins pressure of atleast -25 cmH20

SIGNS OF ADEQUATE REVERSAL

CAUSES OF INADEQUATE REVERSAL


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Inadequate dose of neostigmine.

Overdose of inhalational agents/opioids.

Renal Failure,Hepatic failure

Hypothermia

Electrolyte abnormalities (Hypokalemia, Hypocalcemia)

Associated neuromuscular diseases.

Shock

Acid Base abnormalities especially acidosis. It is

impossible to reverse a patient with pCO2 more than50mmHg.

CAUSES OF INADEQUATE REVERSAL

Drugs which antagonise Neuromuscular


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g g

Blockade

They reverse the block by NDMR only

Phenytoin

Carbamazepine

Calcium

Cholinesterase inhibitors

Azathioprine

Steroids.

Stimulating patterns


85/91

Reflects events at post junctional membrane

Single supra maximal electrical stimuli applied toperipheral motor nerve

Frequency every second (1 Hz) or every 10 seconds(0.1 Hz)

Used for monitoring onset of block Same response to both groups of NMBAs

Response influenced by position of muscle, muscletemp.

Calibration required before relaxation (not suitablefor day-to day clinical practice)

Single twitch (ST)

Stimulating patterns


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Reflects events at pre synaptic membrane

Used successfully for onset, maintenance &recovery of block

Four supra maximal stimuli q 0.5 seconds (2

Hz). May be repeated q 12 15 seconds Advantage: relative ratio of 4th to 1st response

remains the same despite changes in absoluteresponses

Train of four (TOF)

Sti l ti tt


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Normally 50 Hz for 5 sec

Fade with non-depolarizing block

Post-tetanic facilitation

Painful

May produce lasting antagonism

Stimulating patternsTetanus


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Two short (0.2 milliseconds) bursts of 50 Hztetanic stimuli separated by 750 milliseconds

DBS with 3 impulses in each of bursts (3,3)most commonly used

Ratio of second response to the first isequivalent to TOF ratio

Easily seen or felt by the anesthesiologist

Stimulating patternsDouble burst stimulation


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Mutations in the acetylcholine receptor that result

in prolonged open-channel time, similar to that seen

with the immature receptor, can lead to a

myasthenia-like state, even in the presence of

normal receptor numbers. The weakness is usually

related to the prolonged open-channel time. Therole of the immature isoform of the receptor in the

muscle weakness associated with critical illness such

as burns is unknown.

li i li d


90/91

D- Tubocurare It is named so because it was carried in bamboo tubes &

used as arrow poison for hunting by Amazon people.

It has highest propensity to release histamine

It causes maximum ganglion blockade. Because ofganglion blocking & histamine releasing property it can

produce severe hypotension.

Due to histamine release it can produce severe

bronchospasm.

Benzylisoquinoline compounds

Centrally acting muscle relaxants


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These are drugs which produce muscle relaxation through

central mechanism both at supraspinal & spinal level

Polysynaptic reflexes involved in maintenance of muscle

tone are inhibited at both spinal & supraspinal level. It also

produces sedation

Uses

Muscle spasms.

Tetanus : IV diazepam is most effective.

Spastic neurological diseases like cerebral palsy,Spinal

injuries. Close reductions & dislocations in orthopedics.

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