NMB MY COPY
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Transcript of 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?
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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
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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
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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.