Neuromuscular blocking agents its reversal and neuromuscular monitoring.

1. PHARMACOLOGY OF NEUROMUSCULAR BLOCKING
AGENTS ITS REVERSAL AND NEUROMUSCULAR
MONITORING
Moderator : Dr. SHARAD GOEL (PROFSSOR & HOD)
Presenter : Dr. MOHIT TANWAR (PG RESIDENT)

2. What is Neuromuscular Junction (NMJ)
The junction between terminal branch of the motor nerve fiber
and muscle fiber.
Structure of NMJ:
- Presynaptic
- Synaptic cleft
- Post synaptic

4. oPRE SYNAPTIC REGION:
o Synaptic vesicles are present in presynaptic nerve terminal that store acetylcholine.
oAcetylcholine is synthesized from acetyl and choline, reaction catalysed by enzyme
choline acetyltransferase.
oSynaptic vesicles are synthesized in the neuronal cell body in the endoplasmic
reticulum and transported to nerve terminal via micro tubular system.
oTwo pools of vesicles are seen to release Ach , a releasable pool and a reserve pool.
Vesicles in the releasable pool are smaller , limited and close to nerve membrane
where they are bound to the active zone.
oThe majority of the vesicles are sequestered in the reserve pool and tethered to the
cytoskeleton via various proteins including synapsin, actin, synaptotagmin and
spectrin .
o When there is an action potential and calcium ions enter, synapsin becomes
phosphorylated, which frees the vesicle from its attachment to the cytoskeleton and
release into synaptic cleft.
oThe acetylcholine contained in a single vesicle is often referred to as a QUANTUM of
transmitter.

5. Synaptic Cleft :
Synaptic cleft contains basal lamina. It is a thin layer of
spongy reticular matrix through which, the extracellular
fluid diffuses.
An enzyme called acetylcholinesterase (AchE) is attached
to the matrix of basal lamina, in large quantities.
Acetylcholine released into the synaptic cleft is destroyed
very quickly, within one millisecond by the enzyme
Acetylcholinesterase.
Ach is hydrolysed into acetate and choline.

6. EVENTS AT NEUROMUSCULAR JUNCTION:
NERVE ACTION POTENTIAL
↓
SODIUM INFLUX ,DEPOLARISATION
↓
OPENING OF CALCIUM CHANNEL
↓
CALCIUM ENTERS INTO NERVE
↓
ACH RELEASED
↓
ACH BINDS TO THE POST JUNCTIONAL NICOTINIC Ach RECEPTOR (nAchR)
↓
INCREASES SODIUM AND POTASSIUM CONDUCTANCE
↓
DEPOLARISATION OF END PLATE IS PRODUCED
↓
GENERATION OF ACTION POTENTIAL
↓
TRANSMISSION OF ACTION POTENTIAL ALONG SARCOLEMMA TO OPEN
TUBULAR CALCIUM CHANNELS
↓
MUSCLE CONTRACTION

7. NEUROMUSCULAR BLOCKERS :
Neuromuscular blockers are the drugs, which prevent
transmission of impulses from nerve fiber to the muscle
fiber through the neuromuscular junctions.
These drugs are used widely during surgery and trauma care.
Neuromuscular blockers used during anesthesia relax the
skeletal muscles and induce paralysis so that surgery can
be conducted with less complication.
Following are important neuromuscular blockers, which are
commonly used in clinics and research.

8. Decamethonium

9. NEUROMUSCUALR MONITORING:
TOF PATTERN (TRAIN- OF -FOUR)
1) It allows the anesthesiologist to administer these agents with appropriate
dosing.
2) To ensure that the patient recovers adequately from residual effects of
the NMBD.
3) The principle was to produce a pattern of stimulation that did not require
the comparison of evoked responses to a control response obtained
before administration of a neuromuscular blocking drug. The pattern
involved stimulating the ulnar nerve with a TOF supramaximal twitch
stimuli, with a frequency of 2 Hz, that is, four stimuli each separated by
0.5 s. The TOF was then repeated every 10 s (train frequency of 0.1 Hz).

10. Subjective (tectile) evaluation of
neuromuscular response at the
adductor policis m/s in response to
ulnar nerve stimulation.
Black (negative) electrode is distal to
the Proximal Red(positive) electrode.
Subjective (tectile) evaluation of
neuromuscular response at the orbicularis
oculi m/s in response to facial nerve
stimulation.
Black (negative) electrode is distal to the
Proximal Red(positive) electrode.

11. choice of Monitoring sites:
1)Away from surgical sites
2) For visual & tectile monitoring site
should be accessible to anesthetist.
3)NIBP and SpO2 on different limb
4)For UMN disease avoid affected limb.
Area over which electrode are placed:
1)clean skin with alcohol swab
2)should be dry
3)NO Hairs, No oils
4)Do not overlap electrodes
5)Fix electrode with tape

12. When a non-depolarizing agent is given, a typical pattern is observed.
There is a reduction in the amplitude of the evoked responses, with T4
affected first, then T3, followed by T2, and finally T1. This decrement
in twitch height is known as fade. As the non-depolarizing block
becomes more intense, T4 disappears followed by T3, T2, and finally
T1. The reverse is true during recovery from non-depolarizing block:
T1 reappears first followed by T2, T3, and finally, T4 .
The TOF pattern is less useful in monitoring depolarizing
neuromuscular block. During onset of depolarizing block, each of the
four twitches is decreased equally in size, that is, there is no fade.
This is also observed during recovery. However, if larger doses of
depolarizing agent are given, for example in techniques that require
repeated bolus doses or infusions of succinylcholine, then a Phase 2
block may develop. This is a block produced by a depolarizing drug
which develops some of the characteristics of a non-depolarizing
block. With TOF monitoring, fade is observed.

14. ABOUT 0-75% OF Ach R become antagonized when 4th twitch from TOF disappears.
80% when 3rd twitch disappears.
90% when 2nd twitch disappears.
95-100% when 1st twitch disappears.
Adequate relaxation for surgery is present when 1 to 2 twitches of the TOF are present.
Recovery
• Return of 4th response to TOF heralds recovery phase
• T4/T1 ratio > 0.9 exclude clinically important residual NM Blockade
• Antagonism of NM Blockade should not be initiated before at least two TOF responses are observed

15. Depolarizing Muscle Relaxants
SUCCINYLCHOLINE :
The only depolarizing muscle relaxant in clinical use today is
succinylcholine.
Physical Structure Succinylcholine—also called suxamethonium—it
is a long ,thin flexible molecule composed of two molecules of
acetylcholine linked through the acetate methyl groups.
Like acetylcholine stimulate cholinergic receptor at the NMJ and at
Nicotinic(ganglionic) and muscarinic autonomic site(thus cause
increase intraocular & intragastric pressure).

16. Mechanism of Action:
They depolarize muscle end plates by opening Na+
channels (just as ACh does) and initially produce twitching
and fasciculations.
Continuous end-plate depolarization causes muscle
relaxation because the opening of perijunctional
sodium channels is time limited (sodium channels
rapidly “inactivate” with continuing depolarization. After
the initial excitation and opening these sodium channels
inactivate and cannot reopen until the end-plate
repolarizes.

17. ▪ Upper gate- Voltage dependent gate
▪ Lower gate- Time dependent/Inactivation gate
Lower gate- Time dependent/Inactivation gate Lower gate-Time dependent
3 Schematic of the sodium channel. The sodium channel is a transmembrane protein that can be
conceptualized as having two gates. Sodium ions pass only when both gates are open. Opening of the
gates is time dependent and voltage dependent; therefore, the channel possesses three functional states.
At rest, the lower gate is open, but the upper gate is closed. When the muscle membrane reaches
threshold voltage depolarization, the upper gate opens, and sodium can pass . Shortly after the upper
gate opens, the time-dependent lower gate closes. When the membrane repolarizes to its resting voltage,
the upper gate closes, and the lower gate opens.

18. Pharmacodynamics :
Blockade develops faster in centrally located muscles
(larynx, jaw, diaphragm) ; less profound & recovers more
Quickly
So the sequence of blockade is:
(Face-Jaw-Pharynx-Larynx-Respiratory-Trunck m/s-
Limb m/s).
Orbicularis oculi response to Facial nerve stimulation
preferred as indicator of neuromuscular block at laryngeal
muscle .

19. Pharmacokinetics:
Intubating dose 1-1.5mg/kg (I/V)
Infants and small children- 2 mg/kg (I/V) (greater volume of distribution)
Onset of action: 60 sec(1mg/kg of SCh results in complete suppression of
response to neuromuscular stimulation )
Duration of action: 9-13 minutes
Elimination: t ½ :47 sec.
It also appears that there are no advantage to using SCh doses larger than 1.5mg/kg
in a rapid sequence induction of anesthesia.
The drug is hydrolysis by plasmacholinesterase (Butyrylcholinesterase) into
succinic acid and choline.
Eighty percent of the administered dose is hydrolysed before it reaches the NMJ.

20. PHASE I BLOCK:
The end plate depolarization initially stimulates muscles contraction bcoz SCh is not
degraded by Ach, it remain in the neuromuscular junction to cause continuous end plate
depolarization and subsequent m/s relaxation. This is termed as phase I block.
This gives characteristic non Fade equal depression of stimuli in TOF.
PHASE II BLOCK:
Phase II block occurs due to continuous exposure to depolarizing muscle relaxants.
associated with a fade phenomenon.
Phase II block may be seen clinically with doses of SCh >4mg/kg.
Also referred as desensitization block.
Fade is due to the interaction of depolarizing action of SCh on prejunctional ACHRS.
Factors affecting phase 2 block are
Duration of exposure( given as an infusion)
Drug and concentration
Type of muscle(fast/slow)

21.  Short duration of action is due to its rapid hydrolysis by Butyrylcholinestrase(tetrameric
glycoprotein synthesis in liver)
succinylmonocholine and choline-succinic acid and choline.
Neuromuscular block induced by succinylcholine or Mivacurium can be significantly prolonged if
the patient has an abnormal genetic variant of Butyrylcholinesterase.
ACTION TERMINATES AS SCH DIFFUSE AWAY FRM NMJ.
ONSET & DOA depend– RATE OF HYDROLYSIS
Butyrylcholinesterase
Synthesized in liver and found in plasma.
 Level<75%,important for prolongation of Sch effect.
Factors decreasing butyrylcholinesterase activity are:
Advanced liver disease
Malnutrition, burns
Advanced age
Pregnancy
Chemotherapy drugs like cyclophosphamide
Cytotoxic drugs, anticholinestrases, OCPs, MAO inhibitors, metochlopromide.

22. Analysis of butyrylcholinesterase activity involves:
1)determination of 2)biochemical phenotype
enzyme activity.
use of specific enzyme inhibitors
(dibucaine and fluoride) or by
molecular genetics.
Dibucaine number
Dibucaine is a amide group local anesthetic.
Dibucaine Number is the percent of pseudocholinesterase enzyme activity that is
inhibited by dibucaine.
It is important to recognize that the Dibucaine number reflects quality of
cholinesterase enzyme(ability to hydrolyze succinylcholine)
If dibucaine number =80 :normal variant

23. Type of
Butyrylche
Genotype Incidence Dibucaine
number
Response of
Sch
Homozygous
Typical
E1
uE1
u Normal 70-80 Normal
Heterozygous
atypical
E1
uE1
a 1/480 50-60 Lenthened by
50-100%
Homozygous
atypical
E1
aE1
a 1/3200 20-30 Prolonged by
4-8hrs

24. Indications:
Medical procedures requiring short term muscle paralysis
Endotracheal intubation
Neuromuscular surgeries
Electroconvulsive therapy
Orthopedic surgery Fractures alignment & correction of
dislocation
Procedures like
Laryngoscopy
Bronchoscopy
Esophagoscopy.

25. • Side Effects of Succinylcholine:
• Hyperkalemia (Normally leads to 0.5meq/lt increase in K+ which is insignificant )
(d/t upregulation of immature Ach R in Burns, severe abdominal infection, severe
metabolic acidosis, closed head injury patients)
• Increased intraocular pressure(d/t contraction of tonic myofibrils,transient dilation
of choroidal blood vessels)
• Increased intragastric pressure(d/t the intensity of fasciculation of the abdominal
SK m/s, or by direct increase in vagal tone)
• Increased intracranial pressure(d/t increase CO2 and histamine level leads to
vasodilation and increase resistance to venous outflow)
• Myalgias(d/t muscle damage by SCh induced Fasciculations, secreations of
prostaglandin and cyclooxygenase)
• Malignant Hyperthermia(Hypermetabolic disease of skeletal muscles)
• Sinus Bradycardia

26. Contraindications:
Muscular disorders
Muscular dystrophy
Myasthenia gravis
Crush injury
Burns
Glaucoma
Head injury
Neurological disorders: Gullain Barre syndrome
Stroke paralysis
Paraplegia
Hemiplegia

27. NON DEPOLARISING/ COMPETITIVE NMBDs
History
In 1942 Griffith & Johnson suggested that d-tubocuranine
is a safe drug to use during surgery
In 1967 Baird & Reid first administered pancuronium
Vecuronium, a amino steroid & atracurium, a
benzylisoquinolium introduced in 1980
Mivacurium introduced in 1990
All modern agents are entirely synthetic

28. CLASSIFICATION OF NON-DEPOLARISING MUSCLE
RELAXANT:

29. 1.BENZYLISOQUINOLINIUM COMPOUNDS 1
(a)TUBOCURARINE: Onset of action is slow and recovery is
slow
Long duration of action
Not indicated for use in patients with hepatitis or renal
failure
Intubation dose-0.5-0.6 mg/kg
Maintainence dose-0.1-0.2mg/kg
Not used now because of its highest propensity for ganglion
blockade causing severe hypotension, also cause histamine
release .

30. 1(b) ATRACURIUM:
Racemic mixture of 10 sterioisomers, seperated into 3 groups designated, cis-cis, cis-trans and
trans-trans based on their configuration about Tetrahydroisoquinoline.
Should be stored at 4 degree celsius
Intubation dose : 0.5-0.6mg/kg
Maintainence dose-0.1 mg/kg
Infusion dose : 4-10 mcg/kg onset : 2-3 mins
Duration of action : 20-30 mins
Elimination half life -21 mins
Metabolised through 2 pathways-HOFMANN(a spontaneous nonenzymatic chemical breakdown
occurs at physiological pH and temp) elimination & NON SPECIFIC ESTER hydrolysis.
Atracurium is relatively stable at pH 3.0 and 4 degree celcius temperature and becomes unstable
when it is injected into the blood stream and it undergoes spontaneous degradation yielding
LAUDONOSINE and mono quaternary acrylate as metabolites. Laudanosine is about 70%
excreted in the bile and rest in urine Laudanosine easily crosses BBB and has CNS stimulating
properties. However adverse effects are unlikely to occur with atracurium use in operating room
or the ICU.
Can cause dose dependent HISTAMINE release.
As atracurium metabolism is not dependant on hepatic and renal functions ,it is RELAXANT OF
CHOICE for –HEPATIC FAILURE, RENAL FAILURE,NEW BORN (immature hepatic/renal
functions ), OLD AGE , Neuromuscular disease like myasthenia gravis.
It cause Histamine release (flushing,bronchospasm,itching,hypotenion,tachycardia)

31. 1(c) cis-ATRACURIUM:
It is the 1R cis -1’R cis isomer of Atracurium.
Intubation dose -0.15-0.2 mg/kg
Maintenance dose 0.02mg/kg
It represents 15% by weight of the marketed atracurium and more than 50% of the potency.
Like Atracurium it is metabolized by HOFMANN elimination to laudanosine and mono quaternary
acrylate metabolite.
Cis atracurium iss about 4 to 5 times as apotent as Atracurium.There is over 5 times less production
of laudanosine.
There is no ester hydrolysis Does not cause histamine release
1(d) MIVACURIUM :
Consist of mixture of three stereoisomers.
Intubation dose :0.15-0.25mg/kg
Maintenance dose :0.05mg/kg
Time to maximum block:2-3 mins
Duration of action :5-10 mins It is metabolised by butyrlcholinestrase at about 70% to 88 % the rate
of succinylcholine.
Prolonged block is expected in conditions causing low byutyrylcholinestrase levels (eg. Liver disease
, hypoproteinemia, drugs like metoclopramide,neostigmine , betablockers)
May Causes histamine release,especially if administered rapidly.
It cause Histamine release (flushing,bronchospasm,itching,hypotenion,tachycardia)

32. 2.STERIODAL COMPOUNDS
2(a) PANCURONIUM : Potent long acting NMBD with both
vagolytic(block reuptake norepinephrine) and butyrylcholinestrase
inhibiting properties.
Intubation dose :0.08-0.12mg/kg
Maintenance dose :0.02mg/kg
Duration of action : 70-90mins
Elimination half life -132 mins
Metabolism:40-60% of pancuronium is cleared by kidney, 11%
excreted in the bile,15-20 % metabolised by deacetylation in the liver.
Accumulation of the 3-OH metabolite is responsible for prolongation
of the dusration of block induced by Pancuronium.
At room temperature Pancuronium is stable for 6 months.

33. . 2(b) VECURONIUM :
Is simply Pancuronium without the quaternized methyl group, this minor structural
difference means vecuronium has, slightly decreased potency, Loss of vagolytic
properties of pancuronium.
Molecular instability leading to shorter duration of action Increased lipid solubility,
leading to greataer biliary elimination
Intubation dose :0.08-0.12 mg/kg
Infusion dose: 0.01-0.02 mg/kg
Duration of action :40-50 min
Principal organ of elimination is liver 30-40% of vecuronium is cleared in the bile as
parent compound, 30% renally excreted.
Metabolised in liver by acetylation, the 3-OH metabolite has 80% neuromuscular
blocking potency of vecuronium.
Available as lyophilised powder because it is less stable in solution.

34. 2(c) ROCURONIUM:
Fast onset of action
Intubation dose: 0.6 -1.0mg/kg
Maintenance dose:0.1 mg/kg
Duration of action : 20-30mins
Six time less potent than vecuronium Rocuronium
(0.1mg/kg) has been shown to be a rapid (90 sec) and
effective agent to decrease fasciculations and post tetanic
post operative myalgias.
It is Primarily eliminated by liver and excreted in bile.
At room temperature rocuronium is stable for 60 days.
Rocuronium and Sch both are used in RSI(rapid sequence
induction).

35. 3.CHLOROFUMARATES.
3(a) GANTACURIUM:
Ultra short acting drug similar to SCh.
Pattern of blockade similar to SCh.
Dose: 0.2mg/kg
Time of onset is :1-2 mins
Duration of action :5-10 mins
Causes histamine release.
Recovery can be accelerate by Edrophonium, and administer by Exogenous
Cysteine.
3(b) CW 002:
Is benzylisoquinolinium fumarate ester based compounds Investigational
drug
Intermediate duration of action :60-70min
Metabolism and Elimination similar to Gantacurium.

36. FACTORS THAT INCREASES THE POTENCY OF NON
DEPOLARISING NMBDs:
> Inhalational anaesthetics potentiates the neuromuscular blocking effect of non
depolarising NMBDs.
>Rank of order of potentiation : Desflurane > Sevoflurane, Isoflurane > Halothane
> Nitrous oxide – Barbiturates – Opoids – or Propofol anasthesia.
>Some antibiotics: Aminoglycosides, Lincomycin , Clindamycin, Polymixin.
>Hypothermia and Magnesium sulfate
>Combining two non depolarising NMBDs of chemically related drugs have
ADDITIVE effect [eg atracurium and mivacurium]
>Combining two structurally disimilar drugs have SYNERGISTIC effect [eg
rocuroniun and mivacurium]

37. FACTORS THAT DECREASES THE POTENCY OF NON
DEPOLARISING NMBDs:
Resistance has been seen in patients receiving chronic
anticonvulsant therapy.
Patients with bipolar disorder taking LITHIUM , prolongs
the block.
In hyperparathyroidism, hypercalcemia is associated with
decreased sensitivity to atracurium

38. GENERAL PHARMACOLOGY OF NON- DEPOLARISING NMBDs
TEMPERATURE: Hypothermia prolongs blockade by decreasing
metabolism
ACID BASE BALANCE : Respiratory acidosis potentiates blockade and
antagonises its reversal.
ELECTROLYTE ABNORMALITY: Hypokalemia, Hypocalcemia,
Hypermagnesemia augments a non depolarising blockade
AGE :
● Neonate have increased sensitivity because of their immature NMJ. This
sensitivity does not necessarily decrease dosage requirements as neonate’s
greater extracellular space provides largest volume of distribution .
● In ELDERLY AND OBESE , there is prolonged duration of non
depolarising NMBDs except cis atracurium.
‘CONCURRENT DISEASE: Cirrhotic liver disease and kidney failure
results in increase volume of distribution and lower plasma conc. Thus
greater initial loading dose but smaller maintanence dose might be
required in these diseases

39. ADVERSE EFFECTS OF NEUROMUSCULAR BLOCKERS
A) AUTONOMIC EFFECTS: Tachycardia
Hypotension
Dysrythmias – pancuronium + halothane
Bradycardia – when combined with opiods, can even lead to asystole
–Tubocurarine administration is associated with marked ganglion
blockade resulting in hypotension
-Pancuronium has a direct vagolytic effect leading to tachycardia
B) HISTAMINE RELEASE:
Erythma of face, neck, and upper part of torso may develop, as well as
hypotenion and Reflex Tachycardia.
Can cause bronchospasm in patients with hyperactive airway disease.[
Rapacurium has highest incidence – withdrawn]
Seen with d-Tubocurarine, atracurium and mivacurium Histamine
release are decreased by slowing the injection rate.
TREATEMENT: Anti histaminics

40. C) ALLERGIC REACTION:
IgE mediated
Life threatening reactions 1 in 1000 to 1 in 25,000
TREATEMENT: 100% oxygen inhalation
i.v epinephrine-10 to 20 µg/kg
Early tracheal intubation in case of developing angioedema.
Fluids (crystalloids/crystals)
Dysrythmias should be treated , if they occur.
Norepinephrine or a sympathomimetic drug(phenylephrine)
may also be necessary to maintain perfusion pressure.

41. Reversal (Antagonism) of NM blockade:
 WHO NEED REVERSAL?
Who received nondepolarizing NMBDs. .
Given once patient shows some signs of spontaneous
Recovery (spont respiration) & TOF shows Atleast two twitches,
otherwise they might potentiate the effect of non depolarizing NMBDs
Theoretically possible by three principal mechanisms:
1· A decrease in enzymatic metabolism of acetylcholine by
cholinesterase, thereby increasing receptor binding competition.
2. An increase in presynaptic release of acetylcholine
3. A decrease in the concentration of the NMBD, hence, freeing
the postsynaptic receptors

42. ANTAGONISM NEEDED AT:
• NICOTINIC END
ANTICHOLINESTERAS
ES:
• MUSCARINIC END
ANTICHOLINERGICS:
• NEOSTIGMINE
• PYRIDOSTIGMINE
• EDROPHONIUM
• GLYCOPYRROLATE
• ATROPINE
• SCOPOLAMINE

43. NEOSTIGMINE:
• Carbamate with Quaternary Ammonium Group
• lipid Insoluble ; doesn’t cross BBB
• recommended dosage- 0.04 – 0.08 mg/kg (maximum of 5mg in adults)
• repeating the dose has no benefit as AChE are already maximally inhibited
Onset : 5 to 10 minutes ( peak at 10 min)
duration : lasts for more than 1 hour
paediatric and geriatric patients:
onset is more rapid
requires smaller dosing
duration of action is prolonged in GERIATRIC PATIENTS.

44. • Disadvantages – High incidence of nausea and vomiting, pruritis.
Muscarinic side effects are minimized by prior or concomitant
administration of an Anticholinergic.
Glycopyrolate dose with neostigmine: 1/5th to 1/6th .
(Eg if we have given 50 micro grams/kg of neostigmine, we will give 8
micrograms/ kg glycopyrolate)

45. PHYSOSTIGMINE:
 Natural alkaloid derived from Calabar bean
(Physostigma venenosum)
 Tertiary amine
 Lacks quaternary ammonium : lipid soluble
 Doses: 0.01-0.03mg/kg
 Penetrates CNS: limits use as reversal agent effective in reversing: central
anticholinergic actions due to Atropine or Scopolamine over dosages;
Benzodiazepine and volatile anaesthetic induced CNS depression and delirium;
effective in preventing post-operative shivering (0.04mg/kg)
• Almost completely metabolized by plasma esterases.
 Physostigmine may also be used to reverse the ventilatory depression cause by
Morphine without decreasing its analgesic effects
 Physostigmine (40ugm/kg/IV) decreases the incidence of postoperative shivering

46. PYRIDOSTIGMINE :
Carbamate with Quaternary Ammonium Group
only as 20% as potent as Neostigmine
dose : 0.1 to 0.35 mg/kg (Max of 20 mg in adults)
onset : Slower – 10 to 15 minutes
duration : Longer - > 2 hours
preferred Anticholinergic : Glycopyrrolate 0.05 mg per mg of
Pyridostigmine
If Atropine used; 0.1 mg per mg of Pyridostigmine

47. EDROPHONIUM:
Quaternary Ammonium Group
lacks carbamate group
unlike other agents, it forms reversible electrostatic attachment to the
enzyme
less than 10% as potent as Neostigmine
dose : 0.5 – 1 mg/kg
most rapid Onset : 1-2 min
shortest duration / but higher doses prolong the duration to >1 hour

48. SUGAMMADEX:
Physical Structure-It is a novel selective relaxant binding agent.
Three-dimensional structure resembles a hollow truncated cone or doughnut with
a hydrophobic cavity and a hydrophilic exterior.
It is modified Y-cyclodextrin.
MECHANISM:
• Hydrophobic interactions trap the drug (eg, rocuronium) in the cyclodextrin
cavity (doughnut hole), resulting in tight formation of a water-soluble guest–
host complex in a 1:1 ratio.
• Terminates the neuromuscular blocking action and restrains the drug in
extracellular fluid where it cannot interact with Nicotinic Acetylcholine receptors.
• Eliminated unchanged via the kidneys.
Clinical Considerations
• Doses of 4–8 mg/kg.
• Injection of 8 mg/kg, given 3 min after administration of 0.6 mg/kg of
rocuronium, recovery of TOF ratio to 0.9 was observed within 2 min.
• Produces rapid and effective reversal of both shallow and profound
Rocuronium-induced neuromuscular blockade.

49.  Whereas Anticholinesterase drugs, such as neostigmine, are unable
to reverse deeper levels of neuromuscular blockade (e.g., posttetanic
count of 1-2) because of a ceiling effect, sugammadex is effective in
reversing profound neuromuscular blockade.
 Optimal doses of sugammadex of 4.0 mg/kg produced prompt
recovery of the TOF ratio to 0.90 within minutes. Therefore reversal
of moderate and profound rocuronium and vecuronium
neuromuscular blockades can be reliably achieved by administration
of sugammadex, provided a dose of 2.0 and 4.0 mg/kg, respectively,
is used.
 Because neostigmine has neuromuscular effects when given alone,
some spontaneous recovery of the TOF should be evident before it is
given. In contrast, sugammadex has no neuromuscular effects when
given alone. Accordingly, sugammadex can be given even if there is
no response to TOF stimulation. Sugammadex allows a profound
neuromuscular blockade to continue until the end of surgery.

50. Advantages over Anticholineesterases:
No Cardiovascular side effects
No bronchospasm, so safe in pulmonary disease.
Not recommended for use in Renal failure or Renal transplant patients
because sufficient research is not yet been done to ensure safety.
Should be used with caution in patients with hepatobiliary disease.
Reduces effectiveness of OCPs. So a non hormonal contraceptive
method should be used for 7 days after its use in female patients.
Should use Total body weight instead of lean body weight to calculate
Dose of sugammadex in obese patients with bmi above 30.
LBW = Ideal BMI * Height (in meter square) .
Safe for use in pregnant and breast feeding mothers.

51. THANK YOU