Neuro Muscular

Blocking Agents
Neuromuscular junction
Neuromuscular Blocking agents

These are the drugs that act

peripherally at neuromuscular junction &
muscle fiber itself to block neuromuscular
transmission
Classification

Muscle relaxants

Depolarizing muscle Non-depolarizing

relaxants muscle relaxants
Depolarising Muscle Relaxants
Depolarising Muscle Relaxants

• Succinyl choline
• Decamethonium
Succinyl choline (Suxamethonium
chloride)
• In 1949, Succinyl choline was prepared by Dr. Daniel Bovet
• Quaternary ammonium compound
• Works on the nicotinic receptors like Ach

Pharmacokinetics:
• Dosage: 2mg/kg
• Onset of action: 30 - 45seconds
• Duration of action: 5- 10minutes
• Metabolized by pseudocholine esterase (in plasma) into
succinyl monocholine & choline and its excreted in urine
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 Sequence of paralysis

Finger & Limbs &

orbit muscles trunk muscles

Neck
muscles

Intercostal diaphrag
muscle m
Recovery of paralysis occurs in reverse sequence
Uses

• For Endotracheal intubation - as a muscle

relaxant of choice in RSI
• During electro convulsive therapy
• For laryngoscopy, bronchoscopy, esophagoscopy
Contraindication

• Hypersensitivity to drug
• Hyperkalemia
• Major burns
• Multiple trauma
• UMN (upper motor neuron) injury
• Family history of Malignant Hyperthermia
• Non-scholine group [Chettiyar & Vysyas]
 Side effects

• CVS (Bradycardia, cardiac arrest)

• Malignant Hyperthermia
• Hyperkalemia  cardiac arrest
• ↑IOP, ↑ ICP
• ↑Intra gastric pressure  Regurgitation
• Myalgia
• Masseter spasm
• Succinyl choline apnoea:
• Occasionally succinylcholine produces prolonged apnoea due to lack of normal plasma
(pseudo) cholinesterase levels.
• This may be due to  severe liver disease, malnutrients, organophosphorous poisoning,
cancer patients.
Treatment:
• Artificial respiration until the muscle power returns
• Fresh blood or plasma transfusion to restore cholinesterase enzyme level
Non Depolarizing Muscle Relaxants

First muscle relaxant, d-tubocurare was used by

Harold Griffith.
Classification
1. on the basis of chemical structure
Steroidal Benzylisoquinoline
compounds compounds Others
• Pancuronium • d-Tubocurare • Gallamine
• Vecuronium • Metocurine • Alcuronium
• Pipecuronium • Doxacurium • Onium
• Rocuroniun • Atracurium chlorfumrates

• Rapacuronium • Mivacurium
• Cisatracurium
• Mivacurium
2. On the basis of duration of action

Intermediate
Long Acting acting Short acting
• D- Tubocurare • Vecuronium • Mivacurium
• Gallamine • Rocuronium • Rapacurium
• Pancuronium • Atracurium • Gantacurium
• Pipecuronium • Metocurium
• Doxacurium • Cisatracurium
(longest acting)
Clinical Uses

• Co-administrated with anesthetic in the induction

phase to induce muscle paralysis
• Facilitate the surgery
• Facilitate endotracheal intubation
• In ICU settings- in patients requiring prolonged
ventilation especially where it is mandatory to
reduce the work of breathing
Uses of NDMR in Anaesthesia

• Maintenance of anaesthesia
• For intubation where succinylcholine is
contraindicated ( Rocuronium is of choice)
• For precurarization to prevent postoperative
myalgias by succinylcholine (dTC and
rocuronium)
Mechanism of Action

• NDMR acts as competitive receptor.

• They bind to the Ach receptors but
unable to induce ion
channel openings.
• They prevent Ach
from binding and
thus endplate
potentials do not
develop.
Atracurium

• Bisquaternary ammonium Benzylisoquinoline

• Intubating dose- 0.5mg/kg.
• Maintenance- 0.05 to 0.1mg/kg
• Drug of choice in patient with renal and hepatic
dysfunction
• onset of action= 3-5min (0.5mg/kg)
• duration of action= 20-35min
• about 82% is bound to albumin
• Two separate processes for
metabolism
• Ester Hydrolysis (2/3)-catalyzed by nonspecific
esterases
• Hofmann Elimination (1/3)-spontaneous
nonenzymatic chemical breakdown occurs at
physiological pH and temperature
Effects:
• Triggers dose-dependent histamine release that becomes
significant at doses above 0.5 mg/kg
• ↓systemic vascular resistance and ↑cardiac index
• Bronchospasm
• Duration of action can be markedly prolonged by
hypothermia and to a lesser extent by acidosis
• Will precipitate as a free acid if it is introduced into an
intravenous line containing an alkaline solution such as
thiopental
Cisatracurium

• Potent isomer of Atracurium

• Intubating dose= 0.2mg/kg
• Maintainence dose= 0.02mg/kg
• Duration of action = 30-45 min (0.1 mg/kg)
• Metabolism similar to Atracurium
• Hofmann & Ester hydrolysis
• Elimination independent on end- organ function, so
Ideal for ICU @5 μg/kg/min
• Devoid of histamine- releasing properties even at
high doses
Mivacurium

• Benzylisoquinoline derivative
• short duration of action
• Intubating dose= 0.2 or 0.25mg/kg
• Onset: 2-3 mins
• Duration of action: 12-20 mins
• Clearance: Like succinylcholine–metabolized by
pseudocholinesterases
• Side Effects
• Histamine release
• Hypotension, tachycardia, flushing if dose >0.2mg/kg
• Bronchospasm rare
Pancuronium

• Bisquaternary amino steroid compounds

• Intubating dose= 0.12mg/kg
• Longer duration of action = 1.5 to 2 hrs
• Clearance:
• 80% of single dose eliminated unchanged in urine
• 10-40%undergoes hepatic deacetylation to
• 3-desacetylpancuronium (50% as potent as
Pancuronium)
• 17-desacetylpancuronium
• 3,17-desacetylpancuronium
Pancuronium

• CVS EFFECTS-
• Increased HR, BP, and CO after large doses
• Cause is uncertain but vagolytic effects on
postganglionic nerve terminal
• no histamine release
Rocuronium

• Monoquaternary aminosteroid
• Dosage:
• 0.6mg/kg
• 0.9mg/kg
• 1.2mg/kg
• Onset: 1-2 min
• Duration: 20-35 min
• Clearance:
• Largely excreted unchanged in bile (up to 50% in 2 hours)
• Renal excretion >30% in 24 hrs
Rocuronium

• Replacement for succinylcholine for rapid

sequence intubation (>1mg/kg)

• CVS Effects:
• May produce slight vagolytic effect
• Useful in surgery with vagal stimulation
(laparascopic, opthalmologic)
Vecuronium
• Monoquaternary aminosteroid
• Intubating Dose= 0.1mg/kg
• Onset: 3-5 mins
• Duration of blockade: 20-35 mins
• Clearance
• Undergo both hepatic metabolism and renal excretion
• Undergo deacetylation to
• 3- desacetylvecuronium (50% potent as vecuronium)
• 17-desacetylvecuronium
• 3,17- desacetylvecuronium
• CVS Effects
• No CVS effects at clinical doses
• No histamine release
Summary of pharmacology of NDMR
Depolarizing Vs Non Depolarizing
Muscle Relaxants