RIGEL ANN G TRANCE

Neuromuscular junction

Impulse

Calcium ion influx

ACh release and
binding to receptors
Change in membrane
permeability
Decreased transmembrane
potential

Action potential
propagated
Muscular contraction
NMBDs
 Interrupt transmission of nerve impulses at the
neuromuscular junction
 Produce paresis, paralysis of skeletal muscles
 The main site of action of neuromuscular
blocking agents (muscle relaxants) is on the
nicotinic cholinergic receptor at the endplate
of muscle.
TWO TYPES

 Depolarizing
o Mimic actions of Acetylcholine (ACh)
o Succinylcholine (SCh)
• Rapid onset, ultrashort duration of action

 Nondepolarizing
o Interfere with the actions of ACh
o Long, intermediate, or short-acting
Clinical uses
 Produce skeletal muscle relaxation for tracheal
intubation
 Provide optimum surgical working conditions
 LACK ANALGESIC OR ANESTHETIC
EFFECTS
CHOICE OF NMBD
 Speed of onset
 Duration of action
 Route of elimination
 Associated side effects
o Changes in systemic arterial blood pressure or heart
rate, or both
Depolarizing NMBD
SUCCINYLCHOLINE
 0.5-1.5mg/kg IV

 Rapid onset skeletal muscle paralysis (30-60 seconds)

lasting 5-10 mins

 Rapidly hydrolyzed by plasma cholinesterase

• produced by the liver
• Hydrolysis of SCh to inactive metabolites
• Controls the amount of SCh that is hydrolyzed
before reaching the NMJ
Characteristics
 Sustained depolarization of postjunctional
membrane (Phase I Blockade)
o > 3-5 mg/kg IV SCh leads to Phase II Blockade
o Postjunctional membrane repolarized but still
does not respond to ACh (desensitization);
produced by nondepolarizing NMBDs

 Fasciculations – transient generalized skeletal

muscle contractions
NON DEPOLARIZING NMBD

 Compete with ACh for alpha-subunits at the

postjunctional nicotinic cholinergic
receptors
 Prevent changes in ion permeability and
depolarization
 No fasciculations
NON-DEPOLARIZING NMDBs
Nondepolarizing NMBD
 Highly ionized, water-soluble at physiologic pH, limited lipid solubility

 Cannot easily cross lipid membrane barriers such as the blood-brain

barrier, renal tubular epithelium, gastrointestinal epithelium, or
placenta

 Do not produce CNS effects

 Renal tubular reabsorption is minimal

 Oral administration is ineffective

 Maternal administration does not adversely affect the fetus

Categories
1. Long Duration – 1 to 2 hours
2. Intermediate Duration – 20-25 minutes
3. Short Duration – few minutes
4. Ultrashort Duration – less than 1 minute
Long-acting nondepolarizing NMBD

 Pancuronium
• Onset of action: 3-5 mins
• Duration: 60-90 mins
• If with renal failure, plasma clearance is decreased
resulting to a longer duration of action

• 10-15% increase in heart rate, MAP, and cardiac output

Intermediate-acting nondepolarizing NMBD

 Possess efficient clearance mechanisms that

create a shorter duration of action
 VS Pancuronium:
• Similar onset, except Rocuronium
• 1/3 duration of action
• More rapid rate of recovery
• Minimal to absent cardiovascular effects, except
Atracurium
Intermediate-acting nondepolarizing NMBD

 Vecuronium
• Onset of action: 3-5 mins
• Duration:20-35 mins
• Undergoes both hepatic and renal excretion

 Rocuronium
• Onset: 1-2 mins
• Duration: 20-35 mins
• Rapid onset, but less potent
 Vecuronium
• Onset of action: 3-5 mins
• Duration:20-35 mins
• Undergoes both hepatic and renal excretion

• Rocuronium
• Onset: 1-2 mins
• Duration: 20-35 mins
• Rapid onset, but less potent
 Atracurium
• Onset: 3-5 mins
• Duration: 20 mins
• Clearance by chemical mechanism (Hofmann
elimination) and biologic mechanism (Ester
hydrolysis) which are both independent of renal and
hepatic function
• cause hypotension and tachycardia
 Cisatracurium
• Onset: 3-5 mins
• Duration: 20-35 mins
• Undergoes degradation via Hofmann elimination
• In contrast to atracurium, it does not cause hypotension
and tachycardia
Short-acting nondepolarizing NMBD

 Mivacurium
• hydrolyzed by plasma cholinesterase, like
succinylcholine
• mixture of three isomers
• Hypotension, tachycardia, erythema and flushing
THANK YOU