THE NEUROMUSCULAR JUNCTION

Axon
v
Release
Nerve site
terminal

AChE

Ach JF
AChE
receptors

Muscle
End-plate
 Clinical Uses of Neuromuscular Blockers

1. In Anaesthesia
 To relax skeletal muscles/reduce dose of GA

 To facilitate intubation

2. In Electroconvulsive therapy

 To reduce trauma
 TWO MECHANISMS OF ACTION
OF NEUROMUSCULAR BLOCKERS

Competition for binding to nicotinic .1

receptors
)Non-depolarizing/competitive blockers(

Prolonged activation of nicotinic .2

receptors leading to depolarization
block
)Depolarizing/non-competitive blockers(
 SOME IMPORTANT
NEUROMUSCULAR BLOCKERS
Non-depolarizing )Competitive(
Tubocurarine (prototype)
Pancuronium
Vecuronium
Rocuronium
Atracurium Of current
clinical importance
Mivacurium

Depolarizing )Non-competitive(
Suxamethonium (prototype)
COMPARISON OF FEATURES OF DEPOLARIZING
AND NON-DEPOLARIZING BLOCKADE

Non-Depolarizing Depolarizing*
1. Excitation before No Yes
block

2. Block relieved by Yes No

anticholinesterases

No Yes
3. K+ loss from muscle

Dual block at high dose over prolonged period *

 CHARACTERISTICS OF
INDIVIDUAL DRUGS
D-Tubocurarine
 Alkaloid )active ingredient of "curare"
as arrow poison(
 Action lasts about 40 minutes

 Histamine release, hence bronchospasm and

hypotension
 Some ganglion blocking effect
 PANCURONIUM

♣ Generally similar to d-tubocurarine, but less

histamine release and ganglion blockade

♣ Blocks muscarinic receptors on heart, so

causes tachycardia

♣ Rarely used clinically

VECURONIUM AND ROCURONIUM

♣ No histamine release or ganglion block

♣ No block of muscarinic receptors, hence

no tachycardia

♣ )Intermediate duration of action )20-30 min

♣ )Rocuronium has rapid unset of action )1-2 min

 ATRACURIUM AND MIVACURIUM
 Unlike the others, not excreted by kidney,
valuable in patients with kidney disease

 Both hydrolysed by plasma ChE, so short-

acting (atracurium also hydrolyses spontaneously)

 Both have no effect on muscarinic receptors

 Both have only mild and transient histamine

releasing effect
 O
+
C O CH2CH2 N )CH3(3
CH2

CH2
+
C O CH2CH2 N )CH3(3

O
Suxamethonium
)Succinylcholine(
 SUXAMETHONIUM

 Only clinically used depolarizing drug

 Rapid hydrolysis by plasma ChE
 Very fast onset of action )1 min(
ideal for rapid intubation((Rocuronium also used
 Effect about 5 min
 Effect prolonged in plasma ChE deficiency
 May precipitate malignant hyperthermia
 ADVERSE EFFECTS OF
NEUROMUSCULAR BLOCKERS
 Depression of respiration. Respiration must
be supported )all members(
 Hypotension and bronchospasm )especially
with d-tubocurarine(
 Post-operative pain )peculiar to
suxamethonium(
 Hyperkalaemia which may lead to cardiac
arrythmias )suxamethonium(
 ADVERSE EFFECTS OF
NEUROMUSCULAR BLOCKERS )Cont’d(
 Malignant hyperthermia )suxamethonium,
genetically determined(

 Apnea )suxamethonium, genetically

determined(

 Bradycardia )Suxamethonium(

 Increase in intraocular pressure

)Suxamethonium(
 IMPORTANT CLINICAL DRUG
INTERACTIONS INVOLVING NMBs

Aminoglycosides .1

Anti-cholinesterases .2
 LEARNING OBJECTIVES
Compare mechanism of action of depolarizing and .1
non-depolarizing NMBs

Compare the characteristic of block produced by .2

depolarizing and non-depolarizing NMBs

Describe the factors that may influence choice of .3

non-depolarizing NMBs

Understand the influence of serum ChE status on the .4

action of some NMBs

List adverse effects of NMBs with drug examples .5

Understand the basis for the drug interaction .6

between NMBs and aminogycosides or AChEs
Gallamine

 Briefer action than tubocurarine

 No histamine release or ganglion block, hence

no hypotension or bronchoconstriction

 Has some anti-muscarinic effect, hence may

cause tachycardia
 Excreted wholly in urine )relevance in
renal disease(
 SOME COMPETITIVE
NEUROMUSCULAR BLOCKERS