THE NEUROMUSCULAR JUNCTION

Axon v Nerve terminal AChE Ach receptors Muscle End-plate JF AChE Release site

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 Mivacurium

Of current clinical importance

Depolarizing )Non-competitive( Suxamethonium (prototype)

COMPARISON OF FEATURES OF DEPOLARIZING AND NON-DEPOLARIZING BLOCKADE Non-Depolarizing Depolarizing* 1. Excitation before block 2. Block relieved by anticholinesterases 3. K+ loss from muscle No Yes No Yes No Yes

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 shortacting (atracurium also hydrolyses spontaneously)  Both have no effect on muscarinic receptors  Both have only mild and transient histamine releasing effect

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

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

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