Neuromuscular Blocking Agents

why is it important to immobilise the area under surgical investigation

to avoid reflexes and spasms during surgery

relexes are not suppresed until deep anaesthesia

which type of motor neuron is relevant her e

the somatic motor neuron and innervation because its for skeletal muscle

describe somatic motor neurone

• single motor neuron connecting CNS to the skeletal muscle

  • cell bodies are in the brain stem

neuromusclar junction

where a motor neuron communicates with a skeletal muscle fiber to facilitate muscle contraction.

which receptor does ACH bind to at skeletal muscle NMJ

nicotinic receptors

briefly describe ACh release at the NMJ

describe the structure of the nicotinic receptor on the motor end plate

• ligand gated ion channel

• contain a,b,s, and y subunits

• two ACH bind

• CNS and ganglioin nACHr have different subunits

describe how muscle contraction occurs after ACh is released into the synapse

• Ach binds to nicotinic receptors

• = NA+ influx

  = End plate potential

  =NA channels open

  = AP in the muscle cell membrane

  = Muscle contraction

what is excitation-contraction coupling in skeletal muscle

• na+ driven action potential opens l-type calcium channels

• stimulates CICR from intracellular stores and muscle contraction

what do NMBA’s interfere with

with the post synaptic action of ACh

two types of NMBAs and relationship with nicotinic receptor

1. non-depolarising agents : nicotinic antagonists

2. Depolarising blocking agents: weak nicotinic agonists

example of non-depolarising agent

d-turbocurarine

• causes paralysis by blocking NMBM but NOT nerve conduction of muscle contractility

around how many rnicotinic eceptors does d-turbocurarine need to block to have effect

90% bc there is alot of Ach released at NMJ

causes decrease in end plate potential

name a synthetic derivative of d-turbocurarine

rocuronium

describe effect of Tubocurarine on neuromuscular transmission

• reduces the end plate potential amplitude so that no action potential is generated

what is recovery from non depolarising NMBA’s determined by

• by susceptibility to cholinesterase’s and clearance

properties of Rocuronium

non-depolarising agent

• fast onset

• intermediate duration

side effects of non-depolarising blockers

• hypotension (ganglion blockade)

• tachycardia - M2 blockade (some of the drugs)

• Bronchospasm’s (histamine release from mast cells)

• Respiratory failure - assisted ventilation used

• Autonomic ganglion block at high doses

Why might hypotension and tachycardia occur with non depolarising agents

hypotension → ganglion blockade

tachycardia → M2 blockade

example of depolarising agent

succinolylcoline + suxamethonium

how do depolarising agents work

2 phases but basically agonise receptors and desentisise it until muscle is flaccid

phase 1 block of depolarising agents

agent binds to Ach receptor and remains bound

= prolonged depolarisation

= prevents muscle from repolarising

phase 2 block of depolarising agents

the persistent stimulation causes desensitisation (doesn’t respond to the repolarisation)

= channels no longer open in response

= Muscle becomes flaccid as calcium is taken into stores

advantages of depolarising nMBA

• rapid onset

• short duration of action

• less likely to elicit histamine release

side effects of depolarising NMBA

• bradycardia - direct muscarinic action

  • potassium release - inc in cation permeability

• prolonged paralysis

• increased intraocular pressure

• post-operative pain

why can hyperkalaemia be caused by depolarising agents

Normally, during muscle activation, small amounts of potassium ions leak out of muscle cells into the bloodstream as part of the cellular depolarization process.

• when succinylcholine causes a sustained depolarization= more significant release of potassium from the muscle cells into the extracellular fluid.

other uses of NMBA

• lethal injections

• electroconvulsive therapy

what is neostigmine and how does it cause reversal of NMBA

• Achcholinesterase inhibitor

• raises synaptic AXh

• reverses non depolarising block

• potentiates depolarising block

can neostigmine cross the BBB and why

no bc its lipid insoluble = minimised CNS effects

how quickly does neostigmine work

within 1 minute

peak effect in 10 minutes

when is the elimination half life of neostigmine prolonged

in renal disease

side effects of neostigmine

bradycardia

increases PONV and GI disturbances

why can