Surgery - L5 Neuromuscular blockers

Question 1

Neuromuscular blocking agents in Surgery - 3

Answer 1

1. During induction of anaesthesia reflexes may hamper intubation
2. Muscle spasms can occur due to mechanicalmanipulation of limbs & nerves as reflexes not suppressed until deep anaesthesia
3. Neuromuscular blocking agents used to prevent spasms

Question 2

Somatic motor innervation – 3

Answer 2

1. Muscles innervated by somatic nervous system
2. Single motor neuron connecting CNS to skeletal muscle
3. Signals through Ach through nicotinic receptors

Question 3

Neuromuscular Junction: Contraction & Blocking – 6

Answer 3

1. AP conducted along motor nerve, causing depolarisation of neurone, causing Ca influx at nerve terminal.
2. ACh released from storage vesicles into synapse, then can act on receptors in muscle & is metabolised by Ache
3. Ach binds to nicotic receptors causes Na influx causing End Plate Potential (slight depolarisation)
4. Opening voltage-gated Na channels, releasing AP in muscle cell membrane
5. AP opens L-type Ca channels
6. Stimulates Ca2+ -induced Ca2+ release from intracellular stores, leading to contraction.

Question 4

Neuromuscular BlockingAgents (NMBA) - 2

Answer 4

Interfere with post-synaptic action of Ach
1. Non-depolarising agents:nicotinic antagonists
2. Depolarising blocking agents:weak nicotinic agonists

Question 5

Non-depolarizing agents - 4

Answer 5

1.Competitiveantagonists of ACh receptors at the endplate
2. Causes paralysis by blocking neuromuscular transmission but not nerve conduction or muscle contractility
3. Poor oral absorption – safe to eat
4. e.g. Curare

Question 6

d-Tubocurarine & its’ effects on Neuromuscular transmission – 5

Answer 6

1. Binds to nicotinic receptor at NMJ as an antagonist
2. Much more ACh than needed is released when NMJ activated, so need to block about 90% of receptors to have any effect
3. Blocking receptors causes a decrease in end-plate potential
4. Synthetic derivatives now used clinically:gallamine, rocuronium,pancuronium,vecuronium
5. Tubocurarine reduces the end plate potential amplitude so that no action potential is generated

Question 7

S/Es of Non-Depolarising Blockers - 5

Answer 7

1. Hypotension - Due to ganglion blockade
2. M2blockade- tachycardia
3. Histamine release from mast cells - Bronchospasm in sensitive individuals
4. Respiratory failure - Assisted ventilation used
5. Autonomic ganglion block at high doses

Question 8

NMBA MoA - 6

Answer 8

e.g. Decamethonium,suxamethonium
Phase I Block -
1. Depolarising block
2. Bind to nicotinic receptors
3. Prolong ion conductance & depolarisation
4. Persistent stimulation of nicotinic receptors leads to desensitisation
5. Channel no longer open inresponse to transmitter binding to nicotinic receptor
6. Muscle becomes flaccidas Ca2+ tken intostores

Question 9

Advantages of Depolarising NMBA - 3

Answer 9

e.g. Suxamethonium
1. Rapid onset, short duration of action - Useful for intubation (paralyse larynx)
2. Surgery during pregnancy/caesarean section - Suxamethonium ionised so crosses blood-placenta barrier poorly, so does not affect newborn respiration
3. Less likely to elicit histamine release

Question 10

S/Es of Depolarising NMBA - 6

Answer 10

1. Bradycardia-due to direct muscarinic action
2. Potassium release - Increase cation permeability at end plate causes net lossof K+, resultinghyperkalaemiacan cause ventricular dysrhythmia
3. Prolonged paralysis incholinesterasedeficient individuals
4. Increased intraocular pressure due to contraction of extra-ocular muscles
5. Post-operative pain
6. Malignant hyperthermia

Question 11

Differences Between Depolarising & Non-Depolarising NMBA - 2

Answer 11

1. Non-depolarising block is reversible by increasing [Ach] (e.g. by anticholinesterase drugs) - Depolarising block no effect or potentiated
2. Depolarising block produces initial small involuntary twitches

Question 12

Reversal of NMBA – 1 - 3

Answer 12

1. e.g. Neostigmine used to reverse NMBA by acting as Acetylcholinesterase inhibitor
2. This raises ACh in synapse, reversing non-depolarising block
3. Potentiates depolarising block

Question 13

NMBA Neostigmine - 5

Answer 13

1. Competes with ACh on cholinesterase
2. Lipid insoluble, does not cross blood–brain barrier
3. Short duration of action - Slowly metabolised by plasma esterase. Elimination half-life prolonged in renal disease
4. S/E: bradycardia, increases postoperative nausea & vomiting, GI disturbance
5. Anti-muscarinic - glycopyrronium (or hyoscine) – usually co-administered

Question 14

NMBA Sugammadex – 5

Answer 14

1. Chelates aminosteriod non-depolarising blockers
2. Only effective vs rocuronium
3. Avoids use of cholinesterase inhibitors
4. Avoids use of depolarising agents
5. Does not bind atracurium