Lecture 7 - Neuromuscular Blocking Agents

Question 1

Describe Ach release at the NMJ

Answer 1

Action potential conducted along the motor nerve => depolarisation
=> influx of Ca+ at nerve terminal
Ach released from storage vesicles into the synapse
High density of nicotinic receptors
Ach metabolised by acetylcholine esterase’s

Question 2

Describe Ach involvement at the NMJ endplate

Answer 2

Ach binding to nicotinic receptors leads to Na+ influx -> end plate potential
Initiates opening of voltage-gated Na+ channels
Action potential in muscle cell membrane
Na+ driven AP opens L-type calcium channels
Stimulates Ca2+ - induced Ca2+ release from intracellular stores

Question 3

Name the 2 typos of neuromuscular blocking agents

Answer 3

Non-depolarising agents - local anatagonists
Depolarising blocking agents - weak nicotinic agents

Question 4

Define the MOA of non-depolarising agents

Answer 4

Competitive antagonists of Ach receptors at the endplate
Causes paralysis by blocking neuromuscular transmission but not nerve conduction or muscle contractility

Question 5

Define the MOA of D-tubocuraine

Answer 5

Binds to nicotinic receptors at NMJ as an antagonist
Blocking receptors causes a decrease in end-plate potential
Reduces the end-plate potential so that not AP is generated

Question 6

Explain the recovery from NMBA

Answer 6

Determined by the susceptibility to cholinesterases and clearance
paralysis fades post surgery

Question 7

What are the side effects of non-depolarising agents?

Answer 7

Hypotension - due to ganglion blockade
M2 blockade - tachycardia
Histamine release from mast cells
Respiratory failure
Autonomic ganglion block at high doses

Question 8

What is the MOA for depolarising NMBA?

Answer 8

Initially bind and activate nicotinic receptors
Opens end-plate voltage-sensitive Na+ channels
Slowly hydrolysed by cholinesterases
Depolarisation maintained at the end-plate
Loss of electrical excitability
Produces initial twitching of skeletal muscle prior to block

Question 9

Explain a phase 1 block

Answer 9

Depolarising block
Bind to nicotinic receptors
Prolong ion conductance and depolarisation
No repolarisation
Potentiation by AChE inhibitor

Question 10

Explain a phase 2 block

Answer 10

Desensitisation block
Persistent stimulation of nicotinic receptors leads to desensitisation
Channel no longer open in response to transmitter binding to nicotinic receptor
Muscle becomes flaccid as a Ca+ taken into stores

Question 11

Give examples of depolarising NMBA

Answer 11

Decamethonioum and suxamethonium

Question 12

What are the advantages of depolarising NMBA?

Answer 12

Rapid onset and short duration of action
useful for surgery during pregnancy (C-section)

Question 13

What are the side effects associated with depolarising NMBA?

Answer 13

Bradycardia
K+ release
Prolonged paralysis
Increased Intraocular pressure
Post-op pain
Malignant hyperthermia (rare)

Question 14

What are the differences between depolarising and non-depolarising NMBA?

Answer 14

Non-depolarising block is reversible by increasing Ach concentration
Depolarising effect has no effect or potentiated, produces small involuntary twitches

Question 15

What are the other uses of NMBA?

Answer 15

Electroconvulsive Therapy
Lethal injections

Question 16

Describe the reversal of NMBA-1

Answer 16

Advised to reverse the effects of the block
example neostigmine
=> Raises Ach in synapse
=> Reverses non-depolarising block
=> Potentiates depolarising block

Question 17

Describe the reversal of NMBA-2?

Answer 17

example, sugammadex
=> chelates aminosteroid non-depolarising blockers
=> effective against rocuronium

Question 18

Give examples of non-depolarising NMBA

Answer 18

Atracurium, pancuronium, rocuronium, vecuronium, gallamine

Question 19

Describe the MOA of neostigmine

Answer 19

Competes with Ach on cholinesterase
quick onset and duration of action is 20-30 mins

Question 20

What are the side effects of neostigmine?

Answer 20

Post-op N and V and GI disturbances