Neuromuscular blocking agents

Question 1

Motor neurons?

Answer 1

1. Ventral horn of spinal cord - Cell body
2. Axons encapsulated in myeline sheeth to speed up nerve conduction
3. Nodes of Ranvier facilotate saltatory conduction. Increase in conduction speed

Question 2

NMJ?

Answer 2

1. Contains; pre-synaptic terminal(nerve), synaptic cleft (20nm) & post synaptic receptor (Muscle)
2. Pre-synaptic Ach release + Binding to post-synaptic nicotinic Ach receptors.
3. The AchR are neurotransmitters-gated channels opens for 1ms
4. Influx of sodium and efflux of potassium

Question 3

Pre-synaptic nerve terminals ?

Answer 3

1. They contain schwann cells (Structural function, nerve homeostasis & reinnervation)
2. Neuronal Ach receptors (Prejunctional nicotinic receptors, 5 subunits, positive feedback role)
3. Actylcholine

Question 4

Acetylcholine formation?

Answer 4

1. Acetyl-CoA + Choline

2. About 2 pools - Reserve vesicles (20%) & readily released vesicles (80%).

Question 5

Sequence at pre-synaptic terminal ?

Answer 5

1. Nerve impulses activate sodium channels
2. Activation of P-type voltage-dependent calcium channels
3. Influx of calcium into the cell
4. Acetylcholine vesicles released

Question 6

Synaptic cleft?

Answer 6

1. Its about 20-50nm

2. Contains acetylcholinesterase - Ionic site, esteratic site (serine), hydrolysis (10000 molecules)

Question 7

Post-junctional cleft?

Answer 7

1. Consists folds and crests
2. Folds: Very high density of Ach receptors
3. Crests: Voltage gated sodium channels

Question 8

Acetylcholine receptors?

Answer 8

1. Nicotinic
2. About 50million AchR/crest
3. Protein of 5 polypeptide subunits in ring structre forming ionic channel

Question 9

Types of Acetylcholine receptors?

Answer 9

1. Mature/adult junctional AchR

2. Immature/fetal extrajunctional AchR

Question 10

Mature/adult junctional AchR?

Answer 10

1. Consists - 2-alpha, 1-beta, 1-delta & 1-Epsilon
2. High conductivity
3. Very short opening (1ms)

Question 11

Immature/fetal extrajunctional AchR

Answer 11

1. Consists - 2-alpha, 1-beta, 1-delta & 1-gamma
2. Longer opening of channels
3. Low conductance channel
4. Develops after - Burns, sepsis, upper & lower motor neuron injury
5. Sensitive to Sux

Question 12

Upregulation of Immature/fetal extrajunctional AchR?

Answer 12

1. Upper & lower motor neuron defects
2. Prolonged chemical denervation (NMB, MgSO, clostridial toxins)
3. Direct muscle trauma, tumour or inflammation
4. Thermal injury
5. Disuse atrophy
6. Severe infection

All the above could upregulate AchR

Question 13

Types of NMB drugs according to mechanism of action?

Answer 13

1. Preventing Ach release (MgSO, aminoglycosides)
2. Preventing Ach synthesis (Hemicholinum)
3. Depleting Ach stores (Tetanus toxin)
4. Blocking Ach receptors (rocuronium, atracurium)

Question 14

Ideal NMB agent?

Answer 14

See picture..

Question 15

Suxamethonium?

Answer 15

1. It is 2 acetylcholine molecules joined by ester linkage
2. About 10% excreted in urine and minimally hepatically metabolised
3. Hydrolysed by plasma cholinesterase
4. Causes depolarization of receptors
5. Onset 60s, duration 2-3mins

Question 16

Side effect of suxamethonium?

Answer 16

1. Myalgia
2. Cardiac arrhythmia
3. Hyperkalaemia
4. Increase IOP
5. Anaphylaxis & MH

Question 17

Contraindications of Suxamethonium?

Answer 17

1. Severe muscle trauma
2. Burns > 24 hours - 18 months
3. Muscle disease

Question 18

Non-depolarizing agents?

Answer 18

Aminosteroids and Benzylquinolinums

1. Do not alter structural conformity of the AchR
2. Reversible binding to alpha subunit via quaternary ammonium group
3. Highly ionised, water soluble drugs, distributed in plasma and ECF - Small Vd

Question 19

Atracurium?

Answer 19

1. About 0.5mg/kg, onset 2.5mins, lasting 20-35mins
2. metabolised by ester hydrolysis (60%) & Hoffman degradation (40%)
3. Hoffman - pH and temperature dependent.
4. Laudanosine as an inactive metabolite - Epileptogenic properties.
5. May cause histamine release / anaphylaxis
6. Associated with critical illness myopathy
7. No direct CVS effect

Question 20

Cisatracurium? (1 of 10 isomers of atracurium)

Answer 20

1. Dose 0.15-0.2mg/kg, onset 2-3mins, duration 20-35mins
2. Isomer of atracurium
3. Reduced side effect
4. About 3-4 times more potent than atracurium
5. Hoffman degradation - Less laudanosine produced
6. Does not release histamine
7. Greater CVS stability
8. useful for critical illness infusion

Question 21

Vecuronium?

Answer 21

1. Dose 0.1mg/kg, onset 3-4mins, duration 30-45 mins
2. Monoquaternary amine
3. About 30% eliminated in urine
4. Active metabolites (hepatic deacetylation)
5. Avoid repeated doses in renal or hepatic failure
6. No histamine release
7. No CVS effect
8. Partial affinity for sugammadex

Question 22

Rocuronium? Rapid onset curonium

Answer 22

1. Dose 0.6mg/kg, onset 1-1.5mins, duration 30-45 mins
2. About 6-8 times less potent than vecuronium
3. Excreted unchanged in urine (30%) and bile (50%)
4. Dependent on hepatic function
5. No active metabolites
6. Minimal histamine release
7. Mild vagolytic properties - Increases HR
8. Painful on injection and useful for critical illness infusion

Question 23

Factors affecting duration of non-DNMB agents ?

Answer 23

1. Concomitant use of volatile agents
2. pH (Acidosis)
3. Temperature (Hypothermia)
4. Age
5. Hypokalaemia
6. Hypocalcaemia
7. Myasthenia gravis
8. Hepatic & renal diseases

Question 24

Anticholinesterases ?

Answer 24

1. Include; Neostigmine, Edrophonium, Pyridostigmine, Organophosphorous
2. Inhibits acetylcholinesterases
3. Prolongs half-life of Ach
4. Muscarinic effects

Question 25

Cyclodextrans ? Sugammadex

Answer 25

1. About 8 oligosccharides in a cylindrical structure. 2. Lipophilic core and hydrophilic tail 3. Encapsulates rocuronium 4. Sug+Roc complex excreted in urine 5. No muscarinic effects 6. Prolonged QT interval and bradycardia reported

Question 26

Qualitative NMB monitoring ?

Answer 26

1. Nerve stimulator

Question 27

Quantitative NMB monitoring ?

Answer 27

1. Mechanomyography - Ulnar nerve stimulation - Gold standard 2. Electromyography - Measures muscle AP following nerve stimulation - influenced by local temperature & diathermy 3. Acceleromyography - Piezoelectric sensor - Acceleration of stimulated muscle Newton's second law of motion - F=ma

Question 28

Site for nerve stimulation?

Answer 28

1. Adductor pollicis - Adduction of thumb 2. Black -ve close to wrist and red +ve proximally 3. Facial nerve - Less accurate than ulnar nerve. (Orbicularis oculi & corrugator supercilli)

Question 29

Differential muscle sensitivity?

Answer 29

1. Fast in central muscles - Larynx & diaphragm | 2. Slower in peripheral muscles - Adductor pollicis

Question 30

Times to receovery (fastest to slowest)?

Answer 30

Diaphragm > Laryngeal muscles > Corrugator supercilli > Abdominal muscles > Orbicularis oculi > Geniohyoid muscles > Adductor pollicis muscle.

Question 31

TOF?

Answer 31

1. Supremaximal twitch at 2Hz (4 twitches in 2 secs) 2. Twitches are 500ms apart 3. No fade in depolarising agent

Question 32

Phase II block?

Answer 32

1. After > 4mg/kg of Sux 2. Repeat doses or infusion of Sux 3. Fade is noted 4. Post-tetanic potentiation

Question 33

TET? Tetanus

Answer 33

1. Repetitive stimulation at high frequency 50-200Hz for 5 secs 2. Fade with NDNMB increases 3. Affects presynaptic AchR

Question 34

Post-tetanic count ?

Answer 34

1. Tetanic stimulus 50Hz for 5 secs 2. Followed 3secs later by ST stimuli at 1Hz for 20 secs 3. Tetanus mobilises presynaptic Ach release 4. Potentiates response to subsequent stimulation - Postetanic facilitation 5. Assess deep NMB

Question 35

DBS ?

Answer 35

1. Two mini tetanic bursts @ 50Hz within 0.75 sec apart 2. Easy to subjectively assess fade 3. No advantage over TOF

Question 36

Physiological conditions potentiating NMB?

Answer 36

See pictures