HUF 2-68 Neuromuscular blocking drugs

Question 1

What are neuromuscular blocking agents (NMBAs)

Answer 1

• Drugs that block transmission at NMJ
• Muscle relaxants
• Facilitate tracheal intubation and surgical access in general anaesthesia
• Emergency airway management - Rapid Sequence Intubation (RSI)
• ICU: ↑ patient-ventilator synchrony (↓ O2 consumption)

Question 2

Triad of balanced general anaesthesia

Answer 2

1. Unconsciousness
2. Analgesia
   3 Akinesia (muscle relaxation)
   - Permits surgical access
   - Tracheal intubation, mechanical ventilation
   - Need varies for diff. operations

• Diethyl ether: non-specific
  => Introduction of muscle relaxants (NMBA)
  => ↓ Dose of depressant anaesthetics; ↑ surgical conditions

Question 3

Mechanism of NMBA

Answer 3

• Bind competitively to same receptor (nAChR)
• Prevent stimulation by ACh
• Inhibit muscle contraction
• Specific to nACh receptor (except Succinylcholine)
• Nicotinic: neuromusclar
• Muscarinic: parasympathetic

Question 4

Depolarising NMBA: Succinylcholine

Answer 4

• Agonist at nAChR => depolarise ms endplate
• Stimulate muscle (fasciculation)
• Temporarily refractory to stimulation (flaccid paralysis)
• Very raid onset
• Very short duration
• Metabolised by plasma cholinesterase
• Emergency drug

Side effects:

• Bradycardia (esp. children)
• Ms pain
• Hyperkalaemia (burns, ms disease, spinal injury - upregulation of junctional and extra-junctional nAChR)
• ↑ Intragastric, intraocular and intracranial pressure

(Malignant hyperthermia)
(Prolonged action in cholinesterase deficiency)

Question 5

Non-depolarising NMBD

Answer 5

• Competitively antagonise ACh at nAChR

A. Benzylisoquinolines

• Developed by curare
• Metabolised by enzymatic (ester hydrolysis) / non-enzymatic pathways (Hoffman elimination)
• Non-organ dependent elimination
• Tendency to cause histamine release
  1. Atracurium
• 10 stereo-isomers
  2. Cisatracurium
• Isomer of atracurium
• Less histamine release; CVS stable

B. Aminosteroids

• Totally synthetic
• 2 Active sites joined to steroid base
• CVS stable
• Rocuronium, Vecuronium, Pancuronium

Question 6

Monitoring of NMBA

Answer 6

Peripheral nerve stimulator

• Ulnar n.
• Facial n.
• Posterior tibial n.

Question 7

Reversal of non-depolarising NMBD

Answer 7

Anticholinesterase drugs
- ACh rapidly metabolised by AChE
- Anticholinesterase inhibits AChE
- Neostigmine, Edrophonium
- Not specific to nAChR
- mAChR stimulation => Bradycardia
∴ Must be given with atropine

Mechanism of AChE:

1. Binding of ACh to enzyme active site
   - Anionic site: choline
   - Esteratic site: acetyl
2. Formation of enzyme-substrate complex
   - Acetylated enzyme (t1/2 42ms)
3. Regeneration of enzyme (choline, acetic acid)

Mechanism of anticholinesterase:

1. Binding of neostigmine
2. Formation of enzyme-substrate complex
   - Esteratic site: carbamyl (t1/2 30 min)