neuromuscular blocking agents Flashcards

1
Q

what are neuromuscular agents used for and not used for

A

Mainly used by anaesthetists to paralyse patients
Act at neuromuscular junction

Have no sedative action or cause amnesia (memory loss)
No analgesic property
Never used in isolation

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2
Q

clinical use of neuromuscular agents

A
  • Facilitate intubation of the trachea
  • Airway maintenance important for good oxygenation (less chance of vocal cord damage and postoperative hoarseness)
  • NMBA enable control of ventilation intraoperatively
  • Prevent deleterious movements

Neurosurgery = ventilating patients lowers intracranial pressure
Intensive care = improves conditions for ventilation
Lungs = decreases the work of breathing and O2 consumption, therefore barotrauma to the lungs prevented

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3
Q

intubation

A

insertion of an endotracheal tube for airway protection and ventilation

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4
Q

AChR

A
  • Ligand-gated ion channels
  • 5 subunits composed of 500 amino acids
  • Alpha subunits bind ACh (both bound simultaneously)
  • Binding causes conformational change, which opens the channel allowing ions to flow and muscle contraction to occur
  • 1 ACh molecule must bind to each of the 2 alpha subunits to open the channel
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5
Q

AChE

A

In the synaptic cleft within basal lamina
Secreted by muscles
Hydrolyses ACh to acetate and choline
Choline taken up and resynthesized to ACh

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6
Q

mechanism of action of depolarising NMBAs

A

Succinylcholine (SCh) is the only example in use
—
Mimics the effect of ACh. 1 molecule binds simultaneously to the
2 α subunits

Binds to AChR, opens the channel, leads to continuous endplate depolarisation but not allowing repolarisation

—Causes fasciculations followed by relaxation–biphasicaction BUT is not susceptible to hydrolysis by AChE
—
Remains in the cleft until plasma concentration of SCh decreases due to breakdown by plasma/pseudocholinesterase or elimination by the kidney

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7
Q

SCh clinically

A
  • fast onset of action
  • short duration of action: 3-5 minutes
  • elimination half-life <1 minute
  • broken down by pseudocholinesterase
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8
Q

SCh side effects

A
Cant be reversed 
Cardiac dysrhythmias 
Increased intracranial pressure 
Increased intraocular pressure 
Increased intragastrical pressure 
Increased serum K+ 
Muscle pain post-op 
Trigger for malignant hyperpyrexia
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9
Q

uses of SCh

A
  • quickest, safest way to have rapid and complete relaxation for airway control
  • intubating conditions excellent
  • minimal time for aspiration in patients with full stomachs
  • used in emergency conditions
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10
Q

mechanism of action of non-depolarising NMBAs

A

NMBA bind to 1 or both of the αsubunits of the AChR, preventing binding of ACh and therefore prevents opening of the ion channel

Competitive interaction between ACh and NMBA at the AChReceptor

—Requirement for 1 molecule of NMBA to block the receptor but 2 ACh to open it. This bias favors the antagonist (NMBA)
—
The effect depends on relative concentrations of ACh and drug (NMBA)
—
NM block starts when >70% receptors are occupied and is complete when >90% are occupied

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11
Q

chemical structures of NMBAs and examples

A

Benzylisoquinolones —

 - atracurium
 - cisatracurium
 - mivacurium

Aminosteroids

  - rocuronium
  - vecuronium
  - pancuronium
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12
Q

atracurium

A

-onset of action slow = 3-5min

Intermediate duration of action (40mins)

PH and temperature dependent elimination

Cardiovascular effects – hypotension and tachycardia
Skin rash

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13
Q

mivacurium

A

3X more potent than atracurium

Short acting (20mins)

slow onset of 3-5 minutes

hydrolyzed by pseudocholinesterase (non-depolarising though)

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14
Q

rocuronium

A

Intermediate duration of action, longer than SCh

Low potency, requires larger dose

Rapid onset of action

Cardiac effects minimal

Mainly hepatic elimination

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15
Q

Vecuronium

A

Intermediate duration

Slower onset but similar duration to recuronium

Active metabolites secreted in urine therefore not good for
a patient with renal failure

Minimal cardiac effects

Least potential for anaphylaxis

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16
Q

pancuronium

A

Longest acting

High potency, slow onset

Good for long cardiac surgery procedures

Minimal histamine released

Hepatic and renal clearance

17
Q

reversal of NMBAs

A
  • Only needed for non-depolarizing agents
  • Respiratory and upper airway muscles must function normally

2 strategies:
Titrate perfectly for duration of action (DIFFICULT)
Accelerate reversal - (safer and more reliable)
-increase ACh conc at NMJ
-decrease plasma conc of NMBA

18
Q

How do we increase the ACh concentration at the AChR?

A

Drugs which inhibit AChE

-inhibits hydrolysis of ACh therefore increase in ACh concentration at AChR

19
Q

Anti-AChE drugs and side-effects

A

Neostigmine and pyridostigmine

Side effects:
Potent parasympathetic activtity
Vagal effects – bradycardia and bradyarrhythmia’s
Increased salivation and bowel motility
Atropine reverse these parasympathetic effects

20
Q

antidote

A

Another way to get rid of a drug is to bind it = ANTIDOTE
Rocuronium = sugammadex
1:1 binding and then excreted in the urine
Return of muscle function in 2 minutes

21
Q

danger of residual block

A

Ventilatory response to hypoxia is impaired and does not return to normal until TOFR > 0.9
—
Reduced pharyngeal muscle coordination with TOFR 0.6 – 0.8. Risk of airway collapse.
—
Increase mortality and morbidity if patient has residual block

Aspiration, hypoxia, death!
—
Reversal drug only given when a 4th twitch is visible, that is, once spontaneous recovery has begun.

22
Q

monitoring neuromuscular blockage

A
Peripheral nerve is stimulated electrically and the response of the muscle is assessed
—  
Visual assessment of evoked response
—  Mostly used in clinical setting
—  Measure of TOF and TOF fade in 4 evoked twitches
—  
Measurement of evoked response —  
  -Mechanomyography
—  -Electromyography
—  -Accelerometry