Neuromuscular Blocking Agents

Question 1

name a depolarising agent

Answer 1

suxamethonium

Question 2

chemical structure of sux

Answer 2

2 Ach molecules

Question 3

Ampoule of sux

Answer 3

100mg / 2mls

Question 4

Effects of suxamethonium

Answer 4

• rapid profound paralysis in 60 seconds
• ultra short acting = lasts 5 minutes
• fasciculations

Question 5

how is suxamethonium excreted?

Answer 5

Metabolised by pseudocholinesterase that is made by the liver and found freely in plasma

Question 6

Dosing of suxamethonium?

Answer 6

1-2mg/kg and must be stored in the fridge

Question 7

which patients may have prolonged paralysis after sux administration and how should they be managed?

Answer 7

Those with scoline apnea
- abnormal gene that doesn’t make esterase properly

• need to be ventilated and continued sedated until eventually worn off and

or

FFPs

Question 8

side effects of suxamethonium

Answer 8

• myalgia
• parasympathetic = bradycardia
• initial depolarisation = hyperkalemia – cardiac arrest
• scoline apnea
• histamine release
• anaphylaxis
• triggers malignant hyperthermia

Question 9

Contra-Indications of Sux

Answer 9

1. Drug allergy
2. Scoline apnea
3. MH
4. Unknown myopathies
5. Risk of hyperkalemia

Question 10

patients at risk of high K+

Answer 10

• burns
• renal failure
• paralysis

Question 11

name 2 types of non-depolarising agents

Answer 11

a. Benzylisoquinolines
- Curare-based: atracurium, cisatracurium

b. Aminosteroids
- Pancuronium, vecuronium, and rocuronium

Question 12

dosing of non-depolarising

Answer 12

based on lean body mass

Question 13

non-depolarising ampoules

Answer 13

2-5ml in fridge

Question 14

Clinical effects of non-depolarisers

Answer 14

Take longer to act: 1-5 mins
- duration is variable
- no fasiculations

Question 15

how are non-depolarisers metabolised?

Answer 15

• hepatic
• Hoffman degradation

( excreted by renal and liver )

Question 16

name 5 non-depolarising drugs

Answer 16

Pancuronium (rarely used)
Rocuronium (commonest)
Vecuronium
Atracurium
Cisatracurium

Question 17

power that is mixed with water, cheap and frequently used

Answer 17

Vecuronium

Question 18

Pros of vecuronium

Answer 18

CVS and kidney stable
No histamine release

Question 19

Cons of vecuronium

Answer 19

must be avoided in hepatic disease

Question 20

Common and easy solution 50mg in 5mL

Answer 20

Rocuronium

Question 21

Duration of action of vecuronium

Answer 21

Intermediate

Question 22

pros of rocuronium

Answer 22

CVS stable

Question 23

what can be done in a modified rapid sequence induction when sux cannot be used?

Answer 23

Use Rocunonium since 1mg/kg can provide intubating conditions within one minute e.g. in MH

• higher dose = longer acting but usually intermediate action

Question 24

which drug undergoes spontaneous degradation and why is this useful?

Answer 24

Atracurium
- safe in renal and liver failure

Question 25

Side effects of atracurium

Answer 25

- histamine = anaphylaxis - toxic metabolite = laudanosine that can cause CNS toxicity

Question 26

Atracurium duration of action

Answer 26

intermediate

Question 27

isomer of atracurium and why better?

Answer 27

Cisatracurium - no side effects like aura - still spontaneous degradation * slow onset of action

Question 28

how are NMDRs reversed?

Answer 28

ALL non-depolarising muscle relaxants (NMDRs) should be reversed when it is safe to do so… even after the drug has clinically worn off it may still be present in the body and could bind to receptors again Reversal does NOT mean “waking the patient up” Since NMDRs compete with acetylcholine (Ach), they can be reversed by creating enough Ach to displace the NMDR from the nicotinic receptor This can be achieved by inhibiting the enzyme that normally breaks down Ach (acetylcholinesterase)

Question 29

which drugs can be used an NMDRs reversal?

Answer 29

1. Neostigmine 2. Anti-cholinergic agent to act as an anti-muscarinic

Question 30

MOA of neostigmine

Answer 30

Acetylcholinesterase inhibitor > Increases Ach concentration in synaptic cleft > Ach COMPETES with NDMR > But Ach ↑es at both nicotinic and muscarinic receptors which can cause side-effects

Question 31

how to stop muscarinic stimulation of neostigmine?

Answer 31

Atropine or glycopyrrolate > Bronchial secretions > Bronchospasm > Bradycardia > “B”eristalsis (peristalsis)

Question 32

Typical adult reversal doses

Answer 32

Neostigmine 2.5 mg + Glycopyrrolate 0.4–0.6 mg Neostigmine 2.5 mg + Atropine 1 mg

Question 33

Why glycopyrolate attractive?

Answer 33

no cos side effects since doesn't cross BBB, but is expensive

Question 34

When to never give reversal?

Answer 34

With Sux -- since looks like Ash and can hence prolong the action

Question 35

When is it safe to reverse?

Answer 35

If reversal is given too early, Acetylcholine will not be able to effectively displace the muscle relaxant from the nicotinic receptor -- This will lead to inadequate reversal To avoid this we check readiness with a peripheral nerve stimulator -- At least 3 twitches should be present or train of 4 ( even though at this point 75% still blocked ) If a patient is already breathing adequately, it is generally safe to administer muscle relaxant

Question 36

Signs of too quick or inadequate reversal?

Answer 36

- Jerky respiration - Reduced VT ( tidal volume ) - Tracheal tug - Restlessness, may be worsened by hypoxia - Inability to raise head from pillow - Weak hand grip - Poor ability to cough - Ptosis

Question 37

How to manage inadequate reversal?

Answer 37

1. Exclude other causes 2. Maintain ventilation 3. Reverse potentiators 4. PNS 5. Repeat dose max 5mg of Neo

Question 38

Sugammadex

Answer 38

New drug used primarily to reverse rocuronium (also works on vecuronium) A selective relaxant-binding agent (SRBA) Modified sugar that “mops up” any rocuronium by encasing it in its molecular structure; this is excreted renally Can be used at any time  no need to wait as with neostigmine No muscarinic side-effects Very expensive, not available in state