Neuromuscular Blocking Drugs

Question 1

How do volatile anaesthetics affect calcium channels?

Answer 1

They are calcium channel antagonists.

Question 2

Which patient factors are included under risk factors for aspiration of gastric contents and would thus require rapid protection of their airways?

Answer 2

Emergency surgery in patients who have not been fasted
• Trauma patients (trauma results in gastric stasis)
• Comatose patients with a Glasgow Coma Scale (GCS) of less than 8
• Bowel obstruction
• Any suggestion of delayed gastric emptying
• Pregnant women after 12 weeks’ gestation
• History of reflux or hiatus hernia
• Morbid obesity

Question 3

List surgical factors that would where a muscle relaxant would be required.

Answer 3

Microsurgery where any movement or cough would compromise on surgical
technique and outcome, e.g. neurosurgery, ENT, or intra-ocular procedures.
• Laparotomies and laparoscopic surgery require good abdominal muscle relaxation.
• Orthopaedic surgery: Muscle relaxation may help to reduce dislocated joints or
fractured long bones.
• Cardiac and thoracic surgery generally require an immobile, paralysed patient.
• General anaesthesia is provided for psychiatric patients undergoing electroconvulsive
therapy (ECT). Suxamethonium is administered to reduce the motor manifestations
and potential harm that may occur from the induced seizure.

Question 4

Are muscle relaxants used routinely in ventilated patients in ICU?

Answer 4

No, but in a few
instances prolonged ventilation may require neuromuscular blockade (tetanus is a
famous example)

Question 5

What must always be done BEFORE you administer a muscle relaxant?

Answer 5

You must first assess the patient’s airway. Includes opening the mouth opening, neck movement, upper airway/ neck anatomy.
[Done in all anaesthetic cases nonetheless]

Question 6

Where is Ach formed and stored?

Answer 6

Acetylcholine (ACh) is formed and stored in the terminal axon of the motor nerve, in pre-synaptic
vesicles

Question 7

List the various receptor sites of acetylcholine.

Answer 7

The entire
parasympathetic nervous system (PNS); parts of the sympathetic nervous system (SNS) -
63
sympathetic ganglia, adrenal medulla and sweat glands; some neurons in the central nervous
system; and somatic nerves innervating skeletal muscle.

Question 8

Ach diffuses across the cleft and binds with the receptor. Then, a second Ach binds causing a conformation change.
What happens following this conformation change in the receptor?

Answer 8

The central pore opens which results in an influx of sodium.
Threshold potential reached–> depolarisation of the muscle membrane.
Propagation of AP–> increase in intracellular calcium which causes muscle contraction (interaction of actin and myosin)

Question 9

What are the 3 ways in which muscle relaxation may be achieved?

Answer 9

a) Nerve, e.g. local anaesthetics and Botox
b) Neuromuscular junction (this is the site of action of neuromuscular blockers or NMBs)
c) Muscle itself, e.g. dantrolene (treatment for malignant hyperthermia)

Question 10

The 2 classifications of neuromuscular blockers.

Answer 10

Depolarising and non-depolarising agents.

Question 11

what is the mechanism of action for Depolarising NMBs?

Answer 11

chemical similarities to ACh and bind to ACh receptors generating an
action potential. They act as ACh receptor agonists and have a non-competitive mechanism of
action.

Question 12

what is the mechanism of action for Non-depolarising NMBs?

Answer 12

Non-depolarising NMBs also bind to ACh receptors but they do not induce the required receptor
changes for depolarization to occur. They simply prevent ACh from binding. No threshold
potential develops. They therefore function as competitive antagonists. They compete with ACh
for receptors on the post-junctional membrane and can be reversed by increasing the
concentration of ACh. In the early stages the bond is very strong and they cannot be displaced
by high concentrations of Ach.

Question 13

Which reflexes/functions will be lost due to administration of neuromuscular blockers?

Answer 13

Inability to maintain an airway (loss of muscle tone)
• Inability to breathe and cough
• Loss of laryngeal reflex

Question 14

Why is it important to call the depolarising and non-depolarising agents “neuromuscular blockers” and not muscle relaxants?

Answer 14

Specificity. Muscle relaxants is a broad term which can also refer to benzodiazepines such as midazolam/diazepam. Neuromuscular blockers is a more accurate term and narrows down that which you are referring to.
They ARE muscle relaxants, but has a specific mode of action, one that is different to the mechanism of action of the benzodiazepines.

Question 15

What drug factors can potentiate/prolong the action of muscle relaxants?

Answer 15

Inhalational anaesthetic agents

Aminoglycoside antibiotics, e.g. gentamycin

Question 16

What electrolyte factors can potentiate/prolong the action of muscle relaxants?

Answer 16

↓ calcium
↑ magnesium
↑ or ↓ potassium

Question 17

How can temperature affect the action of muscle relaxants?

Answer 17

Hypothermia potentiates suxamethonium

Hyperthermia potentiates the non-depolarisers

Question 18

Which pH imbalance potentiates/ prolongs the action of muscle relaxants?

Answer 18

Acidosis

Question 19

Depolarising Agent?

Answer 19

Suxamethonium (Scoline®, succinylcholine) is the only depolarizing agent in current
use and is short acting with a very rapid onset. It is the classic relaxant for a rapid
sequence induction.

Question 20

Short acting non-depolarising agent.

Answer 20

Mivacurium (Mivacron ®) – not routinely used or available in South Africa

Question 21

Intermediate acting non-DA

Answer 21

Vecuronium (Norcuron®)
• Rocuronium (Esmeron®) – in high dose, can be used for rapid sequence induction
• Atracurium (Tracrium®) — useful for patients in renal failure
• Cisatracurium (Nimbex®) — an isomer of atracurium also used for patients in renal
failure

Question 22

Long acting non-DA

Answer 22

Pancuronium (Pavulon®) (no longer in widespread use, being phased out)

Question 23

Chemical structure of Suxamethonium chloride

Answer 23

Consists of two molecules of ACh linked together with two quaternary amine groups

Question 24

What is the dose for sux and how quickly does it cause paralysis?

Answer 24

A dose of 1 mg/kg

profound paralysis in 60 seconds

Question 25

What is paralysis preceded by when administering sux? Why does this happen?

Answer 25

Paralysis is preceded by fasciculations as a result of random depolarization of myofibrils, causing uncoordinated contractions

Question 26

Who is at risk when given sux?

Answer 26

Renal failure patients with K+ > 5,0 mmol/L; patients who have had massive tissue injury, e.g. burns and crush injury; and those who have disuse of their muscles over weeks to months, e.g. patients living with paraplegia, stroke patients, and end-stage disease

Question 27

Why are hyperkalaemic states relevant when administering sux?

Answer 27

Depolarisation results in the release of K+ from the muscle into the plasma. A single dose of suxamethonium increases plasma K+ by 0,5 mmol/L. Can worsen condition and cause dysrhythmias and asystole.

Question 28

Side effects of sux.

Answer 28

Hyperkalaemia Hyperkalaemia leads to dysrhythmias and asystole bradycardia which may lead to cardiac arrest malignant hyperthermia

Question 29

Upon receiving repeated doses of suxamethonium, a patient enters a state of bradycardia. What should be administered?

Answer 29

a vagolytic drug, e.g.atropine

Question 30

What enzyme breaks sux down?

Answer 30

``` plasma cholinesterase (also called pseudocholinesterase or butyrylcholinesterase) ```

Question 31

In which patients is the action of pseudocholinesterase reduced in?

Answer 31

reduced in patients with hypothermia, liver disease, pregnant women and if the patient is taking another drug that requires this enzyme for its breakdown.

Question 32

an inherited disorder of pseudocholinesterase where the enzyme produced is chemically different to the normal enzyme with resultant varying degrees of activity and prolonged paralysis.

Answer 32

Scoline Apnoea

Question 33

How to treat a patient if discovered to have scoline apnoea?

Answer 33

Ensure adequate sedation whilst continuing mechanical ventilation until muscle power returns as the suxamethonium is metabolised. Alternatively, fresh frozen plasma (FFP) may be transfused to accelerate suxamethonium degradation, as plasma contains the necessary enzyme, plasma cholinesterase.

Question 34

Irrelevant question? | What was the first NMB agent?

Answer 34

Curare. obtained from a South American vine, the curare plant

Question 35

Which ND NMB's are benzylissoquinolones?

Answer 35

atracurium, cisatracurium and mivacurium

Question 36

Which ND NMB's are aminosteroids?

Answer 36

Vecuronium, rocuronium and pancuronium

Question 37

Vecuronium

Answer 37

Dose: 0,1 mg kg-1 Presentation: White powder in ampoule contains 4 mg. Usually dilute to 2 mg ml-1 with sterile water. Features: • Cardiovascularly stable; occasional bradycardia especially when given with etomidate and / or fentanyl. • No histamine release. 66 • Relies on hepato-biliary excretion and therefore safe in renal failure patients (only 15 % renally excreted)

Question 38

Rocuronium

Answer 38

Dose: 0.45 – 1.2 mg kg-1 (depending on the clinical situation, patient and surgical factors) Presentation: 5 ml ampoules containing 50 mg (10 mg ml-1) Features: • The “ROC” in Rocuronium stands for “Rapid Onset Curare” • A low dose results in a slow onset of action—3-5 minutes before patient can be intubated, with a subsequently short duration of action • A high dose (0.9–1.2 mg kg-1) facilitates intubation within 60 - 90 s, however it then has a long duration of action (up to an hour) as opposed to suxamethonium • Cardiovascularly stable; mild ↑ in BP and HR

Question 39

Atracurium

Answer 39

Dose: 0.5 mg kg-1 Presentation: 10 mg ml-1 solution Features: • Cardiovascularly stable but it can release histamine and cause hypotension • Metabolism via nonspecific esterases and non-enzymatic chemical breakdown occurring at physiologic pH and temperature • Safe in renal failure

Question 40

Cisatracurium

Answer 40

``` Dose: 0,15 mg kg-1 Presentation: Ampoules containing either 5 mg or 10 mg with a concentration of 2 mg ml-1 Features: • Useful in liver and renal failure • NO histamine release ```

Question 41

Difference in location of muscarinic vs nicotinic receptors.

Answer 41

Nicotinic receptors are located on the autonomic ganglia and in skeletal muscle (blocked by the non-depolarising muscle relaxants). Muscarinic receptors are located on end-organ effector cells in the heart (sinoatrial and atrioventricular nodes); smooth muscle (bronchi and GIT) and glands (salivary and lacrimal). They are blocked by anticholinergic drugs such as atropine and glycopyrrolate.

Question 42

What is the name of the NDA reversal agent

Answer 42

Neostigmine

Question 43

Mechanism of action of neostigmine? How does reversal work, w.r.t. Ach

Answer 43

AchE is inhibited by neostigmine. Normally ACh is rapidly degraded by acetyl cholinesterase (AChE) within milliseconds. By inhibiting this enzyme with Neostigmine, there will be more ACh available to compete with the NMBs and displace them and reverse their effect.

Question 44

What is a side effect of administering neostigmine

Answer 44

If an AChE inhibitor is administered ; Ach concentration will increase at all cholinergic receptors. The unwanted parasympathetic manifestations of this are bradycardia, bronchospasm and bronchosecretion, increased bowel motility and pupillary constriction

Question 45

How are the side effects of neostigmine treated?

Answer 45

acetylcholinesterase inhibitor neostigmine is always given with an anticholinergic blocking the muscarine receptors. The two antimuscarinic (or anticholinergic) drugs in common use are atropine and glycopyrrolate

Question 46

Dose of neostigmine

Answer 46

0,04 - 0,05 mg kg-1 Adults, ( 2,5 mg)

Question 47

Dose of glycopyrrolate

Answer 47

0,01 - 0,015 mg kg-1 ( 0,4 - 0,6 mg )

Question 48

Dose of atropine

Answer 48

0,02 mg kg-1 (1 - 1,2 mg)

Question 49

When is it safe to administer a reversal agent, clinically? | Is this way reliable?

Answer 49

exhibiting signs of spontaneous recovery from the neuromuscular blockade are a gag reflex, breathing, coughing, and eye opening. Sustained head lift for 5 - 10 seconds; sustained hand squeeze; and sustained jaw grip of tongue depressor Nope, not reliable.

Question 50

Best way to determine patient readiness for reversal?

Answer 50

Peripheral nerve stimulation, aka Train of Four.

Question 51

How does the train of four work?

Answer 51

If ≥ 3 twitches are present, and ≥ 30 minutes since the last dose of muscle relaxant has been administered, then the reversal can safely be given

Question 52

Which nerves can be used for train of four?

Answer 52

Ulnar at the wrist; facial nerve; common peroneal at neck of the fibula; and the posterior tibial at the ankle

Question 53

What is a twitch and when are twitches useful?

Answer 53

1 short duration 0,1-1 Hz stimulus. Useful immediately after administering a muscle relaxant when you want to be sure that the patient is paralysed before intubation.

Question 54

Define train of four, including the frequency required.

Answer 54

used to monitor the degree of neuromuscular block and assess for reversibility; 4 twitches of 2 Hz each applied over 2 seconds.

Question 55

How does suxamethonium differ from rocuronium, for example, with regards to train of four twitches.

Answer 55

For sux, there is no fade, the twitches are all the same height, simply reduced in size. Rocuronium exhibits fade, (1st twitch is bigger than the 4th twitch

Question 56

Signs of inadequate reversal.

Answer 56

1. Jerky respiration 2. Poor chest expansion with ↓ tidal volume 3. Tracheal tug 4. Restlessness, which may be aggravated by hypoxia 5. Inability to raise the head from the pillow 6. Weak hand grip 7. Poor ability to cough 8. Ptosis

Question 57

Name of the medication with the brand name Bridion.

Answer 57

Sugammadex.

Question 58

What is the mechanism of action and chemical structure of sugammadex?

Answer 58

Has the ability to rapidly encapsulate amino-steroid neuromuscular blocking agents, promoting their dissociation from nicotinic receptors at the neuromuscular junction and terminating their action. It is a modified gammacyclodextrin, a cyclic oligosaccharide carbohydrate

Question 59

What is Sugammadex mainly used for and what other NMBA's can it also be used for?

Answer 59

rocuronium, but is also effective against | vecuronium and pancuronium (i.e. the amino-steroids)

Question 60

True or false: Sugammadex can't be used for benzylisoquinolones.

Answer 60

Trueness!