23.3 Rocuronium + Antagonists

Question 1

a) Outline the mechanisms of spontaneous recovery from neuromuscular blockade following the
administration of rocuronium. (2 marks)

Answer 1

> > After the administration of rocuronium,
there is a dynamic association
and dissociation of the rocuronium
with the nicotinic receptors.

> > Redistribution of the drug occurs
down its concentration gradient
into the plasma,
once plasma levels start to decrease.

> > The reduction in plasma concentration
is driven by metabolism in the liver
and excretion in the bile.

Question 2

b) Which classes of drugs can be used to antagonise the action of rocuronium (2 marks) and how do
they work? (5 marks)

Answer 2

1. Reversible acetylcholinesterase inhibitors:
   neostigmine.

Neostigmine hydrolyses acetylcholinesterase
by forming a carbamylated enzyme complex
with the esteratic site,

thus increasing amount of acetylcholine at neuromuscular junction and
competing with residual rocuronium

2. Cyclodextrins: sugammadex.

Sugammadex has a ring-like structure with
a hydrophilic outer surface and
lipophilic inner surface that
encapsulates the lipophilic rocuronium.

Question 3

c) What are the advantages and disadvantages of these antagonist drugs? (11 marks)

Answer 3

Reversible acetylcholinesterase inhibitor

Adv
• Cheap.
• Familiar.

Disadvantages

• Unwanted muscarinic receptor action ***
causing bradycardia, gut stimulation
(possibly with implications on
anastomotic integrity),

secretions, bronchospasm,
urinary retention.

• Co-administration of glycopyrrolate
to mitigate muscarinic effects
results in dry mouth, tachycardia.

• No use in CICO when
neuromuscular blocking drug
has just been given.

• Observer error in train-of-four monitoring
may lead to overestimation of level of
reversibility, resulting in ineffective
administration or premature administration
with the possibility of recurarisation.

Sugammadex:

• With appropriate dosing,
reverses from full paralysis with
rocuronium, useful in ‘can’t
intubate, can’t oxygenate’(CICO)
situations.

• Effective for rocuronium and
vecuronium for routine reversal.

• In typical circumstances, no risk
of recurarisation due to
irreversible encapsulation of
neuromuscular blocking drug.

• No significant cardiovascular effects.

• May be used to temporarily reverse
neuromuscular block intraoperatively.

• Facilitates rapid turnover of cases
that require full paralysis but are
of short duration such as airway
or laparoscopic surgery.

• Facilitates reversal of
neuromuscular blockade in
patients with myotonic
dystrophy for whom
neostigmine should be avoided.

Disadvantages:

• Flucloxacillin and fusidic acid
may displace neuromuscular
blocking drug from sugammadex,
potentiating block.

• Sugammadex will encapsulate
progesterone, reducing the
efficacy of hormonal contraceptives.

• Cost.

• Potential for allergic reactions.

• Not effective against
benzylisoquinoliniums.