C H A P T E R 2 8
Neuromuscular junction blocking agents
437
who do not adapt to the drugs effectively, use the drugs
for prolonged periods, have certain underlying conditions
or take certain drugs that are known to affect cardiovas-
cular receptors. Prolonged drug use may also result in
gastrointestinal (GI) dysfunction related to paralysis of
the muscles in the GI tract; constipation, vomiting, regur-
gitation and aspiration may occur. Pressure ulcers may
develop because the person loses reflex muscle movement
that protects the body. Hyperkalaemia may occur as a
result of muscle membrane alterations.
Clinically important drug–drug interactions
Many drugs are known to react with the non-
depolarising NMJ blockers. Some drug combinations
result in an increased neuromuscular effect. Halogen-
ated hydrocarbon anaesthetics such as halothane cause
a membrane-stabilising effect, which greatly enhances
the paralysis induced by the non-depolarising NMJ
blockers. If these drugs are used together for a pro
cedure, dose adjustments are necessary, and individuals
should be monitored closely until they recover fully.
A combination of non-depolarising NMJ blockers and
aminoglycoside antibiotics (e.g. gentamicin) also leads
to increased neuromuscular blockage. Individuals who
receive this drug combination require a lower dose of the
non-depolarising NMJ blocker and prolonged support
and monitoring after the procedure.
Calcium-channel blockers may also greatly increase
the paralysis caused by non-depolarising NMJ blockers
because of their effects on the calcium channels in the
muscle. If this combination cannot be avoided, the dose
of the non-depolarising NMJ agent should be lowered
and the person should be monitored closely until
complete recovery occurs.
If non-depolarising NMJ blockers are combined
with cholinesterase inhibitors, the effectiveness of the
non-depolarising NMJ blockers is decreased because
of a build-up of ACh in the synaptic cleft. Combination
with xanthines (e.g. theophylline, aminophylline) could
result in reversal of the neuromuscular blockage. Indi-
viduals receiving this combination of drugs should be
monitored very closely during the procedure for the
potential of early arousal and return of muscle function.
Do not mix the drug with any alkaline solutions
such as barbiturates because a precipitate may form,
making it inappropriate for use.
atracurium
cisatracurium
pancuronium
rocuronium
vecuronium
suxamethonium
100
Onset
Duration
90
Minutes
80
70
60
50
40
30
20
10
0
FIGURE 28.3
Onset and duration of non-depolarising NMJ blockers.
Prototype summary: Pancuronium
Indications:
As an adjunct to general anaesthesia;
to induce skeletal muscle relaxation; to reduce the
intensity of muscle contractions in electroconvulsive
therapy; to facilitate the care of people undergoing
mechanical ventilation.
Actions:
Occupies the muscular cholinergic receptor
site, preventing ACh from reacting with the
receptor; does not cause activation of muscle cells;
causes a flaccid paralysis.
Pharmacokinetics:
Route
Onset
Duration
IV
4–6 mins
120–180 mins
T
1/2
:
89 to 161 minutes; metabolised in the tissues,
excreted unchanged in the urine.
Adverse effects:
Respiratory depression, apnoea,
bronchospasm, cardiac arrhythmias.
D
epolarising neuromuscular
junction
(NMJ)
blocker
There is only one agent classified as a depolarising NMJ
blocker: succinylcholine, also known as suxamethonium
(generic).
Therapeutic actions and indications
Suxamethonium, a depolarising NMJ blocker, attaches
to the ACh-receptor site on the muscle cell, causing a
prolonged depolarisation of the muscle. This depolar-
isation causes stimulation of the muscle and muscle
contraction (seen as twitching) and then flaccid paral-
ysis. Both effects cause muscles to stop responding to
stimuli and paralysis occurs.
Suxamethonium has a rapid onset and a short
duration of action because it is broken down by cho-
linesterase in the plasma. Unlike endogenous ACh,
however, suxamethonium is not broken down instantly.
The result is a prolonged contraction of the muscle,
which cannot be re-stimulated. Eventually a gradual
repolarisation occurs as continually stimulated channels
