C H A P T E R 2 8
Neuromuscular junction blocking agents
435
gastric acid if the meat were eaten raw, it was safe for
humans. Curare was first purified for clinical use as
the NMJ blocker tubocurarine, which has since been
replaced with more refined drugs that can control onset
and duration of effect. Non-depolarising NMJ blockers
include atracurium (
Tracrium
), cisatracurium (
Nimbex
),
mivacurium (
Mivacron
), pancuronium (generic), rocu-
ronium (
Esmeron
) and vecuronium (
Norcuron, Vecure
).
Therapeutic actions and indications
Non-depolarising NMJ blockers are used when clinical
situations require or desire muscle paralysis (see
Table 28.1 for preferred uses). Therapeutically, non-
depolarising NMJ blockers:
• Serve as an adjunct to general anaesthetics during
surgery when reflex muscle movement could interfere
with the surgical procedure or the delivery of gas
anaesthesia.
• Facilitate mechanical intubation by preventing
resistance to passing of the endotracheal tube and
in situations in which people “fight” or resist the
respirator.
• Facilitate various endoscopic diagnostic procedures
when reflex muscle reaction could interfere with the
procedure.
• Facilitate electroconvulsive therapy when intense
skeletal muscle contractions as a result of electric
shock could cause the person broken bones or other
injury.
Pharmacokinetics
All non-depolarising NMJ blockers are similar in struc-
ture to ACh and compete with ACh for the muscle
Ach-receptor site (Figure 28.2). As a result, they occupy
the muscular cholinergic receptor site and do not allow
stimulation to occur. These agents do not cause the
activation of muscle cells, and consequently muscle
contraction does not occur. Because they are not broken
down by acetylcholinesterase, their effect is longer
lasting than that of ACh. The non-depolarising NMJ
blockers are hydrophilic instead of lipophilic, so they do
not readily cross the blood–brain barrier and have little
effect on the ACh receptors in the brain.
Non-depolarising NMJs are metabolised in the
serum, although metabolism is dependent on the liver to
produce the needed plasma cholinesterases. Most of the
metabolites are excreted in the urine.
Each non-depolarising NMJ blocker differs in terms
of time of onset and duration (Figure 28.3). The drug of
choice in any given situation is determined by the pro-
cedure being performed, including the estimated time
involved.
Contraindications and cautions
Non-depolarising NMJ blockers are contraindicated
in the following conditions: known allergy to any of
these drugs
to prevent hypersensitivity reactions
; myas-
thenia gravis
because blocking of the ACh cholinergic
receptors aggravates the neuromuscular disease
(which
results from destruction of the ACh-receptor sites)
and
increases the muscular effects
(see Chapter 32); renal or
hepatic disease,
which could interfere with the metabo-
lism or excretion of these drugs, leading to toxic effects
;
and pregnancy.
Caution should be used in people with any family or
personal history of
malignant hyperthermia
, a serious
adverse effect associated with these drugs that is charac-
terised by extreme muscle rigidity, severe hyperpyrexia
(fever), acidosis and death in some cases,
because malig-
nant hyperthermia can occur with the use of these
drugs.
Caution should also be used in the following
circumstances: pulmonary or cardiovascular dysfunc-
tion,
which could be exacerbated by the paralysis of the
respiratory muscles and resulting changes in perfusion
and respiratory function
;
altered fluid and electrolyte
BOX 28.1
Drug therapy across the lifespan
NMJ-blocking agents
CHILDREN
Children require very careful monitoring and support
after the use of NMJ blockers.These agents are used by
anaesthetists who are skilled in their use and with full
support services available.
The non-depolarising NMJs are preferable because of
the lack of muscle contraction with its resultant discomfort
on recovery. Suxamethonium is usually preferred when a
very short-acting, rapid-onset blocker is needed (e.g. for
intubation).
ADULTS
Adults need to be monitored closely for full return of
muscle function. If suxamethonium is used, they need
to be told that they will experience muscle pain and
discomfort when the procedure is over.
PREGNANCY AND BREASTFEEDING
The NMJs are used during pregnancy and breastfeeding
only if the benefit to the mother outweighs the potential
risk to the fetus or neonate.
OLDER ADULTS
Because older people often also have renal or hepatic
impairment, they are more likely to have toxic levels of
the drug related to changes in metabolism and excretion.
The older person should receive special efforts to provide
skin care to prevent skin breakdown, which is more likely
with older skin.The older person may require longer
monitoring and regular orienting and reassuring.
