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P A R T 4
Drugs acting on the central and peripheral nervous systems
M
any injuries and accidents result in local damage to
muscles or the skeletal anchors of muscles. These injuries
may lead to muscle spasm and pain, which may be of
long duration and may interfere with normal function-
ing. Damage to central nervous system (CNS) neurons
may cause a permanent state of muscle
spasticity
—sus-
tained muscle contractions—as a result of loss of nerves
that help to maintain balance in controlling muscle
activity.
Neuron damage, whether temporary or perma-
nent, may be treated with skeletal muscle relaxants.
Most skeletal muscle relaxants work in the brain and
spinal cord, where they interfere with the cycle of muscle
spasm and pain. However, the botulinum toxins and
dantrolene enter muscle fibres directly. See Box 25.1 for
discussion of the use of these muscle relaxants in various
age groups.
NERVES AND MOVEMENT
Posture, balance and movement are the result of a con-
stantly fluctuating sequence of muscle contraction and
relaxation. The nerves that regulate these actions are
the spinal motor neurons. These neurons are influenced
by higher-level brain activity in the lower areas of the
brain, the
cerebellum
(associated with conscious muscle
movements) and
basal ganglia
(associated with uncon-
scious muscle movements). This brain activity provides
coordination of contractions, and the cerebral cortex
allows conscious thought to regulate movement.
Nutritional:
Muscle contraction
Spinal reflexes
The spinal reflexes are the simplest nerve pathways
that monitor movement and posture (see Figure 25.1).
Spinal reflexes can be simple, involving an incoming
sensory neuron and an outgoing motor neuron, or more
complex, involving
interneurons
that communicate
with the related centres in the brain. Simple reflex arcs
involve sensory receptors in the periphery and spinal
motor nerves. Such reflex arcs make up what is known
as the
spindle gamma loop system
; they respond to
stretch receptors or spindles on muscle fibres to cause a
muscle fibre contraction that relieves the stretch. In this
system, nerves from stretch receptors form a synapse
with gamma nerves in the spinal cord, which send an
impulse to the stretched muscle fibres to stimulate their
contraction. These reflexes are responsible for maintain-
ing muscle tone and keeping an upright position against
the pull of gravity and are important in helping venous
return when the contracting muscle fibres massage veins
BOX 25.1
Drug therapy across the lifespan
Skeletal muscle relaxants
CHILDREN
The safety and effectiveness of most of these drugs have
not been established in children. Agents have been used,
with adjustments to the adult dosage based on the child’s
age and weight.
Baclofen is often used to relieve the muscle spasticity
associated with cerebral palsy. A caregiver needs intensive
education in the use of the intrathecal infusion pump and
how to monitor the child for therapeutic as well as adverse
effects.
Dantrolene is used to treat upper motor neuron
spasticity in children.The dosage is based on body weight
and increases over time.The child should be screened
regularly for CNS and gastrointestinal (including hepatic)
toxicity.
ADULTS
Adults being treated for acute musculoskeletal pain
should be cautioned to avoid driving and to take safety
precautions against injury because of the related CNS
effects, including dizziness and drowsiness.
Adults complaining of muscle spasm pain that may
be related to anxiety often respond very effectively to
diazepam, which is a muscle relaxant and anxiolytic.
PREGNANCY AND BREASTFEEDING
Women of childbearing age should be advised to use
contraception when they are taking these drugs. If a
pregnancy does occur, or is desired, they need counselling
about the potential for adverse effects. Women who are
breastfeeding should be encouraged to find another
method of feeding the baby because of the potential for
adverse drug effects on the baby.
Premenopausal women are also at increased risk for
the hepatotoxicity associated with dantrolene and should
be monitored very closely for any change in hepatic
function and given written information about the prodrome
syndrome that often occurs with hepatic toxicity.
OLDER ADULTS
Older people are more likely to experience the adverse
effects associated with these drugs—CNS, gastrointestinal
and cardiovascular. Because older people often also have
renal or hepatic impairment, they are also more likely
to have toxic levels of the drug related to changes in
metabolism and excretion.
If dantrolene is required for an older person, lower
doses and more frequent monitoring are needed to assess
for potential cardiac, respiratory and liver toxicity.
Older women who are receiving hormone replacement
therapy are at the same risk for development of
hepatotoxicity as premenopausal women and should
be monitored accordingly.
