388
P A R T 4
Drugs acting on the central and peripheral nervous systems
structures. Because the spasticity is caused by nerve
damage in the CNS, it is a permanent condition. Spastic-
ity may result from an increase in excitatory influences
or a decrease in inhibitory influences within the CNS.
The interruption in the balance among all of these
higher influences within the CNS may lead to exces-
sive stimulation of muscles, or
hypertonia
, in opposing
muscle groups at the same time, a condition that may
cause contractures and permanent structural changes.
This control imbalance also results in a loss of coordi-
nated muscle activity.
For example, the signs and symptoms of cerebral
palsy and paraplegia are related to the disruption in the
nervous control of the muscles. The exact presentation
of any chronic neurological disorder depends on the
specific nerve centres and tracts that are damaged and
how the control imbalance is manifested.
■■
Movement and muscle control are regulated by spinal
reflexes and the upper CNS, including the basal
ganglia, cerebellum and cerebral cortex.
■■
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.
■■
The pyramidal tract in the cerebellum coordinates
intentional muscle movement, and the extrapyramidal
tract in the cerebellum and basal ganglia coordinates
involuntary muscle activity.
■■
Muscle or skeletal damage may send a multitude of
stimuli to the spinal cord and result in muscle spasms
or extended contraction.
■■
Damaged motor neurons can cause muscle spasticity
and impaired movement and coordination.
CENTRALLY-ACTING SKELETAL MUSCLE
RELAXANTS
Centrally-acting skeletal muscle relaxants (Table 25.1)
include baclofen (
Lioresal
) and orphenadrine (
Norflex
).
Diazepam (
Valium
), a drug widely used as an anxiety
agent (see Chapter 20), has also been shown to be an
effective centrally-acting skeletal muscle relaxant. It
may be advantageous in situations in which anxiety may
be precipitating the muscle spasm.
Other measures in addition to these drugs should be
used to alleviate muscle spasm and pain. Such modal-
ities as rest of the affected muscle, heat applications
to increase blood flow to the area to remove the pain-
causing chemicals, physical therapy to return the muscle
to normal tone and activity, and anti-inflammatory
agents (including non-steroidal anti-inflammatory drugs
[NSAIDs]) if the underlying problem is related to injury
or inflammation may help. This may be aided by use of
a combined product such as orphenadrine and paraceta-
mol (
Norgesic
).
Therapeutic actions and indications
The centrally-acting skeletal muscle relaxants work in
the CNS to interfere with the reflexes that are causing the
muscle spasm. Because these drugs lyse or destroy spasm,
they are often referred to as spasmolytics. Although the
exact mechanism of action of these skeletal muscle relax-
ants is not known, it is thought to involve action in the
upper or spinal interneurons. The primary indication for
the use of centrally-acting skeletal muscle agents is the
relief of discomfort associated with acute, painful mus-
culoskeletal conditions as an adjunct to rest, physical
therapy and other measures. Because these drugs work
in the upper levels of the CNS, possible depression must
KEY POINTS
Transverse
tubule
Sarcoplasmic
reticulum
Stretched
Contracted
Mitochondria
H band I band
A band
Myosin
Actin
Sarcomere
Myofibrin
Muscle
fibre
Terminal
cisternae
FIGURE 25.2
When stimulation stops, calcium ions are actively
transported back into the sarcoplasmic reticulum, resulting in
decreased calcium ions in the sarcoplasm. The removal of calcium
ions restores the inhibitory action of troponin–tropomyosin;
cross-bridge action is impossible in this state.
