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Drugs that affect skeletal muscles fall into two major therapeutic
groups: those used during surgical procedures and in intensive care
units to cause paralysis (i.e., neuromuscular
blockers), and those used to reduce spasticity in a variety
of neurologic conditions or to reduce muscle spasm following muscle
injury or inflammation (i.e., spasmolytics)
(Figure 33–1). Neuromuscular blocking drugs interfere with
transmission at the neuromuscular end plate and lack central nervous
system activity. These compounds are used primarily as adjuncts
to general anesthesia. Drugs in the spasmolytic group have traditionally
been called “centrally acting” muscle relaxants
because most of them act at multiple sites in the central nervous
system (CNS) rather than at the neuromuscular end plate. However,
two spasmolytic drugs—dantrolene and botulinum toxin—act in or
near skeletal muscle with no significant central effects. Spasmolytic
drugs (with one exception) do not prevent muscle contraction but
rather decrease neuronal excitability. For basic and clinical pharmacology
of neuromuscular blocking drugs, see Chapter 5.
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Spasticity is characterized by an increase in tonic stretch reflexes
and flexor muscle spasms (i.e., increased basal muscle tone), together
with muscle weakness and a reduction in viscoelastic muscle properties.
It is often associated with cerebral palsy, multiple sclerosis,
spinal cord injury, and stroke. These conditions often involve abnormal
function of the bowel and bladder as well as skeletal muscle. The
mechanisms underlying spasticity in these types of neurologic injury
appear to involve not only the stretch reflex arc itself but also
higher centers in the CNS (upper motor neuron lesions), with damage
to descending pathways in the spinal cord, resulting in loss of supraspinal
inhibition to the alpha and gamma motor neurons in the anterior
horn of the spinal cord. With damage to descending pathways, upper
motor neurons from the cerebral cortex and brain stem nuclei no
longer modulate spinal reflexes, and no longer activate the spinal
cord inhibitory interneuron pools. The decrease in activity in the
inhibitory interneurons results in increased excitability of alpha
motor neurons in the cord. Some of the components involved in these descending
inhibitory pathways are shown in Figure 33–2.
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Pharmacologic therapy can ameliorate some of the signs and symptoms
of neurologic injury spasticity by modifying the stretch reflex
arc or, in the case of dantrolene, by interfering directly with skeletal
muscle (i.e., excitation-contraction coupling). The ...