Spasmolytic Drugs

SPASMOLYTIC DRUGS

Spasticity is characterized by an increase in tonic stretch reflexes and flexor muscle spasms (ie, increased basal muscle tone) together with muscle weakness. It is often associated with spinal injury, cerebral palsy, multiple sclerosis, and stroke. These conditions often involve abnormal function of the bowel and bladder as well as skeletal muscle. The mechanisms underlying clinical spasticity appear to involve not only the stretch reflex arc itself but also higher centers in the CNS (ie, upper motor neuron lesion), with damage to descending pathways in the spinal cord resulting in hyperexcitability of the alpha motoneurons in the cord. Pharmacologic therapy may ameliorate some of the symptoms of spasticity by modifying the stretch reflex arc or by interfering directly with skeletal muscle (ie, excitation-contraction coupling). The important components involved in these processes are shown in Figure 27–10.

Drugs that modify this reflex arc may modulate excitatory or inhibitory synapses . Thus, to reduce the hyperac-tive stretch reflex, it is desirable to reduce the activity of the Ia fibers that excite the primary motoneuron or to enhance the activ-ity of the inhibitory internuncial neurons. These structures are shown in greater detail in Figure 27–11.

A variety of pharmacologic agents described as depressants of the spinal “polysynaptic” reflex arc (eg, barbiturates [phenobarbi-tal] and glycerol ethers [mephenesin]) have been used to treat these conditions of excess skeletal muscle tone. However, as illus-trated in Figure 27–11, nonspecific depression of synapses involved in the stretch reflex could reduce the desired GABAergic inhibitory activity, as well as the excitatory glutamatergic trans-mission. Currently available drugs can provide significant relief from painful muscle spasms, but they are less effective in improv-ing meaningful function (eg, mobility and return to work).