TIZANIDINEorder

Skeletal muscle relaxants are a heterogeneous group of medications. As a class, they are structurally and pharmacologically diverse. Muscle relaxants are used to treat two different types of underlying conditions:

• spasticity from upper motor neuron syndromes
• muscular pain or spasms from peripheral musculoskeletal conditions

Although muscle relaxants have by convention been classified into one group, the Food and Drug Administration(FDA) has approved only a few medications in this class for treatment of spasticity. The remainder are approved for treatment of musculoskeletal conditions.

Drugs classified as skeletal muscle relaxants include:

• baclofen (Lioresal)
• carisoprodol (Soma)
• chlorzoxazone (Paraflex)
• cyclobenzaprine (Flexeril)
• dantrolene (Dantrium)
• metaxalone (Skelaxin)
• methocarbamol (Robaxin)
• orphenadrine (Norflex)
• tizanidine (Zanaflex)

Muscle relaxants for treatment of spasticity

Spasticity is a state of increased muscular tone with exaggeration of the tendon reflexes. Some of the more common conditions associated with spasticity and requiring treatment include multiple sclerosis, spinal cord injury, traumatic brain injury, cerebral palsy, and poststroke syndrome. In many patients with these conditions, spasticity can be disabling and painful with a marked effect on functional ability and quality of life.

The upper motor neuron syndrome is a complex of signs and symptoms that can be associated with exaggerated cutaneous reflexes, autonomic hyperreflexia, dystonia, contractures, paresis, lack of dexterity, and fatigability. Spasticity from the upper motor neuron syndrome can result from a variety of conditions affecting the cortex or spinal cord.

Only baclofen, dantrolene, and tizanidine are approved for treatment of spasticity. There is fair evidence that baclofen and tizanidine are roughly equivalent for efficacy in patients with spasticity, but insufficient evidence to determine the efficacy of dantrolene compared to baclofen or tizanidine. Tizanidine is associated with more dry mouth and baclofen with more weakness.

Muscle relaxants for treatment of musculoskeletal conditions

Muscle spasm is defined as a sudden involuntary contraction of one or more muscle groups and is usually an acute condition associated with muscle strain (partial tear of a muscle) or sprain (partial or complete rupture of a ligament). Common musculoskeletal conditions causing tenderness and muscle spasms include fibromyalgia, tension headaches, myofascial pain syndrome, and mechanical low back pain or neck pain. If muscle spasm is present in these conditions, it is related to local factors involving the affected muscle groups.

The skeletal muscle relaxants carisoprodol, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, and orphenadrine are approved for treatment of musculoskeletal disorders.

Clinical studies show, that cyclobenzaprine, carisoprodol, orphenadrine, and tizanidine are effective compared to placebo in patients with musculoskeletal conditions (primarily acute back or neck pain). Cyclobenzaprine has been evaluated in the most clinical trials and has consistently been found to be effective.

Efficacy

Most studies have shown the skeletal muscle relaxants to be more effective than placebo in the treatment of acute painful musculoskeletal disorders and muscle spasm, while efficacy was less consistent when treating chronic disorders. When muscle relaxants were used alone, they were not consistently superior to simple analgesics in relieving pain. When the skeletal muscle relaxants were used in combination with analgesics, pain relief is superior to either agent used alone. Studies have suggested that these drugs are effective, have tolerable side effects, and can be an adjunct in the treatment of painful musculoskeletal conditions with associated muscle spasm.

No studies have documented superior efficacy of one skeletal muscle relaxant over another.

Side Effects and Adverse reactions

• All skeletal muscle relaxants may cause sedation (drowsiness, dizziness).
• Baclofen may cause severe central nervous system depression with cardiovascular collapse and respiratory failure.
• Dantrolene has a potential for hepatotoxicity. Overt hepatitis has been most frequently observed between the third and twelfth months of therapy. Risk of hepatic injury appears to be greater in women, in patients over 35 years of age and in patients taking other medications in addition to dantrolene.
• Carisoprodol has some potential for dependence and withdrawal symptoms.
• Cyclobenzaprine, closely related to the tricyclic antidepressants, causes the expected lethargy and anticholinergic side effects, and may have some toxicity in overdose and in combination with other substances.
• Tizanidine may cause low blood pressure, but this may be controlled by starting with a low dose and increasing it gradually. The drug may rarely cause liver damage.
• Methocarbamol and chlorzoxazone may cause harmless color changes in urine - orange or reddish-purple with chlorzoxazone and purple, brown, or green with methocarbamol. The urine will return to its normal color when the patient stops taking the medicine.

By Yury Bayarski