Orphenadrine

Definition

Skeletal muscle relaxants are drugs that relax striated muscles (those that control the skeleton). They are a separate class of drugs from the muscle relaxant drugs used during intubations and surgery to reduce the need for anesthesia and facilitate intubation.

Purpose

Skeletal muscle relaxants may be used for relief of spasticity in neuromuscular diseases, such as multiple sclerosis, as well as for spinal cord injury and stroke. They may also be used for pain relief in minor strain injuries and control of the muscle symptoms of tetanus. Dantrolene (Dantrium) has been used to prevent or treat malignant hyperthermia in surgery.

Description

Although the muscle relaxants may be divided into only two groups, centrally acting and peripherally acting, the centrally acting group, which appears to act on the central nervous system, contains 10 drugs which are chemically different, while only dantrolene has a direct action at the level of the nerve-muscle connection.

Baclofen (Lioresal) may be administered orally or intrathecally for control of spasticity due to neuromuscular disease.

Carisoprodol (Soma), chlorphenesin (Maolate), chlorzoxazone (Paraflex), cyclobenzaprine (Flexeril), diazepam (Valium), metaxalone (Skelaxin), methocarbamol (Robaxin), and orphenadrine (Norflex) are used primarily as an adjunct for rest in management of acute muscle spasms associated with sprains. Muscle relaxation may also be an adjunct to physical therapy in rehabilitation following stroke, spinal cord injury, or other musculoskeletal conditions.

Diazepam and methocarbamol are also used by injection for relief of tetanus.

Recommended dosage

Dose varies with the drug, route of administration, and purpose. There may be individual variations in absorption that require doses higher than those usually recommended, particularly with methocarbamol. Consult specific references for further information.

Precautions

All drugs in this class may cause sedation. Baclofen, when administered intrathecally, may cause severe central nervous system (CNS) depression with cardiovascular collapse and respiratory failure.

Diazepam may be addictive. It is a controlled substance under federal law.

Dantrolene has a potential for hepatotoxicity. The incidence of symptomatic hepatitis is dose related, but may occur even with a short period of doses at or above. Even short periods of doses at or above 800 mg per day greatly increases the risk of serious liver injury. 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.

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.

Most drugs in this class are well tolerated.

Not all drugs in this group have been evaluated for safety in pregnancy and breast feeding.

Baclofen is pregnancy category C. It has caused fetal abnormalities in rats at doses 13 times above the human dose. Baclofen passes into breast milk, and breast feeding while taking baclofen is not recommended.

Diazepam is category D. All benzodiazepines cross the placenta. Although the drugs appear to be safe for use during the first trimester of pregnancy, use later in pregnancy may be associated with cleft lip and palate. Diazepam should not be taken while breast feeding. Infants who were breast fed while their mothers took diazepam were excessively sleepy and lethargic.

Dantrolene is category C. In animal studies it has reduced the rate of survival of the newborn when given in doses seven times the normal human dose. Mothers should not breast feed while receiving dantrolene.

Interactions

Skeletal muscle relaxants have many potential drug interactions. Individual references should be consulted.

Because these drugs cause sedation, they should be used with caution with other drugs that may also cause drowsiness.

The activity of diazepam may be increased by drugs that inhibit its metabolism in the liver. These include cimetidine, oral contraceptives, disulfiram, fluoxetine, isoniazid, ketoconazole, metoprolol, propoxyphene, propranolol, and valproic acid.

Dantrolene may have an interaction with estrogens. Although no interaction has been demonstrated, the rate of liver damage in women over the age of 35 who were taking estrogens is higher than in other groups.

Key Terms

Central nervous system

The brain and spinal cord.

Intrathecal

Introduced into or occurring in the space under the arachnoid membrane which covers the brain and spinal cord.

Pregnancy category

A system of classifying drugs according to their established risks for use during pregnancy. Category A: Controlled human studies have demonstrated no fetal risk. Category B: Animal studies indicate no fetal risk, but no human studies, or adverse effects in animals, but not in well-controlled human studies. Category C: No adequate human or animal studies, or adverse fetal effects in animal studies, but no available human data. Category D: Evidence of fetal risk, but benefits outweigh risks. Category X: Evidence of fetal risk. Risks outweigh any benefits.

Sedative

Medicine used to treat nervousness or restlessness.

Spasm

Sudden, involuntary tensing of a muscle or a group of muscles.

Tranquilizer (minor)

A drug that has a calming effect and is used to treat anxiety and emotional tension.