Orphenadrine

Substance abuse and dependence are steadily increasing problems in the United States. Many substances of abuse are prescription medications or closely related to drugs with established medical uses. Most physicians are aware of the more commonly abused prescription medications, such as benzodiazepines and narcotics. [1] The abuse potential of centrally acting skeletal muscle relaxants is not as well recognized.

Illustrative Case

A 38-year-old man came to a county health department requesting refills of atenolol for hypertension and carisoprodol for a "bad back." The patient gave a vague history of back problems dating from an accident that had occurred four years earlier. An orthopedic surgical procedure had been performed without benefit. He was unemployed because of chronic back pain.

The patient was obese; trunk flexion at the waist was limited to 15 degrees, as was lateral bending to both sides. A surgical scar was noted in the lumbar region, and palpalation revealed moderate tenderness over the right lower lumbar and sacroiliac areas. Sensation was decreased along the lateral side of the right thigh, but all reflexes and muscle strength in the legs were normal and symmetric.

The prescriptions for carisoprodol and atenolol were renewed, and medical records were requested from the patient's previous physician. Two months after the first visit, the patient requested a refill of carisoprodol, but this request was denied. One month later, the patient was re-examined, and the clinical picture had remained unchanged. The patient requested more carisoprodol, and the prescription was renewed at this time. Later that week, a community pharmacist reported that the patient had returned for a refill of the carisoprodol prescription only four days after receiving a month's supply. The pharmacist was instructed not to refill the prescription until the next month.

Two months later, the patient requested another refill of the carisoprodol prescription. The patient's medical records had not yet arrived from his previous physician, and a second request for the records was made. A one-month supply of carisoprodol was prescribed pending receipt of the records. Later that day, another tommunity pharmacist telephoned to confirm the prescription, because the patient had received this medication from two other physicians.

Telephone calls to various community pharmacies and emergency departments revealed that in the preceding four months the patient had filled prescriptions from seven different physicians for at least 1,132 carisoprodol tablets. The patient had not requested or received narcotics during this time.

Before the patient could be seen again in the office, he died of cardiac arrhythmia due to chronic drug abuse. Carisoprodol levels were not measured, but toxicology analysis revealed small amounts of carboxy-THC, hydromorphone, diphenhydramine, nicotine, caffeine and benzodiazepines in the urine.

The patient's previous medical records revealed a history of carisoprodol abuse and complications. Three years before the patient's death, an orthopedic surgeon had noted that the patient was using "too much" carisoprodol. One year later, the patient had been hospitalized because of generalized seizures after an overdose of carisoprodol. The patient had recovered from this episode within 24 hours and left the hospital against medical advice, thus limiting further evaluation.

Discussion

Biochemically, skeletal muscle relaxants are a diverse group of drugs. Cyclobenzaprine (Flexeril), for example, is closely related to the tricyclic antidepressants. [2] Baclofen (Lioresal) is a gamma-aminobutyric acid derivative, [3] and carisoprodol (Soma) is chemically related to meprobamate (Equanil, Miltown). [4] The mechanism of action of skeletal muscle relaxants is unknown, but animal studies suggest that they preferentially depress polysynaptic reflexes. [5,6] Because of this pharmacologic diversity, the risk for misuse, the lethal dose and the treatment in case of overdosage are specific to the drug ingested.

Despite their unrelated chemical structures, all of these agents possess sedative properties, [5] and they are abused mainly for this effect. At high doses, skeletal muscle relaxants have been described as producing "a buzz" (baclofen), [3] "euphoria" (carisoprodol) [4] and "mood enhancement and pleasant disperceptions" (orphenadrine [Norgesic]). [7]

The extent to which skeletal muscle relaxants are abused is unclear, since only limited published data are available. Of cases involving skeletal muscle relaxant ingestion reported to the Rush-Presbyterian-St. Luke's Poison Control Center in Chicago over a one-year period, 10.7 percent were related to intentional misuse or abuse. [8] The Drug Abuse Warning Network collects data on abused substances identified during encounters at 756 hospital emergency departments. In 1987, skeletal muscle relaxants were reported as the substance of abuse in 1,324 instances. Cyclobenzaprine and carisoprodol were ranked 44th and 54th, respectively, among 234 abused drugs reported to the network. [9]

Skeletal muscle relaxants are frequently used in combination with other central nervous system depressants, such as alcohol, benzodiazepines or narcotics. Skeletal muscle relaxants are used in three main ways: to prolong the effect of alcohol or a narcotic drug, to increase the effect of the primary drug of abuse or to achieve the same effect with a smaller amount of alcohol or narcotic.

Prescriptions for skeletal msucle relaxants are usually easier to obtain than prescriptions for narcotics and are often less expensive. Addicts sometimes substitute skeletal muscle relaxants when a narcotic is not available. In these circumstances, high doses of a skeletal muscle relaxant may be used to achieve the desired sedative or mood-altering effect.

Skeletal muscle relaxants are less commonly used alone or as the primary drug of abuse. Abuse of carisoprodol has been reported more often in the English literature than abuse of other skeletal muscle relaxants, probably because of its close similarity to meprobamate. Abusers of either carisoprodol or meprobamate demonstrate signs of tolerance, and also suffer withdrawal symptoms of anxiety, tremors, insomnia and, occasionally, hallucinations or seizures. [10]

Abuse of carisoprodol often begins after the drug has been prescribed for appropriate medical reasons. In an abuse situation, intake of the drug soon escalates beyond the amount prescribed for the medical indication. Higher doses are needed to achieve the sedative effects and to avoid the withdrawal symptoms. [4,11] Addicts then begin making multiple visits to emergency departments and physicians to obtain prescriptions. This increasing use may lead to an acute overdose.

The main clinical features of skeletal muscle relaxant overdose relate to CNS depression and consist of stupor, respirtory depression, coma and, ultimately, death. [5,6,8] Cyclobenzaprine has toxic effects similar to those of the tricyclic antidepressants, including cardiac arrhythmias and seizures. [2] Some of the skeletal muscle relaxants, including cyclobenzaprine and orphenadrine, have anticholinergic side effects, such as dry mouth or blurred vision. [5] Meprobamate is a primary metabolite of carisoprodol, and overdose may result in acute circulatory failure and shock. [10,12]

Physicians today are alert to requests from patients for narcotics or benzodiazepines and are rightly concerned about the addictive potential of these drugs. [13] However, relatively few physicians are aware of the addictive potential of skeletal muscle relaxants. Lack of awareness on the part of physicians of the potential for skeletal muscle relaxant abuse contributes to the problem. The fact that these drugs are not controlled substances may lead to complacency on the part of prescribers. Some of the drugs, such as carisoprodol, may even be ordered by mail through veterinary supply houses. [11]

When skeletal muscle relaxants are prescribed in cases of acute injury, treatment should be continued for short periods only. In patients with chronic pain, consideration should be given to the use of other medications, such as antidepressants, and to other modalities, such as transcutaneous electrical nerve stimulation, physical therapy and biofeedback. Health care providers should be concerned about requests for frequent refills of skeletal muscle relaxants or requests for refills before the expected completion of a prescription.

In known or suspected addicts, especially persons who abuse CNS depressants such as alcohol, narcotics or benzodiazepines, skeletal muscle relaxants should be prescribed with caution because of the potentiating effects and the possibility of abuse. [14] Physicians should try to avoid prescribing skeletal muscle relaxants for recovering addicts, just as they avoid prescribing narcotics or other addictive substances.

NANCY C. ELDER, M.D. is an academic fellow in family medicine and clinical instructor at the University of Missouri-Columbia School of Medicine. She graduated from the University of Minnesota Medical School-Minneapolis and completed a residency in family practice at Good Samaritan Medical Center, Phoenix.

References

[1] Giannini AJ, Price WA, Giannini MC. Contemporary drugs of abuse. Am Fam Physician 1986;33(3):207-16 [Published erratum appears in Am Fam Physician 1986;33(5):43].

[2] O'Riordan W, Gillette P, Calderon J, Stennes RL. Overdose of cyclobenzaprine, the tricyclic muscle relaxant. Ann Emerg Med 1986; 15:592-3.

[3] May CR. Baclofen overdose. Ann Emerg Med 1983;12:171-3.

[4] Morse RM, Chua L. Carisoprodol dependence: a case report. Am J Drug Alcohol Abuse 1978;5:527-30.

[5] Elenbaas JK. Centrally acting oral skeletal muscle relaxants. Am J Hosp

Pharm 1980;37:1313-23.

[6] Bianchine JR. Drugs for Parkinson's disease: centrally acting muscle relaxants. In: Goodman AG, Goodman LS, Gilman A, eds. Goodman and Gilman's Pharmacological basis of therapeutics. 6th ed. New York: Macmillan, 1980:448-91.

[7] Schifano F, Marra R, Magni G. Orphenadrine abuse [Letter]. South Med J 1988;81:546-7.

[8] Lebby TI, Dugger K, Lispcomb JW, Leikin JB. Skeletal muscle relaxant ingestion. Vet Hum Toxicol 1990;32:133-5.

[9] National Institute on Drug Abuse Statistical Series. Data from the Drug Abuse Warning Network (DAWN), 1987. Rockville, Md.: U.S. Department of Health and Human Services, 1988; (series 1; no. 7).

[10] Harvey SC. Hypnotics and sedatives. In: Goodman AG, Goodman LS, Gilman A, eds. Goodman and Gilman's Pharmacological basis of therapeutics. 6th ed. New York: Macmillan, 1980:365-7.

[11] Luehr JG, Meyerle KA, Larson EW. Mail-order (veterinary) drug dependence [Letter]. JAMA 1990;263:657.

[12] Kintz P, Tracqui A, Mangin P, et al. Fatal meprobamate self-poisoning. Am J Forensc Med Pathol 1988;9:139-40.

[13] Farnsworth MG. Benzodiazepine abuse and dependence: misconceptions and facts. J Fam Pract 1990;31:393-400.

[14] Soma prescribing information. Cranbury, N.J.: Wallace Laboratories, 1987.

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