CASE REPORTS studies of brown recluse spider venom. Infect Immunol 10:1412, shown capable of producing a morphine-like Dec 1974 17. Denny WF, Dilltha CJ, Morgan PN: Hemotoxic effect of euphoria.4 Morphine-like addiction is also theo- Loxosceles recluses venom: In vivo and in vitro studies. J Lab Clin Med 64:291-298, Aug 1964 retically possible following prolonged use of the 18. Hershey FB, Aulenbacher CE: Surgical treatment of brown recluse bites. Ann Surg 170:300, Aug 1969 drug at high doses. 19. Russell FE, Wainschel J, Gertsch WJ: Bites of spiders and other arthropods. Cufr Ther 864-867, 1974 Recently, I encountered a case of deliberate 20. Berger RS: A critical look at therapy for the brown re- cluse spider bite. Arch Dermatol 107:298, 1973 abuse of diphenoxylate hydrochloride, and ord- ered a computer search of the literature for fur- ther information. Considering the frequency with which this drug is prescribed, its schedule V rat- Refer to: Rubinstein JS: Deliberate abuse of diphenoxylate hy- drochloride, a schedule V narcotic. West J Med 1-31: ing, and the great demand among abusers for its 148-150, Aug 1979 opiate congeners, it was surprising to discover that deliberate abuse of diphenoxylate hydro- chloride for its subjective effects has never been Deliberate Abuse of reported in the literature. Diphenoxylate Report of a Case Hydrochloride, a Schedule A 32-year-old man came to the psychiatric outpatient clinic with complaints of anxiety and V Narcotic depression over his inability to carry out his duties JONATHAN S. RUBINSTEIN, MD satisfactorily at work. California The patient had a long history of drug abuse, Beverly Hills, including the intravenous abuse of heroin, and at DIPHENOXYLATE is a meperidine congener fre- age 24 had been admitted to hospital for what he quently prescribed in the treatment of diarrhea. described as an inadvertent overdose. Following The drug is available in both tablet and liquid this experience he became "more cautious" in his form (Lomotil, Colonil); each tablet and each 5 use of drugs, resolved to stop using heroin; the ml dose of the liquid contains 2.5 mg of diphen- patient broke all contact with the street scene, oxylate hydrochloride and 0.025 mg of atropine but continued to abuse pills, in particular bar- sulfate. Diphenoxylate hydrochloride is a schedule biturates, as well as prescription opiates such as V narcotic.' pentazocine and propoxyphene. In addition, the The chemical structure of diphenoxylate hydro- patient related that he had, over the past year, chloride is similar to that of meperidine,2 and the begun to abuse diphenoxylate hydrochloride, tak- drug carries many of the risks and hazards char- ing large doses of the drug intermittently, but acteristic of the opiates. Mild side effects include never more than once or twice a week for periods drowsiness, rash, dizziness, depression and nausea. of up to several weeks at a time. Treatment of overdose or individual hypersensi- The patient's first experience with the drug had tivity reaction is simUar to that for meperidine or been with a prescription given to his wife by morphine intoxication. Prolonged monitoring of her doctor as prophylaxis before an intended trip the patient is essential because, although there abroad. He had found the bottle of pills and, might be an initial response to narcotic antagon- not being familiar with the drug, had looked it up ists, life-threatening respiratory depression may in the Physicians' Desk Reference. He had learned occur as late as 30 hours following ingestion.2 that it was an opiate and, in large doses, could Several cases of accidental overdose in chiIkpfn produce opiate-like effects. The patient enjoyed have been reported.3 the sensation, and then began taking the drug As with other opiates, the drug also has a regularly. He found that most physicians would potential for abuse. Though at therapeutic ranges issue a prescription for diphenoxylate hydrochlo- (20 mg of diphenoxylate hydrochloride per day ride with little question when he complained of or less, in divided doses) opioid effects do not diarrhea, even when he would specifically request occur, doses of 40 to 60 mg at a time have been the drug by name. On several occasions he in- formed the physician that he was about to em- Dr. Rubinstein is a third-year resident in psychiatry at the Olive View Medical Center, Sylmar, California. bark on an extended trip abroad, and received Submitted December 6, 1978. large supplies of the drug. The patient would Reprint requests to: Jon Rubinstein, MD, 14445 Olive View Dr., Sylmar, CA 91342. ordinarily take 60 to 100 tablets for the desired

148 AUGUST 1979 * 131 * 2 CASE REPORTS effect, which he described as a euphoria qualita- appraising the extent to which the drug is being tively similar to that produced by other orally abused. The relatively high cost of the medica- taken opiates. Concomitant ingestion of alcohol tion, even when obtained through licit channels, or other drugs seemed to result in potentiation as well as the fact that diphenoxylate hydrochlo- of the effects. ride even as a salt is virtually insoluble in water5 On one occasion the patient shared a quantity and therefore cannot be abused parenterally, may of the drug with a friend who reported experienc- be contributory. This by no means, however, ing a similar high. The patient did not report obviates the possibility that deliberate abuse of having been bothered by any adverse atropinic the drug, though hitherto unreported, may be side-effects at his usual dosage. The largest single widespread. At present I am collecting and docu- amount he ever took was about 140 tablets; at menting a more extensive series of cases. this dosage he did experience pronounced dryness It has been stated that subtherapeutic amounts of the mouth, and woke up the following morning of atropine sulfate have been added to the com- with nausea and a severe headache. Though his pound to discourage deliberate overdosage2 (P 1449) euphoria at the higher dosage was significantly This contention seems to conflict, however, with enhanced, the patient says he ordinarily restricts experimental data. Doses of less than 2 mg of his dosage of the drug for several reasons: ( 1 ) He atropine are, in an adult, unlikely to produce any is afraid of damaging his gastrointestinal tract, clinically significant dysphoric effects.6 Therefore, (2) he conscientiously wishes to avoid addiction even 60 tablets, which is a quantity significantly and (3) the cost of the drug, even when pur- beyond that which is theoretically required to chased at a pharmacy (as opposed to the street produce a morphine-like euphoria, would not price), is fairly expensive. contain a sufficient amount of atropine sulfate to disturb the patient sufficiently, presumably, to Discussion discourage deliberate overdosage. This is par- That this drug is abused is not either astonish- ticularly true because many opiate abusers are ing or remarkable; any medication-no matter characteristically willing to tolerate considerable how ostensibly innocuous-carries with it the amounts of distress to obtain their high, "paying potential for abuse. What is remarkable is the the price" not only in physical discomfort, but ease with which this drug, a narcotic, is obtained, often, ultimately, in the typical, erosive, down- and the apparent willingness of many physicians ward-spiral of the addicts' life-style. to issue prescriptions to a patient with little or The case reported here raises a number of no question. questions. Clearly, there is a need for a height- Many physicians seem unaware either of the ened level of awareness among physicians con- opioid pharmacological structure of diphenoxylate cerning the pharmacological nature of the sub- hydrochloride or of its consequent potential for stance and its potential hazards, including the abuse and dependency. An informal survey I possibility of deliberate abuse and of habituation. conducted among physicians at two academic Certainly a greater index of suspicion should be centers seems to confirm this. Of 20 physicians exercised when prescribing this medication for interviewed (all of whom stated they prescribed patients with histories of drug abuse, those who the drug "at least occasionally," and some said specifically request the drug by name and especi- they did so "often") only six were aware of the ally those patients who express a desire for inor- pharmacological structure of the medication and dinately large quantities of the medication. In of its potential for abuse. Ironically, in our case addition, one must question the clinical sagacity report the patient apparently had made more of prescribing a narcotic-containing compound assiduous use of the Physicians' Desk Reference, for any patient with diarrhea before potentially for his own purposes than had the prescribing less hazardous drugs have been given an adequate physician. trial. There is, unquestionably, no paucity of The absence of previous case reports is puzzling. nonnarcotic medications, many of proven efficacy The patient's statement regarding the enthusiastic as well as safety, available on the market today. reaction of his friend to the drug suggests that his experience is neither idiosyncratic nor unique, Summary though the patent's lack of contact with the Diphenoxylate hydrochloride is a drug fre- street scene renders him incapable of accurately quently prescribed in the treatment of diarrhea.

THE WESTERN JOURNAL OF MEDICINE 149 CASE REPORTS Though it is chemically related to meperidine, Report of a Case deliberate abuse or dependency on this drug has In a 16-year-old girl with stage IV non- never been reported. A case is presented in which Hodgkin lymphoma in relapse despite multiple the patient had been using the drug regularly, in chemotherapy regimens, increasing sore throat, large doses, for its morphine-like euphoriant ef- fever and dysphagia developed. The patient was fects. He had been obtaining the drug easily from admitted to hospital. After specimens for culture physicians, and a heightened level of awareness were obtained, treatment was started with cepha- among doctors concerning the abuse potential of lothin, gentamicin and carbenicillin because of this drug should result in greater vigilance in the compromised immune status and possible prescribing it. sepsis. REFERENCES Initial showed mild 1. Jaffe JH: Narcotic analgesics In Goodman LS, Gilman A examination pharyngeal (Eds): The Pharmacological Basis of Therapeutics. New York, inflammation and enlarged, tender cervical nodes. The Macmillan Co, 1970, pp 237-275 2. Physicians' Desk Reference. Oradell, NJ, Medical Economics, Blood and urine cultures showed no growth and 1977, p 1448 3. Marsh AR, Lammiman D: Lomotil-A dangerous drug. JR a throat culture showed flora and Candida Nav Med Serv 60:149-150, Winter 1974 normpal 4. AMA Drug Evaluations. Acton, MA, Publishing Sciences albicans. A complete blood count at admission Group, Inc, 1973, p 794 5. Fraser HF, Isbell H: luman pharmacology and addictiveness showed 600 leukocytes, a hematocrit reading of of ethyl 1-(3-cyano-3,3-phenylpropyl) -4-phenyl-4-piperidine car- boxylate hydrochloride (R-1132, diphenoxylate). Bull Narcot 13: 22 percent and a platelet count of 13,000, with 29.43, 1961 6. Innes IR, Nickerson M: Drugs inhibiting the action of ace- bleeding noted from venipuncture sites and the tylcholine on structures innervated by postganglionic parasym- pathetic nerves (antimnuscarinic or atropinic drugs), In Goodman nose. After six units of platelet transfusion, the LS, Gilman A (Eds): The Pharmacological Basis of Therapeu- tics. New York, The Macmillan Co, 1970 pp 524-547 platelet count was 20,000, with continued bleed- ing. Because a throat culture showed Candida, am- Refer to: Cochran JH Jr, Fee WE Jr, Maze A: Epiglottitis in an photericin was added to the regimen on the immunosuppressed host. West J Med 131:150-152, Aug 1979 second hospital day. At this time the sore throat and dysphagia were worse, the patient was un- able to swallow her saliva and mild airway ob- Epiglottitis in an struction was present. A lateral neck roentgeno- gram (Figure 1) was obtained and showed a Immunosuppressed Host typical enlarged epiglottis consistent with epiglot- titis. Otolaryngologic consultation was obtained JOHN H. COCHRAN, JR., MD and examination showed a pale, swollen epiglottis Denver with edema compromising the supraglottic airway. WILLARD E. FEE, JR., MD It was felt that neither an atraumatically placed AUBREY MAZE, MD endotracheal tube nor the most meticulous trache- Stanford, California ostomy was a safe procedure because of thrombo- cytopenia refractory to treatment associated with EPIGLOTTITIS is an acute infection of the supra- bleeding. It was elected to begin administration glottic larynx with a major risk of airway ob- of corticosteroids, 12 mg of dexamethasone (De- struction secondary to cellulitis and edema. Diag- cadron) given intravenously, followed by 4 mg nosis is made by history and examination of the every six hours. Within 12 hours the patient's epiglottis by lateral neck x-ray study or, prefer- condition was improved, and she was able to ably, indirect mirror examination. Treatment con- swallow her own saliva and some liquids. Eight- sists of maintaining an airway, and administration een hours later a repeat lateral neck roentgeno- of antibiotics, oxygenated mist and probably gram showed no abnormalities (Figure 2). Two corticosteroids. This case presented unique thera- days later the patient had resumed a regular diet peutic problems because of the underlying ma- and the epiglottis was found to be normal on lignancy, impaired immune status, previous ther- examination. She was discharged home 11 days apy and essentially irreversible coagulopathy. after admission without sequelae. From the Division of Otolaryngology, Department of Surgery (Cochran and Fee), Department of Anesthesia (Maze), Stanford Discussion University Medical Center, Stanford, California. Submitted December 19, 1978. Epiglottitis is traditionally classified as an infec- Reprint requests to: Willard E. Fee, Jr., MD, Division of tious disease of the larynx, but because of its Otolaryngology, Stanford University Medical Center, Stanford, CA 94305. morbidity and mortality it would be better to

150 AUGUST 1979 * 131 * 2