Social drugs

Carl Salzman and Alan I. Green

4 The abuse of various drugs, many of which have no current medical use, continues to be widespread. This year's chapter will review certain general effects of drug abuse: renal toxicity, infection and flashback. In addition, a number o f specific agents will be discussed in some detail.

Renal toxicity Abused street drugs such as heroin, amphetamines, phencyclidine, pentazocine and codeine are known to cause renal damage (1R). Acute renal failure, associated with rhabdomyolysis, has been described, although the exact etiology is unknown (1R). Some investigators have suggested it might be due to nephrotoxicity of myoglobin. Hypotension-based acute renal failure has been reported in heroin addicts. A recent paper described 2 cases of acute renal failure following phencyclidine (PCP) intoxication thought to be due to hyperuricemic nephropathy (2c). The authors suggest that blood uric acid be measured in all patients with major PCP intoxication. All these forms of acute renal failure carry a good prognosis if proper management, including hemodialysis (when necessary), is employed. Acute renal insufficiency, secondary to bacterial endocarditis and viral hepatitis, has been described in drug addicts. The renal toxicity is a glomerulonephritis thought to be secondary to circulating immune complexes; it tends to clear with the underlying condition ( I R ) . Immune complexes were thought to be involved in the pathogenesis of 3 cases of membranoproliferative glomerulonephritis type I following 2- to 3-year histories of parenteral pentazocine abuse (3c). All patients devel-

Side Effects of Drugs Annual 8 M.N.G. Dukes, editor 9 Elsevier Science Publishers B.V., 1984 ISBN 0 444 90339 9 $0.80 per article pet page (transactional system) $0.20 per article per page (licensing system)

Social drugs oped the nephrotic syndrome with hypertension and hematuria. The authors postulated that the drug itself, additives used in the drug preparation or microorganisms might have been related to the immune complex development. Chronic renal failure has been reported to occur as a result of subcutaneous or intravenous drug abuse (I R). In heroin addicts, it may be due to a focal sclerosis involving some of the glomeruli. In such cases, the prognosis is poor, unless the heroin use ceases; some patients with a mild condition have had an improvement in renal function with a switch to oral methadone. With intravenous amephetamine use, a systemic vasculitis or polyarteritis may cause the renal failure. In this case as well, renal function can stabilize after amphetamine use stops. When heroin or amphetamine is abused subcutaneously ('skin popping'), the abusers may be at risk for developing the nephrotic syndrome due to induction o f amyloidosis.

Infection Intravenous drug use is often complicated by various infections: ceUulitis, abscesses, septic arthritis, osteomyelitis, endocarditis, hepatitis, pneumonia and malaria have all been reported (4c). Ophthalmologic complications have been described as well, including septic retinitis, talc emboli, retinal neovascularization and metastatic endophthalmitis (5c). The cases of endophthalmitis have generally been caused by Candida albicans. One recent report implicated Aspergillus flavus in metastatic endophthalmitis found in an intravenous cocaine user (7c). Aspergillosis endophthalmitis is usually thought to have a poor prognosis. In this case, however, when the patient was treated with vitrectomy and antifungal agents, useful vision was restored. A second report described a case of focal submacular septic choroiditis, secondary to an embolus, resulting in permanent monocular loss of central vision in a heroin and phenmetrazine abuser

(5c).

Social drugs Necrotizing fasciitis, an infection of subcutaneous and fascial tissues, has been reported in 2 i.e. cocain abusers (4c). The infection, which at first resembled a cellulitis, caused severe local disease, as well as systemic toxic symptoms. The pathogens were a mixture of anaerobes and aerobes. The authors speculated that the infection was caused by the accidental subcutaneous intramuscular injection of cocaine, a vaseconstrictor. Their successful therapy employed antimicrobials effective against both types of pathogens. Some drug abuse related infections result from non-parenteral use. A report from the Centers for Disease Control described an outbreak of enteritis caused by Salmonella meunchen traced to contaminated marijuana samples (6c). The authors suggested that the salmonella infection was caused by hand to mouth or cigarette to mouth contact.

Flashback A recent article summarized the literature on flashback phenomena and reported on an in-depth study of one case (8R). Flashback phenomena are defined as h return of hallucinogenic effects after the immediate drug effect has worn off. They are often reported as visual intrusions, but other sensory modalities may also be involved, as may distortions in time sense, self-image or reality sense. Typical flashback effects include: perceptual distortions, depersonalizations, anxiety, disorientation, 'union with the world', various bodily sensations, and spontaneous and recurring images (8 R). Flashbacks have been estimated to occur in approximately 23% of a drug-using population (8R). The rate of their occurrence may be daily or nearly so (21% in one sample), 2 or 3 times monthly (18%), or every m o n t h or so (43%) (sR). Most individuals seem to have decreasing frequency of experiences, but 18% may have an increase (9c). Some individuals continue to experience flashbacks for years. Continued marijuana use following the hallucinogen use is thought to be related to their existence; alcohol, stress and even pleasurable thoughts have been implicated as well (8R). Very little is known about the etiology of flashback phenomena. Theories include psychological, organic or social deficits. Psychological studies of individuals with

45 flashbacks have provided conflicting data. Some subjects seem to have normal character structure while others have an obsessivecompulsive or hysterical make-up; some are characterized as frivolous, spontaneous, outspoken, or active, while others are described as regressive, immature, maladjusted, vulnerable, passive or thought disordered (8R). The careful study of one ease seemed to detect some organic abnormalities on neurophysiological, EEG and blood flow measures (8~R). The authors called for careful neurophysiologic and neuropsychologic assessment of individuals with flashback phenomena. Cannabis and pregnancy (SEDA-4, 26; SEDA-5, 28; SEDA-6, 32; SEDA-7, 39) As noted in previous reviews teratogenie effects of marijuana have been searched for, but the resulting data is equivocal. Although the cannabinoids may increase in utero fetal loss, the effects on viable offspring are uncertain (10R). In the male, testosterone levels are decreased in users, and sperm motility and concentration may be lowered; there is no proof, however, that fertility is affected. There is one report that tetrahydrocannabinol may have deleterious effects on the primary oocytes of young female mice; the clinical significance for humans is u n k n o w n (10R). In a study of pregnant women, marijuana use was associated with a shorter gestation period and less maternal weight gain. No effect on birth weight, length of labor or labor difficulty was found ( l l C ) . Yet, in another study, labor itself was found to be more hazardous and the newborns exhibited more meconium staining in the marijuana users than in non-users (12c). When neonatal behavior was examined, babies born to heavy marijuana users had increased tremors, startles and altered visual responsiveness at 2 to 4 days of age. These symptoms were attenuated by day 30, and at 1 year of age no developmental abnormalities were noted (11r

Pentazocine and tripelennamine (SEDA-7,

39) As reported previously, drug users inject oral preparations of pentazocine (Talwin) and tripelennamine (Pyribenzamine). Some users employ the combination when heroin

46

C. Salzman and A.I. Green

is not available; others seem to prefer it If gas chromatography with nitrogen (13C). On the streets, the combination is detection (GC-N2), which is much more known as T's and Blues (or B's). The 'T' sensitive, is used as a standard, GC-FID is a pentazocine hydrochloride tablet; misses more than 80% of the PCP positive 'Blue' is a tripelennamine tablet. The user urines. crushes the tablets in water, filters the mixture and injects the filtrate intravenously. Cocaine (SEDA-7, 38) Toxic effects have been described: Annual 7 A rise in cocaine use (along with a similar discussed resulting pulmonary lesions; dermatologic complications have been seen increase in the complications from its use) as well (14c). A recent article reported on has been noted since t h e eariy 1970's. A neurological effects o f the combination recent review described the toxicity (15c). Seizures, thought to be due to either reaction, which results from adrenergic emboli or toxic effects of the tripelennamine, stimulation of the central nervous, cardiowere seen in half o f the patients studied. A vascular, and respiratory systems (19R). number of patients had strokes or CNS Symptoms m a y include: tachycardia, tachyinfections. The strokes were probably the pnea, hypertension, euphoria and hyperresult of foreign b o d y emboli. The CNS activity. Hyperpyrexia and a paradoxical infections were quite serious - in one case respiratory depression m a y be observed leading to death, in the others to pehnanent following high doses. Death may result from destruction of brain tissue. The cultured cardiac or respiratory collapse. A recent organisms included aspergillus, nocardia, report described a serious pulmonary edema that developed in a 36-year-old man shortly streptococcus and pseudomonas. Heaney and Gotlieb have described a case after injecting 'freebase' cocaine intraof granulocytopenia which developed in a venously (20c). ('Freebase' is a purified man known to be an intravenous user of form o f cocaine prepared by solvent T's and Blues (24c). The granulocyte count extraction. It is usually smoked or inhaled.) began to recover by the fourth hospital day. Despite vigorous intensive care treatment, The authors speculated that the abuse of the man died from the pulmonary edema T's and Blues was a 'highly probable' cause within 3 hours. In other reported fatal of the complication (24c). overdoses, convulsions and death have usually occurred quickly (within minutes). Phencyclidine Most patients who have survived for the first 3 hours after the overdose have been likely Phencyclidine (PCP) abuse continues to to recover. Treatment of the toxicity be a major medical problem. Several investi- reaction includes respiratory and cardiogators have recently reported on the in- vascular resuscitative measures. Short-acting toxication syndrome. One group attempted barbiturates, benzodiazepines and propranoto classify the syndrome in terms of major lol have all been used with some success and minor patterns of symptoms (16c). (19R). Major patterns included one o f the following symptoms: acute brain syndrome, toxic Miscellaneous social drugs psychosis, catatonia or coma. Minor patterns included lethargy or stupor, and some mix- Volatile nitrites As described in Annual 7 (p. 39), amyl nitrite and butyl nitrite are ture of violence, agitation, euphoria and bizarre behavior in an alert and oriented inhaled to produce stimulant and aphropatient. The authors found that patients disiac effects. Such use, however, is known with major patterns had greater need for to be associated with toxicity. A recent hospitalization and more medical com- report suggests that if taken orally, amyl nitrite may produce a life-threatening form plications than those with minor patterns. The most c o m m o n medical complication of methemoglobinemia (21c). In the case described, successful treatment involved seen was rhabdomyolysis, which in some cases led to acute renal failure (see Renal resuscitation and the administration o f methylene blue. toxicity, above) (16 C, 17c). Another group noted the insensitivity o f routine gas chromatography with flame ionization detection Caffeine-containing street drugs A letter described 2 cases o f toxicity after taking (GC-FID) for PCP assay in the urine (18c).

Social drugs caffeine-containing street drugs ( 2 2 c ) . In b o t h cases, severe abdominal cramping, vomiting, tachycardia, tachypnea and a n x i e t y were found. One patient was combative and hostile.

'New synthetic heroin' In parts o f California, a m i x t u r e o f MPTP (1-methyl-4-phenyl1,2,5,6-tetrahydropyridine) with trace a m o u n t s o f MPPP (1-methyl-4-phenyl-4p r o p i o n o x y p i p e r i d i n e ) - a meperidine analog o f which MTPT is a b y p r o d u c t - has been sold on the streets u n d e r the n a m e o f

47 'new synthetic heroin'. There have been 4 case reports o f the striking d e v e l o p m e n t o f parkinsonism within 1 w e e k of the intravenous use o f this m i x t u r e ( 2 3 c ) . All the patients responded to L-dopa and carbidopa, but 5 m o n t h s later t h e y all continued to require it. The authors suspected that MPTP was the o f f e n d i n g agent, and that it caused actual loss o f ceils in the substantia nigra. They r e c o m m e n d e d t h e evaluation of the drug for the p r o d u c t i o n of an animal m o d e l o f Parkinson's disease.

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Med. Assoc., 244, 1224. 14. Padilla RS, Becker L, Hoffman H et al (1979) Cutaneous and venous complications of pentazocine abuse. Arch. Dermatol., 115, 975. 15. Caplan LR, Thomas C, Banks G (1982) Central nervous system complications of addiction to 'T's and Blues'. Neurology, 32, 623. 16. McCarron MM, Schulze BW, Thompson GA et al (1981) Acute phencyclidine intoxication: clinical patterns, complications and treatment. Ann. Emerg. Med., 10, 290. 17. Barton CH, Sterling ML, Vaziri ND (1981) Phencyclidine intoxication: clinical experience in 27 cases confirmed by urine assay. Ann. Emerg. Med., 10, 243. 18. Fallis RJ, Amitine A, Werner LP et al (1982) Massive phencyclidine intoxication. 3". Nerv. Ment. Dis., 170, 217. 19. Gay GR (1982) Clinical management of acute and chronic cocaine poisoning. Ann. Emerg. Med., 11, 562. 20. AUred RJ, Ewer S (1981) Fatal pulmonary edema following intravenous 'freebase' cocaine use.Ann. Emerg. Med., 10, 441. 21. McGrath RB, Perry SM (1982) The production of methemoglobin by amyl nitrite. Resp. Care, 27, 959. 22. May DC, Long T, Madden R et al (1981) Caffeine toxicity secondary to street drug ingestion. Ann. Emerg. Med., 170, 549. 23. Langston JW, Ballard P, Tetrud JW et al (1983) Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science, 219, 979. 24. Heaney RM, Gotlieb N (1983)Granulocytopenia after intravenous abuse of pentazocine and terpelennamine ('T's and Blues'). South. Med. J., 76, 654.