- Email: [email protected]
Drugs of abuse
Alan I. Green, Eric J. Watsky and Carl Salzman
4
Drugs of abuse to assist in weight control. The cardiomyopathy cleared within 1 year following discontinuation of amphetamine use (7c).
Amphetamines Abuse of amphetamines has grown rapidly in recent years. A report from Hawaii suggests that their use in the form of 'crystal', a smokable crystalline form of methamphetamine, now challenges cocaine in popularity (1R). In Japan, where there was a history of epidemic use following World War II (2R), amphetamine abuse represents a major current problem. The toxic effects of amphetamines are considerable. A recent retrospective study of 127 emergency-room patients with acute amphetamine toxicity detailed a constellation of presenting symptoms, including seizures, chest pain, agitation, confusion, delusions, hallucinations and suicidality (3c). The issue of possible long-term nervous system toxicity is discussed below (4R).
Neonatal effects Neonatal and maternal morbidity resulting from methamphetamine abuse have been described in a recent study; decreased growth, premature delivery, fetal distress, and anemia were noted (8c). Follow-up data suggested that development in the 1st year was normal, although severe neurological abnormalities such as dystonias, apraxia, tremor, hypotonia, hemiparesis and visual motor impairment have occurred in individual cases (9R). Neurological effects 3,4,-Methylenedioxymethamphetamine (MDMA) is used both as a 'recreational' drug and as an adjunct to psychotherapy (10c). Its potential neurotoxic effects have been discussed in the recent literature. Neurotoxicity has been reported in animal models; in such models a degeneration of serotonin neurons has been observed (1 If). However, study of the neurological effects of MDMA, based on the serum prolactin response to intravenous tryptophan, showed statistically insignificant blunting in the expected rise of serum prolactin (12c). The debate about the neurotoxicity of M DMA continues (13R). Further research will be required to resolve the issue.
Cardiovascular effects The cardiac toxicity of acute amphetamine use is well known; myocardial ischemia, myocardial infarction and arrhythmias can occur. A report of sudden death associated with the use of 3,4-methylenedioxymethamphetamine (MDMA) - - a synthetic amphetamine analog - - highlighted the potential arrhythmogenic effect of the drug in a patient with Wolff-Parkinson-White syndrome (5c). Another report described a paradoxical rise in blood pressure in a 40-year-old man who was administered the beta-blocker practolol in an emergency room after ingesting p-methylamphetamine and N,p-dimethylamphetamine. The further rise in blood pressure was likely due to c~-adrenoceptor stimulation not suppressed by the beta-blocker (6c). A 3rd report described congestive cardiomyopathy in a 48-year-old woman who was taking methamphetamine pills
Obstetrical effects The sympathomimetic effects of amphetamines can have important consequences during pregnancy. A recent casereport described a 19-year-old-pregnant woman who experienced convulsions and a variable blood pressure in her 36th week of pregnancy. A diagnosis of eclampsia was made. Subsequently, it was discovered that she had been taking amphetamine. In retrospect, the features of eclampsia were atypical (14c).
9 1991 Elsevier Science Publishers B.V.
Psychiatric effects A recent report described the acute subjective effects of MDMA. In a
Side Effects o f Drugs Annual 15 M.N.G. Dukes and J.K. Aronson, editors
27
28 study of a university population, an increased sense of intimacy was noted commonly (90~ visual hallucinations occurred in 20070 of the subjects. Low energy, depressed mood and poor concentration were reported by 21 - 36070 of the subjects 1 day after use (15c). Another report noted that MDMA may also cause panic attacks (16R). Psychosis has long been reported in association with the use of amphetamines. A recent 9year survey in Japan documented 216 admissions for psychotic states associated with methamphetamine (17c). The subjects had a wide age range, an apparent high rate of recurrence, and a prolonged time for symptom resolution. Another report described 2 cases of paranoid psychosis associated with the use of amphetamines to treat narcolepsy (18c). Finally, a case of paranoid psychosis in a 22-year-old woman who took phentermine for weight control was recently described (19c).
Respiratory
effects Crystal methamphetamine can be smoked. A recent case-report suggested that pulmonary edema can be a potential complication (20R). One patient, a 28-year-old woman, who presented with 3 weeks of lethargy, nausea and non-productive cough, had a history of acute and chronic crystal methamphetamine smoking. A normal heart size and bilateral diffuse interstitial infiltrates were noted on chest X-ray. Severe shortness of breath and hypotension necessitated temporary support of vital functions. The authors speculated elsewhere that the pulmonary edema was caused by an amphetamine-induced increase in pulmonary endothelial permeability (21c). Urologicaleffects
Peripherala-adrenoceptor effects of amphetamines can result in bladder neck contraction (22g). A recent case-report described the development of a hypocompliant neuropathic bladder in a 32-year-old man with a history of chronic intravenous amphetamine abuse (23c). The man had experienced hesitancy and urgency over a period of 2 months before he developed pain and hematuria. A venogram revealed bilateral hydronephrosis with a thickwalled bladder. Prazosin (an al-adrenoceptor blocker) resulted in a symptomatic improvement (23c).
Chapter 4 A.L Green, E.J. Watsky and C. Salzman
Cannabis (SED-11, 78; SEDA-12, 34; SEDA-13, 24) Cannabis continues to be the most widely used illicit drug in the United States. This is true despite surveys which show a recent reduction in marijuana use (2Ac, 25R). The side effects of the use or abuse of cannabis have been extensively reviewed in previous Annuals (SEDA4 - 13). However, new reports continue to appear in the literature (25R).
Memory effects
In adults, cannabis reduces attention and impairs short-term memory (26 c, 27R). A recent carefully controlled study of adolescents showed that those dependent on cannabis had defects on the Benton Visual Retention Test and the Wechsler Memory Scale Prose Passages while using cannabis. Although the cannabis users improved somewhat with a 6-week abstinence, their short-term memory deficits remained. The authors suggested that adolescents with pre-existing learning disabilities or cognitive dysfunction may be at increased risk for problems following the heavy use of marijuana (26C, 27R).
Pediatric
effects Accidental ingestion of marijuana by young children has not been frequently described. However, a recent report from British Columbia described 6 children, aged 17 months to 3 years, who had ingested marijuana which had been left in an accessible place by adults. The 6 children became drowsy and stuporous. Three of them became comatose; one had airways obstruction. All of them recovered without incident. The authors suggested that the rapid onset of drowsiness, with dilated pupils and hypotonia, and without other evidence of an etiology, should raise the question of cannabis ingestion. They further suggested the need to educate adults about the dangers of cannabis ingestion in children (24c). Psychological effects Acute anxiety, depersonalization, derealization, paranoia and panic reactions are known to occur in cannabis users (28g). Whether a true psychosis can occur following the use of cannabis is still a matter of debate (28R). According to a recent Swedish study, there may be an association between heavy cannabis use and schizophrenia (29 R,
Drugs of abuse Chapter 4 30R). However, it is not clear at this point, what the etiological significance of this association might be (30R). Respiratory effects Since cannabis is generally smoked its pulmonary effects are important. Marijuana smoke contains the pulmonary irritants and carcinogens typically found, in tobacco smoke. Of course, instead of nicotine, marijuana contains A9-tetrahydrocannabinol (A9-THC), which is itself thought to be a respiratory irritant (25R). Marijuana smokers tend not to use filter-tip cigarettes and tend to inhale the smoke deeply. These factors make the risk of damage from marijuana smoke potentially greater than from tobacco smoke. However, since there is not a large cadre of individuals who have used marijuana chronically for many years, the data about the pulmonary consequences of marijuana smoking continue to come from either animal studies or scattered reports in humans. The toxic pulmonary effects of marijuana have not yet been fully elucidated (25R). Animal studies suggest that marijuana smoke can impair defenses against infection and cause cancer of the pulmonary system. Studies in humans suggest that marijuana can produce airways injury, can damage pulmonary defense mechanisms, and may contribute to chronic respiratory symptoms in young people (25R). A recent report described 3 cases of isolated uvulitis resulting from marijuana smoking (31c).
Cocaine (SED-11, 11; SEDA-12, 35;
SEDA-13, 25; SEDA-14, 28) (see also Chapter 1) Last year's chapter (SEDA-14) was devoted entirely to the side effects of cocaine abuse. Since that time, numerous review articles and studies have continued to document the potential morbidity and toxicity of the drug. The data suggest that virtually all organ systems are at risk of damage. Cardiovascular effects Research has documented a more direct connection between cocaine use and coronary artery spasm. A recent study of 45 patients found decreased coronary sinus blood flow and left coronary artery
29 diameter following intranasal cocaine compared to saline (32c). This observation reinforced previous theories which suggested that cocaine-induced coronary spasm caused nonQ-wave infarctions in cocaine users (33c). Additional support for the role of coronary spasm has come from an autopsy report of a chronic cocaine abuser; an organized mural thrombus found in the patient's coronary arteries suggested repeated damage to the endothelial surface (34c). A report of ST-elevation during withdrawal suggests that even cocaine withdrawal may produce coronary vasospasm (35c). Other cardiac effects of cocaine continue to be described. A recent case-report described reversible cardiomyopathy in a 35-year-old cocaine user (36c). An aortic rupture reported in a 45-year-old man was thought to have been caused by increases in heart rate, blood pressure and cardiac contractility secondary to cocaine (37c). Lastly, a large study reported a substantially higher risk of palpitation in those who had used cocaine more than 5 times as compared to those who had not (38c). Hyperthermia Reports of hyperthermia associated with cocaine abuse continue to appear. One of these was in a 30-year-old man who developed seizures, hyperthermia, and renal failure leading to death following intravenous cocaine (39c). The patient's condition resembled the neuroleptic malignant syndrome, as discussed in previous Annuals. Effects in pregnancy The use of cocaine during pregnancy produces important effects in the fetus and the neonate. Cocaine use has been reportedly associated with an increase in spontaneous abortion, fetal death, fetal distress, precipitous labor, abruptio placentae, and fetal meconium (40R). Abnormalities of neurobehavioral function and development as well as cardiovascular status have been described in neonates born to women who use cocaine (40R). The recent literature contains a number of further reports of the toxic effects of cocaine in infants. An echoencephalographic study of full-term infants born to cocaine- or amphetamine-using mothers revealed a higher percentage of CNS abnormalities (35070) compared with the typical percentage in a normal infant
30 population (5%) (41c). The abnormalities included evidence of intraventricular hemorrhage, necrosis, and cavitary lesions in these infants, all of whom had uncomplicated perinatal periods (41 c). In another report, the case of an infant with evidence ofa caudothalamic hemorrhage was described in detail (42c). The authors of this report proposed hypoxemia-induced alterations in the fetal circulation as the basis for the in-utero hemorrhages (42c). Neonatal seizures in infants of cocaine-abusing mothers may also occur (43c). Lastly, seizures have also been described in an infant who ingested cocaine while crawling around the parents' home (44c). The recent literature also includes a number of reports related to the use of cocaine during pregnancy. Two ruptured ectopic pregnancies were described in young women shortly after the use of cocaine (45c). Although confirmatory laboratory tests were lacking in these cases, the authors cautioned that cocaine use may conceivably increase the risk of such rupture (45c). Another study compared the outcome of pregnancy in women currently under treatment for drug abuse with the outcome in controls. The study confirmed that preterm delivery, low birth weight and abruptio placentae were more likely in pregnancies in substance-abusingwomen than in controls. The women who were using cocaine were at highest risk (46c). In another study from the same center, the effect of prenatal care was assessed. The report concluded that while adequate prenatal care lessened the perinatal consequences of cocaine use, such consequences were not entirely eliminated (47c). A 3rd study examined withdrawal phenomena in neonates of substance-abusing mothers (48c). Mild withdrawal phenomena were equally common in infants born to either cocaine- or heroin-abusing mothers. However, infants of mothers who were cocaine and heroin abusers were more likely to have withdrawal reactions than those whose mothers had been using either substance alone. The authors speculated that the apparent synergistic effect of these two substances may be due to increased CNS sensitivity related to the reported kindling effects of cocaine (48c). Perinatal effects in infants born to cocaineabusing women have been reported by 2 groups. The 1st group noted that cardiovascular dysfunction during the first 2 days of
Chapter 4 A.1. Green, E.J. Watsky and C. Salzman life occurred in infants born to cocaine-abusing mothers. Cardiac output and volume were decreased and blood pressure was higher. The authors suggested that infants born to mother who have recently used cocaine may be at risk of cardiovascular complications (49c). The 2nd group did an epidemiological study of urogenital anomalies in infants born to women who had used cocaine early in their pregnancy; their report confirmed earlier data which suggested an increase in such abnormalities (50c). Neurological effects There are many neurological effects of cocaine and recent reports have discussed a number of them in detail. Neurovascular complications, including ischemia, and intracerebral and subarachnoid hemorrhages, have been noted (51c). A study of 47 cases of cerebrovascular accidents in cocaine abusers reported that intracranial hemorrhages outnumber cerebral infarctions in such patients (52c). The seizure-inducing potential of cocaine is well known. In a recent study of 403 cocaine abusers requiring medical care, none of whom had a prior seizure history, 7.9% had developed seizures from cocaine (53c). Most of the seizures were generalized, but complex partial seizures have also been reported (54c). Lastly, a patient was described who experienced dystonia during withdrawal from cocaine (55c). The patient, a 15-year-old girl with a history of sporadi~ cocaine abuse, had no known exposure to antipsychotic drugs and responded well to intravenous diphenhydramine (55c). Psychiatric effects Cocaine use is associated with a number of psychiatric symptoms. Persistent insomnia, reduced energy, anxiety, paranoia, poor appetite, and depression are more common in those who have used cocaine more than 25 times than in those who have not (56c). A recent case-report described a 27-yearold man who developed auditory hallucinations after using both cocaine and an over-the-counter cold preparation containing chlorpheniramine maleate and phenylpropanolamine bitartrate. The thought disorder apparently induced him to murder a friend (57c). Renal effects Reports of rhabdomyolysis associated with cocaine abuse continue to appear (58c - 60c). In a study comparing cocaine
31
Drugs of abuse Chapter 4 and heroin abusers, renal function in the heroin abusers was compromised more than in the cocaine abusers, but all of the patients recovered full renal function (59c). A case-report of the use of the alkaloidal form of cocaine ('crack') noted a reversible increase in serum creatinine phosphokinase (CPK) and creatinine (58c). However, abrupt progression to renal insufficiency is common and dialysis may be required (60c). Renal excretion of its benzoylecgonine metabolite is the means for detection of cocaine in the urine. This metabolite can be detected in the urine for 2 - 3 days after a single dose of cocaine (61r). However, 3 case-reports suggest that with chronic use of high dosages of cocaine, benzoylecgonine may be detected in the urine for up to 3 weeks after use (62c).
Respiratory effects
Snorting or smoking cocaine can have dramatic effects on the respiratory system. A case-report has noted that the erosive effects of cocaine-snorting can include destruction of the nasal septum, with resulting saddle deformity of the nose and lesions of the palate and pharynx (63c). As described in previous Annuals (SEDA-8, 46; SEDA-14, 5), pneumomediastinum, pneumothorax and pulmonary edema, hemorrhage, and infiltrates can develop from smoking cocaine. A recent report reconfirms that pulmonary edema can occur (64c). This report described 5 cases in which bilateral infiltrates were detected by chest X-rays in otherwise healthy cocaine smokers. The authors suggested that the infiltrates may have been caused by increased endothelial permeability (64c).
Urological effects
Cocaine can be responsible for sexual dysfunction. Two cases of priapism have been described in men who applied topical cocaine to the glans penis (65c).
Miscellaneous effects
In addition to the organ systems already described, cocaine has toxic effects on the liver, cornea, and teeth. Centrilobular hepatic necrosis associated with cocaine abuse has been documented on histopathological examination (66c). A recent case-report described damage to the corneal epithelium in a 20-year-old cocaine abuser (67R). Finally, cocaine use has been associated with the wearing away of tooth enamel, due to
the erosive effects of cocaine hydrochloride powder dissolved in saliva (68R).
Opioids The medical side effects of opioid abuse are well known. They include infections, foreign body embolism, AIDS, glomerulonephritis, and cardiovascular problems. In a recent study the frequency of cardiac abnormalities found at necropsy was examined in a group of known opioid abusers. The sample included those whose deaths were considered to be directly related to substance abuse and those who might have had other causes of death; 96~ of the subjects had cardiac abnormalities and 58~ of the deaths were cardiac-related. The authors noted that although their sample might be unusually skewed toward cardiac disease, substanceabuse patients appear to be at increased risk of cardiac problems (69R). Heroin There have been 3 recent reports of side effects directly related to heroin abuse. The first involved a comparison of costal chondritis in heroin addicts and in patients who had undergone thoracic surgery. The report suggested that costal chondritis presented more frequently in heroin addicts than in the normal population. The heroin addicts developed the syndrome more quickly than the postsurgical group, but were less likely to require surgical correction (70c). A 2nd paper described the nephrotic syndrome with renal amyloidosis in a patient who abused heroin subcutaneously. The authors speculated that skin infections resulting from subcutaneous heroin use might be responsible for the development of amyloid in such patients (71c). A 3rd report described 3 cases of severe asthma that developed shortly after the inhalation of heroin. Two of the patients died (72c).
Pentazocine (SED-11, 86, SEDA-12, 37; SEDA-13, 29) As discussed in previous Annuals (SEDA-7 - 13), pentazocine may be abused intravenously in combination with methylphenidate or tripelennamine. The intravenous use of crushed tablets can result in various pulmonary problems. A recent report described 2 patients who developed pulmonary granulomatosis (73c). In both cases, women in their 30s, the initial diagnosis was not clear. One pa-
32 tient was t h o u g h t to have sarcoidosis, the o t h e r a connective tissue disease. It was only after the history o f p e n t a z o c i n e abuse h a d b e e n elucidated t h a t the diagnosis o f p u l m o n a r y g r a n u l o m a tosis was c o n f i r m e d . The a u t h o r s suggested that u n k n o w n drug abuse can p r o d u c e pulm o n a r y g r a n u l o m a t o s i s resembling p u l m o n a r y connective tissue diseases or p u l m o n a r y hypertension (73c).
Chapter4
A.L Green, E.J. Watsky and C. Salzman
Codeine
Codeine, the most commonly prescribed opioid in the U n i t e d States, is a drug with a relatively low p o t e n t i a l for addiction, mainly because it does not cause e u p h o r i a (74R). H o w e v e r , if a b u s e does occur side effects m a y result. A recent report has suggested that codeine a b u s e m a y be associated with obsessive compulsive behavior. In 2 patients with obsessive compulsive s y m p t o m s remission o c c u r r e d after codeine was w i t h d r a w n (75c).
REFERENCES 1. Jackson JG (1989) Hazards of smokable methamphetamine (Letter). N. Engl. J. Med., 321, 907. 2. Litovitz T (1983) Amphetamines. In: LM Haddad, JF Winchester (Eds,), Clinical Management o f Poisoning and Drug Overdose. W.B. Saunders, Philadelphia, p. 469. 3. Derlet RW, Rice P, Howowitz BZ, Lord RV (1989) Amphetamine toxicity: experience with 127 cases. J. Emergency Med., 7, 157. 4. Peroutka SJ (1989) 'Ecstasy': a human neurotoxin? (Letter). Arch. Gen. Psychiatry, 46, 191. 5. Suarez RV, Riemersma R (1988) 'Ecstasy' and sudden cardiac death. Am. J. Forens. Med. Pathol. , 9, 339. 6. Bal TS, Gutteridge DR, Johnson B (1989) Adverse effects of the use of unusual phenethylamine compounds sold as illicit amphetamine. Med. Sci. Law, 29, 186. 7. Jacobs LJ (1989) Reversible dilated cardiomyopathy induced by methamphetamine. Clin. CardioL, 12, 725. 8. Oro AS, Dixon SD (1987) Perinatal cocaine and methamphetamine exposure: maternal and neonatal correlates. J. Pediatr., 111, 571. 9. Dixon SD (1989) Effects of transplacental exposure to cocaine and methamphetamine on the neonate. West. J. Med., 150, 436. I0. Grinspoon L, Bakalar JB (1986) Can drugs be used to enhance the psychotherapeutic process? Am. J. Psychother., 40, 393. 1t. Schmidt CJ (1987) Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. J. PharmacoL Exp. Ther., 240, 1. 12. Price LH, Ricaurte GA, Krystal JH, Heninger GR (1989) Neuroendocrine and mood responses to intravenous L-tryptophan in 3,4-methylenedioxymethamphetamine (MDMA) users. Arch. Gen. Psychiatry, 46, 20. 13. Grob C, Bravo G, Walsh R (1990) Second thoughts on 3,4-methylenedioxymethamphetamine (MDMA) neurotoxicity (Letter). Arch. Gen.
Psychiatry, 47, 288. 14. Elliott RH, Rees GB (1990) Amphetamine ingestion presenting as eclampsia. Can. J. Anaesth., 37, 130. 15. Peroutka S J, Newman H, Harris H (1988) Subjective effects of 3,4-methylenedioxymethamphetamine in recreational users. Neuropsychopharmacology, 1, 273. 16. Whitaker-Azmitia PM, Aronson TA (1989) 'Ecstasy' (MDMA)-induced panic (Letter). Am. J. Psychiatry, 146, 119. 17. Nakatani Y, Yoshizawa J, Yamada H et al (1989) Methamphetamine psychosis in Japan: a survey (Letter). Br. J. Addict., 84, 1548. 18. Leong GB, Shaner AL, Silva JA (1989) Narcolepsy, paranoid psychosis, and analeptic abuse. Psychiatr. J. Univ. Ottawa, 14, 481. 19. Devan GS (1990) Phentermine and psychosis. Br. J. Psychiatry, 156, 442. 20. Nestor TA, Tamamoto WI, Kam TH (1989) Acute pulmonary oedema caused by crystalline methamphetamine (Letter). Lancet, 2, 1277, 21. Nestor TA, Tamamoto WI, Kam TH, Schultz T (1989) Crystal methamphetamine-induced acute pulmonary edema: a case report. Hawaii Med. J., 48, 457. 22. Weiner N (1985) Norepinephrine, epinephrine and the sympathomimetic amines. In: AG Gilman, LS Goodman, TW Rail, F Murad (Eds.), ThePharmacologicat Basis o f Therapeutics, 7th ed., Macmillan Publishing Co., New York, p. 155. 23, Worsey J, Goble NM, Stott M, Smith JB (1989) Bladder outflow obstruction secondary to intravenous amphetamine abuse. Br. J. Urol., 64, 320. 24, Macnab A, Anderson E, Susak L (1989) Ingestion of cannabis: a cause of coma in children. Pediatr. Emergency Care, 5, 238. 25. Tashkin DP (1990) Pulmonary complications of smoked substance abuse. West. J. Med., 152, 525. 26. Schwartz RH, Gruenewald P J, Klitzner M, Fedio P (1989) Short-term memory impairment in
Drugs o f abuse
Chapter 4
cannabis-dependent adolescents. Am. J. Dis. Child., 143, 1214. 27. Anonymous (1989) Short-term memory impairment in chronic cannabis abusers (Editorial). Lancet, 2, 1254. 28. Thornicroft G (1990) Cannabis and psychosis: is there epidemiological evidence for an association? Br. J. Psychiatry, 157, 25. 29. Solomons K, Neppe VM (1989) Cannabis - - its clinical effects. South Afr. Med. J., 76, 102. 30. Negrete JC (1989) Cannabis and schizophrenia (Editorial). Br. J. Addict., 84, 349. 31. Guarisco JL, Cheney ML, LeJeune Jr FE, Reed HT (1988) Isolated uvulitis secondary to marijuana use. Laryngoscope, 98, 1309. 32. Lange, RA, Cigarroa RG, Yancy Jr CW et al (1989) Cocaine-induced coronary-artery vasoconstriction. N. Engl. J. Med., 321, 1557. 33. Kossowsky WA, Lyon AF, Chou SY (1989) Acute non-Q wave cocaine-related myocardial infarction. Chest, 96, 617. 34. Stenberg RG, Winniford MD, Hillis LD et al (1989) Simultaneous acute thrombosis of two major coronary arteries following intravenous cocaine use. Arch. PathoL Lab. Med., 113, 521. 35. Nademanee K, Gorelick DA, Josephson MA et al (1989) Myocardial ischemia during cocaine withdrawal. Ann. Intern. Med., 111, 876. 36. Chokshi SK, Moore R, Pandian NG, Isner JM (1989) Reversible cardiomyopathy associated with cocaine intoxication. Ann. Intern. Med., 111, 1039. 37. Gadaleta D, Hall MH, Nelson RI, (1989) Cocaine-induced acute aortic dissection. Chest, 96, 1203. 38. Petronis KR, Anthony JC (1989) An epidemiologic investigation of marijuana and cocaine-related palpitations. Drug Alcohol Depend., 23, 219. 39. Bauwens JE, Boggs JM, Hartwell PS (1989) Fatal hyperthermia associated with cocaine use. West. J. Med., 150, 210. 40. Howard J (1989) Cocaine and its effects on the newborn. Dev. Med. Child Neurol., 31, 255. 41. Dixon SD, Bejar R (1989) Echoencephalographic findings in neonates associated with maternal cocaine and methamphetamine use: incidence and clinical correlates. J. Pediatr., 115, 770. 42. Spires MC, Gordon EF, Choudhuri M et al (I 989) Intracranial hemorrhage in a neonate following prenatal cocaine exposure. Pediatr. Neurol., 5, 324. 43. Kramer LD, Locke GE, Ogunyemi A, Nelson L (1990) Neonatal cocaine-related seizures. J. Child Neurol., 5, 60. 44. Rivkin M, Gilmore HE (1989) Generalized seizures in an infant due to environmentally acquired cocaine. Pediatrics, 84, 1100. 45. Thatcher SS, Corfman R, Silverman DG, DeCherney AH (1989) Cocaine use and acute rupture of ectopic pregnancies. Obstet. Gynecol., 74, 478.
33 46. Keith LG, MacGregor S, Friedell Set al (1989) Substance abuse in pregnant women: recent experience at the perinatal center for chemical dependence of Northwestern Memorial Hospital. Obstet. Gynecol., 73, 715. 47. MacGreggor SN, Keith LG, Bachicha JA, Chasnoff IJ (1989) Cocaine abuse during pregnancy: correlation between prenatal care and perinatal outcome. Obstet. Gynecol., 74, 882. 48. Fulroth R, Phillips B, Durand DJ (1989) Perinatal outcome of infants exposed to cocaine and/or heroin in utero. Am. J. Dis. Child., 143, 905. 49. Van de Bor M, Walther FJ, Ebrahimi M (1990) Decreased cardiac output in infants of mothers who abused cocaine. Pediatrics 85, 30. 50. Ch~vez GF, Mulinare J, Cordero JF (1989) Maternal cocaine use during early pregnancy as a risk factor for congenital urogenital anomalies. J. Am. Med. Assoc., 262, 795. 51. Jacobs IG, Roszler MH, Kelly JK et al (1989) Cocaine abuse: neurovascular complications. Radiology, 170, 223. 52. Klonoff DC, Andrews BT, Obana WG (1989) Stroke associated with cocaine use. Arch. Neurol., 46, 989. 53. Pascual-Leone A, Dhuna A, Altafullah 1, Anderson DC (1990) Cocaine-induced seizures. Neurology, 40, 404. 54. Ogunyemi AO, Locke GE, Kramer LD, Nelson L (1989) Complex partial status epilepticus provoked by 'crack' cocaine. Ann. Neurol., 26, 785. 55. Choy-Kwong M, Lipton RB (1989) Dystonia related to cocaine withdrawal: a case report and pathogenic hypothesis. Neurology, 39, 996. 56. Estroff TW, Schwartz RH, Hoffmann NG (1989) Adolescent cocaine abuse. Clin. Pediatr., 28, 550. 57. Strauss A (1989) Homicidal psychosis during the combined use of cocaine and an over-thecounter cold preparation. J. Clin. Psychiatry, 50, 147. 58. Steingrub JS, Sweet S, Teres D (1989) Crackinduced rhabdomyolysis. Crit. Care Med. , 17, 1073. 59. Ahijado F, Lufio de Vinuesa SGJ (1990) Acute renal failure and rhabdomyolysis following cocaine abuse. Nephron, 54, 268. 60. Pogue VA, Nurse HM (1989) Cocaineassociated acute myoglobinuric renal failure. Am. J. Med., 86, 183. 61. Hawks RL, Chiang CN (1988) Urine testing for drugs of abuse. In: National Institute on Drug Abuse Research Monograph Series, Vol. 73. US Government Printing Office, Washington, DC, p. 93. 62. Weiss RD, Gawin FH (1988) Protracted elimination of cocaine metabolites in long-term high-dose cocaine abusers. Am. J. ivied., 85, 879. 63. Deutsch HI_, Millard Jr DR (1989) A new cocaine abuse complex. Arch. OtolaryngoL Head Neck Surg., 115, 235.
34 64. Hoffman CK, Goodman PC (1989) Pulmonary edema in cocaine smokers. Radiology 172, 463. 65. Rodriguez-BlazquezHM, CardonaPE, RiveraHerrera JL (1990) Priapism associated with the use of topical cocaine. J. UroL 143, 358. 66. Wanless IR, Dore S, Gopinath N et al (1990) Histopathology of cocaine hepatotoxicity: report of four patients. Gastroenterology, 98, 497. 67. McHenry JG, Zeiter JH, Madion MP, Cowden JW (1989) Corneal epithelial defects after smoking crack cocaine (Letter). Am. J. Ophthalmol., 108, 732. 68. Krutchkoff DJ, Eisenberg E, O'Brien JE, Ponzillo JJ (1990) Cocaine-induced dental erosions (Letter). N. EngL J. Med., 322, 408. 69. Dressier FA, Roberts WC (1989) Modes of death and types of cardiac diseases in opiate addicts: analysis of 168 necropsy cases. Am. J. Cardiol., 64, 909.
Chapter 4
A.L Green, E.J. Watsk,v and C. Salzman
70. Zapatero J, Longo JL, Carreno Monteagudo I L (1988) Costal chondritis in heroin addicts: a comparative study with postsurgical chondritis. Br. J. Dis. Chest, 82, 341. 71. Campistol JM, Montoliu J, Soler-Amig6 Jet al (1988) Renal amyloidosis with nephrotic syndrome in a Spanish subcutaneous heroin abiaser. NephroL Dial vs. Transplant., 3, 471. 72. Hughes S, Calverley PMA (1988) Heroin inhalation and asthma. Br. J. Med., 297, 1511. 73. Newell GC, Reginato A J, Auerbach D et al (1988) Pulmonary granulomatosis secondary to pentazocine abuse mimicking connective tissue diseases. Am. J. Med., 85, 890. 74. Rowden AM, Lopez JR (1989) Codeine addiction: response. Ann. Pharmacother., 23, 475. 75. Senjo M (1989) Obsessive-compulsive disorder in people that abuse codeine. Acta Ps,vchiatr. Scand., 79, 619.
4
Drugs of abuse to assist in weight control. The cardiomyopathy cleared within 1 year following discontinuation of amphetamine use (7c).
Amphetamines Abuse of amphetamines has grown rapidly in recent years. A report from Hawaii suggests that their use in the form of 'crystal', a smokable crystalline form of methamphetamine, now challenges cocaine in popularity (1R). In Japan, where there was a history of epidemic use following World War II (2R), amphetamine abuse represents a major current problem. The toxic effects of amphetamines are considerable. A recent retrospective study of 127 emergency-room patients with acute amphetamine toxicity detailed a constellation of presenting symptoms, including seizures, chest pain, agitation, confusion, delusions, hallucinations and suicidality (3c). The issue of possible long-term nervous system toxicity is discussed below (4R).
Neonatal effects Neonatal and maternal morbidity resulting from methamphetamine abuse have been described in a recent study; decreased growth, premature delivery, fetal distress, and anemia were noted (8c). Follow-up data suggested that development in the 1st year was normal, although severe neurological abnormalities such as dystonias, apraxia, tremor, hypotonia, hemiparesis and visual motor impairment have occurred in individual cases (9R). Neurological effects 3,4,-Methylenedioxymethamphetamine (MDMA) is used both as a 'recreational' drug and as an adjunct to psychotherapy (10c). Its potential neurotoxic effects have been discussed in the recent literature. Neurotoxicity has been reported in animal models; in such models a degeneration of serotonin neurons has been observed (1 If). However, study of the neurological effects of MDMA, based on the serum prolactin response to intravenous tryptophan, showed statistically insignificant blunting in the expected rise of serum prolactin (12c). The debate about the neurotoxicity of M DMA continues (13R). Further research will be required to resolve the issue.
Cardiovascular effects The cardiac toxicity of acute amphetamine use is well known; myocardial ischemia, myocardial infarction and arrhythmias can occur. A report of sudden death associated with the use of 3,4-methylenedioxymethamphetamine (MDMA) - - a synthetic amphetamine analog - - highlighted the potential arrhythmogenic effect of the drug in a patient with Wolff-Parkinson-White syndrome (5c). Another report described a paradoxical rise in blood pressure in a 40-year-old man who was administered the beta-blocker practolol in an emergency room after ingesting p-methylamphetamine and N,p-dimethylamphetamine. The further rise in blood pressure was likely due to c~-adrenoceptor stimulation not suppressed by the beta-blocker (6c). A 3rd report described congestive cardiomyopathy in a 48-year-old woman who was taking methamphetamine pills
Obstetrical effects The sympathomimetic effects of amphetamines can have important consequences during pregnancy. A recent casereport described a 19-year-old-pregnant woman who experienced convulsions and a variable blood pressure in her 36th week of pregnancy. A diagnosis of eclampsia was made. Subsequently, it was discovered that she had been taking amphetamine. In retrospect, the features of eclampsia were atypical (14c).
9 1991 Elsevier Science Publishers B.V.
Psychiatric effects A recent report described the acute subjective effects of MDMA. In a
Side Effects o f Drugs Annual 15 M.N.G. Dukes and J.K. Aronson, editors
27
28 study of a university population, an increased sense of intimacy was noted commonly (90~ visual hallucinations occurred in 20070 of the subjects. Low energy, depressed mood and poor concentration were reported by 21 - 36070 of the subjects 1 day after use (15c). Another report noted that MDMA may also cause panic attacks (16R). Psychosis has long been reported in association with the use of amphetamines. A recent 9year survey in Japan documented 216 admissions for psychotic states associated with methamphetamine (17c). The subjects had a wide age range, an apparent high rate of recurrence, and a prolonged time for symptom resolution. Another report described 2 cases of paranoid psychosis associated with the use of amphetamines to treat narcolepsy (18c). Finally, a case of paranoid psychosis in a 22-year-old woman who took phentermine for weight control was recently described (19c).
Respiratory
effects Crystal methamphetamine can be smoked. A recent case-report suggested that pulmonary edema can be a potential complication (20R). One patient, a 28-year-old woman, who presented with 3 weeks of lethargy, nausea and non-productive cough, had a history of acute and chronic crystal methamphetamine smoking. A normal heart size and bilateral diffuse interstitial infiltrates were noted on chest X-ray. Severe shortness of breath and hypotension necessitated temporary support of vital functions. The authors speculated elsewhere that the pulmonary edema was caused by an amphetamine-induced increase in pulmonary endothelial permeability (21c). Urologicaleffects
Peripherala-adrenoceptor effects of amphetamines can result in bladder neck contraction (22g). A recent case-report described the development of a hypocompliant neuropathic bladder in a 32-year-old man with a history of chronic intravenous amphetamine abuse (23c). The man had experienced hesitancy and urgency over a period of 2 months before he developed pain and hematuria. A venogram revealed bilateral hydronephrosis with a thickwalled bladder. Prazosin (an al-adrenoceptor blocker) resulted in a symptomatic improvement (23c).
Chapter 4 A.L Green, E.J. Watsky and C. Salzman
Cannabis (SED-11, 78; SEDA-12, 34; SEDA-13, 24) Cannabis continues to be the most widely used illicit drug in the United States. This is true despite surveys which show a recent reduction in marijuana use (2Ac, 25R). The side effects of the use or abuse of cannabis have been extensively reviewed in previous Annuals (SEDA4 - 13). However, new reports continue to appear in the literature (25R).
Memory effects
In adults, cannabis reduces attention and impairs short-term memory (26 c, 27R). A recent carefully controlled study of adolescents showed that those dependent on cannabis had defects on the Benton Visual Retention Test and the Wechsler Memory Scale Prose Passages while using cannabis. Although the cannabis users improved somewhat with a 6-week abstinence, their short-term memory deficits remained. The authors suggested that adolescents with pre-existing learning disabilities or cognitive dysfunction may be at increased risk for problems following the heavy use of marijuana (26C, 27R).
Pediatric
effects Accidental ingestion of marijuana by young children has not been frequently described. However, a recent report from British Columbia described 6 children, aged 17 months to 3 years, who had ingested marijuana which had been left in an accessible place by adults. The 6 children became drowsy and stuporous. Three of them became comatose; one had airways obstruction. All of them recovered without incident. The authors suggested that the rapid onset of drowsiness, with dilated pupils and hypotonia, and without other evidence of an etiology, should raise the question of cannabis ingestion. They further suggested the need to educate adults about the dangers of cannabis ingestion in children (24c). Psychological effects Acute anxiety, depersonalization, derealization, paranoia and panic reactions are known to occur in cannabis users (28g). Whether a true psychosis can occur following the use of cannabis is still a matter of debate (28R). According to a recent Swedish study, there may be an association between heavy cannabis use and schizophrenia (29 R,
Drugs of abuse Chapter 4 30R). However, it is not clear at this point, what the etiological significance of this association might be (30R). Respiratory effects Since cannabis is generally smoked its pulmonary effects are important. Marijuana smoke contains the pulmonary irritants and carcinogens typically found, in tobacco smoke. Of course, instead of nicotine, marijuana contains A9-tetrahydrocannabinol (A9-THC), which is itself thought to be a respiratory irritant (25R). Marijuana smokers tend not to use filter-tip cigarettes and tend to inhale the smoke deeply. These factors make the risk of damage from marijuana smoke potentially greater than from tobacco smoke. However, since there is not a large cadre of individuals who have used marijuana chronically for many years, the data about the pulmonary consequences of marijuana smoking continue to come from either animal studies or scattered reports in humans. The toxic pulmonary effects of marijuana have not yet been fully elucidated (25R). Animal studies suggest that marijuana smoke can impair defenses against infection and cause cancer of the pulmonary system. Studies in humans suggest that marijuana can produce airways injury, can damage pulmonary defense mechanisms, and may contribute to chronic respiratory symptoms in young people (25R). A recent report described 3 cases of isolated uvulitis resulting from marijuana smoking (31c).
Cocaine (SED-11, 11; SEDA-12, 35;
SEDA-13, 25; SEDA-14, 28) (see also Chapter 1) Last year's chapter (SEDA-14) was devoted entirely to the side effects of cocaine abuse. Since that time, numerous review articles and studies have continued to document the potential morbidity and toxicity of the drug. The data suggest that virtually all organ systems are at risk of damage. Cardiovascular effects Research has documented a more direct connection between cocaine use and coronary artery spasm. A recent study of 45 patients found decreased coronary sinus blood flow and left coronary artery
29 diameter following intranasal cocaine compared to saline (32c). This observation reinforced previous theories which suggested that cocaine-induced coronary spasm caused nonQ-wave infarctions in cocaine users (33c). Additional support for the role of coronary spasm has come from an autopsy report of a chronic cocaine abuser; an organized mural thrombus found in the patient's coronary arteries suggested repeated damage to the endothelial surface (34c). A report of ST-elevation during withdrawal suggests that even cocaine withdrawal may produce coronary vasospasm (35c). Other cardiac effects of cocaine continue to be described. A recent case-report described reversible cardiomyopathy in a 35-year-old cocaine user (36c). An aortic rupture reported in a 45-year-old man was thought to have been caused by increases in heart rate, blood pressure and cardiac contractility secondary to cocaine (37c). Lastly, a large study reported a substantially higher risk of palpitation in those who had used cocaine more than 5 times as compared to those who had not (38c). Hyperthermia Reports of hyperthermia associated with cocaine abuse continue to appear. One of these was in a 30-year-old man who developed seizures, hyperthermia, and renal failure leading to death following intravenous cocaine (39c). The patient's condition resembled the neuroleptic malignant syndrome, as discussed in previous Annuals. Effects in pregnancy The use of cocaine during pregnancy produces important effects in the fetus and the neonate. Cocaine use has been reportedly associated with an increase in spontaneous abortion, fetal death, fetal distress, precipitous labor, abruptio placentae, and fetal meconium (40R). Abnormalities of neurobehavioral function and development as well as cardiovascular status have been described in neonates born to women who use cocaine (40R). The recent literature contains a number of further reports of the toxic effects of cocaine in infants. An echoencephalographic study of full-term infants born to cocaine- or amphetamine-using mothers revealed a higher percentage of CNS abnormalities (35070) compared with the typical percentage in a normal infant
30 population (5%) (41c). The abnormalities included evidence of intraventricular hemorrhage, necrosis, and cavitary lesions in these infants, all of whom had uncomplicated perinatal periods (41 c). In another report, the case of an infant with evidence ofa caudothalamic hemorrhage was described in detail (42c). The authors of this report proposed hypoxemia-induced alterations in the fetal circulation as the basis for the in-utero hemorrhages (42c). Neonatal seizures in infants of cocaine-abusing mothers may also occur (43c). Lastly, seizures have also been described in an infant who ingested cocaine while crawling around the parents' home (44c). The recent literature also includes a number of reports related to the use of cocaine during pregnancy. Two ruptured ectopic pregnancies were described in young women shortly after the use of cocaine (45c). Although confirmatory laboratory tests were lacking in these cases, the authors cautioned that cocaine use may conceivably increase the risk of such rupture (45c). Another study compared the outcome of pregnancy in women currently under treatment for drug abuse with the outcome in controls. The study confirmed that preterm delivery, low birth weight and abruptio placentae were more likely in pregnancies in substance-abusingwomen than in controls. The women who were using cocaine were at highest risk (46c). In another study from the same center, the effect of prenatal care was assessed. The report concluded that while adequate prenatal care lessened the perinatal consequences of cocaine use, such consequences were not entirely eliminated (47c). A 3rd study examined withdrawal phenomena in neonates of substance-abusing mothers (48c). Mild withdrawal phenomena were equally common in infants born to either cocaine- or heroin-abusing mothers. However, infants of mothers who were cocaine and heroin abusers were more likely to have withdrawal reactions than those whose mothers had been using either substance alone. The authors speculated that the apparent synergistic effect of these two substances may be due to increased CNS sensitivity related to the reported kindling effects of cocaine (48c). Perinatal effects in infants born to cocaineabusing women have been reported by 2 groups. The 1st group noted that cardiovascular dysfunction during the first 2 days of
Chapter 4 A.1. Green, E.J. Watsky and C. Salzman life occurred in infants born to cocaine-abusing mothers. Cardiac output and volume were decreased and blood pressure was higher. The authors suggested that infants born to mother who have recently used cocaine may be at risk of cardiovascular complications (49c). The 2nd group did an epidemiological study of urogenital anomalies in infants born to women who had used cocaine early in their pregnancy; their report confirmed earlier data which suggested an increase in such abnormalities (50c). Neurological effects There are many neurological effects of cocaine and recent reports have discussed a number of them in detail. Neurovascular complications, including ischemia, and intracerebral and subarachnoid hemorrhages, have been noted (51c). A study of 47 cases of cerebrovascular accidents in cocaine abusers reported that intracranial hemorrhages outnumber cerebral infarctions in such patients (52c). The seizure-inducing potential of cocaine is well known. In a recent study of 403 cocaine abusers requiring medical care, none of whom had a prior seizure history, 7.9% had developed seizures from cocaine (53c). Most of the seizures were generalized, but complex partial seizures have also been reported (54c). Lastly, a patient was described who experienced dystonia during withdrawal from cocaine (55c). The patient, a 15-year-old girl with a history of sporadi~ cocaine abuse, had no known exposure to antipsychotic drugs and responded well to intravenous diphenhydramine (55c). Psychiatric effects Cocaine use is associated with a number of psychiatric symptoms. Persistent insomnia, reduced energy, anxiety, paranoia, poor appetite, and depression are more common in those who have used cocaine more than 25 times than in those who have not (56c). A recent case-report described a 27-yearold man who developed auditory hallucinations after using both cocaine and an over-the-counter cold preparation containing chlorpheniramine maleate and phenylpropanolamine bitartrate. The thought disorder apparently induced him to murder a friend (57c). Renal effects Reports of rhabdomyolysis associated with cocaine abuse continue to appear (58c - 60c). In a study comparing cocaine
31
Drugs of abuse Chapter 4 and heroin abusers, renal function in the heroin abusers was compromised more than in the cocaine abusers, but all of the patients recovered full renal function (59c). A case-report of the use of the alkaloidal form of cocaine ('crack') noted a reversible increase in serum creatinine phosphokinase (CPK) and creatinine (58c). However, abrupt progression to renal insufficiency is common and dialysis may be required (60c). Renal excretion of its benzoylecgonine metabolite is the means for detection of cocaine in the urine. This metabolite can be detected in the urine for 2 - 3 days after a single dose of cocaine (61r). However, 3 case-reports suggest that with chronic use of high dosages of cocaine, benzoylecgonine may be detected in the urine for up to 3 weeks after use (62c).
Respiratory effects
Snorting or smoking cocaine can have dramatic effects on the respiratory system. A case-report has noted that the erosive effects of cocaine-snorting can include destruction of the nasal septum, with resulting saddle deformity of the nose and lesions of the palate and pharynx (63c). As described in previous Annuals (SEDA-8, 46; SEDA-14, 5), pneumomediastinum, pneumothorax and pulmonary edema, hemorrhage, and infiltrates can develop from smoking cocaine. A recent report reconfirms that pulmonary edema can occur (64c). This report described 5 cases in which bilateral infiltrates were detected by chest X-rays in otherwise healthy cocaine smokers. The authors suggested that the infiltrates may have been caused by increased endothelial permeability (64c).
Urological effects
Cocaine can be responsible for sexual dysfunction. Two cases of priapism have been described in men who applied topical cocaine to the glans penis (65c).
Miscellaneous effects
In addition to the organ systems already described, cocaine has toxic effects on the liver, cornea, and teeth. Centrilobular hepatic necrosis associated with cocaine abuse has been documented on histopathological examination (66c). A recent case-report described damage to the corneal epithelium in a 20-year-old cocaine abuser (67R). Finally, cocaine use has been associated with the wearing away of tooth enamel, due to
the erosive effects of cocaine hydrochloride powder dissolved in saliva (68R).
Opioids The medical side effects of opioid abuse are well known. They include infections, foreign body embolism, AIDS, glomerulonephritis, and cardiovascular problems. In a recent study the frequency of cardiac abnormalities found at necropsy was examined in a group of known opioid abusers. The sample included those whose deaths were considered to be directly related to substance abuse and those who might have had other causes of death; 96~ of the subjects had cardiac abnormalities and 58~ of the deaths were cardiac-related. The authors noted that although their sample might be unusually skewed toward cardiac disease, substanceabuse patients appear to be at increased risk of cardiac problems (69R). Heroin There have been 3 recent reports of side effects directly related to heroin abuse. The first involved a comparison of costal chondritis in heroin addicts and in patients who had undergone thoracic surgery. The report suggested that costal chondritis presented more frequently in heroin addicts than in the normal population. The heroin addicts developed the syndrome more quickly than the postsurgical group, but were less likely to require surgical correction (70c). A 2nd paper described the nephrotic syndrome with renal amyloidosis in a patient who abused heroin subcutaneously. The authors speculated that skin infections resulting from subcutaneous heroin use might be responsible for the development of amyloid in such patients (71c). A 3rd report described 3 cases of severe asthma that developed shortly after the inhalation of heroin. Two of the patients died (72c).
Pentazocine (SED-11, 86, SEDA-12, 37; SEDA-13, 29) As discussed in previous Annuals (SEDA-7 - 13), pentazocine may be abused intravenously in combination with methylphenidate or tripelennamine. The intravenous use of crushed tablets can result in various pulmonary problems. A recent report described 2 patients who developed pulmonary granulomatosis (73c). In both cases, women in their 30s, the initial diagnosis was not clear. One pa-
32 tient was t h o u g h t to have sarcoidosis, the o t h e r a connective tissue disease. It was only after the history o f p e n t a z o c i n e abuse h a d b e e n elucidated t h a t the diagnosis o f p u l m o n a r y g r a n u l o m a tosis was c o n f i r m e d . The a u t h o r s suggested that u n k n o w n drug abuse can p r o d u c e pulm o n a r y g r a n u l o m a t o s i s resembling p u l m o n a r y connective tissue diseases or p u l m o n a r y hypertension (73c).
Chapter4
A.L Green, E.J. Watsky and C. Salzman
Codeine
Codeine, the most commonly prescribed opioid in the U n i t e d States, is a drug with a relatively low p o t e n t i a l for addiction, mainly because it does not cause e u p h o r i a (74R). H o w e v e r , if a b u s e does occur side effects m a y result. A recent report has suggested that codeine a b u s e m a y be associated with obsessive compulsive behavior. In 2 patients with obsessive compulsive s y m p t o m s remission o c c u r r e d after codeine was w i t h d r a w n (75c).
REFERENCES 1. Jackson JG (1989) Hazards of smokable methamphetamine (Letter). N. Engl. J. Med., 321, 907. 2. Litovitz T (1983) Amphetamines. In: LM Haddad, JF Winchester (Eds,), Clinical Management o f Poisoning and Drug Overdose. W.B. Saunders, Philadelphia, p. 469. 3. Derlet RW, Rice P, Howowitz BZ, Lord RV (1989) Amphetamine toxicity: experience with 127 cases. J. Emergency Med., 7, 157. 4. Peroutka SJ (1989) 'Ecstasy': a human neurotoxin? (Letter). Arch. Gen. Psychiatry, 46, 191. 5. Suarez RV, Riemersma R (1988) 'Ecstasy' and sudden cardiac death. Am. J. Forens. Med. Pathol. , 9, 339. 6. Bal TS, Gutteridge DR, Johnson B (1989) Adverse effects of the use of unusual phenethylamine compounds sold as illicit amphetamine. Med. Sci. Law, 29, 186. 7. Jacobs LJ (1989) Reversible dilated cardiomyopathy induced by methamphetamine. Clin. CardioL, 12, 725. 8. Oro AS, Dixon SD (1987) Perinatal cocaine and methamphetamine exposure: maternal and neonatal correlates. J. Pediatr., 111, 571. 9. Dixon SD (1989) Effects of transplacental exposure to cocaine and methamphetamine on the neonate. West. J. Med., 150, 436. I0. Grinspoon L, Bakalar JB (1986) Can drugs be used to enhance the psychotherapeutic process? Am. J. Psychother., 40, 393. 1t. Schmidt CJ (1987) Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. J. PharmacoL Exp. Ther., 240, 1. 12. Price LH, Ricaurte GA, Krystal JH, Heninger GR (1989) Neuroendocrine and mood responses to intravenous L-tryptophan in 3,4-methylenedioxymethamphetamine (MDMA) users. Arch. Gen. Psychiatry, 46, 20. 13. Grob C, Bravo G, Walsh R (1990) Second thoughts on 3,4-methylenedioxymethamphetamine (MDMA) neurotoxicity (Letter). Arch. Gen.
Psychiatry, 47, 288. 14. Elliott RH, Rees GB (1990) Amphetamine ingestion presenting as eclampsia. Can. J. Anaesth., 37, 130. 15. Peroutka S J, Newman H, Harris H (1988) Subjective effects of 3,4-methylenedioxymethamphetamine in recreational users. Neuropsychopharmacology, 1, 273. 16. Whitaker-Azmitia PM, Aronson TA (1989) 'Ecstasy' (MDMA)-induced panic (Letter). Am. J. Psychiatry, 146, 119. 17. Nakatani Y, Yoshizawa J, Yamada H et al (1989) Methamphetamine psychosis in Japan: a survey (Letter). Br. J. Addict., 84, 1548. 18. Leong GB, Shaner AL, Silva JA (1989) Narcolepsy, paranoid psychosis, and analeptic abuse. Psychiatr. J. Univ. Ottawa, 14, 481. 19. Devan GS (1990) Phentermine and psychosis. Br. J. Psychiatry, 156, 442. 20. Nestor TA, Tamamoto WI, Kam TH (1989) Acute pulmonary oedema caused by crystalline methamphetamine (Letter). Lancet, 2, 1277, 21. Nestor TA, Tamamoto WI, Kam TH, Schultz T (1989) Crystal methamphetamine-induced acute pulmonary edema: a case report. Hawaii Med. J., 48, 457. 22. Weiner N (1985) Norepinephrine, epinephrine and the sympathomimetic amines. In: AG Gilman, LS Goodman, TW Rail, F Murad (Eds.), ThePharmacologicat Basis o f Therapeutics, 7th ed., Macmillan Publishing Co., New York, p. 155. 23, Worsey J, Goble NM, Stott M, Smith JB (1989) Bladder outflow obstruction secondary to intravenous amphetamine abuse. Br. J. Urol., 64, 320. 24, Macnab A, Anderson E, Susak L (1989) Ingestion of cannabis: a cause of coma in children. Pediatr. Emergency Care, 5, 238. 25. Tashkin DP (1990) Pulmonary complications of smoked substance abuse. West. J. Med., 152, 525. 26. Schwartz RH, Gruenewald P J, Klitzner M, Fedio P (1989) Short-term memory impairment in
Drugs o f abuse
Chapter 4
cannabis-dependent adolescents. Am. J. Dis. Child., 143, 1214. 27. Anonymous (1989) Short-term memory impairment in chronic cannabis abusers (Editorial). Lancet, 2, 1254. 28. Thornicroft G (1990) Cannabis and psychosis: is there epidemiological evidence for an association? Br. J. Psychiatry, 157, 25. 29. Solomons K, Neppe VM (1989) Cannabis - - its clinical effects. South Afr. Med. J., 76, 102. 30. Negrete JC (1989) Cannabis and schizophrenia (Editorial). Br. J. Addict., 84, 349. 31. Guarisco JL, Cheney ML, LeJeune Jr FE, Reed HT (1988) Isolated uvulitis secondary to marijuana use. Laryngoscope, 98, 1309. 32. Lange, RA, Cigarroa RG, Yancy Jr CW et al (1989) Cocaine-induced coronary-artery vasoconstriction. N. Engl. J. Med., 321, 1557. 33. Kossowsky WA, Lyon AF, Chou SY (1989) Acute non-Q wave cocaine-related myocardial infarction. Chest, 96, 617. 34. Stenberg RG, Winniford MD, Hillis LD et al (1989) Simultaneous acute thrombosis of two major coronary arteries following intravenous cocaine use. Arch. PathoL Lab. Med., 113, 521. 35. Nademanee K, Gorelick DA, Josephson MA et al (1989) Myocardial ischemia during cocaine withdrawal. Ann. Intern. Med., 111, 876. 36. Chokshi SK, Moore R, Pandian NG, Isner JM (1989) Reversible cardiomyopathy associated with cocaine intoxication. Ann. Intern. Med., 111, 1039. 37. Gadaleta D, Hall MH, Nelson RI, (1989) Cocaine-induced acute aortic dissection. Chest, 96, 1203. 38. Petronis KR, Anthony JC (1989) An epidemiologic investigation of marijuana and cocaine-related palpitations. Drug Alcohol Depend., 23, 219. 39. Bauwens JE, Boggs JM, Hartwell PS (1989) Fatal hyperthermia associated with cocaine use. West. J. Med., 150, 210. 40. Howard J (1989) Cocaine and its effects on the newborn. Dev. Med. Child Neurol., 31, 255. 41. Dixon SD, Bejar R (1989) Echoencephalographic findings in neonates associated with maternal cocaine and methamphetamine use: incidence and clinical correlates. J. Pediatr., 115, 770. 42. Spires MC, Gordon EF, Choudhuri M et al (I 989) Intracranial hemorrhage in a neonate following prenatal cocaine exposure. Pediatr. Neurol., 5, 324. 43. Kramer LD, Locke GE, Ogunyemi A, Nelson L (1990) Neonatal cocaine-related seizures. J. Child Neurol., 5, 60. 44. Rivkin M, Gilmore HE (1989) Generalized seizures in an infant due to environmentally acquired cocaine. Pediatrics, 84, 1100. 45. Thatcher SS, Corfman R, Silverman DG, DeCherney AH (1989) Cocaine use and acute rupture of ectopic pregnancies. Obstet. Gynecol., 74, 478.
33 46. Keith LG, MacGregor S, Friedell Set al (1989) Substance abuse in pregnant women: recent experience at the perinatal center for chemical dependence of Northwestern Memorial Hospital. Obstet. Gynecol., 73, 715. 47. MacGreggor SN, Keith LG, Bachicha JA, Chasnoff IJ (1989) Cocaine abuse during pregnancy: correlation between prenatal care and perinatal outcome. Obstet. Gynecol., 74, 882. 48. Fulroth R, Phillips B, Durand DJ (1989) Perinatal outcome of infants exposed to cocaine and/or heroin in utero. Am. J. Dis. Child., 143, 905. 49. Van de Bor M, Walther FJ, Ebrahimi M (1990) Decreased cardiac output in infants of mothers who abused cocaine. Pediatrics 85, 30. 50. Ch~vez GF, Mulinare J, Cordero JF (1989) Maternal cocaine use during early pregnancy as a risk factor for congenital urogenital anomalies. J. Am. Med. Assoc., 262, 795. 51. Jacobs IG, Roszler MH, Kelly JK et al (1989) Cocaine abuse: neurovascular complications. Radiology, 170, 223. 52. Klonoff DC, Andrews BT, Obana WG (1989) Stroke associated with cocaine use. Arch. Neurol., 46, 989. 53. Pascual-Leone A, Dhuna A, Altafullah 1, Anderson DC (1990) Cocaine-induced seizures. Neurology, 40, 404. 54. Ogunyemi AO, Locke GE, Kramer LD, Nelson L (1989) Complex partial status epilepticus provoked by 'crack' cocaine. Ann. Neurol., 26, 785. 55. Choy-Kwong M, Lipton RB (1989) Dystonia related to cocaine withdrawal: a case report and pathogenic hypothesis. Neurology, 39, 996. 56. Estroff TW, Schwartz RH, Hoffmann NG (1989) Adolescent cocaine abuse. Clin. Pediatr., 28, 550. 57. Strauss A (1989) Homicidal psychosis during the combined use of cocaine and an over-thecounter cold preparation. J. Clin. Psychiatry, 50, 147. 58. Steingrub JS, Sweet S, Teres D (1989) Crackinduced rhabdomyolysis. Crit. Care Med. , 17, 1073. 59. Ahijado F, Lufio de Vinuesa SGJ (1990) Acute renal failure and rhabdomyolysis following cocaine abuse. Nephron, 54, 268. 60. Pogue VA, Nurse HM (1989) Cocaineassociated acute myoglobinuric renal failure. Am. J. Med., 86, 183. 61. Hawks RL, Chiang CN (1988) Urine testing for drugs of abuse. In: National Institute on Drug Abuse Research Monograph Series, Vol. 73. US Government Printing Office, Washington, DC, p. 93. 62. Weiss RD, Gawin FH (1988) Protracted elimination of cocaine metabolites in long-term high-dose cocaine abusers. Am. J. ivied., 85, 879. 63. Deutsch HI_, Millard Jr DR (1989) A new cocaine abuse complex. Arch. OtolaryngoL Head Neck Surg., 115, 235.
34 64. Hoffman CK, Goodman PC (1989) Pulmonary edema in cocaine smokers. Radiology 172, 463. 65. Rodriguez-BlazquezHM, CardonaPE, RiveraHerrera JL (1990) Priapism associated with the use of topical cocaine. J. UroL 143, 358. 66. Wanless IR, Dore S, Gopinath N et al (1990) Histopathology of cocaine hepatotoxicity: report of four patients. Gastroenterology, 98, 497. 67. McHenry JG, Zeiter JH, Madion MP, Cowden JW (1989) Corneal epithelial defects after smoking crack cocaine (Letter). Am. J. Ophthalmol., 108, 732. 68. Krutchkoff DJ, Eisenberg E, O'Brien JE, Ponzillo JJ (1990) Cocaine-induced dental erosions (Letter). N. EngL J. Med., 322, 408. 69. Dressier FA, Roberts WC (1989) Modes of death and types of cardiac diseases in opiate addicts: analysis of 168 necropsy cases. Am. J. Cardiol., 64, 909.
Chapter 4
A.L Green, E.J. Watsk,v and C. Salzman
70. Zapatero J, Longo JL, Carreno Monteagudo I L (1988) Costal chondritis in heroin addicts: a comparative study with postsurgical chondritis. Br. J. Dis. Chest, 82, 341. 71. Campistol JM, Montoliu J, Soler-Amig6 Jet al (1988) Renal amyloidosis with nephrotic syndrome in a Spanish subcutaneous heroin abiaser. NephroL Dial vs. Transplant., 3, 471. 72. Hughes S, Calverley PMA (1988) Heroin inhalation and asthma. Br. J. Med., 297, 1511. 73. Newell GC, Reginato A J, Auerbach D et al (1988) Pulmonary granulomatosis secondary to pentazocine abuse mimicking connective tissue diseases. Am. J. Med., 85, 890. 74. Rowden AM, Lopez JR (1989) Codeine addiction: response. Ann. Pharmacother., 23, 475. 75. Senjo M (1989) Obsessive-compulsive disorder in people that abuse codeine. Acta Ps,vchiatr. Scand., 79, 619.