Postgraduate Medicine
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Medical complications of substance abuse W. Robert Lange MD, MPH, Nancy White RNC, MS & Nancy Robinson RN, BSN To cite this article: W. Robert Lange MD, MPH, Nancy White RNC, MS & Nancy Robinson RN, BSN (1992) Medical complications of substance abuse, Postgraduate Medicine, 92:3, 205-214, DOI: 10.1080/00325481.1992.11701450 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701450
Published online: 17 May 2016.
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Citing articles: 1 View citing articles
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Date: 02 July 2016, At: 21:01
-@CME credit article
Medical complications of substance abuse
W. Robert Lange, MD, MPH
Nancy White, RNC, MS
Nancy Robinson, RN, BSN
Downloaded by [Monash University Library] at 21:01 02 July 2016
Preview Drug abusers are heir to a number of Ills, ranging from irregular menses in marijuana users to endocarditis in parenteral drug abusers. Primary care physicians encounter substance abuse often but may not always recognize Its medical complications. What conditions signal the presence of abuse, and which complications need to be ruled out in known addicts? The answers to these and other questions can be found in this review of the well- and little-known complications that can occur with substance abuse.
From an economic and public health perspective, the effects of substance abuse in the United States are staggering. For example, life expectancy is actually dedining in one subset of the population-IS- to 24-year-oldsand drug abuse and its social consequences, including accidents, homicide, suicide, and AIDS, are largely responsible. Furthermore, substance abuse is a common thread in most instances of crime and violence, including such domestic offenses as elder, spouse, and child abuse. Various estimates suggest that more than 80% of people who kill themselves or someone else are under the influence of drugs or motivated by a need to obtain them. Substance abuse is also integrally involved in many cases of unintentional injury (eg, most
automobile mishaps, burns, falls). About 50% of people whose lives are lost in fires are legally drunk at the time of death.' Epidemiologic studies show that the majority of drowning victims have appreciable concentrations of alcohol or other abusable substances in their system. 2 In a study of patients being treated for accidental injuries in an emergency department in Philadelphia, 74.5% tested positive for illicit drugs; cocaine was the substance found most often (in 54.4% of patients), followed by cannabinoids (in 37.2%). 3 Substance abuse has a variety of additional medical consequences, which can be considered in several different contexts. The following discussion, which excludes the spectrum of psychiatric manifestations, reviews medical complications by organ
system (table 1), even though a number of sequelae cannot be dearly linked to a particular organ system and some processes (eg, retroviral infection) affect multiple systems. Cardiac complications Substance abuse can result in a variety of cardiac complications. Cocaine use, for example, has been known to cause arrhythmias, ischemia, infarction, sudden death, cardiomyopathy, endocarditis, myocarditis, and cor pulmonale. Arrhythmias have also been associated with abuse of amphetamines, hallucinogens, and the many agents that have anticholinergic properties.• Alcohol use can result in a host of rhythm disturbances, including episodes of atrial fibrillation in binge drinkers ("holiday heart syndrome"). Abusers of inhalants are at increased risk, because some solvents sensitize the heart to catecholamines, making subsequent arrhythmias more serious and difficult to treat. Ischemia and infarction occur as a result of an increased demand for oxygen by the myocardium or a decreased supply to it. Tobacco, which decreases the oxygen supply to the heart as well as to other
continued
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PCP is likely to increase blood pressure and in high doses can produce a true hypertensive emergency.
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Table 1. Complications of substance abuse
Cardiac
Gastrointestinal
Arrhythmias Ischemia/infarction Sudden death Cardiomyopathy Endocarditis Myocarditis Cor pulmonale
Chronic constipation Abdominal cramping and diarrhea Anorexia Organ irritation Hepatitis Cirrhosis Hepatocellular carcinoma
Vascular
Immunologic
Hypertension Ruptured aorta Air embolism Thrombophlebitis Arteritis
Impaired immune function
Neurologic
Seizures Ischemia Stroke Infections Organic brain dysfunction Movement disorders/parkinsonian syndrome Peripheral nerve lesions Pulmonary
Respiratory depression Acute pulmonary edema Foreign-body reactions Pneumothorax Infections Malignant disease
206
Reproductive
Irregular menses Infertility Sexual dysfunction Alterations in hormonal patterns Alterations in sperm count, motility, and morphology Possible chromosomal breaks Premature labor Miscarriage/stillbirth Other complications of pregnancy Neonatal distress Congenital anomalies
organs, is responsible for more ischemic hean disease than any other abusable substance. Cocaine and other sympathomimetic drugs increase oxygen demand by increasing cardiac work (blood pressure, stroke volume, hean rate) and at the same time decrease oxygen supply through vasoconstriction. 5 Sudden death may occur with substance abuse, and coronary vasospasm is increasingly considered to be the pathophysiologic mechanism. Users of stimulants, such as cocaine, may experience vasospasm as an acute action of the drug or as a manifestation of withdrawal. 6 Drugs that have a direct toxic effect on cardiac tissue may cause cardiomyopathy, which interferes with the contractile process. Alcohol is responsible for most cases of cardiomyopathy related to substance abuse, but cocaine and crystal methamphetamine ("ice") 8 have also been linked with the condition. Endocarditis in parenteral drug abusers usually is due to injection of unsterile material, which seeds hean valves, and often affects individuals who have no preexisting disease or valvular anomaly. Infections of the right side of the hean are
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Use of various "designer'' drugs may result in conditions resembling catatonia or parkinsonian syndrome.
more common in drug abusers than in other populations but are still only half as common as infections of the left side.9 The aortic valve is most often involved, followed by the mitral and then the tricuspid; up to 10% of cases involve more than one valve. The incidence of staphylococcal and candida! infection is higher in parenteral drug abusers than in other populations, and the infection is more likely to be resistant to antibiotics.
Vascular complications All stimulant drugs can increase blood pressure. Phencyclidine hydrochloride (PCP), often classified as a hallucinogen, has both stimulant and sedative properties and is particularly likely to increase blood pressure; high doses can produce a true hypertensive emergency. 10 Rupture of the aorta or heart can occur as a result of trauma or as a complication of preexisting disease. However, cocaine in high doses, particularly if smoked, can directly result in such ruprure. 4 Parenteral drug abusers are subject to air embolism from inadvertent injection of air. Small amounts of air injected into a vein are usually well tolerated, but large amounts can be danger-
ous, and any amount injected into the arterial system can be catastrophic. Thrombophlebitis is a common sequela of repeated venous insult in parenteral drug abusers. It is being identified with increasing frequency in cocaine abusers, who may use injections two to three times more often than their opiate-abusing counterparts. Arteritis may result from any injection into an artery. In addition to direct trauma by injection, arteries can be sensitive to a number of drugs and are particularly sensitive to amphetamines. This may be due to a secondary vasculitis, injected impurities, both, or some other unknown facror. 11
Neurologic complications Seizures, usually of the grand mal type, can occur as part of the acute drug effect (of stimulants, typically) or as a consequence of withdrawal from alcohol, benwdiazepines, or sedative-hypnotics. Ischemia caused by substance abuse can affect the nervous system. Blanching of the brain has been observed in animal models as an acute, direct effect of cocaine use. Certain filler or cutting materials can also cause ischemia. For example, the retinal artery is
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particularly sensitive to quinine and talc, and filler-induced retinal artery ischemia resulting in blindness has been reported. 12 Substance abuse has emerged as the leading risk factor for stroke in young adults. Both thrombotic and hemorrhagic events have been associated with a variety of agents. 13 Infections of the central nervous system (CNS) can be due to primary infection of the brain or to seeding from a primary infection elsewhere (eg, endocarditis). Tetanus is a CNS infection that in the United States disproportionately affects heroin addicts, who have a higher casefatality rate than nonaddicts. 14 For reasons that are unclear, quinine (often used as a cutting agent) facilitates tetanus transmission.15 Among addicts, women appear more likely than men to get tetanus, 16 in part because fewer women than men have current immunization status and adequate antibody titers. In addition, women may expend their superficial veins and resort to skin-popping sooner than men. 15 Skin-popping favors tetanus transmission because Clostridium tetani organisms thrive in an anaerobic environment. The differential diagnosis of
continued
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Foreign-body reactions in the lungs are common in parenteral drug abusers because the pulmonary microvasculature is the primary filter of injected solute.
organic brain syndrome in substance abusers is complex. The syndrome may be the direct result of drug toxicity, a manifestation of ischemia or stroke, or a reflection of postanoxic damage from respiratory depression. Use of various "designer" drugs may result in conditions resembling catatonia or parkinsonian syndrome.17 The mechanisms for this are unclear, but one such drug, 3,4-methylenedioxymethamphetamine (MDMA), or "ecstasy, , appears to produce sequelae by permanently altering central serotonergic pathways. Peripheral nerve lesions may be the direct result of nerve trauma or a toxic effect of a drug. Spinal insults, usually attributable to trauma, may be drug-induced; for example, heroin use has occasionally been associated with acute transverse myelitis.
Pulmonary complications Many abusable substances, including opiates and sedativehypnotics, produce central respiratory depression. Concomitant alcohol intake further depresses respiratory drive. Acute pulmonary edema can occur with opiate overdose and has been observed with toxicity from heroin, propoxyphene, and
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methadone hydrochloride. Frothing at the mouth is characteristic in cases of fatal overdose. Opiateinduced pulmonary edema is mediated through permeability mechanisms rather than vascular pressure changes. Clinically, it needs to be differentiated from aspiration pneumonia. Even though opiate excess can produce pulmonary edema, a pharmacologic enigma is that pulmonary edema resulting from left ventricular failure can be treated with opiate. At one time, morphine sulfate was believed to reverse pulmonary edema of cardiac origin merely by reducing anxiety. However, it is now known to achieve its salutary effect by decreasing peripheral resistance and thereby increasing peripheral vascular capacity. Foreign-body reactions in the lungs are common in parenteral drug abusers because the pulmonary microvasculature is the primary filter of injected solute. The drugs involved typically have a purity range of 4o/o to 6o/o; this means that about 95% of injected material is filler, which is often insoluble, seldom sterile, and generally not inen. Adulterants often become lodged in the lung periphery, resulting in microinfarcts that can progress to
fibrosis, pulmonary hypenension, and eventually, marked impairment. Foreign material (eg, tar and related substances left after incomplete combustion) can also be introduced into the respiratory system through smoking. Paraquat, an herbicide often used in Mexico and elsewhere to eradicate marijuana, is a known pulmonary toxicant, even when ingested. Surveys have indicated that 21 o/o of marijuana samples from the southwestern United States and 4o/o nationwide contain paraquat. 18 Evidence that residual paraquat is pyrolyzed when marijuana is burned is incomplete. Pneumothorax can result from faulty injection technique: During attempts to inject a drug into the jugular system, the needle may accidentally penetrate the apex of the lung. Bullous disease secondary to smoking can also cause pneumothorax. (Bullous disease is a manifestation of chronic obstructive pulmonary disease, generally emphysema.) Not surprisingly, a variety of pulmonary infections are associated with drug abuse, and a number of mechanisms are possible. Smoking can cause bronchitic changes and associated continued
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Marijuana use has been epidemiologically linked with head and neck tumors in young adults.
infection. Drugs that produce vomiting and respiratory depression (eg, opiates) can result in aspiration pneumonia. Injection of unsterile material can lead to pneumonia and pulmonary abscess. In one retrospective survey, 19 pulmonary infections were the most frequently occurring type of infection observed in hospitalized drug addicts. Pneumonia is so common in substanceabusing populations that its prevalence can be used as a measure of community levels of drug abuse. 2° Finally, tuberculosis is a common, serious, and increasing problem in intravenous drug users, particularly those infected with human immunodeficiency virus type 1 (HN-1). Malignant tumors of the respiratory tree, such as parabronchial carcinomas of the lower airway, are most often caused by tobacco abuse. The combination of tobacco and alcohol abuse has been associated with rumors of the larynx, and a number of tobacco products can produce malignant growths of the lip and tongue. The use of marijuana has been epidemiologically linked with head and neck rumors in young adults-an age-group in which this type of rumor used to be relatively uncommon. 21 The etio-
W. Robert Lange, MD, MPH Nancy White, RNC, MS Nancy Robinson, RN, BSN Dr Lange (middle) is on the staff of Johns Hopkins Hospital and is also clinical director, Addiction Research Center, National Institute on Drug Abuse, Johns Hopkins University Bayview Research Campus, Baltimore. Ms White (right) is a nurse researcher with a special interest in the epidemiology of psychiatric disorders, and Ms Robinson (left) is a nurse educator whose area of interest is preventive healthcare; both are affiliated with the Addiction Research Center.
logic mechanisms have not been clearly delineated, but a number of theories have been advanced.
Gastrointestinal complications A variety of abusable drugs can produce alterations in gastrointestinal tract physiology. For example, regular opiate use can cause a state of tonic contraction and result in chronic constipa-
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tion. (This is the rationale for using paregoric and opiate congeners to manage diarrhea.) Opiate withdrawal is characterized . by both abdominal cramping and diarrhea. Stimulants, including nicotine and some hallucinogens, are anorexiants, and their use may result in weight loss. Some agents, including alcohol, are toxic to the
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Parenteral dnag abusers often have biologic false-positive results on tests for rheumatoid factor and syphilis.
dence of impaired immune function, false-positive results on a number of clinical laboratory tests, including those for rheumatoid factor and syphilis, often occur in these patients. Regular marijuana smoking may alter concentrations of immunoglobulins, depress natural killer cell activity, suppress T-lymphocyte populations, and cause abnormalities in monocellular macrophage and neutrophil function. 26 Advanced malignant disease of the head and neck in young marijuana smokers may reflect, in part, the ability of ~ -tetrahydrocannabinol (THC), the active ingredient in cannabis, to suppress both humoral and Immunologic effects cell-mediated immunity. Even before the AIDS epidemic The effects of cocaine on imbegan, it was dear that many par- mune function are less dear. Naenteral drug abusers had a detive South Americans who chew ranged immune system. In light coca leaves (for stimulation and of the epidemic, there has been perhaps as a remedy for altitude increasing concern that drugs of sickness) have been reponed to abuse could be cofactors in the show evidence of altered cellnatural history of HIV infection, mediated immunity (on tuberworsening the patient's immune culin testing, for example). 17 status and exacerbating his or her Findings of in vitro studies and clinical condition. Asymptomatic · studies in animals suggest that parenteral drug abusers often excocaine depresses immune rehibit generalized lymphadenopasponses, a phenomenon partially thy, hypergarnmaglobulinemia, antagonized by alcohol. Findings and high titers of circulating imof studies in humans have been mune complexes. As further evimixed. oral cavity, esophagus, stomach, duodenum, pancreas, and liver. Liver disorders associated with drug abuse range from hepatitis (including the chronic-persistent and chronic-active types) to cirrhosis to primary hepatocellular carcinoma. Hepatitis may be chemically induced or caused by a virus. Substance abuse is a risk factor for hepatitis A, B, C, and 0. 22 Recent surveys have substantiated that more than 80% of parenteral drug abusers have serologic evidence of past infection with hepatitis B23 or hepatitis C. 24 Hepatitis prevalence is another measure of the degree of substance abuse in a community. 2'
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9
Regular opiate use has been reponed to decrease the number of circulating T lymphocytes. Interestingly, this may be reversed, at least in part, with use of naloxone hydrochloride (Narcan). 28 Whether this is a nonspecific effect of withdrawal or specific evidence of heroin's immunosuppressive propenies is unclear. Patients receiving long-term methadone maintenance have less immunologic derangement, suggesting that such therapy promotes normalization of cellular immune function. Alcohol abuse also induces changes in the immune system; the relatively high incidence of infections and tumors observed in alcoholics may be a consequence of these changes. Sir William Osler's observation many decades ago that alcoholism is perhaps the most potent predisposing factor for bacterial pneumonia29 is supponed by current findings that alcohol abuse affects lymphocyte function, disturbs cytokine production and activity, and modifies endotoxin responses.
Reproductive complications Opiate use and marijuana use have both been linked to irregular menses and temporary infer-
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Management of the pregnant heroin addict calls for methadone maintenance rather than detoxification.
tility in women and to decreased libido and a partern of delayed ejaculation in men. 16 There is evidence that TH C can decrease sperm count, affect sperm motility, and alter sperm morphology. 30 In addition, THC appears to decrease levels of circulating testosterone and to adversely affect the female hormonal cycle. There have been reports of chromosomal breaks in culrured lymphocytes obtained from heroin addicts who also abuse marijuana; these reports have been tempered by other accounts suggesting that damage is less prevalent with long-term methadone maintenance. 31 The threats to a pregnant heroin addict and her fetus are not limited to drug toxicity but also include poor diet and hygiene, a propensity not to seek prenatal care, and a high risk of exposure to multiple infections, including sexually transmitted diseases. Hepatitis B infection is particularly damaging: Every year in the United States, 16,500 children born to mothers with circulating hepatitis B virus have not only a 90% risk of becoming infected but also an 85% to 90% probability of becoming chronic carriers of the virus. 32
Pregnancy in heroin users can be tricky to diagnose. Amenorrhea is common in these women, which makes it a nonspecific indicator of pregnancy. In addition, symptoms of heroin withdrawal, particularly nausea, vomiting, and abdominal cramping, can mimic morning sickness and false labor. Tubal pregnancies, with their accompanying diagnostic difficulties, are relatively common in this population, given the high incidence of sexually transmined diseases. Both because of these difficulties and because urine pregnancy tests have a false-positive rate of up to 5%, a serum test for the beta subunit of human chorionic gonadotropin is indicated in addicts. 33 Ultrasound at 5 to 6 weeks is the most sensitive diagnostic tool for establishing pregnancy. 34 Management of the pregnant heroin addict calls for methadone maintenance (at a dosage sufficient to deter further illicit drug use) 3 ~ rather than detoxification. Acute withdrawal can be difficult for the mother and fatal for the fetus. Management during labor and delivery, like diagnosis of pregnancy, can be tricky in addicts. Methadone dosing too close to delivery can result in uterine
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atony and ensuing hemorrhage. On the other hand, withholding methadone for too long can precipitate withdrawal and induce vigorous uterine contractions and sudden delivery.
Summary and conclusion Substance abuse is involved in many instances of intentional and unintentional injury. It can also cause medical complications that affect various organ systems-among them, the cardiac, vascular, neurologic, pulmonary, gastrointestinal, immunologic, and reproductive systems. Even though there is pressure to create a new medical specialty to specifically address substance-abuse issues, the truth is that any physician, regardless of specialty, may encounter patients with substanceabuse problems. Alcoholism and drug abuse, with their associated psychosocial and clinical ramifications and complications, cut across all specialty fields. Consequently, all physicians need to be familiar with the spectrum of clinical problems associated with substance abuse and comfortable with continued
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addressing these problems prudently and promptly. IW
-®
Earn credit on this anide. See CME Quiz.
Address for correspondence: W. Roben Lange, MD, MPH, Addiction Research Center, National Institute on Drug Abuse, 4940 Eastern Ave, Baltimore, MD 21224.
Rdi:ralces 1. Howland J, Hinpon R. Alcohol as a risk factor for injuries or death due to fires and bums: review of the literature. Public Health Rep 1987;102(5):475-83 2. Patcua MJ, Biddinger Pw. Characteristics of drowning deaths in North Carolina. Public Health Rep 1988;103(4):406-11 3. ~ UW, Gcnaer SG, Gnu WC, et ai. Complications of drug misuse. Curr Opin Psychiatr 1991;4:454-9 4. Blumencbal RS, Flaherty JI. Recognizing cardiac crises in cocaine abusers: acute care for ischemia, Ml, cardiomyopathy-nen in young patients. J Crit Illness 1990;5(3):225-39 S. Isner JM, Cbok.sbi SK. Cocaine and vasospasm. (Editorial) N Engl J Med 1989;321 (23): 1604~
6. Nadcmanee K, Gorelick DA, Josephson MA, et ai. Myocardial ischemia during cocaine withdrawal. Ann Intern Med 1989; Ill (II): 876-80 1. w-as, LoddwtJT, Schwartt RG. Dilated cardiomyopathy and cocaine abuse: report of two cases. Am J Med 1986;81 (4):699701 8. Hong R, Maauyama I!, Nur K. Cardiomyopathy associated with the smoking of crystal methamphetamine. JAMA 1991 ;265(9): 1152-4 9. Levine DP. Inkctious endocarditis in intravenous drug abusers. In: Levine DP, Sobel JD,
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eds. Infections in intravenous drug abusers. New York: Oxford Univ Press, 1991:251-85 10. Schnoll SH. Aiding the drug abuser. Hosp Med 1983;(Aug):ll6-55 11. Margolis MT, Newton 1H. Methamphetamine ("speed") arteritis. Neuroradiology 1971;2(3):179-82 12. Mames RN, Spoor TC. Ocular manifestations of intravenous drug abuse. In: Levine, Sobel, eds,' pp 167-82 13. Kaku DA, Lowenstein DH. Emergence of recreational drug abuse as a major risk factor for stroke in young adults. Ann Intern Med 1990; 113(11):821-7 14. Cberubin CE. Epidemiology of tetanus in narcotic addicts. NY State J Med 1970;70(2): 267-71 1S. W'alfonl BB. Clinical complications of drug abuse. In: Drug abuse: a guide for the primary care physician. Chicago: American Medical Assn, 1981:177-202 16. Lerinson A. Manke RL, Shein MK. Tetanus in heroin addicts. JAMA 1955; 157(8): 658~
17. Centas for Disease ConttoL Street-drug contaminant causing parkinsonism. MMWR 1984;33(24):351-2 18. Landrigan PJ, Powdl KE,James LM, et ai. Paraquat and marijuana: epidemiologic risk assessment. Am J Public Health 1983; 73(7):784-8 19. Scheidcger C, Zimmerli W. Infectious complications in drug addicts: seven-year review of 269 hospitalized narcotics abusers in Switzerland. Rev Infect Dis 1989;11(3):486-93 [erratum, Rev Infect Dis 1990; 12(1 ): 165] 20. ~ UW, Lange WR. Serious infections other than human immunodeficiency virus among intravenoUs drug abusers. J Infect Dis 1990;16l(May):894-902 [erratum,} Infect Dis 1990;162(6):1421] 21. Donald P. Advanced malignancy in the young marijuana smoker. In: Friedman H, Specter S, Klein Tw, eds. Advances in experimental medicine and biology. Vol 288. Drugs of abuse, immunity, and immunodeficiency. New York: Plenum Press, 1991 :33-46 22. Mutchnick MG, Lee HH; Pdeman RR. Liver disease associated with intravenous drug
IIUIIaT~-
abuse. In: Levine, Sobel, eds,' pp 286-305 23. Lange WR, Moore JD, Kreider SD. The prevalence of serological markers to hepatitis A and hepatitis B in drug abuse personnel. Am J Prev Med 1986;2(2):109-15
24. Donahue JG, Ncbon KE, Munoz A. et ai. Antibody to hepatitis C virus among car-
diac surgery patients, homosexual men, and intravenous drug users in Baltimore, Maryland. AmJ Epidemiol1991;134(10):1206-11 25. Alc:undcr M. Indicators of drug abuse: hepatitis. NIDA Res Monogr 1977;(10):123-9 26. Klein Tw, Newton C, Friedman H. Inhibition of natural killer cell function by marijuana components. J Toxicol Environ Health 1987;20(4):321-32 27. GocdatJJ. Recreational drugs: relationship to AIDS. Ann NY Acad Sci 1984;437: 192-9 28. Novick DM, Ocbshom M, Kreek MJ. In vivo and in vitro studies of opiates and cellular immunity in narcotic addicts. In: Friedman et al, eds," pp 159-70 29. Nelson S, Bagby G, Andresen J, et al. The effects of ethanol, tumor necrosis factor, and granulocyte colony-stimulating factor on lung antibacterial d&nses. In: Friedman et al, eds," pp 24 5-54 30. Kolodny RC, Masters WH, Koloclncr RM, et ai. Depression of plasma testosterone levels alter chronic intensive marihuana use. N EnglJ Med 1974;290(16):872-4 31. Falek A. Hollingsworth E Opiates and human chromosome alterations. lnt J Addict 1980;15(2):155~3
32. Butterfield CR, Shoddey M, San Miguel G, et ai. Routine screening for hepatitis B in an obstetric population. Obsret Gynecol 1990; 76(1):25-7 33. Martin JN Jr, Martin Rw, Hess LW, et ai. Pregnancy-associated substance abuse and addiction: cunent concepts and management. ) Miss State Med Assoc 1988;29(12):369-74 34. CbasnofFIJ. Perinatal effects of cocaine. Contemp Ob/Gyn 1987;(May):163-79 35. ZwdJcn JE, Payte JI. Methadone maintenance in the treatment of opioid dependence: a current perspective. West J Med 1990; 152(5): 588-99
• VOL 92/NO 3/SEPTEMBER 1, 1992/POSTGRAOUATE MEDICINE
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Medical complications of substance abuse W. Robert Lange MD, MPH, Nancy White RNC, MS & Nancy Robinson RN, BSN To cite this article: W. Robert Lange MD, MPH, Nancy White RNC, MS & Nancy Robinson RN, BSN (1992) Medical complications of substance abuse, Postgraduate Medicine, 92:3, 205-214, DOI: 10.1080/00325481.1992.11701450 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701450
Published online: 17 May 2016.
Submit your article to this journal
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [Monash University Library]
Date: 02 July 2016, At: 21:01
-@CME credit article
Medical complications of substance abuse
W. Robert Lange, MD, MPH
Nancy White, RNC, MS
Nancy Robinson, RN, BSN
Downloaded by [Monash University Library] at 21:01 02 July 2016
Preview Drug abusers are heir to a number of Ills, ranging from irregular menses in marijuana users to endocarditis in parenteral drug abusers. Primary care physicians encounter substance abuse often but may not always recognize Its medical complications. What conditions signal the presence of abuse, and which complications need to be ruled out in known addicts? The answers to these and other questions can be found in this review of the well- and little-known complications that can occur with substance abuse.
From an economic and public health perspective, the effects of substance abuse in the United States are staggering. For example, life expectancy is actually dedining in one subset of the population-IS- to 24-year-oldsand drug abuse and its social consequences, including accidents, homicide, suicide, and AIDS, are largely responsible. Furthermore, substance abuse is a common thread in most instances of crime and violence, including such domestic offenses as elder, spouse, and child abuse. Various estimates suggest that more than 80% of people who kill themselves or someone else are under the influence of drugs or motivated by a need to obtain them. Substance abuse is also integrally involved in many cases of unintentional injury (eg, most
automobile mishaps, burns, falls). About 50% of people whose lives are lost in fires are legally drunk at the time of death.' Epidemiologic studies show that the majority of drowning victims have appreciable concentrations of alcohol or other abusable substances in their system. 2 In a study of patients being treated for accidental injuries in an emergency department in Philadelphia, 74.5% tested positive for illicit drugs; cocaine was the substance found most often (in 54.4% of patients), followed by cannabinoids (in 37.2%). 3 Substance abuse has a variety of additional medical consequences, which can be considered in several different contexts. The following discussion, which excludes the spectrum of psychiatric manifestations, reviews medical complications by organ
system (table 1), even though a number of sequelae cannot be dearly linked to a particular organ system and some processes (eg, retroviral infection) affect multiple systems. Cardiac complications Substance abuse can result in a variety of cardiac complications. Cocaine use, for example, has been known to cause arrhythmias, ischemia, infarction, sudden death, cardiomyopathy, endocarditis, myocarditis, and cor pulmonale. Arrhythmias have also been associated with abuse of amphetamines, hallucinogens, and the many agents that have anticholinergic properties.• Alcohol use can result in a host of rhythm disturbances, including episodes of atrial fibrillation in binge drinkers ("holiday heart syndrome"). Abusers of inhalants are at increased risk, because some solvents sensitize the heart to catecholamines, making subsequent arrhythmias more serious and difficult to treat. Ischemia and infarction occur as a result of an increased demand for oxygen by the myocardium or a decreased supply to it. Tobacco, which decreases the oxygen supply to the heart as well as to other
continued
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PCP is likely to increase blood pressure and in high doses can produce a true hypertensive emergency.
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Table 1. Complications of substance abuse
Cardiac
Gastrointestinal
Arrhythmias Ischemia/infarction Sudden death Cardiomyopathy Endocarditis Myocarditis Cor pulmonale
Chronic constipation Abdominal cramping and diarrhea Anorexia Organ irritation Hepatitis Cirrhosis Hepatocellular carcinoma
Vascular
Immunologic
Hypertension Ruptured aorta Air embolism Thrombophlebitis Arteritis
Impaired immune function
Neurologic
Seizures Ischemia Stroke Infections Organic brain dysfunction Movement disorders/parkinsonian syndrome Peripheral nerve lesions Pulmonary
Respiratory depression Acute pulmonary edema Foreign-body reactions Pneumothorax Infections Malignant disease
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Reproductive
Irregular menses Infertility Sexual dysfunction Alterations in hormonal patterns Alterations in sperm count, motility, and morphology Possible chromosomal breaks Premature labor Miscarriage/stillbirth Other complications of pregnancy Neonatal distress Congenital anomalies
organs, is responsible for more ischemic hean disease than any other abusable substance. Cocaine and other sympathomimetic drugs increase oxygen demand by increasing cardiac work (blood pressure, stroke volume, hean rate) and at the same time decrease oxygen supply through vasoconstriction. 5 Sudden death may occur with substance abuse, and coronary vasospasm is increasingly considered to be the pathophysiologic mechanism. Users of stimulants, such as cocaine, may experience vasospasm as an acute action of the drug or as a manifestation of withdrawal. 6 Drugs that have a direct toxic effect on cardiac tissue may cause cardiomyopathy, which interferes with the contractile process. Alcohol is responsible for most cases of cardiomyopathy related to substance abuse, but cocaine and crystal methamphetamine ("ice") 8 have also been linked with the condition. Endocarditis in parenteral drug abusers usually is due to injection of unsterile material, which seeds hean valves, and often affects individuals who have no preexisting disease or valvular anomaly. Infections of the right side of the hean are
IIUIIaTANCa ABUa • VOL 92/NO 3/SEPTEMBER 1. 1992/POSTGRADUATE MEDICINE
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Use of various "designer'' drugs may result in conditions resembling catatonia or parkinsonian syndrome.
more common in drug abusers than in other populations but are still only half as common as infections of the left side.9 The aortic valve is most often involved, followed by the mitral and then the tricuspid; up to 10% of cases involve more than one valve. The incidence of staphylococcal and candida! infection is higher in parenteral drug abusers than in other populations, and the infection is more likely to be resistant to antibiotics.
Vascular complications All stimulant drugs can increase blood pressure. Phencyclidine hydrochloride (PCP), often classified as a hallucinogen, has both stimulant and sedative properties and is particularly likely to increase blood pressure; high doses can produce a true hypertensive emergency. 10 Rupture of the aorta or heart can occur as a result of trauma or as a complication of preexisting disease. However, cocaine in high doses, particularly if smoked, can directly result in such ruprure. 4 Parenteral drug abusers are subject to air embolism from inadvertent injection of air. Small amounts of air injected into a vein are usually well tolerated, but large amounts can be danger-
ous, and any amount injected into the arterial system can be catastrophic. Thrombophlebitis is a common sequela of repeated venous insult in parenteral drug abusers. It is being identified with increasing frequency in cocaine abusers, who may use injections two to three times more often than their opiate-abusing counterparts. Arteritis may result from any injection into an artery. In addition to direct trauma by injection, arteries can be sensitive to a number of drugs and are particularly sensitive to amphetamines. This may be due to a secondary vasculitis, injected impurities, both, or some other unknown facror. 11
Neurologic complications Seizures, usually of the grand mal type, can occur as part of the acute drug effect (of stimulants, typically) or as a consequence of withdrawal from alcohol, benwdiazepines, or sedative-hypnotics. Ischemia caused by substance abuse can affect the nervous system. Blanching of the brain has been observed in animal models as an acute, direct effect of cocaine use. Certain filler or cutting materials can also cause ischemia. For example, the retinal artery is
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particularly sensitive to quinine and talc, and filler-induced retinal artery ischemia resulting in blindness has been reported. 12 Substance abuse has emerged as the leading risk factor for stroke in young adults. Both thrombotic and hemorrhagic events have been associated with a variety of agents. 13 Infections of the central nervous system (CNS) can be due to primary infection of the brain or to seeding from a primary infection elsewhere (eg, endocarditis). Tetanus is a CNS infection that in the United States disproportionately affects heroin addicts, who have a higher casefatality rate than nonaddicts. 14 For reasons that are unclear, quinine (often used as a cutting agent) facilitates tetanus transmission.15 Among addicts, women appear more likely than men to get tetanus, 16 in part because fewer women than men have current immunization status and adequate antibody titers. In addition, women may expend their superficial veins and resort to skin-popping sooner than men. 15 Skin-popping favors tetanus transmission because Clostridium tetani organisms thrive in an anaerobic environment. The differential diagnosis of
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Foreign-body reactions in the lungs are common in parenteral drug abusers because the pulmonary microvasculature is the primary filter of injected solute.
organic brain syndrome in substance abusers is complex. The syndrome may be the direct result of drug toxicity, a manifestation of ischemia or stroke, or a reflection of postanoxic damage from respiratory depression. Use of various "designer" drugs may result in conditions resembling catatonia or parkinsonian syndrome.17 The mechanisms for this are unclear, but one such drug, 3,4-methylenedioxymethamphetamine (MDMA), or "ecstasy, , appears to produce sequelae by permanently altering central serotonergic pathways. Peripheral nerve lesions may be the direct result of nerve trauma or a toxic effect of a drug. Spinal insults, usually attributable to trauma, may be drug-induced; for example, heroin use has occasionally been associated with acute transverse myelitis.
Pulmonary complications Many abusable substances, including opiates and sedativehypnotics, produce central respiratory depression. Concomitant alcohol intake further depresses respiratory drive. Acute pulmonary edema can occur with opiate overdose and has been observed with toxicity from heroin, propoxyphene, and
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methadone hydrochloride. Frothing at the mouth is characteristic in cases of fatal overdose. Opiateinduced pulmonary edema is mediated through permeability mechanisms rather than vascular pressure changes. Clinically, it needs to be differentiated from aspiration pneumonia. Even though opiate excess can produce pulmonary edema, a pharmacologic enigma is that pulmonary edema resulting from left ventricular failure can be treated with opiate. At one time, morphine sulfate was believed to reverse pulmonary edema of cardiac origin merely by reducing anxiety. However, it is now known to achieve its salutary effect by decreasing peripheral resistance and thereby increasing peripheral vascular capacity. Foreign-body reactions in the lungs are common in parenteral drug abusers because the pulmonary microvasculature is the primary filter of injected solute. The drugs involved typically have a purity range of 4o/o to 6o/o; this means that about 95% of injected material is filler, which is often insoluble, seldom sterile, and generally not inen. Adulterants often become lodged in the lung periphery, resulting in microinfarcts that can progress to
fibrosis, pulmonary hypenension, and eventually, marked impairment. Foreign material (eg, tar and related substances left after incomplete combustion) can also be introduced into the respiratory system through smoking. Paraquat, an herbicide often used in Mexico and elsewhere to eradicate marijuana, is a known pulmonary toxicant, even when ingested. Surveys have indicated that 21 o/o of marijuana samples from the southwestern United States and 4o/o nationwide contain paraquat. 18 Evidence that residual paraquat is pyrolyzed when marijuana is burned is incomplete. Pneumothorax can result from faulty injection technique: During attempts to inject a drug into the jugular system, the needle may accidentally penetrate the apex of the lung. Bullous disease secondary to smoking can also cause pneumothorax. (Bullous disease is a manifestation of chronic obstructive pulmonary disease, generally emphysema.) Not surprisingly, a variety of pulmonary infections are associated with drug abuse, and a number of mechanisms are possible. Smoking can cause bronchitic changes and associated continued
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Marijuana use has been epidemiologically linked with head and neck tumors in young adults.
infection. Drugs that produce vomiting and respiratory depression (eg, opiates) can result in aspiration pneumonia. Injection of unsterile material can lead to pneumonia and pulmonary abscess. In one retrospective survey, 19 pulmonary infections were the most frequently occurring type of infection observed in hospitalized drug addicts. Pneumonia is so common in substanceabusing populations that its prevalence can be used as a measure of community levels of drug abuse. 2° Finally, tuberculosis is a common, serious, and increasing problem in intravenous drug users, particularly those infected with human immunodeficiency virus type 1 (HN-1). Malignant tumors of the respiratory tree, such as parabronchial carcinomas of the lower airway, are most often caused by tobacco abuse. The combination of tobacco and alcohol abuse has been associated with rumors of the larynx, and a number of tobacco products can produce malignant growths of the lip and tongue. The use of marijuana has been epidemiologically linked with head and neck rumors in young adults-an age-group in which this type of rumor used to be relatively uncommon. 21 The etio-
W. Robert Lange, MD, MPH Nancy White, RNC, MS Nancy Robinson, RN, BSN Dr Lange (middle) is on the staff of Johns Hopkins Hospital and is also clinical director, Addiction Research Center, National Institute on Drug Abuse, Johns Hopkins University Bayview Research Campus, Baltimore. Ms White (right) is a nurse researcher with a special interest in the epidemiology of psychiatric disorders, and Ms Robinson (left) is a nurse educator whose area of interest is preventive healthcare; both are affiliated with the Addiction Research Center.
logic mechanisms have not been clearly delineated, but a number of theories have been advanced.
Gastrointestinal complications A variety of abusable drugs can produce alterations in gastrointestinal tract physiology. For example, regular opiate use can cause a state of tonic contraction and result in chronic constipa-
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tion. (This is the rationale for using paregoric and opiate congeners to manage diarrhea.) Opiate withdrawal is characterized . by both abdominal cramping and diarrhea. Stimulants, including nicotine and some hallucinogens, are anorexiants, and their use may result in weight loss. Some agents, including alcohol, are toxic to the
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Parenteral dnag abusers often have biologic false-positive results on tests for rheumatoid factor and syphilis.
dence of impaired immune function, false-positive results on a number of clinical laboratory tests, including those for rheumatoid factor and syphilis, often occur in these patients. Regular marijuana smoking may alter concentrations of immunoglobulins, depress natural killer cell activity, suppress T-lymphocyte populations, and cause abnormalities in monocellular macrophage and neutrophil function. 26 Advanced malignant disease of the head and neck in young marijuana smokers may reflect, in part, the ability of ~ -tetrahydrocannabinol (THC), the active ingredient in cannabis, to suppress both humoral and Immunologic effects cell-mediated immunity. Even before the AIDS epidemic The effects of cocaine on imbegan, it was dear that many par- mune function are less dear. Naenteral drug abusers had a detive South Americans who chew ranged immune system. In light coca leaves (for stimulation and of the epidemic, there has been perhaps as a remedy for altitude increasing concern that drugs of sickness) have been reponed to abuse could be cofactors in the show evidence of altered cellnatural history of HIV infection, mediated immunity (on tuberworsening the patient's immune culin testing, for example). 17 status and exacerbating his or her Findings of in vitro studies and clinical condition. Asymptomatic · studies in animals suggest that parenteral drug abusers often excocaine depresses immune rehibit generalized lymphadenopasponses, a phenomenon partially thy, hypergarnmaglobulinemia, antagonized by alcohol. Findings and high titers of circulating imof studies in humans have been mune complexes. As further evimixed. oral cavity, esophagus, stomach, duodenum, pancreas, and liver. Liver disorders associated with drug abuse range from hepatitis (including the chronic-persistent and chronic-active types) to cirrhosis to primary hepatocellular carcinoma. Hepatitis may be chemically induced or caused by a virus. Substance abuse is a risk factor for hepatitis A, B, C, and 0. 22 Recent surveys have substantiated that more than 80% of parenteral drug abusers have serologic evidence of past infection with hepatitis B23 or hepatitis C. 24 Hepatitis prevalence is another measure of the degree of substance abuse in a community. 2'
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Regular opiate use has been reponed to decrease the number of circulating T lymphocytes. Interestingly, this may be reversed, at least in part, with use of naloxone hydrochloride (Narcan). 28 Whether this is a nonspecific effect of withdrawal or specific evidence of heroin's immunosuppressive propenies is unclear. Patients receiving long-term methadone maintenance have less immunologic derangement, suggesting that such therapy promotes normalization of cellular immune function. Alcohol abuse also induces changes in the immune system; the relatively high incidence of infections and tumors observed in alcoholics may be a consequence of these changes. Sir William Osler's observation many decades ago that alcoholism is perhaps the most potent predisposing factor for bacterial pneumonia29 is supponed by current findings that alcohol abuse affects lymphocyte function, disturbs cytokine production and activity, and modifies endotoxin responses.
Reproductive complications Opiate use and marijuana use have both been linked to irregular menses and temporary infer-
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Management of the pregnant heroin addict calls for methadone maintenance rather than detoxification.
tility in women and to decreased libido and a partern of delayed ejaculation in men. 16 There is evidence that TH C can decrease sperm count, affect sperm motility, and alter sperm morphology. 30 In addition, THC appears to decrease levels of circulating testosterone and to adversely affect the female hormonal cycle. There have been reports of chromosomal breaks in culrured lymphocytes obtained from heroin addicts who also abuse marijuana; these reports have been tempered by other accounts suggesting that damage is less prevalent with long-term methadone maintenance. 31 The threats to a pregnant heroin addict and her fetus are not limited to drug toxicity but also include poor diet and hygiene, a propensity not to seek prenatal care, and a high risk of exposure to multiple infections, including sexually transmitted diseases. Hepatitis B infection is particularly damaging: Every year in the United States, 16,500 children born to mothers with circulating hepatitis B virus have not only a 90% risk of becoming infected but also an 85% to 90% probability of becoming chronic carriers of the virus. 32
Pregnancy in heroin users can be tricky to diagnose. Amenorrhea is common in these women, which makes it a nonspecific indicator of pregnancy. In addition, symptoms of heroin withdrawal, particularly nausea, vomiting, and abdominal cramping, can mimic morning sickness and false labor. Tubal pregnancies, with their accompanying diagnostic difficulties, are relatively common in this population, given the high incidence of sexually transmined diseases. Both because of these difficulties and because urine pregnancy tests have a false-positive rate of up to 5%, a serum test for the beta subunit of human chorionic gonadotropin is indicated in addicts. 33 Ultrasound at 5 to 6 weeks is the most sensitive diagnostic tool for establishing pregnancy. 34 Management of the pregnant heroin addict calls for methadone maintenance (at a dosage sufficient to deter further illicit drug use) 3 ~ rather than detoxification. Acute withdrawal can be difficult for the mother and fatal for the fetus. Management during labor and delivery, like diagnosis of pregnancy, can be tricky in addicts. Methadone dosing too close to delivery can result in uterine
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atony and ensuing hemorrhage. On the other hand, withholding methadone for too long can precipitate withdrawal and induce vigorous uterine contractions and sudden delivery.
Summary and conclusion Substance abuse is involved in many instances of intentional and unintentional injury. It can also cause medical complications that affect various organ systems-among them, the cardiac, vascular, neurologic, pulmonary, gastrointestinal, immunologic, and reproductive systems. Even though there is pressure to create a new medical specialty to specifically address substance-abuse issues, the truth is that any physician, regardless of specialty, may encounter patients with substanceabuse problems. Alcoholism and drug abuse, with their associated psychosocial and clinical ramifications and complications, cut across all specialty fields. Consequently, all physicians need to be familiar with the spectrum of clinical problems associated with substance abuse and comfortable with continued
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addressing these problems prudently and promptly. IW
-®
Earn credit on this anide. See CME Quiz.
Address for correspondence: W. Roben Lange, MD, MPH, Addiction Research Center, National Institute on Drug Abuse, 4940 Eastern Ave, Baltimore, MD 21224.
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6. Nadcmanee K, Gorelick DA, Josephson MA, et ai. Myocardial ischemia during cocaine withdrawal. Ann Intern Med 1989; Ill (II): 876-80 1. w-as, LoddwtJT, Schwartt RG. Dilated cardiomyopathy and cocaine abuse: report of two cases. Am J Med 1986;81 (4):699701 8. Hong R, Maauyama I!, Nur K. Cardiomyopathy associated with the smoking of crystal methamphetamine. JAMA 1991 ;265(9): 1152-4 9. Levine DP. Inkctious endocarditis in intravenous drug abusers. In: Levine DP, Sobel JD,
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eds. Infections in intravenous drug abusers. New York: Oxford Univ Press, 1991:251-85 10. Schnoll SH. Aiding the drug abuser. Hosp Med 1983;(Aug):ll6-55 11. Margolis MT, Newton 1H. Methamphetamine ("speed") arteritis. Neuroradiology 1971;2(3):179-82 12. Mames RN, Spoor TC. Ocular manifestations of intravenous drug abuse. In: Levine, Sobel, eds,' pp 167-82 13. Kaku DA, Lowenstein DH. Emergence of recreational drug abuse as a major risk factor for stroke in young adults. Ann Intern Med 1990; 113(11):821-7 14. Cberubin CE. Epidemiology of tetanus in narcotic addicts. NY State J Med 1970;70(2): 267-71 1S. W'alfonl BB. Clinical complications of drug abuse. In: Drug abuse: a guide for the primary care physician. Chicago: American Medical Assn, 1981:177-202 16. Lerinson A. Manke RL, Shein MK. Tetanus in heroin addicts. JAMA 1955; 157(8): 658~
17. Centas for Disease ConttoL Street-drug contaminant causing parkinsonism. MMWR 1984;33(24):351-2 18. Landrigan PJ, Powdl KE,James LM, et ai. Paraquat and marijuana: epidemiologic risk assessment. Am J Public Health 1983; 73(7):784-8 19. Scheidcger C, Zimmerli W. Infectious complications in drug addicts: seven-year review of 269 hospitalized narcotics abusers in Switzerland. Rev Infect Dis 1989;11(3):486-93 [erratum, Rev Infect Dis 1990; 12(1 ): 165] 20. ~ UW, Lange WR. Serious infections other than human immunodeficiency virus among intravenoUs drug abusers. J Infect Dis 1990;16l(May):894-902 [erratum,} Infect Dis 1990;162(6):1421] 21. Donald P. Advanced malignancy in the young marijuana smoker. In: Friedman H, Specter S, Klein Tw, eds. Advances in experimental medicine and biology. Vol 288. Drugs of abuse, immunity, and immunodeficiency. New York: Plenum Press, 1991 :33-46 22. Mutchnick MG, Lee HH; Pdeman RR. Liver disease associated with intravenous drug
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abuse. In: Levine, Sobel, eds,' pp 286-305 23. Lange WR, Moore JD, Kreider SD. The prevalence of serological markers to hepatitis A and hepatitis B in drug abuse personnel. Am J Prev Med 1986;2(2):109-15
24. Donahue JG, Ncbon KE, Munoz A. et ai. Antibody to hepatitis C virus among car-
diac surgery patients, homosexual men, and intravenous drug users in Baltimore, Maryland. AmJ Epidemiol1991;134(10):1206-11 25. Alc:undcr M. Indicators of drug abuse: hepatitis. NIDA Res Monogr 1977;(10):123-9 26. Klein Tw, Newton C, Friedman H. Inhibition of natural killer cell function by marijuana components. J Toxicol Environ Health 1987;20(4):321-32 27. GocdatJJ. Recreational drugs: relationship to AIDS. Ann NY Acad Sci 1984;437: 192-9 28. Novick DM, Ocbshom M, Kreek MJ. In vivo and in vitro studies of opiates and cellular immunity in narcotic addicts. In: Friedman et al, eds," pp 159-70 29. Nelson S, Bagby G, Andresen J, et al. The effects of ethanol, tumor necrosis factor, and granulocyte colony-stimulating factor on lung antibacterial d&nses. In: Friedman et al, eds," pp 24 5-54 30. Kolodny RC, Masters WH, Koloclncr RM, et ai. Depression of plasma testosterone levels alter chronic intensive marihuana use. N EnglJ Med 1974;290(16):872-4 31. Falek A. Hollingsworth E Opiates and human chromosome alterations. lnt J Addict 1980;15(2):155~3
32. Butterfield CR, Shoddey M, San Miguel G, et ai. Routine screening for hepatitis B in an obstetric population. Obsret Gynecol 1990; 76(1):25-7 33. Martin JN Jr, Martin Rw, Hess LW, et ai. Pregnancy-associated substance abuse and addiction: cunent concepts and management. ) Miss State Med Assoc 1988;29(12):369-74 34. CbasnofFIJ. Perinatal effects of cocaine. Contemp Ob/Gyn 1987;(May):163-79 35. ZwdJcn JE, Payte JI. Methadone maintenance in the treatment of opioid dependence: a current perspective. West J Med 1990; 152(5): 588-99
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