Critical Reviews in Oral Biology and Medicine, 3(3):163-184 (1992)

Oral Effects of Drug Abuse

Terry D. Rees, D.D.S., M.S.D.
Chairman and Professor, Periodontics Department, Baylor College of Dentistry, 3302 Gaston Avenue, Dallas, Texas 75246
ABSTRACT: Drug abuse is a major problem in the U.S. and most other countries of the world today. Many studies, surveys, and case reports have described the adverse social and medical effects of drug abuse; yet surprisingly little is known about the specific effects of many of these drugs in the oral cavity. This article reviews the current state of knowledge concerning the systemic and oral effects of drugs of abuse and the dental management of addicted patients.
KEY WORDS: opiates, hallucinogens, cannabis, cocaine, amphetamines, alcohol.

1. INTRODUCTION
Mood-altering drugs have been used by man for many purposes throughout recorded history. In some instances, such agents were used as components of religious ceremonies, while in other cultures substances such as coca leaves were chewed by native populations to increase endurance and to relieve hunger and fatigue (Gargiulo et al., 1985, Hamner and Villegas, 1969). In other circumstances, mood-altering agents were and are used for medical purposes. Cocaine, for example, was widely available in the U.S. during the late 19th century for use as a stimulant, or a local anesthetic in dentistry, opthalmology, and otolaryngology (Friedlander and Gorelick, 1988). Clearly, however, the most common use for mood-altering drugs has essentially been for "recreational" or social purposes. Although possessing some medicinal properties, alcohol has been used recreationally for thousands of years and alcoholism has been described since the 1st century B.C. Cocaine and opium have been in use at least since the 6th century (Council on Dental Practice, 1987). Today, the use and abuse of mood-altering drugs in the U.S. creates staggering figures and estimates. For example, it is reported that 22 million Americans have used cocaine at least
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once, while 2 to 4 million Americans have used it regularly. At least one half million individuals have significant problems with cocaine abuse (Friedlander and Gorelick, 1988; Council on Dental Practice, 1987). Despite these large numbers, cocaine ranks only third among drugs of abuse, with ethyl alcohol representing the most widely used substance, followed by cannabis (such as marijuana and hashish). The Federal Drug Enforcement Agency lists at least 171 other drugs capable of being abused, and new drugs with abuse potential are constantly being developed. In addition to alcohol, the agents of abuse fall into the general categories of narcotics, depressants, stimulants, hallucinogens (Council on Dental Practice, 1987), and solvents and inhalants (Rosenbaum, 1981). A majority of American teenagers and adults use ethyl alcohol and an estimated 12 million suffer from some aspect of alcohol abuse (Christen, 1983; Duggan et al., 1991). Despite these large estimates, relatively little is known conclusively regarding the factors that cause people to use such drugs and even less is known regarding chemical dependency (Council on Dental Practice, 1987; Jenike, 1991). In the past, with the exception of alcohol, substance dependency was a phenomenon that was primarily limited to socially disadvantaged individ-

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uals and to those of high socioeconomic status who possess the financial means and access to purchase drugs of abuse. Today, however, drug users are distributed proportionately among the general population in all social strata (Friedlander and Mills, 1985). In general terms, initiation of drug use begins between 15 and 35 years of age, although wide age variations are often described with the age of first-time users becoming progressively younger (Rosenbaum, 1981). Polydrug use is extremely common. One survey indicated that 61% of U.S. high school seniors had used a drug at least once and 40% had used more than one type of drug. Marijuana and alcohol are the two most commonly used "entry" drugs, with others added subsequently. Polydrug use compounds the difficulty of determining the long-term effects of specific drugs. For example, 31% of all alcoholics and 51% of teenagers and young adult alcoholics are addicted to other drugs in addition to alcohol. Among individuals with drug abuse problems causing hospitalization or death, polydrug use ranges from 34 to 50%. Among alcoholics, barbiturates, narcotic analgesics, and stimulants are the most frequently used additional drugs (Council on Dental Practice, 1987). Drug abuse is commonly associated with significant detrimental psychological, nutritional, and social changes, any of which can markedly affect the general and oral health of the individual user. The stereotypical drug addict is pictured as an undereducated individual living in a very low socioeconomic environment. This individual is unable to purchase adequate supplies of food, general and oral hygiene are neglected, and there is little interest in seeking medical or dental treatment other than as a possible mechanism for obtaining prescription drugs of abuse (Rosenbaum, 1981; Mark, 1980; Scheutz, 1985; Scheutz, 1984a). Certainly, many users of drugs do fall into this category, especially those addicted to parenterally administered agents or to alcohol. Conversely, however, drug abuse can and often does occur in individuals who are financially solvent and who lead reasonably normal lives. The purpose of this article is to review the current state of knowledge concerning the systemic and oral effects of drugs of abuse and the dental management of addicted patients. Many
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studies, surveys, and case reports have been presented in the medical literature regarding substance abuse, but surprisingly little is conclusively known today about the specific effects of drugs of abuse in the oral cavity. Many studies relative to dental effects were conducted in drug treatment centers, meaning that oral health features described are predominantly associated with patients addicted to parenterally administered agents. Case reports describe oral conditions found in a particular individual or individuals, but do not necessarily represent typical features associated with a particular drug. In other instances, animal experiments were described and the results of such studies cannot necessarily be applied to humans (Scheutz, 1985; Scheutz, 1984a; Scheutz, 1986b, Di Cungo et al., 1981; Harbour and Smith, 1988; Davis and Baer, 1971; Shapiro et al., 1970; Lowenthal, 1967; Colon, 1972; Silverstein, 1973; Scheutz, 1986a; Scheutz, 1984c; Scheutz et al., 1983; Williamson and Davis, 1973; Kothur et al., 1991).

II. DEFINITIONS
The following definitions are important.
1.

2.

Addiction - physical and psychologic dependency, associated with tolerance to a drug and withdrawal symptoms with a persistent disposition to relapse to drug use after abstinence has been achieved and physical dependency reversed (Newman, 1983). Abuse - a pattern of pathologic behavior associated with continued use of a drug or

3.

4.

drugs despite persistent social, psychologic, or physical problems caused by drug use (Friedlander and Mills, 1985). Dependence - continued substance use caused by a physical or psychological need for a substance. Tolerance to the effects of the drug and development of characteristic withdrawal symptoms are required (Jenike, 1991). Tolerance - a need for markedly increased quantities of a drug in order to achieve the desired results (Rosenbaum, 1981; Friedlander and Mills, 1985).

5.

Withdrawal - psychological or physiological symptoms developed following discontinuance of drug use (Rosenbaum, 1981; Friedlander and Mills, 1985).

III. THE PATIENT WHO ABUSES DRUGS

The psychologic makeup of substance abusers was recently studied by Mirin et al. (1988) and others (Jenike, 1991; Rounsaville et al., 1982; De Leon and Jainchill, 1981). They found that a substantial number of patients under treatment for substance abuse disorders also manifested nondrug-related psychiatric disorders. It should be recognized, however, that findings in patient populations within a substance abuse facility may not be representative of all abusers. Institutionalized addicts have either recognized that they have a problem and have sought treatment for that problem or they were forced by society to seek assistance. Many of these patients are institutionalized repeatedly for their addiction (Haddox and Jacobson, 1972). In contrast, a significant number of individuals who are dependent on alcohol or narcotics and who have developed a high tolerance to such drugs are still able to discontinue use of the drugs without relapse (Newman, 1983; De Leon and Jainchill, 1981). Psychiatric evaluation is difficult because the signs and symptoms manifested may be the result of an ongoing underlying psychiatric disorder or they may reflect manifestations of drug intoxication or of damage from chronic substance abuse. They may also be features of drug withdrawal or any combination of the above (Mirin et al., 1988). It is certainly possible, however, that individuals with affective disorders, such as depression or excessive anxiety, may use drugs to alter their psychologic states (Jenike, 1991). In any event, patients withdrawing from drug abuse may experience affective disorders (De Leon et al., 1973; Charlesworth and Dempsey, 1982). For example, opiate withdrawal may be associated with depression, while rapid methadone detoxification may result in a severe psychosis such as schizophrenia (Mirin et al., 1988). Stimulant abusers may use agents such as cocaine in a subconscious attempt at self-treatment for depression and with-

drawal may result in a rebound depression (Jenike, 1991; Mirin et al., 1988). Patients who abuse depressive agents such as benzodiazepines or sedatives may do so to mask an anxiety disorder that will resurface upon withdrawal. It is important for dentists to be aware that patients under medical treatment for drug detoxification may be taking prescribed drugs such as tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), or lithium to counteract the psychiatric effects of their withdrawal (Mirin et al., 1988). Drugs of this nature may have a profound effect on the outcome of dental treatment unless appropriate precautions are taken. A familial component may be present in individuals who practice substance abuse. When families of substance abuse patients were evaluated, approximately 30% of relatives suffered from at least one psychopathologic disorder. Among male relatives, there was an increased expectancy rate for alcoholism, while female relatives had a higher expectancy rate for affective disorders. As discussed later, propensity to alcoholism appears to represent an inherited trait, especially among men, but studies do not affim a correlation between alcoholism in first-degree relatives and abuse of other substances (Mirin et al., 1988). Drug addiction appears to be closely associated with an increase in medical disorders, at least as reflected by reports from drug addiction treatment centers. In most instances, those reports reflect data obtained from users of parenterally administered drugs, most commonly the opiates and usually heroin. Commonly reported disorders include AIDS (Barone et al., 1990; Waterson, 1983) and hepatitis or other liver diseases (Webster et al., 1977; White, 1973; Cherubin et al., 1976). Other infections are common, to include pulmonary disease, skin infections, venereal diseases, and infective endocarditis (Scheutz, 1986b; Webster et al., 1977; Davis et al., 1983; Ayer and Cutright, 1974; Briggs et al., 1967). The incidence of cardiovascular diseases, diabetes mellitus, and gastrointestinal disorders also increases (Webster et al., 1977; Briggs et al., 1967). White (1973) reported that skin infections were usually associated with subcutaneous injections of heroin ("skin popping"), while uncontrolled diabetes mellitus was related
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to the lifestyle of addiction that leads to inconsistent monitoring of blood glucose levels, sporadic administration of insulin, inadequate diet control, and severe systemic illness. Most drug addicts smoke tobacco and frequently overuse analgesics, tranquilizers, sedatives, and laxatives (Webster et al., 1977). Parenteral drug users are especially susceptible to human immunodeficiency virus (HIV) infection and hepatitis A (HAV), hepatitis B (HBV) (Scheutz et al., 1983; Cherubin, 1976; Mangla et al., 1976; Centers for Disease Control, 1988; Mathiesen et al., 1979), and hepatitis C (HCV) (Widell et al., 1982; Lenzi et al., 1990; Bortolotti, 1982; Weiland, 1981). Hepatitis B or C may be associated with chronic aggressive hepatitis in 15 to 25% of fonner addicts, as compared to 5 to 10% of the general population who have been infected with HBV or HCV (Scheutz, 1986b; Lowenthal, 1967; Weiland et al., 1981). In a related study, Schalm et al. (1983) found that drug addicts were equally as capable as nonaddicted individuals in developing antibodies to hepatitis B virus when vaccinated against the virus. Conversely, Rumi et al. (1991) reported that a significant number of institutionalized drug users failed to develop antibodies when vaccinated against HBV, perhaps due to an altered immune status in these individuals. Liver function tests are often elevated in narcotic addicts (Cherubin et al., 1976; Mangla et al., 1976), suggesting the possibility of a direct hepatotoxic effect of parenterally administered opiates or their contaminants (Ireton et al., 1974). Gorodetzky et al. (1968), however, conducted an experiment on humans who were made dependent on morphine administered subcutaneously and sustained in this state for 6 to 8 months. They found no evidence of significant changes in liver enzyme levels associated with long-term moxphine administration. They concluded that the high instance of abnormal liver enzymes found in morphine and heroin addicts was not due to a direct hepatotoxic effect of the drugs. Viral hepatitis and HIV transmission among drug addicts is almost certainly related to intravenous drug injection because of the use and repeated reuse of unsterile needles and needle sharing (Webster et al., 1977). It is probable, however, that the lifestyle of chronic substance
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abusers of low socioeconomic status may predispose abusers to transmission of HIV and viral hepatitis. Sexual promiscuity is common, living conditions may be unsanitary, and immune deficiencies may result in association with malnutrition, multiple systemic diseases, and polydrug use, especially with alcohol (Blanck et al., 1979). Sexual transmission of HAV and HBV has been demonstrated in humans and animals (Kani et al., 1991; Perillo etal., 1979; Scott etal., 1980) and suggested for hepatitis C (Tedder et al., 1991). HBV has been isolated in human saliva and its transmission demonstrated by subcutaneous injections in monkeys, but oral and nasal exposure to saliva did not result in transmission (Scott et al., 1980; Bancroft et al., 1977). Recent evidence has affirmed that hepatitis C (formerly non-A, non-B hepatitis) is caused by a specific virus transmitted in blood and blood products (Velazquez et al., 1990; Zuckerman, 1990; Tremolada et al., 1991). Another form of non-A, non-B hepatitis may be transmitted endemically in an unsanitary environment such as that of drug abusers of low socioeconomic status (Velazquez et al., 1990). Some 10 to 30% of HCV-infected patients develop chronic liver disease and that number may be higher among individuals with depressed immune responses (Moestrup et al., 1986). The delta agent is a viral antigen often found in liver cells of individuals suffering from acute or chronic hepatitis. The virus is a defective RNA agent capable of replicating within hepatocytes, but it is not able to produce a protein coat (Scheutz, 1986b). The delta virus requires the presence of HBV to be functional and its primary reservoir appears to be parenteral drug users. It is believed to be the major cause of the increased incidence of severe liver disease and chronic hepatitis among parenteral drug addicts (De Cock et al., 1986). Experimentally, severe liver damage occurred when HBV antigen and the delta antigen were injected into chimpanzees susceptible to infection with human hepatitis B virus (Rizzetto et al., 1980). Parenteral drug abusers are prone to multiple infections related to the use of nonsterile equipment. Additionally, however, it has been suggested that materials used to dilute opiates (sucrose, baking soda, starch, talc, quinine, and

powdered milk) (Rosenbaum, 1981; Ayer and Cutright, 1974) may serve as a source of pathogenic microorganisms as well as foreign material introduced into the bloodstream (The Medical Letter, Inc., 1990). Endocarditis involving the tricuspid valve on the right side of the heart is often reported, but lesions are not limited to that valve (Davis et al., 1983, Ayer and Cutright, 1974). Bacteremias caused by unusual organisms may occur due to the abuser's compromised immune status. Infective endocarditis has been described from causative organisms such as neisseria mucosus (Davis et al., 1983), Escherichia coli, Klebsiella-aerobacter, Pseudomonas aeruginosa, and several species of candida (Louria et al., 1967). In one incident of neisseria endocarditis, the organism neisseria mucosus was cultured from the sputum of a parenteral drug user who habitually licked the injection needle (Davis et al., 1983). In other instances, the infectious agent may be obtained from the skin in the site of injection (Rosenbaum et al., 1981). Cocaine abuse has been associated with a variety of cardiac disorders that include angina pectoris and myocardial infarction (Cregler and Mark, 1986; Pastemack et al., 1985; Isner et al., 1986), and sudden cardiac death may occur due to acute cocaine toxicity (Pallasch et al., 1989; Cregler and Mark, 1985).

IV. EFFECTS ON THE IMMUNE SYSTEM

There is considerable evidence to suggest that the immune system may be significantly altered in patients practicing substance abuse (Donahoe, 1988). Additionally, there is increasing awareness that the immune system engages in complex regulatory interactions with the central nervous system and the endocrine system (Harbour and Smith, 1988; Donahoe, 1988; Weber, 1988). Drugs of abuse may adversely affect various components of this interactive system. Opiates, for example, affect the central nervous system and the immune system by competing with endogenously manufactured opiates at various receptor sites in the brain and attaching to opiate receptors on T lymphocytes and leukocytes (Harbour and Smith, 1988; Donahoe, 1988; Donahoe and Falek, 1988). Cocaine, phencyclidine, mari-

juana, benzodiazepines, barbiturates, and alcohol are all capable of suppressing or, in certain circumstances, enhancing immune function in vivo and in vitro (Weber, 1988; MacGregor, 1987). Cocaine and amphetamines are reported to decrease total lymphocyte counts in animals, but no research data are available in man (MacGregor, 1987). Marijuana has been studied in animals using doses and concentrations considerably greater than those levels found in human subjects. In animals, marijuana impairs cellular and hormonal immune response, but, to date, there is no conclusive evidence to associate marijuana abuse with an increased prevalence of opportunistic infections or malignancies (Hollister, 1988). Amyl nitrite was reported to be associated with altered lymphocyte counts and functions, but this was not confirmed by experiments conducted in mice (Waterson, 1983; MacGregor, 1987). Alcohol abuse has been demonstrated to be associated with immune suppression, but in many instances, this may be the result of liver damage or malnutrition (Jerrells et al., 1988; Dunne, 1989). Alcohol ingestion, however, may reversibly alter the production and function of both T and B lymphocytes, leading to reduced circulating lymphocyte counts. Macrophage activation and phagocytic activity may be diminished, and granulocyte chemotaxis and adherence to capillary walls is adversely affected. Meanwhile, beta endorphins in the brain are reduced, leading to an altered activity of natural killer cells by the immunoneuronal route (Donahoe, 1990; Jerrells et al., 1988; Alcock, 1990). Experimental and clinical findings as described above suggest that abuse of opiates and alcohol, and perhaps other drugs, may significantly alter susceptibility to infection. At present, there is no direct evidence to confirm a relationship between alcohol abuse and development of AIDS (MacGregor, 1987; Mohs and Watson, 1990). Some evidence, however, suggests that HIV infection in parenteral drug addicts may lead to exacerbation of complaints and, possibly, more rapid progression to outright AIDS (MacGregor, 1987). Intravenous (i.v.) drug use has been clearly associated with HIV transmission and i.v. drug abusers constitute approximately 21 to 28% of
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reported AIDS cases in the U.S. (U.S. Department of Health and Human Services, 1990). This relationship is undoubtedly attributable to needle sharing in parenteral drug users (Friedlander and Mills, 1985), but the immunosuppression clinically demonstrated in opiate addicts who are not HIV positive suggests that opiate-derived immunosuppression may enhance HIV infection and the rate of progress to outright AIDS (MacGregor, 1987). The direct effect of opiate addiction on immune status is, however, still conjectural (Donahoe and Falek, 1988). Mohs and Watson (1990) recently reviewed the role of ethyl alcohol-induced malnutrition as a potential cause of immunosuppression especially related to AIDS. Alcoholism is traditionally associated with faulty dietary intake, leading to protein and calorie deficiencies. Additionally, alcohol abuse alters gastrointestinal absorption of nutrients and their transformation to metabolically active forms. Simultaneously, alcohol intake increases the utilization requirements for a variety of nutrients. Alcohol-associated liver damage may have profound effects on metabolism, activation, and storage of nutrients. Specific nutritional components such as vitamins A, B,, B2, B6, B12, C, and D, folic acid, iron, and zinc may also be adversely affected (Mohs and Watson, 1990). The immunosuppressive effects of these deficiencies may be generally reversible with abstinence from alcohol unless liver damage has occurred. Nonetheless, evidence such as this suggests that excessive alcohol intake should be avoided in HIV-positive individuals.

V. GENERAL ORAL FEATURES OF CHEMICAL DEPENDENCY

The specific oral effects of various drugs of abuse will be discussed later in this review. A number of oral diseases and disorders have been described, however, that may relate to most individuals who engage in substance abuse. For example, chronic chemical abuse is generally associated with a markedly decreased self-image, depression, and a lack of motivation, all of which may impact oral health and adversely influence compliance with oral hygiene procedures and keeping dental appointments (Scheutz, 1985; U.S.
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Department of Health and Human Services, 1990). Additionally, dental care assumes a low priority in the life of an addict whose primary preoccupation ultimately may become the need to obtain drugs to support their habit. In many instances, a distressed financial state discourages addicts from seeking dental care, and, if treatment is requested, the only financially acceptable option may be extraction of involved teeth. Conversely, an addict may choose to retain an untreated carious tooth as a possible mechanism for obtaining a prescription for a potent analgesic agent. Finally, chronic use of some drugs may mask the pain of untreated dental disease (Rosenbaum, 1981). Several drugs of abuse such as opiates, amphetamines, barbiturates, miscellaneous hallucinogens, marijuana, and alcohol have been reported to produce xerostomia. This lowers salivary pH and promotes plaque and calculus accumulation, with resultant increases in incidence of caries and periodontal disease (Scheutz, 1985; Scheutz, 1984a; Scheutz, 1986b; Shapiro et al., 1970; Colon, 1972; Westerhof et al., 1983; Draizin et al., 1975). Not all studies confirm an association, however, between drug abuse and xerostomia (Di Cugno et al., 1981; Scheutz, 1984). DiCugni et al. (1981) studied salivary secretion in patients using amphetamines, marijuana, and other drugs and were unable to detect reduced parotid salivary flow in patients using marijuana as their predominant drug. The authors did, however, identify alterations in salivary composition in all groups, together with a higher caries index. Many reports describe an increased caries rate among drug addicts (Scheutz, 1984a; Scheutz, 1986b; Lowenthal, 1967; Scheutz, 1984b), and cervical and smooth surface carious lesions have been found much more frequently in drug addicts than in the general population (Scheutz, 1984a; Lowenthal, 1967; Hecht and Friedman, 1949). Carious lesions may present with a smooth, darkly stained, ebumated appearance in drug-using patients (Scheutz, 1984a). The reported increase in the caries rate may relate to the poor oral hygiene mentioned earlier. Additionally, however, several authors have indicated that addicts, particularly those using parenteral drugs, may crave refined carbohydrates either in an effort to counteract xerostomia (Co-

Ion 1972, Colon 1974) - due to inherent nutritional deficiencies or constipation associated with drug use (Hecht and Friedman, 1949; Carter, 1978) - or for unexplained reasons (Lowenthal, 1967). Refined sugar is often used as a diluent for injected drugs, and addicts are reported to crave sweets and routinely ingest them at the time of drug injection (Scheutz, 1986b). Other general dental findings may include: an increase in bruxism (Christen, 1983; Colon, 1972; Hecht and Friedman, 1949; Davis et al., 1987; Friedlander et al., 1987), tooth hypersensitivity (Scheutz, 1986a) and necrotizing ulcerative gingivitis in patients undergoing drug withdrawal (perhaps due to the psychological stress of withdrawal) (Westerhof et al., 1983). An increase in traumatic injuries to the face, jaws,- and oral cavity may occur (Ayer and Cutright, 1974; Scheutz, 1984b), possibly due to the technique of slapping drug users in an effort to revive those showing symptoms of overdose. Drug-addicted dental patients may experience an inordinate degree of anxiety over dental treatment, a fear of dental needles, and a low pain tolerance (Scheutz, 1986a; Martin and Inglis, 1965). The anxiety and low pain threshold may relate to general personality traits of addicts, who are often egocentric, immature, and insecure (Scheutz, 1986a). Conversely, however, a tolerance to local anesthetics and conscious sedation agents has been found in drug abusers, suggesting that conventional quantities of local anesthetics may be insufficient to allow the patient to undergo a pain-free dental experience (Kimbrough, 1975). Oral mucosal lesions may be more common in drug-addicted individuals compared with the nonaddicted (Scheutz, 1986b). Increased incidence of leukoplakia and leukoedema of the palate have been described among institutionalized addicts (Scheutz, 1984b). As previously noted, however, the majority of drug abusers also use tobacco regularly and perhaps excessively (Scheutz, 1986b; Webster et al., 1977; Scheutz, 1984b). Salonen et al. (1990) examined 920 Swedish patients from the general population and found a positive correlation between tobacco use and leukoplakia, frictional white lesions, coated tongue, hairy tongue, and excessive melanin pigmentation. Leukoplakia has been found to be

strongly associated with use of smokeless tobacco (Grady et at., 1990), and the relationship of tobacco and alcohol as co-factors in oral, laryngeal, and pharyngeal carcinoma is well established (Craig and Friedman, 1986; McMichael and Puzio, 1988; Barnes and Johnson, 1986; Brugere et al., 1986; Macgregor, 1989). Smoking has also been correlated with chronic oral candidiasis and depressed polymorphonuclear leukocyte chemotaxis and mobility (Macgregor, 1989). The net result is that heavy tobacco use may contribute to the increase of oral mucosal lesions reported in substance abusers, and tobacco consumption may enhance immune depression in the drug-addicted population. Lifestyle effects of substance abuse were recently illustrated by a case report describing frostbite of the oral cavity in an individual attempting to inhale an aerosolized propane propellant to achieve euphoria (Elliott, 1991). Increased hyperpigmentation of oral tissues has been reported among parenteral drug abusers, but a direct correlation has not been established (Westerhof et al., 1983). There is, however, presumptive evidence to suggest that lifestyle factors within the drug community may be at least partly responsible for such findings. Tobacco smoking may result in increased gingival pigmentation (Amir et al., 1991). Polydrug use of substances such as barbiturates or meprobamate may result in fixed drug eruptions with associated pigmentary incontinence. Use of agents such as quinine to dilute or cut opiates may have a similar effect. Oral contraceptives may be used commonly among sexually promiscuous female drug abusers, leading to associated oral melasma (Granstein and Sober, 1981). Oral melanotic macules have been described as a feature of HIV infection, or of its treatment with zidovudine or other therapeutic drugs (Ficarra et al., 1990; Furth and Kazakis, 1987; Merenich et al., 1989). Recently, Ficarro et al. (1990) compared HIV seropositive patients with a control group of healthcare workers at low risk for AIDS. They found no significant difference in the incidence of oral melanotic pigmentation between the two groups, but progressive and recurrent pigmented lesions were found exclusively in the HIV-positive population.

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VI. SPECIFIC DRUGS OF ABUSE

A. Opiates
Opiate drugs include morphine, heroin, meperidine (Demerol), hydromorphone (Dilaudid), methadone, and codeine. Other nonopiate agents, such as propoxyphene and pentazocine, may produce a similar addiction (Jenike, 1991). Opiates primarily have sedative and analgesic effects on the central nervous system. Euphoria and relief from tension may often be the goal of those who use these drugs excessively, although chronic opiate use can be accompanied by increasing depression (Mirin et al., 1988). Heroin is a semisynthetic opiate that continues to be heavily abused in the U.S. It is prepared by extraction from the poppy (Papaver somniferum) as morphine, then acetylated to diacetylmorphine (heroin). The drug is imported into the U.S. in relatively pure form, then diluted with various agents, including quinine, powdered milk, lactose, mannitol, baking soda, or other materials (The Medical Letter, Inc., 1990). The agent may be injected intravenously or subcutaneously, and it may be taken orally or nasally (Westerhof et al., 1983). Complications include overdose, infective endocarditis and other infections, pulmonary emboli, fibrosis, and hepatitis or other liver disorders (Briggs et al., 1967; Black et al., 1979; Luria et al., 1967). Overdose leads to respiratory depression, coma, hypotension, and bradycardia. The overdose can be reversed with naloxone (Narcan) and withdrawal symptoms are treated with methadone or clonidine (Catapres) (The Medical Letter, Inc., 1990). Withdrawal symptoms include severe agitation, but withdrawal is not considered life threatening, although recidivism is high (Rosenbaum, 1981). Overdose with other opiates can also be reversed with naloxone, but propoxyphene (Darvon) and pentazocine (Talwin) may require considerably larger dosages (The Medical Letter, Inc., 1990). Habitual long-term use of heroin may occur without addiction, but most reports suggest that approximately 50% of users will become addicted. As mentioned earlier, the heroin addict suffers from a marked increase in dental caries and periodontal disease for a variety of reasons, including neglect of oral health, failure to seek
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dental care, malnutrition, intense craving for sweets, and anxiety regarding dental treatment (Colon, 1974; Rosenstein, 1975; Shapier et al., 1970; Yahya and Watson, 1987; Picozzi et al., 1972). Shapiro (1971) compared oral health profiles of active heroin addicts vs. former addicts and found oral disease to be higher in active addicts, but not significantly increased. No statistically significant differences were found between former addicts and incarcerated nonaddicts, again suggesting that the lifestyle of the socioeconomically disadvantaged leads to increased oral disease in both addicted and nonaddicted individuals. Westerhoff et al. (1983) reported finding hyperpigmentation of the tongue with or without ulceration in 9 of 47 individuals who smoked heroin and methaqualone and inhaled the vapors. Histologically, the tongue lesions were consistent with a fixed drug eruption. Morphine, a natural opiate, is believed to depress the body's immune system, which could at least contribute to the propensity for periodontal disease described in opiate addicts. Morphine primarily affects the cellular immune system, and T-cell defects have been associated with increases in oral fungal and viral infections and has also been associated with advancing periodontal disease (Kinane et al., 1989). Opiate withdrawal is usually not life-threatening, unlike withdrawal from substances such as barbiturates or other sedative hypnotics. Withdrawal signs, however, may provide clues of addiction. Early features of heroin or morphine withdrawal usually begin 8 to 12 h after the last injection and include sweating, a slightly elevated body temperature, rhinorrhea, lacrimation, and dilated pupils. Later signs include agitation with muscular twitching and joint pain, nausea, vomiting, diarrhea, and tachycardia (Jenike, 1991). Methadone is often used to detoxify patients addicted to other opiates. The detoxification process in the U.S. must be completed within 21 d, but methadone maintenance may be continued following detoxification under special circumstances. The drug is taken orally and does not induce tolerance or known long-term adverse effects (Jenike, 1991). Some methadone mixtures,

however, contain large quantities of sugar that may predispose the individual to dental caries (Scheutz, 1986a; Lewis, 1990; Bigwood and Coelho, 1990; Hutchinson, 1990).

B. Hallucinogens
Hallucinogens have the capability of distorting perception, leading to difficulty in differentiating reality from the imagined. Tolerance is a feature of excessive use, but withdrawal symptoms do not occur and hallucinogens do not produce physical dependence. The most commonly used hallucinogens include lysergic acid diethylamide (LSD), mescaline (peyote), phencyclidine (PCP), and psilocybin. Dose effect of these drugs usually lasts from 8 to 12 h. Patients may experience strong feelings of introspection or depersonalization, but a toxic psychosis may also be associated with bizarre behavior, extreme excitement, or panic reaction. On occasion, patients may require hospitalization for weeks because of prolonged post-agent psychoses (Jenike, 1991).

though many other cannabinoids have been identified, as well as a multitude of other chemical compounds. The smoke of cannabis may contain numerous potential carcinogens such as carbon monoxide, acetaldehyde, toluene, nitrosamine, naphthalene, benzanthracene, and benzopyrene. In fact, marijuana may contain twice as many carcinogens as an equivalent weight of tobacco (Nahas, 1986). The effect sought by users of cannabis is euphoria, producing a state of contentment, loss of inhibitions, and heightened self-awareness (Jenike, 1991). Tolerance does not occur in man
with small infrequent doses, but it has been demonstrated with heavy prolonged use of the drug (Nahas, 1986; Hollister, 1986). Physical dependence may occur with heavy use, although withdrawal reactions are relatively mild. Neither tolerance nor withdrawal are commonly reported with social use of the drug (Hollister, 1986). Hollister (1986) has stated that the adverse effects of cannabis are difficult to determine conclusively for several reasons. Animal studies usually involve the administration of very large quantities of the drug over short periods of time, while in humans the use patterns are generally intermittent and the agent is consumed in relatively low dosages. Additionally, the use of cannabis is often combined with tobacco, alcohol, and a variety of other illegal drugs. Finally, cannabis is frequently used by young individuals who are in relatively good health. Tennant et al. (1971) studied the effect of heavy chronic hashish use in a group of 31 soldiers. They reported an increased incidence of bronchial complaints very similar to those found in tobacco smokers. Rhinopharyngitis was relatively prevalent and, in some incidences, apparently related to a hypersensitivity response to the drug. Diarrhea and abdominal cramps occurred in some of the patients. Later reports have confirmed respiratory impairment with heavy marijuana use. Tachycardia has been described during intoxication, but to date there is little evidence to suggest that the cardiovascular system is permanently affected (Nahas, 1986). There is, however, increasing evidence that precancerous changes may occur within the respiratory tract and the oral cavity as a result of heavy cannabis use, especially if the material is used in con171

C. Cannabis
Cannabis is sometimes classified as a hallucinogenic agent (Rosenbaum, 1981; Nahas, 1986), but a high dosage of the drug is required to produce that effect. Cannabis (marijuana and hashish) may be the most frequently used illegal drug in the U.S. (Nahas, 1986). It is reported that approximately 60% of Americans have experimented with the drug and an estimated 20 million use marijuana regularly (Jenike, 1991). Hashish is prepared by obtaining resin from the tops of the hemp plant (cannabis sativa), while marijuana is prepared from the entire plant. Hashish may be from five to ten times more potent as a euphoric than marijuana (Tennant et al., 1971), and hashish oil is even more potent (Nahas, 1986). Cannabis may be smoked as a cigarette or in a pipe. As many as 2000 metabolites are produced in the body when cannabis is smoked. These accumulate in fat, liver, lung, and spleen and may remain in fat stores for weeks after ingestion. The primary euphoric found in cannabis is A-9-tetrahydrocannabinol (THC), al-

junction with other carcinogenic substances such as tobacco and alcohol (Nahas, 1986; Donald, 1986). Cannabis smoking may produce adverse effects on the brain, resulting in an acute panic reaction or a toxic psychosis, such as acute paranoia, or mania with associated delusions and hallucinations. A specific cannabis psychosis such as the amotivational syndrome has not been confirmed (Hollister, 1986). Behavioral dysfunction and psychiatric illnesses are associated with heavy cannabis use, but it is likely that the mental disturbance precedes the heavy cannabis consumption rather than vice versa (Jenike, 1991; Hollister, 1986). On occasion, severe dysphoric reactions to marijuana may be treated with benzodiazepines, but a specific treatment is usually not required (The Medical Letter, Inc., 1990). Flashback memories of events associated with drug use have been described during the nondrugged state in some cannabis users, although this phenomenon is more commonly associated with LSD and related hallucinogens (Hollister, 1986). Recently, marijuana has been found to be capable of retarding maturation of monocytes, perhaps partially explaining its reported ability to impair immune system functions (Tennant et al., 1971; Stockwell, 1988). Decreased numbers of T and B lymphocytes have also been reported, although these effects appear to be temporary and reversible after cessation of use of the drug (Yahya and Watson, 1987; Nahas, 1986). The immunosuppressive effect of the drug is much more profound in experimental animals than in man, and its importance in humans has not been clearly established (Hollister, 1988). Cannabis has been used for many centuries as a therapeutic agent in a variety of disorders that include neuralgia, postpartum psychosis, and insomnia. More recently, it has been advocated as an antiemetic for patients receiving cancer chemotherapy and to alleviate pain and anxiety in terminally ill cancer patients. It has also been demonstrated to reduce intraocular pressure when topically applied to the eye in treatment of glaucoma. It is also reported to be of some value in relief of involuntary muscle spasms and as an anticonvulsant (Hollister, 1986). A recent case report offered evidence suggesting that marijuana
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use may ameliorate ulcerative colitis, although the mechanism of action is not clear (Baron et al., 1990). Adverse effects of cannabis on the oral cavity have been reported, but not studied extensively under experimental conditions. Several reports have identified xerostomia as a possible physiologic effect of heavy use (Di Cugno et al., 1981; Valentine et al., 1985). Warnock and Shalla (1975) described a shift toward an immature epithelial cell type on the tongue and palate of heavy marijuana smokers. Edema and erythema of the uvula have been reported with heavy use of hashish (Schwartz, 1984). All of these changes may relate to the fact that cannabis burns at a higher temperature than tobacco and is, therefore, potentially even more irritating to oral mucosa. Gingival enlargement resembling phenytoininduced gingival hyperplasia has been reported in conjunction with heavy cannabis use (Baddour et al., 1984; Layman, 1978). This may be accompanied by gingivitis and alveolar bone loss. Leukoplakia also was reported as a common feature of heavy marijuana use by the same authors. Colon (1980) described frequent occurrence of oral papillomas in three groups of incarcerated patients who were heavy marijuana users and who displayed poor oral hygiene. Lesions were located in unusual oral sites, such as lingual gingiva, which are not normally exposed to extensive trauma or chronic irritation. Oral leukoedema and occasional hyperkeratosis has also been described in conjunction with marijuana smoking (Baddour et al., 1984). Donald (1986) recently offered clinical evidence associating heavy marijuana use with an increased incidence of squamous cell carcinoma. He attributed this to the epithelial changes associated with the drug (Warnock and Shalla, 1975) and the potential carcinogens found in marijuana smoke. Silverstein et al. (1978) detected a higher incidence of caries and periodontal disease in individuals who were heavy users of marijuana, assumably as a result of the lifestyle effects of habitual drug abuse (Silverstein et al., 1978; Pallasch and Joseph, 1987). Horowitz and Nersasian (1978) reviewed the pharmacological action of marijuana in relation to therapeutic drugs used in dentistry. They con-

cluded that the sympathomimetic effects of marijuana might be synergistically enhanced by administration of local anesthetics containing epinephrine or by the use of gingival retraction cord containing epinephrine. The tachycardia and peripheral vasodilation associated with acute marijuana toxicity could be enhanced and even reach life-threatening levels if epinephrine is used and anxiety could be significantly elevated. The authors concluded that dental patients who use marijuana heavily should be advised to discontinue use for at least 1 week before dental treatment.

D. Cocaine
Cocaine is an ancient drug, and evidence has been found of its use before the beginning of recorded history. The coca leaf was apparently chewed for its euphoric effect, but the drug also played a role in religious ceremonies among Indian cultures in Peru and other countries and it may have served as a general anesthetic for early surgical procedures. Through the centuries, its use increased and today millions of people are addicted to chewing the coca leaf (Hamner and Villegas, 1969; Cregler and Mark, 1986). Cocaine is a hydrochloride salt extract of the coca leaf. Sigmund Freud, among others, popularized its medical use in the treatment of a variety of illnesses and as a local anesthetic (Gargiulo et al., 1985; Lee et al., 1991). It was also used to treat alcoholism and opiate addiction (Gargiulo et al., 1985; Friedlander and Gorelick, 1988; Lee et al., 1991). Ultimately, the highly addictive properties of the drug were recognized and it became illegal in the U.S. in 1914 (Lee et al., 1991). Since the 1950s, cocaine has been primarily abused by individuals of middle to upper socioeconomic class who could afford the high cost of the agent (Washton et al., 1983). It is available as a white crystalline powder, which can be taken orally, intranasally, vaginally, rectally, or injected subcutaneously or intravenously (Cregler and Mark, 1986). Beginning in 1986, however, a technique was developed allowing the material to be prepared in solid form (crack) and smoked. Subsequently, the substance became available to

drug users of all socioeconomic levels. It is estimated that as many as 30 million Americans have used cocaine since 1986 (Lee et al., 1991). Cocaine is a euphoric, capable of producing hallucinations and enhanced feelings of mental and physical prowess. The drug is rapidly absorbed when smoked or injected intravenously, creating an intense euphoria and the potential for rapid tolerance. There is an increased risk for toxicity and a powerful addiction to crack (Jenike, 1991; Lee et al., 1991). Cocaine abuse may result in severe psychopathologic effects such as delirium, paranoia, anxiety or depression, schizophrenia, or mania (cocaine psychosis) (Friedlander and Gorelick, 1988). Toxicity may produce anxiety, convulsions, hypertension, cardiac erythema, and elevated body temperature (Friedlander and Gorelick, 1988; Jenike, 1991; Cregler and Mark, 1986; Pastemack et al., 1985; Pallasch et al., 1989; Lee et al., 1991; Leary and Johnson, 1987). Atypical angina, myocardial ischemia, infarction, and death may occur (Cregler and Mark, 1986; Cregler and Mark, 1985; Mathias, 1986). Withdrawal may feature severe depression mixed with irritability and anxiety (Jenike, 1991). Snorting of cocaine powder intranasally often results in irritation of the nasal mucosa, causing sneezing, sniffing, rhinitis, and ulceration or perforation of the nasal septum following heavy longterm use (Lee et al., 1991). Cocaine has been demonstrated in vitro to depress the immune response with very high concentrations of drug, but in vivo studies are conflicting, some indicating immune suppression while others show stimulation of the immune system or no effect under various experimental circumstances. Neurohumoral alterations of immunity, however, have been confirmed (Watzl and Watson, 1990). The greatest risk of infection appears to be the potential for transmission of HIV and other agents through i.v. administration. Chronic long-term cocaine abuse is associated with the lifestyle-related oral conditions described previously. Friedlander and Gorelick (1988) indicated that cocaine intoxication may be associated with cervical abrasion of teeth and gingival laceration due to overly vigorous tooth brushing and flossing while "high". Severe bruxism and flattened cuspal inclines may also be more common among cocaine addicts, accom173

panied by increased frequency of temporomandibular joint disorders. The authors, however, offered no experimental evidence to support these impressions. In a recent case report, Leary and Johnson (1987) described severe dental erosion of occlusal and cervical surfaces of posterior teeth accompanied by masticatory muscular tenderness, temporomandibular joint clicking, and hypersensitivity of the involved dentition. The patient was ultimately diagnosed as an abuser of cocaine and other drugs, having applied nitric acid to his teeth during the manic phase of a psychopathologic disorder in an effort to stop "voices" emitting from his teeth. Occasionally, cocaine users rub the drug on the gingiva or oral mucosa either to obtain relief from oral discomfort by taking advantage of cocaine's local anesthetic effects or to test the drug's purity by its ability to produce gingival numbness (Waterson, 1983). This method is also used to absorb the drug without adverse intranasal effects. It has been reported to occasionally result in the development of grossly inflamed, profusely bleeding gingiva associated with epithelial desquamation (Gargiulo et al., 1985; Dello Russo and Temple, 1982). Yukna (1991) presented a series of case reports describing gingival and alveolar bone damage due to chronic gingival application of cocaine. Gargiulo et al. (1985) studied histologic specimens of such a lesion and noted superficial vasculitis and necrosis in involved areas, suggesting an ischemic effect from the vasoconstricting action of the cocaine. Addicts who chew coca leaves often mix the leaf with slaked lime (calcium hydroxide) prior to use. The leaf wad is then chewed for 2 to 3 h. This technique is reported to be frequently associated with glossitis and leukoedema of the buccal mucosal on the side where the wad is held while being chewed. No evidence of epithelial dysplasia or malignancy was found, however, in a review of 46 buccal biopsies obtained from coca leaf chewers unless the individual was also using alcohol and tobacco (Hamner and Villegas, 1969).

soconstriction, and elevated blood pressure. Local or systemic vasculitis and renal failure have been reported (Jenike, 1991). Most stimulants in this class are prescription drugs, yet they are frequently abused because they cause a sense of well-being, combat sleepiness, suppress appetite, and are relatively easy to obtain. Tolerance develops with reasonable rapidity. Drugs in this category include dextroamphetamine (dexedrine), methamphetamine, phentermine, phenmetrazine, phenylpropanolamine, methylphenidate, prophylhexedrine, and ephedrine (Jenike, 1991; The Medical Letter, Inc., 1990). The drugs are usually swallowed or injected intravenously, but one solid form, d-methamphetamine (ice, crystal), can be smoked. Phenylpropanolamine is often found in over-the-counter medications (The Medical Letter, Inc., 1990). 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy, XTC, Adam) is an underground amphetamine derivative that is highly toxic (Davis et al., 1987). Acute overdose of stimulants may feature severe hyperthermia, hypertension, tachycardia, and occasionally refractory shock and death. Bruxism and increased muscle tension are noted frequently (Davis et al., 1987). Symptoms of intoxication may include headache, nausea, tremor of extremities, anorexia, and dilated pupils. Physical withdrawal is not difficult, but profound psychologic dependence may develop. Patients may become anxious, extremely labile, and paranoid during withdrawal. Benzodiazepines, haloperidol, or propranolol may be used during withdrawal. A long-lasting postwithdrawal depression may occur that requires treatment with antidepressants (Jenike, 1991). Any of the above-mentioned therapeutic agents may be associated with severe oral xerostomia.

F. Alcohol
Alcoholism is chronic, progressive, and potentially fatal. Tolerance and physical dependency develop and pathologic organ changes may occur as a direct or indirect consequence of alcohol ingestion (Christen, 1983; Friedlander et al., 1987). Although ethyl alcohol is not an illicit drug, it is the most widely used mood-altering substance in the U.S., Europe, and much of the world (Christen, 1983). Additionally, it is fre-

E. Amphetamines and Related

Compounds
Stimulants such as amphetamines are sympathomimetic agents that induce tachycardia, va174

quently used by those who abuse illicit drugs; alcohol, along with tobacco, may often play a significant role in the development of adverse medical and dental effects among drug abusers (Council on Dental Practice, 1987). As many as 100 million Americans over the age of 15 regularly use alcohol, and an estimated 12 million are alcohol abusers (Council on Dental Practice, 1987; Christen, 1983). Alcohol is being consumed with increasing frequency by children and young teenagers (Christen, 1983). Unlike users of many of the illicit drugs of abuse, alcoholics are found in all socioeconomic and educational strata. For example, alcohol abuse is reported to be very common among the Aborigines of Australia, a group of low socioeconomic status, yet the condition is only somewhat less frequent in the general population of Austrialia (Thomson, 1984). As a socially accepted mood-altering substance, ethyl alcohol has been used throughout history for a variety of religious, societal, and medicinal purposes. Alcohol is classified as a central nervous system depressant, although initially, and in smaller quantities, it has a transient stimulatory effect (Christen, 1983). Considerable controversy exists regarding factors that lead to alcoholism. At present, it appears that a complicated combination of physiological and psychological factors interact to produce a compulsion to ingest excessive amounts of the substance. There is strong evidence that genetic factors have a role in alcoholism. Alcoholism tends to run in families, while other types of mental illnesses are no more common in families of alcoholics than in the general population (Tabakoff and Hoffman, 1988). A family tendency to alcoholism could reflect environmental influences conducive to alcohol ingestion, but studies on adopted siblings and twins confirm that identical twins demonstrate a higher concordance rate for alcoholism than fraternal twins. Genetic factors seem to play a role in individual responses to alcohol, alcohol metabolism, and drinking patterns (Tabakoff and Hoffman, 1988). As mentioned earlier, drug abusers also tend to come from families with a high rate of alcoholism (Mirin et al., 1988), while in many instances alcoholics with or without a family history of the disease may manifest a primary

psychiatric disorder. This suggests a synergism between the genetic trait and psychiatric factors. In a recent review, West et al. (1986) noted that at least four studies strongly support a relationship between loneliness and depression and alcoholism. Evidence of a genetically derived tendency to alcoholism has led to a search for physiological and biochemical markers that will be predictive of the tendency. Some evidence links low levels of monoamine oxidase (MAO) and high blood levels of alanine transferase with alcoholic vulnerability. Liver enzymes such as alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT) may be elevated in habitual problem drinkers with liver disease (Watson et al., 1986). Although such results are promising, to date no clearly distinctive biological markers have been identified (Tabakoff and Hoffman, 1988). Other biologic factors tend to correlate with the genetic risk of alcoholism. High genetic risk individuals, for example, appear to have an innate tolerance to the substance and demonstrate less effect at ingestion levels that may be intoxicating for those who are not genetically at risk. Encephalographic changes are sometimes noted in alcoholics, suggesting altered neurotransmitter responses in the brain (Tabakoff and Hoffman, 1988). Duggan et al. (1991) recently reported successful identification of alcoholism in families of hospitalized children by using a questionnaire regarding family demographics and questions concerning alcohol use. They found evidence of alcoholism in 15% of the 147 families studied and the families were distributed among all socioeconomic and demographic strata. Pediatricians had failed to recognize any but one of the alcoholdependent families, suggesting that all families must be screened if those with problems with alcohol are to be identified. This information offers the hope that an effective screening mechanism for detection of alcoholics can be developed for clinical use in medicine and dentistry (Duggan et al., 1991; Graham, 1991; MacDonald, 1991). Many studies affirm a relationship between excessive alcohol consumption and medical disorders. The fetal alcohol syndrome is found in
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the offspring of mothers who consume relatively large quantities of alcohol during pregnancy. This condition features fetal changes that include growth retardation, facial abnormalities, and mental retardation, but even moderate alcohol consumption during pregnancy is associated with fetal effects such as low birth weight, especially if the mother also smoked cigarettes (Wright et al., 1983). Chronic alcohol abuse has many metabolic effects. Ethyl alcohol is principally metabolized in the liver by means of a variety of pathways, including (1) ethanol dehydrogenase that converts ethanol to acetaldehyde, (2) the microsomal ethanol oxidating system that affects lipid metabolism, and (3) the catalase system that oxygenizes ethanol in the presence of hydrogen peroxide (Girard et al., 1987). The microsomal alterations in the microsomal ethanol-oxygenating system associated with chronic use leads to enhanced metabolism of other drugs. This may explain the increased tolerance noted in alcoholics for local anesthetics and other drugs (Lieber, 1987). There is also an increased conversion of prescription drugs into potential hepatotoxins or carcinogenic agents. Meanwhile, acute ethanol ingestion may be associated with metabolic inhibition of some drugs, increasing blood levels of drugs and the risk of toxic effects (Lieber, 1987; Kumar and Rex, 1991). The sinusoidal cells that filter blood in the liver are adversely affected by alcohol ingestion, perhaps contributing to the accumulation of fat in the liver (Fraser et al., 1986). Phagocytosis is decreased in the liver, altering the host resistance to viral infection and perhaps predisposing the alcoholic to viral hepatitis. Liver dysfunction may affect clearance of very low-density serum lipoproteins, putting the patient at an increased risk for cardiovascular disease (Girard et al., 1987). Folate deficiency and other nutritional disorders may occur, such as defects in storage of vitamin B12 and megaloblastic or hemolytic anemia (Girard et al., 1987; Lindenbaum, 1987). Iron deficiency anemia may occur due to gastrointestinal bleeding, but serum iron levels are more often elevated (Lindenbaum, 1987). Meanwhile, toxic effects of alcoholism result in damage to bone marrow hematopoietic precursor cells. Platelet function and numbers are
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diminished (Lindenbaum, 1987, Javors and Bowden, 1987, Mikhailidis et al., 1990, Ballard, 1989) and white blood cell abnormalities result, including leukopenia and altered polymorphonuclear neutrophilic migration. Circulatory lymphocytes are diminished in number and macrophage killing may be diminished (Girard et al., 1987; Lindenbaum, 1987; Ballard, 1989; Mufti et al., 1989). The cumulative results of these hematologic disruptions include hemorrhagic complications associated with delayed coagulation, an increased tendency to cardiovascular thrombosis and altered response to infection (Girard et al., 1987; Ballard, 1989). Diseases of the skin have been associated with alcoholism by case reports, but there is little evidence of specific cutaneous signs associated with alcohol ingestion. The cutaneous effects of alcohol-related liver disease, alcohol-induced nutritional deficiency, and alcohol-related metabolic disturbances are, however, fairly well established (Shellow, 1983). Spider angiomata are prominently dilated subcutaneous arterioles that may appear on the face of individuals with alcoholic liver dysfunction. Small pinpoint to peasized white spots may also occur, reflecting a neurovascular dysfunction related to spider angiomata. Acnea rosacea does not occur exclusively in patients with alcoholic liver disease, but it is commonly associated with that disorder. The condition manifests as a flushing or rubefacience of the skin, usually in the center of the face and often affecting the nose, creating a bulbous, flushed condition known as rhinophyma (Rees, 1980). Hepatic disease may be associated with jaundice or a dirty, gray pigmentation of skin known as biliary melanoderma that is associated with liver cirrhosis (Shellow, 1983). Nutritional deficiencies occur in alcoholic patients for a variety of reasons. Metabolic demands are increased with alcohol consumption, but anorexia may be a feature of the disease. Gastrointestinal inflammation caused by alcohol may lead to iron loss from internal bleeding. Conversely, iron levels sometimes increase in alcoholics due to ingestion of beer and wine or the exaggerated absorption of ferric iron caused by the action of alcohol on gastric mucosa. Absorption of nutrients is often impaired, however, and

as mentioned earlier, metabolism in the liver may be disrupted. Chronic pancreatitis occasionally occurs in association with low intake of protein, fat, and carbohydrate. Trace metals may be deficient, including zinc, selenium, and magnesium. These deficiencies may adversely affect immune function (Dunne, 1989; Alcock, 1990; Davis, 1986; Christen, 1983). The milieu of disorders associated with alcoholism results in significantly altered host resistance and predisposes patients to general and oral infections. It is also possible that alcoholinduced immune suppression may accelerate the progress of disorders such as AIDS, diabetes mellitus, malignancy, and many others (Dunne, 1989). Alcohol consumption may affect most cells of the body, making tissues more sensitive to carcinogens by increasing the permeability of cell membranes (Mufti et al., 1989). Oral epithelial cells have been demonstrated to atrophy in animals subjected to large quantities of ethanol. Basal cell pleomorphism occurs and there is a tendency toward epithelial dysplasia. Valentine et al. (1985) studied tongue biopsies in humans who ingested known levels of alcohol and tobacco. In high alcohol and tobacco users, the lingual epithelium was thinner and the basal cell layer was hypertrophied. These changes occurred in the absence of clinically visible tissue damage. Information such as this, coupled with the nutritional deficiencies and liver diseases commonly found in alcoholics, may signify that the host immune defenses are suppressed, while simultaneously oral epithelium is structurally altered. This may render the individual or animal far more susceptible to malignancy. A direct relationship has been demonstrated between oropharyngeal cancer and alcohol consumption coupled with tobacco smoking (Christen, 1983; Craig and Triedman, 1986; McMichael and Puzio, 1988; Brugere et al., 1986). Ethyl alcohol may be a cancer promoter capable of causing chemical irritation and increased absorption of carcinogens dissolved in the alcohol. For example, beer and wine may contain a larger quantity of carcinogenic contaminants and they are more closely associated with oral malignancy than whiskey, although some brands of Scotch whiskey have been found to contain trace amounts

of the carcinogen N-nitrosodimethylamine (Baden, 1987). Recently, Bergler et al. (1989) examined oral mucosal tissue samples for expression of epithelial growth factors. They compared tissue from patients with oral squamous cell carcinoma against samples of tissue from patients who heavily used alcohol and tobacco, but who had no tumors. Tumor-free nonsmokers and nondrinkers acted as controls. The authors found significantly increased levels of epidermal growth factor expression in both experimental groups vs. controls. This suggests that chronic irritation with agents such as tobacco and alcohol may stimulate cellular proliferation and that such proliferation may be associated with oral malignant transformation. Oral changes include desiccation and inflammation of the mucosa, producing a magenta discoloration. This may be associated with the drying effect of alcohol with concomitant nutritional deficiencies or with candidiasis (Shellow, 1983; Rees, 1980). Salivary gland function may be impaired in alcoholics and asymptomatic enlargement of the parotid glands and, occasionally, the submandibular gland occur (Christen, 1983). Initially, high concentrations of alcohol are associated with increased salivary flow, but, ultimately, fatty degeneration of the salivary glands may take place for unexplained reasons, leading to xerostomia. It is highly likely that the cellular changes associated with the nutritional and metabolic effects of alcoholism may predispose alcoholics to more rapidly destructive periodontal disease, but this has not been proven or adequately studied. Increased incidence of dental caries, periodontal disease, and tooth loss has been described (Christen, 1983; Friedlander et al., 1987; Kranzler et al., 1990), however, especially in males, although Kranzler et al. (1990) found no association between alcohol consumption and oral hygiene effectiveness. The incidence of dental attrition is increased secondary to an increased tendency to bruxism, especially during sleep (Christen, 1983; Friedlander et al., 1987). Increased incidence of craniofacial trauma and reduced responsiveness to local anesthetics occur as described previously for other drug abusers, and alcoholic patients may require larger
17-7

quantities of general anesthesia to induce sleep. Ultimately, however, the central nervous system depressant effects of general anesthesia may be more profound in the alcoholic patient (Grady et al., 1990). Increased tolerance to other drugs such as the diazepines may occur, while drug metabolism may be increased in alcoholic patients free of liver disease and decreased in those with liver disorders. Alcoholic patients may be particularly prone to postoperative bleeding diatheses, delayed wound healing, and postoperative infections (Friedlander et al., 1987).

G. Nicotine
Recent evidence has confmned that tobacco (nicotine) should be classified as a drug of abuse. Nicotine stimulates the release of dopamine in the brain and may affect the neuroendocrine system in a manner similar to cocaine, heroin, or other addictive drugs. Nicotine generates tolerance and withdrawal symptoms, and it may serve as the initial drug of abuse in addicted individuals. The adverse effects of tobacco on the oral cavity have been reviewed recently (Christen et al., 1991) and, therefore, will not be included in this review.

VIl. DENTAL MANAGEMENT

Dental management of the addicted patient is predicated on the clinician being aware of the possibility of substance abuse in the American population. In many instances, the patient may be able to mask the addiction (Council on Dental Practice, 1987), but the alert practitioner may sometimes detect the previously described signs and symptoms. Williamson and Davis (1973) identified general symptoms of abuse as marked anxiety, multiple physical complaints, depression, obsessive thoughts, belligerent behavior, paranoia, obesity, suicidal thoughts, and bizarre appearance or dress. These symptoms, of course, may also be reflective of a nondrug-related psychosis, but they are indications that medical consultation may be necessary. The health questionnaire and follow-up verbal questioning should provide the patient with
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the opportunity to indicate an existing drug problem. It is certainly proper to question the patient about past and current use of drugs. If drug use is acknowledged, what is the substance being used? What is the quantity and is it being used currently? Close medical/dental coordination is imperative in the known or suspected drug abuser (Friedlander and Mills, 1985). Scheutz (1986a) has demonstrated that parenteral drug abusers are more anxious than the general population and more fearful of dental treatment. On occasion, addictive patients may use their drug of preference prior to a dental appointment to alleviate their anxiety. If this should occur, the dental treatment should be postponed. If patients are receiving methadone maintenance, it is probably best to continue regular administration of the methadone throughout dental treatment to avoid development of withdrawal symptoms (Jenike, 1991). Parenteral drug abusers may experience a reduced response to local anesthetics (Friedlander and Mills, 1985; Bigwood and Coelho, 1990) and significantly larger amounts of anesthetics may be required to provide pain-free dental therapy (Council on Dental Practice, 1987; Kimbrough, 1975; Splaver and Williams, 1970). Parenteral abusers are also more prone to oral infections (Lewis, 1990). Dental management of the cocaine-addicted patient may prove frustrating because of the tendency to recurrent caries and periodontal disease associated with any drug abuse. Management should be directed toward avoidance of a medical emergency in the dental office. Addicts may have a tendency to premedicate themselves with cocaine prior to dental appointments to reduce their anxiety. Therefore, careful observation of the patient is necessary to detect symptoms of intoxication. General anesthesia should be avoided and local anesthetics containing epinephrine should be used with caution to prevent enhancement of sympathomimetic effects of the drug. A special concern, of course, is the avoidance of a cardiovascular crisis featuring tachycardia and myocardial ischemia (Friedlander and Gorelick, 1988; Lee et al., 1991; Chiodo and Rosenstein, 1986; Isaacs et al., 1987). Pallasch et al. (1989) suggested medical consultations be considered for cocaine-addicted patients. They advocated con-

scious sedation plus local anesthesia for dental procedures. Benzodiazepines would be the therapeutic choice for sedation since these agents are used in treatment of cocaine toxicity. Patients under treatment should be carefully monitored for changes in vital signs. In most instances, elective surgical procedures should be avoided in the alcoholic patient. If surgery is necessary, however, or if the patient is only suspected of alcohol abuse, the dentist should consider the use of screening blood tests prior to the procedure. The following tests have been recommended: complete blood count with differential and platelet count, prothrombin time (PI), partial thromboplastin time (PTT), and sequential multiple analysis (SMA) to include total protein, albumin, and liver transaminases such as AST, ALT, and GGT. Of the transaminases, GTT may be the most sensitive indicator of liver dysfunction associated with alcohol abuse (Friedlander et al., 1987). Patients with blood test abnormalities should be referred to their physician for appropriate evaluation and treatment prior to performing extensive dental procedures (Rees, 1980). Dental treatment is no different in the addicted patient than in the nonaddicted (Williamson and Davis, 1973). Postoperative pain medication should be avoided, however, when possible. If pain medication is necessary, aspirin, acetaminophen, or a nonsteroidal antiinflammatory agent such as ibuprofen is preferred (Council on Dental Practice, 1987). These drugs may be contraindicated, however, if the patient is experiencing complications such as gastrointestinal disorders, liver dysfunction, or a blood dyscrasia. If pain medication is required, only the minimal amount necessary should be prescribed and the patient monitored carefully during use. If pain is relatively severe, a mild narcotic such as codeine may be necessary (Splaver and Williams, 1970). If so, medication should be controlled, if possible, by a reliable family member or friend to minimize the chance of abuse (Council on Dental Practice, 1987). Intravenous sedation and nitrous oxide oxygen sedation should probably be avoided due to the potential for cardiovascular or respiratory depression in drug or alcohol abusers (Friedlander and Mills, 1985; Kimbrough, 1975; Splaver and

Williams, 1970; Henry et al., 1990; Miers and Smith, 1989). Nitrous oxide oxygen itself is a mood-altering inhalant capable of being abused, especially by dentists and others with access to the necessary equipment (Sterman and Coyle, 1983). Addicted patients may experience xerostomia as a feature of their drug abuse. Consequently, mouth rinses containing alcohol should be avoided or only minimally prescribed. Use of a mouth rinse with high alcohol content might even precipitate relapse into alcohol abuse in the abstaining polydrug abuser. It should also be noted that some evidence exists to suggest an increased risk of oral malignancy in association with longterm use of mouth rinses with high alcohol content (Winn et al., 1991). The parenteral drug abuser may be suffering from undiagnosed HBV or HIV infection or be potentially susceptible to development of infective endocarditis in the event dental treatment induces a bacteremia. Wound healing may be markedly retarded and patients may be especially prone to infection. All of these factors must be taken under consideration, but it is incorrect to assume that drug-dependent patients are unmanageable. A basic knowledge of symptomatology coupled with close medical/dental cooperation and consideration of the patient's health status can result in successful dental therapy without undue stress or risk to the addicted or abstaining drug abuser (Williamson and Davis, 1973).

REFERENCES
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