Tobacco Documents Online

I I I I I I I G O T H' S MEDICAL PHARMACOLOGY Wesley G. Clark, Ph.D. Associate Professor Department of Pharmacology Southwestern Medical School The University of Texas Southwestern Medical Center at Dallas Dallas, Texas I I I I I I I I D. Craig Brater, M.D. Professor of Medicine and Pharmacology Chairman Department of Medicine Director of Clinical Pharmacology Indiana University School of Medicine Indianapolis, Indiana Alice R. Johnson, Ph.D. Professor Department of Biochemistry The University of Texas Health Center at Tyler Tyler, Texas Thirteenth Edition with 421 illustrations Mosby Year Book St Louis Bait more Boston Chicago London Pt+iladeiph a Sydney Toronto

I I I I I I I I I I I I I I I I Chapter 34 Drug abuse and dependence The optoids. central nen*ous s%stem depres,anth and ,ttmulant,. hallucinc ,en~. cannabinoids !marijuanai. and some inhalants ha~e in commun the .thilit% to pro6ucV euphoria. and thus the% provide positive reinforcement. Their reinfc rcin, prc,pt,rtte~ ma~ lead to repeated intermittent usage or, eventuall\, to chronic usaue. Comipuki%e drug taking (a form of dependence) may develop with continued use. Emphasis in thi~ chapter is placed on the characteristics of these drugs that lead to abuse and depen- dence. The general pharmacologv of manN of the drugs is discussed else\,% here. Drugs within each class have qualitatively similar effects. TERMINOLOGY In contemporary society, the term drug abuse has become synonymous with the nonmedical use of drugs to alter one's mental state. Individuals self-administer both prescription and illicit drugs in attempts to alter mood, to alter perception of realit., to experience unique sensations, and/or to improve physical or mental capabilities. In general, society establishes what constitutes drug abuse by its laws and social taboos. Consequently, a particular drug-taldng behavior in one society or in a particular situation may be considered drug abuse, whereas in another it may be considered appropriate. A term that is often used in place of drug abuse is drug dependence. Dependence is defined by the World Health Organization as drug self-administration that is detrimental to the individual or society. The term encompasses the biologic interaction between drugs and an individual, independently of social norms. Use of this term may be confusing because dependence also refers to alterations in physiologic or psycho- logic states that occur with chronic drug use. Accordingly, in this chapter drug abuse will refer to detrimental drug use, and dependence will denote alterations in physio- logic or psychologic conditions secondary to chronic drug administration. Perhaps the term used most often when dealing with drug abuse is addiction. Addiction, as defined by Seevers,' is a state of chronic compulsive drug use charac- terized by an overwhelming desire to continue obtaining and taking drugs, physical dependence, a tendency to increase dose, and a detrimental effect on the individual taking the drug. Because this term is often used inappropriately and does not encom- pass many aspects of drug abuse, its usefulness is limited. Indeed. it is more appro- priate to characterize drug use in terms of degree and type of dependence. Chronic administration of the drugs discussed below can lead to two types of dependence: psychologic and physical. Psychologic dependence is an emotional and 336 mental preoccupation with drug acquisition and use to receive some positive reinforce-

I I I I I I I I I I I I I I I I I 7_MAP'E? 34 Drug aduse ano aeDenoerce mrnt Dru_ u5a,r becomes a habit necessar. for the subject s~~rl] heuit kll ciru<<, discussed in this chapter can produce ps%choloeic dependence. In contrast. not all uf them produce ph% sical dependence. Physical deuendence is an altered ph' % sioluLn( condition caused b% chronic exposure to a druQ. It results in reproducible ph\ swloEtc siens and symptoms when the druz is %%tthdrawn abruptl% These st,ns and s%tnptcm» constitute the abstinence or uithdraual syndrome and occur after chronic use of opiates. barbiturates. antian.riety agents. ethanol. and nonbarbiturate sedatkes Table 34-1,. Chronic use of many drugs leads to development of tolerance Table 34-1 ~ Toler- ance is a phenomenon in which prior exposure to a drug decreases the response to a gi%en dose: thus more drug is necessan- to produce the desired effect. Tolerance that develops as a consequence of enhanced elimination of a drug (for example, induction of hepatic enzymes) is called dispositional or metabolic tolerance. Tolerance that develops as a result of adaptive processes within cells is termed functional or cellular tolerance. In addition, persons who chronically self-administer drugs often learn to modify their behavior (usually toward normal) while under the influence of the drug. This adaptation is called behacioral tolerance. When a person becomes tolerant to one drug, he often becomes tolerant to other drugs as well. This phenomenon is termed cross-tolerance. There are two types of cross-tolerance. $pecific cross-tolerance occurs among srugs within a given pharmaco- logic class, presumably because they have similar mechanisms of action at the cellular level (that is, via the same receptors, second messengers, and so forth). :4onspecific cross-tolerance occurs when drugs share a common and inducible metabolic pathway. Thus enhanced metabolism produced by one drug increases metabolism of another. Note that specific cross-tolerance is related to cellular tolerance, whereas nonspecific cross-tolerance is a dispositional tolerance. TABLE 3a-1 Companson of commonly abused drugs Psychobgic Phystcal Drug category Tolerance depenoence dependence• Psychotogemc, 0pioids X X X Barb turates Xt X X Anuanx ety agents Xt X X Ethyl alcohol Xt X X Amphetam nes X X Xt Coca ne X X Xt Nicotine X X LSD X X X Phencychdine X X xt Cannabinoids X X Xt Inhalants 17 X Xt A oetwfetl aDStrence synOrOrM oCWts atter appupt OrscOntuiWtKKn tt* ttk taerance w,m retnai ettects tin reiatnNy higr1 OOses

1 338 SE_'~Cti =ouP Jtne, D,^s x,tr `1,cr-;~e- ~_ ._ 1 I I I r I 1 I I I I I I I I I I I Finall,,. an indiN idu il %~ ho is ph.5icalk dependent on me cln,s (0 a _nc•i1 e i,t•. ;,tiI substitute another of that clas, to pre% ent ah,t nence. Thu c'ru>a clr~, v,c/ „r( i 11"'el t" therapeutic ad%antd,e in controllin; s%niptoms of %k ithdra%~al %~ hile dc•to,\it\ ijs f>,c- tients %% ho are ph% sicull~ dependent. OPlOIDS Dru¢s are classified as opioids see Chapter 31 if the% bind ~terec»pecifi(..ilk to > opioid receptors and possess some nwrphine-like actn tth. In ndditimi to naturalh occurrinz opium. morphine. and eodeine. this class includes setttis\ nthetic ec,tnt)e und> such as heroin (also known as horse. smack. junk, H;. oxymurphune. and h~drerinor- phone as well as s,,'nthetic compounds such as meperidine, niethadone. pentaLucnic• (Ts), and propox}phene. Such opioids are used therapeuticall% to relie~r pain. to treat diarrhea and dy senter.. and to suppress cou-h. Characteristics of Opioids are abused primaril' v for their euphoric and sedati.e effects. The euphoria abuse is characterized by feelings of peace and contentment. Normal concerns and an..iet,. are diminished or absent. Initial use of opioids, however, may produce di sphuria rather than euphoria. Furthermore, opioids can produce some central nervous sYstem stimulation, including activation of the chemoreceptor trigger zone and consequentl. nausea or vomiting. Heroin is the most widely abused opioid. Users believe heroin is more euphoric than other opioids, but its abuse potential is equivalent to that of morphine. Indeed. after administration, heroin is rapidly hydrolyzed to morphine. It acts more rapidly than morphine, however, because it enters the brain more readily. This may largely account for the preference of users for heroin. When heroin is administered intravenously, the user may experience a thrilling sensation, in the lower abdominal area, that has been compared to a sexual oreasm. This is accompanied by feelings of warmth and tingling. Because opioids depress the central nervous system, users may become sedated. The degree of sedation depends on the dose taken and on the user's level of tolerance to the opioid. In nontolerant individuals, opioids can induce sleep and vivid dreams. Opioids also depress respira- tion, and many produce marked miosis (pin-point pupils). The patterns of opioid abuse vary widely. Some individuals use the drugs sporad- ically for recreation and do not become dependent. Others become both psychologi- cally and physically dependent. Chronic use of opioids does not necessarily result in mental or physical deterioration. Many persons dependent on opioids function well in society, maintaining careers and family life provided they take the drug on a regular basis. Others tend to sacrifice "normal" lives for the sake of increased drug experi- ences. These individuals are consumed with drug-seeking and drug-taking behaviors and often use many different drugs. There are no known predictors of the pattern of dependence that will develop. Tolerance and When opioids are used regularly, pronounced tolerance lessens most of their dependence effects, including sedation, euphoria, and respiratory depression. In contrast, their miotic and constipating actions persist. The degree and rapidity of tolerance develup-

I I I I I I I 1 I I I I I I I I I CHAP'ca 3.4 Drug aDuse and eeDenoence ment are dependent on the opioid tal:en, the dose, and the frequenc% of admim~ tion. Because tolerance develops to the reinforcing actions of opiotds, most u increase dusage over time. Upon withdra%val tolerance rapidly diminishes. Coi quently, tolerant individuals often withdraw intentionall% for short periods to red the amount of drug the% need. Although a high degree of cross-tolerance de%e; among opioids that act at the same receptor subtype, that is µ. 6. or K, less cr tolerance develops between agonists that act predominantl} at different recepcvr subtypes. Pronounced psychologic and physical dependence develop rapidl% durine contin- uous use of opioids. As in the case of tolerance, the degree of dependence varies with the individual, the drug administered, and the dosage. It is often the psychologic dependence, rather than the physical dependence, that dictates continued use of the drug and/or recidivism after withdrawal. Upon cessation of drug usage. however, persons who are physically dependent exhibit a characteristic abstinence syndrome. For the shorter acting opioids, such as heroin or morphine, symptoms appear about 8 hours after the last dose and reach peak intensity between 36 and 72 hours. Lacrima- tion, rhinorrhea. yawning, and diaphoresis develop between 8 and 12 hours. At about 13 hours, restless sleep may occur. At about 20 hours, gooseflesh, dilated pupils, agitation, and tremors usually appear. During the second and third day, the abstinence syndrome is at its peak, with symptoms and signs of weakness, insomnia, chills, intestinal cramps, nausea, vomiting, diarrhea, violent yawning, muscle aches in the legs, severe low back pain, elevation of blood pressure and pulse rate, diaphoresis, and gooseflesh. Although withdnvral is generRlly not life-threztening (that is, convulsions do not occur), fluid depletion during the withdrawal period has rasilted in cardiovas- cular collapse and death. At any point during the course of withdrawal, administration of an opioid agonist in adequate dosage will dramatically eliminate the symptoms and restore a state of apparent normalcy (cross-dependence). Although the duration of the syndrome is roughly 7 to 10 days, mild symptoms may persist for months, and the "craving" for opioids may continue for years. Other opioid abstinence syndromes are qualitatively similar to that of morphine or heroin. Opioids with a longer duration of action, such as methadone, usually produce a milder and more prolonged syndrome. Opioid abstinence syndromes also develop in babies born to opioid-dependent mothers, because these newborns are physically dependent. Withdrawal is character- ized by high-pitched crying, tremors, hvperreflexia sucking of the fist sneezing, yawning, vomiting, and hyperthermia. With heroin dependence the abstinence syn- drome usually appears in the first day of life. Withdrawal symptoms may not occur for days in babies born to methadone-dependent mothers. These babies need to be detoxified slowly by first administering sufficient opioid (usually paregoric) to control signs and symptoms; opioid dosage is then tapered. There are two components to treatment of opioid dependence: withdrawal (detox- Treatment of op+oid ification) and rehabilitation. Withdrawal can be accomplished over several days by dependence gradually reducing the dosage of the opioid on which the user is dependent. More

I I I I I I I I I I I I I I I I I I 340 SEZ'1Grv FOUR Other Drugs rth P'or'.re"; .:e^.-3 ' often, however, methadone is used for detoxification. \fethadont io,r n,<<., other opioids. is well absorbed when administered orall~. and h, a lon,.:er dunatu,n w action than other opioids. Thus, graduallv decreasing doses need he gTt%en onl,% Wncr i<i a 24-hour period, and parenteral administration is avoided. Furthermore. thr nirtha- done abstinence s>-ndrome is less severe than that produced b\ heroin or morphtnc. In methadone maintenance programs, as in detoxification. methadone is ;uh,t:- tuted for the opioid that the patient has been abusing. The patient is n:,t detomfied. however. but is given a high dail\ dose of methadone to maintain tolerance and dependencei. The rationales are (1) that exposure to additional opioid isuperimpo~,ed on the methadone) outside the clinic environment should lack reinforcing qualities and (2) that patients who no longer need to engage in illegal and time-consuming drug- seeldng behavior will pursue more useful activities. Although programs invol,-ine methadone maintenance and psvchologic counseling appear somewhat successful in decreasing recidivism rates, many patients eventually return to illicit opioid use.° y'24 Clonidine (see Chapter 21) reduces the severity of opioid withdrawal, probabl% b\ depressing preganglionic sympathetic nerve activity.ll It appears to be a safe nonopi- oid therapy that diminishes withdrawal symptoms.i •32 Because a major side effect of clonidine is hypotension, the drug should be used with caution. After detoxification, rehabilitation, a far more difficult task, confronts the clinician. The craving for opioids persists for months to years after detoxification and results in exceedingly high rates of recidivism. One adjunctive approach to rehabilitation after detoxification utilizes a narcotic antagonist. Administration of a pure opioid antagonist should prevent the reinforcing effects of opioid agonists and thus diminish opioid abuse. Naltrexone, a long-acting antagonist, has been used for this purpose with some success.15 Of course, such treatment must not be started before detoxification is complete, because the antagonist will precipitate abstinence in an opioid-dependent individual. Medical problems of Other medical problems also occur secondary to opioid use. A major problem with opioid abuse most illicit drugs is not knowing the amount of drug an individual is taking. Street heroin is usually 2% to 5% opioid. The remaining powder comprises adulterants that increase the volume. A user who obtains an unusually pure sample of drug may overdose unintentionally. As mentioned above, tolerance to the actions of opioids reverses quickly upon withdrawal. Consequently, overdose is likely after withdrawal if a user takes a dose that was effective previously when he was still tolerant. Overdose is characterized by respiratory and central nervous system depression and miosis (although not all overdose patients have pin-point pupils). Death occurs as a result of respiratory arrest and/or noncardiogenic pulmonary edema. The opioid antagonist naloxone (Narcan,l reverses the apnea and coma caused by opioid overdose. In an opioid-dependent individual, naloxone can precipitate a full abstinence syndrome. Although the drug may be needed to treat an overdose, such patients may rapidly go from coma into withdrawal; extreme caution is essential. Naloxone neither depresses respiration nor enhances toxic effects of barbiturates or other central nervous system depressants, and it is often used in the emergency room to differentiate opioid from

I cHa,P-E? 34 Drug aause ana deoenoence 3-:' I I I I I I I I I I I I I I I I I centrsi denreti,ant merdc»e. Because its action is shurt-lived. repeated adn ini,tr.~h ~n i5 lil:el~ to he necessar.. Patients ~%ho exhibit a,alutan response to a,in_le du„c ()f naloxone should be obsened for a proloneed period before discharae. Additional medical problems are secondan to intra%enous opioid adminiutration with unsterile needles. These complications include AIDS. \tral hep,itttts, hactenal and fungal infections, chronic li\er disease. thrombophlehitis. cellulitu. and local abscesses. Further danQer arises from foreign substances intentionalk or accidentalk added b% the supplier as adulterants to dilute cut the drug. Recentl\. ne4k "de,i,ner" dru(gs ha~.e appeared. They are so-named because the\ are designed \~ith unic1ue chemical substitutions to circumvent the law. while producing effects similar to their illegal counterparts. One such meperidine analog was found to be contaminated with 1-meth~ l--I-phenvl-1.2.3.6-tetrahydropyridine (MPTP). which causes selective deQen- eration of nigrostriatal dopamine neurons and a syndrome similar to Parkinsons dis- ease isee Chapter 30).'y Finally, although opioid users are not likely to be hostile or aggressive while on the drug, their need for more drug to avoid abstinence as tolerance develops may cause many chronic users to engage in criminal activities. Included within this class of compounds are the barbiturates, nonbarbiturate CENTRAL NERVOUS sedatives, antianxiety agents. and alcohol (see Chapter 29). Such drugs are used SYSTEM medically to relieve anxiety, induce sleep, and control seizures. Abuse of central DEPRESSANTS depressants is more common than that of opioids and often originates with their medical use. In general, short-acting barbiturates are preferred by abusers. This class includes Barbiturates secobarbital (reds, red devils, red birds), pentobarbital (yellow jackets), and amobar- Cr+ARACrERisncs OF bital (blues, blue heavens). They are abused for feelings of tranquility, relaxation, and AeusE disinhibition. As with opioids, patterns of abuse vary greatly from occasional to com- pulsive chronic use. Unlike opioids, however, long-term administration of these drugs can cause physical or mental deterioration of the user. Effects of barbiturates include sedation (without analgesia), decreased mental activity, slowed speech, and emotional lability. Individuals taking these drugs appear as if intoxicated with ethyl alcohol. Higher doses produce ataxia, diplopia, nystagmus, vertigo, stupor, sleep, and, eventu- ally, respiratory depression. coma, and death. The risk of overdose with these agents is high because actions of central depressants are additive with one another. Further- more, because these agents decrease mental acuity and impair memon•, individuals ma% ingest more drug than they intend in a short period of time. Treatment of acute barbiturate overdose involves maintaining respiration and supporting the cardiovascu- lar system. There is no specific antagonist that will reverse the apnea or coma. ~ 10 Eke 3lditfY! iAi iAtO7LiCat1A$ zCtionS Uf dEVCIi( TOLERANCE AND p =&vKkdS wekwS the rejOfpiCiag pCppflFti?5 of t}lese DEPENDENCE ay.ens{ r~~~~P,~, ~+cage over time. A component of the tolerance is dispositional because chronic use of barbiturates can induce hepatic microsomal enzymes. Func- tional tolerance also develops, but the mechanism remains unknown. Uttle tokrance

I I I I I I I I I I I I I I I I 342 SEC':Oh ;:CUA Other Or;,qs ~v rr. develops to the lethal actions of these drugs. Thus, as dosage is increased. the ris{. ~,i overdose becomes greater. Chronic use of barbiturates can produce both ps' vchologic and ph~ sical dence. and acute withdrawal produces a dangerous abstinence s\ndrome. .-\< «<th opioids, the onset and sevent~ of abstinence is dependent on the drue used. ~%ith- drawal of short-acting drugs 2enerall} produces more rapid and se~ere s%mpto>tn, Unlike opioids. however, withdrawal from barbiturates is often life-threatening. With- drawal symptoms progress from weakness, restlessness. tremulousness, and insomnia to abdominal cramps, nausea, vomiting, hyperthermia, orthostatic hypotension, confu- sion, disorientation, and, eventually, convulsions, including status epilepticus. Asita- tion and hyperthermia may lead to exhaustion and cardiovascular collapse. «'ith short-acting barbiturates, convulsions are most likely to appear during the second or third day of abstinence. With long-acting barbiturates, such as phenobarbital. convul- sions are less likely, but if they do occur it is usually between the third and eighth da~ of abstinence. TaE.anuENr oF Treatment of barbiturate withdrawal requires hospitalization. First, patients are saRarruwirE stabilized on a suitable barbiturate, usually pentobarbital. The dosage is titrated to the DEPENDENCE individual patient. Dosage is subsequently tapered over the next 7 to 14 days. The long withdrawal period is required to minimize the likelihood of an abstinence svn- drome and convulsions. Babies born to mothers who are physically dependent on central nervous system depressants will also be dependent. The newborn abstinence syndrome is similar to that described for opioids, but is more dangerous. As with adults, babies are first stabilized on a central nervous system depressant, usually a benzodiazepine, then detoxified by gradually reducing the dosage. Nonbarbiturate There are numerous other central nervous system depressants that have the sedatives and potential for abuse. These include meprobamate, methaqualone (quaalude. ludes), antianxiery agents glutethimide, chloral hydrate, and the benzodiazepines. Like barbiturates, these drugs are abused for euphoria, feelings of tranquility, and the intoxication they produce. Effects of overdose with most of these agents are similar to those of the barbiturates. Benzodiazepines, however, are less powerful than barbiturates; severe respiratorv depression and coma are unlikely, but if they occur flumazenil (see p. 270) can reverse them.z Methaqualone in large doses may produce convulsions, pulmonary edema, and respiratory arrest. As with barbiturates, tolerance and cross-tolerance develop to the sedative and reinfbrcing properties of the nonbarbiturate sedatives including the benzodiazepines. but little tolerance is observed to the lethal effects. Strong psychologic and physical dependence can develop with chronic use of these drugs.' Abrupt withdrawal mav produce a life-threatening abstinence syndrome. The severity of withdrawal depends on the drug used, the amount taken, and the duration of abuse. For example, with- drawal from therapeutic doses of diazepam generally produces anxiety and irritability, but rarely results in convulsions.

~ :HAP7ER 3s Drug aDuse ana eecenoence I I I I I I I I I I I I I I I I I .Alcohol abuse is still the most serious drus abuse problem in «'estern socirt\- ti ETHYL ALCOHOL not in all countnes. Alcohol is a contnbutinQ factor in S5r'c to 50c'c of cases of mantLil Characteristics ot violence and 10~`c of occupational injuries. Some 1-S.000 or more traffic deaths about abuse 40%) in the United States are alcohol related. .Alcohol is a central ners ous s%stem depressant, and e%en small amounts decrease mental acuit\ and impair motor coordination. This compound is abused for intoxicatinQ and euphoric feelings and for relief from anxiet.. Acute ingestion of relati%el\ small doses of alcohol produces feelings of warmth and relaxation, with onl% slight impair- ment in motor skills. Higher doses may produce paradoxic stimulation with feelings of buovanc\ and exaggerated emotions. Further escalation of dosage can cause marked impairment of motor skills, slurred speech, unsteady gait, stupor, and ultimatel\ unconsciousness. Genetic factors appear to be important in the predisposition to alcohol depen- dence. Familial occurrence of alcoholism is well documented, and the risk of becom- ing an alcoholic increases with the number of close relatives who are alcoholics. A higher rate of alcohol dependence occurs in identical twins as compared with fratemal twins. Furthermore, children from families of alcoholics, when adopted by other families show a fourfold higher risk of alcoholism than controls, whereas children of nonalcoholics reared by alcoholics are at no greater risk than controls.'s As with other central nervous system depressants, both dispositional and functional Tolerance and tolerance develop when alcohol is ingested chronically. Cross-tolerance between alco- dependence hol and other central nervous system depressants likewise has components of both dispositional and functional tolerance. Chronk use of aloohol can produce both psy- , chologic and physical dependence, and the abstinenee syndrome may be life threat- ening. Withdrawal symptoms appear within a few hours after the last dose of alcohol and are characterized by tremors, weskmess, awdety, intestbd cramps, and hyperre- flexia. Between 12 and 24 hours after the last dose, patients may have visual halluci- nations. By 48 hours, an acute neurologic syndrome may become apparent, with confusion, disorientation, and delusional thinldng. When this syndrome is accompa- nied by gross tremors it is called "delirium tremens." Convulsions are less common than with barbiturate withdrawal. If the abstinence syndrome is not fatal, the patient will recover by the fifth to the seventh day after the drug is withdrawn. The treatment of alcohol dependence, like that of other types of drug dependence, Treatment of alcohol requires detoxification and rehabilitation, Because the abstinence syndrome can be dependence fatal, a strategy similar to that used for other central depressants should be employed. However, alcoholic patients often require fluids, nutrients, and vitamins (especially B vitamins) prior to detoxification to counter nutritional deficiencies. Patients are stabi- lized on another central nervous system depressant, usually a benzodiazepine, the dosage of which is gradually reduced. For rehabilitation, Alcoholics Anonymous presents a unique and often pivotal source of help for alcoholics. In addition, the drug disulfiram (Antabuse) may help

I I I I I I I I I I I I I I I I I I I 344 SE-Tiorr =OuR Othe! Jruqs .v,c^ ~ o^~e^r ~a^r a-~. _ minimize recidi~i,ni h% deto.ified alcoholics '- When patients takin_ di>iilhr.Lm iu,t.t e%en a~niall an uunt oi ,ilcvhol. the, become ph%sicall%. ill due- t ~ccnn il. t;i, ;i acetaldeh%de. Presumahl%. this illness or the potential for it pro%ides ~ut} cirnt lit-_a- ti~e reinforcement to discouraze drinlong. The use of disulfiram oho,ie u~k rt.,{iurt•, compliance on the part oi the alcoholic. Medical problems of Chronic use of alcohol can result in pathologic conditions and diseases not u,uall~ aicoho/ abuse associated .vith other types of drug abuse. These include cirrho~is of the li\ er .~ tth ()r without complications of portal hypertension , peripheral pohneuropath\. alcohulic gastritis. Korsakoffs psychosis. and «'ernickes encephalopathv. Some of these are believed to be consequences of nutritional deficiencies. Howe%er. alcohol appear; to contribute directl\ to the pathogenesis of the liver disease. Prenatal exposure to alcohol may produce developmental defects in the hrain with motor dysfunction. hypotonia. cognitive deficiencies, and microcephal%.As man\ as ?Cc of all babies born in the Western world may suffer to some extent from this fetal alcohol syndrome. Finally, there is evidence that alcoholism interferes with immune function and thereby predisposes individuals to infection.23 CENTRAL NERVOUS Drugs in this class include amphetamines (bennies, dex), methamphetamine (meth. SYSTEM speed, crystal, ice, crank), cocaine (coke, crack rock, snow, toot), methylphenidate, and ST/MULANTS the less potent stimulants caffeine and nicotine. Amphetamines and Because the characteristics of dependence on amphetamine and cocaine are quite cocaine similar, they will be discussed together. Indeed, there is evidence that experienced Cr+aaAcrERrsncs OF users cannot distinguish between the subjective effects of these drugs.t0 The major aeusE difference between amphetamine and cocaine is in their durations of action. with cocaine being much shorter acting than amphetamine. Amphetamines have been used medically as appetite suppressants and to treat narcolepsy and attention-deficit hyperactivity disorder. These potent stimulants are abused for their ability to cause euphoria, elevate mood, enhance a sense of well- being, and reduce fatigue. They are also taken in attempts to enhance mental or physical performance. Amphetamines are usually taken orally, sniffed, or injected intravenously. Administration bv the latter route quickly produces a short-lived. ex- tremely pleasant sensation (rush). Recently, a highly purified form ("ice") of metham- phetamine that can be smoked has appeared.s This potent form for delivery of the drug is likely to increase the incidence of methamphetamine overdose; a large dose of drug can be absorbed quickly, without the need for intravenous injection. In moderate doses, amphetamines produce a sense of well-being. They tend to lower anxiety and social inhibitions, to elevate mood, and to increase self-confidence. Users feel that their physical and mental abilities are heightened and that performance of simple tasks is enhanced. Amphetamines also promote insomnia and loss of appetite. At higher doses, they reduce mental acuity and impair performance of complex tasks. Users become anxious, restless, irritable, and irrational. Symptoms of amphetamine