Disorders of personality and behavior due to alcohol abuse

Lyudmyla T. Snovyda

Alcohol action

• Alcohol affects virtually every organ system in the body and, in high doses, can cause coma and death. It affects several neurotransmitter systems in the brain, including opiates, GABA, glutamate, serotonin, and dopamine. Increased opiate levels help explain the euphoric effect of alcohol, while its effects on GABA cause anxiolytic and sedative effects.

Alcohol action

• Alcohol inhibits the receptor for glutamate. Long-term ingestion results in the synthesis of more glutamate receptors. When alcohol is withdrawn, the central nervous system experiences increased excitability. Persons who abuse alcohol over the long term are more prone to alcohol withdrawal syndrome than persons who have been drinking for only short periods. Brain excitability caused by long-term alcohol ingestion can lead to cell death and cerebellar degeneration, Wernicke-Korsakoff syndrome, tremors, alcoholic hallucinosis, delirium tremens, and withdrawal seizures. Opiate receptors are increased in the brains of recently abstinent alcoholic patients, and the number of receptors correlates with cravings for alcohol.

Alcoholism

• also known as alcohol dependence, is a common disorder. At all ages alcoholism is more common among males than females; however, given the somewhat later age of onset in females, the ratio tends to decrease in higher age groups. Overall the ratio is probably 3:1. Alcoholics and alcohol abusers are recurrently and persistently beset with an urge to drink, an urge that is of sufficient compellingness for them to continue to drink despite the fact that because of their drinking they sustain substantial damage to their

health and personal or business affairs.

ONSET

• The onset of alcoholism or alcohol abuse is generally insidious and spans many years. For men, onset is generally dated to the late teens ; or the early twenties; however, most alcoholics are not recognized . as such until their late twenties or early thirties, and many more years may pass before the alcoholic or someone else recognizes the need for treatment. Although some otherwise typical onsets have been described in patients over 60, it is rare for the onset to occur past the age of 45.

CLINICAL FEATURES

• the urge to drink may be experienced as a craving, an imperious need, or a compulsion;

• almost all alcoholics deny they have a problem with drinking or rationalize it one way or another.

• they are often quick to lay blame for their drinking on situations or other people;

• stressful events may be followed by increased alcohol consumption, the alcoholic is also intoxicated during the good times, or simply the neutral times of life.

CLINICAL FEATURES

• Most alcoholics make attempts to control their drinking, and although they may have some successes, these are generally short-lived. This "loss of control" was at one point considered the hallmark of the alcoholic. However, it may be just as fair to say that the hallmark is rather a sense of a need to control. Normal people do not experience a need to control their drinking; they simply stop, without giving it a second thought.

• When alcoholics do drink, most eventually become intoxicated, and it is this recurrent intoxication that eventually brings their lives down in ruins.

CLINICAL FEATURES

• Friends are lost, health deteriorates, marriages are broken, children are abused, and jobs terminated. Yet despite these consequences the alcoholic continues to drink Many undergo a "change in personality." Previously upstanding individuals may find themselves lying, cheating, stealing, and engaging in all manner of deceit to protect or cover up their drinking. Shame and remorse the morning after may be intense; many alcoholics progressively isolate themselves to drink undisturbed. An alcoholic may hole up in a motel for days or a week, drinking continuously. Most alcoholics become more irritable; they have a heightened sensitivity to anything vaguely critical. Many alcoholics appear quite grandiose, yet on closer inspection one sees that their self-esteem has slipped away from them.

CLINICAL FEATURES

• Most alcoholics also display an alcohol withdrawal syndrome when they either reduce or temporarily cease consumption. Awakening with the "shakes" and with the strong urge for relief drinking is a common occurrence; many alcoholics eventually succumb to the "morning drink" to reduce their withdrawal symptoms.

• Some degree of tolerance occurs in all alcoholics. Here the alcoholic finds that progressively larger amounts must be consumed to get the desired degree of intoxication; if the amount is not increased, the

alcoholic finds that the degree of intoxication becomes less and less.

Alcohol intoxication.• The intoxicated patient is a familiar sight in any emergency

room, and the determination of a blood alcohol level (BAL) is a commonplace procedure.

• BAL by convention may be expressed as milligrams per deciliter, or, as it is often charted, milligrams percent (mg%). Roughly speaking, in a 70 kg person BAL rises anywhere from 15 to 25 mg/dl with every 15 ml of rapidly ingested pure ethyl alcohol. This amount of ethanol is found in 1 ounce of 100 proof liquor, one 12-ounce bottle of beer, or about one glass (6 ounces) of wine. Given that most "social drinkers," or alcohol-naive persons, become intoxicated at a BAL of 100 mg/dl, simple arithmetic shows that for such a person only about four drinks, or beers, or glasses of wine are required to produce intoxication.

Alcohol intoxication.• In mild intoxication most individuals feel somewhat euphoric,

they talk more and tend to shed their inhibitions. Reckless behavior may be seen; sexual indiscretion may be evident; irritability may occur. Some individuals, however, may not so well. A suspicious person, if intoxicated, may develop ideas of persecution; a mildly depressed person may become tearful and morose.

• In moderate intoxication behavior tends to become coarse; improprieties are commonplace. Thinking is slow; inattentiveness occurs, and the person is slow in responding to anything, even dangerous situations. The face is flushed, the conjunctivae reddened, and the pupils dilated. Slurred speech, nystagmus, ataxia, and generalized incoordination are present.

Alcohol intoxication.• In severe intoxication stupor may occur. Ataxia is so severe that

Standing is impossible. Vertigo is common, and persistent vomiting may occur.

• Eventually if the BAL continues to rise, coma will supervene. Respiratory depression may occur, and death may ensue from respiratory arrest.

• If sleep should come to the intoxicated person, it tends to be heavy and dreamless. As the BAL falls the person often wakes up and has trouble falling back asleep.

• After the intoxication has passed most experience a "hangover." Headache is common, as is a pervasive dysphoria . Mild tremulousness and diaphoresis may occur; nausea is common, and the person may vomit. Depending on the degree of intoxication, a hangover may last anywhere from several hours up to almost the entire day.

Blackouts(palimpsests).• Blackouts are characterized by a dense anterograde amnesia. During

the blackout intoxicated individuals appear outwardly unchanged; however, for the duration of the blackout, events fail to enter their memory. After "coming to" these individuals have no recollection of what was said or done during the blackout. Although the vast majority of blackouts occur during alcohol intoxication, they may also occasionally be seen in intoxication with other sedative-hypnotics, in particular high-potency benzodiazepines. Importantly, although most patients with blackouts are alcoholics, this is not always the case, as blackouts may also occur in social drinkers who simply consume more than is typical for them.

Blackouts(palimpsests).• Upon recovery from a blackout, drinkers often recount that

they remember everything up to a certain time and then "went blank." Some patients go to sleep during a blackout, and when they awaken wonder how they got home or got to bed.

• Upon recovery from a blackout, most patients are worried about what they did during the blackout. The car may be checked for evidence of an accident; indirect questions may be put to others in a discreet effort to find out if anything untoward happened.

Pathological intoxication.• |Classically, pathological intoxication is said to occur when,

consuming a relatively small amount of alcohol, drinkers undergo a marked change in behavior, often becoming agitated or violent, afterwards having at best a spotty memory for the event.

• Occurring after as little as one or two drinks, the change in behavior may be dramatic. A polite and unassuming person may start a fist fight; a well-mannered person may suddenly take offense if a date happens to look at someone else, flying into a jealous rage. This change may persist for only a few minutes, or up to hours. Upon recovery the drinker typically has difficulty in recalling everything that happened, and occasionally may report complete amnesia for the event.

Alcohol withdrawal.• Alcohol withdrawal, commonly known as "the shakes,"

may occur in anyone after excessive, prolonged use of alcohol.

• In full-blown alcohol withdrawal, drinkers are apprehensive, anxious, and easily startled; they may pace agitatedly up and down the hall. Depressed mood and irritability are common. The tremor is quite characteristic; it tends to be coarse and is evident not only in the hands but also in the lips, tongue, and eyelids. In severe cases drinkers may literally "shake like a leaf" and be unable to hold things or even at times to stand up. Diaphoresis, at

times profuse, is often present.

Alcohol withdrawal.• Most have trouble concentrating and thinking clearly;

memory tends to be poor. Although fatigue is prominent, most are also unable to sleep.

– Headache, dry mouth, anorexia, nausea, and vomiting are common; diarrhea may occur.

• On examination the temperature, pulse, respirations, and systolic blood pressure may all be elevated. The pupils are dilated, and the deep tendon reflexes are hyperactive. Rarely, one may see transient myoclonus, choreiform movements or parkinsonism.

• Occasionally patients may have isolated, brief, vague, visual hallucinations or illusions, or rarely a few auditory hallucinations. If these do occur they tend to appear as the withdrawal symptoms reach their height.

Alcohol withdrawal seizures.• Alcohol withdrawal seizures, also known as "rum fits," are

a rare accompaniment of the alcohol withdrawal syndrome. They generally occur only after many years of heavy drinking and repeated episodes of withdrawal and are seen in from 1% to 3% of patients withdrawing from alcohol.

• For the most part, alcohol withdrawal seizures present as otherwise unremarkable generalized tonic-clonic seizures. In about a quarter of the cases, however, the seizures have a focal onset.

• Most patients have just one seizure; occasionally, however, patients have a cluster of two or three and rarely as many as six. Rarely, status epilepticus occurs.

Delirium tremens.• Delirium tremens, also known as alcohol withdrawal

delirium and more commonly as "DTs," develops in the setting of the alcohol withdrawal syndrome, and is seen in about 5% of hospitalized alcoholics. It is characterized by gross accentuation of the tremor and autonomic signs and by the development of confusion, disorientation, and hallucinations.

• the patient is generally agitated, markedly tremulous, and very easily startled; mydriasis and generalized hyperreflexia are prominent,as are such autonomic signs as diaphoresis, tachycardia, elevated blood pressure, and

increased respirations.

Delirium tremens.• Visual hallucinations are very common; they tend to be

extremely vivid and complex. Often the patient sees insects or animals: dogs circle the bed; rats eat at the toes; bugs crawl on the arms and face. They may cringe in fear or try to swat them away. At times the patient may see simply a benign procession of animals, which he may watch from the bed as if it were an amusing procession. Curiously one also often sees a predilection for hallucinating strings or threads; the patient may pick them out of the air or warn the physician to avoid running into one stretched across the hospital room. Often the visual hallucinations may be provoked by suggestion. In the classic "string test" the examiner holds her hands about a foot and a half apart, the thumbs and index fingers apposed, several feet in front of the patient and asks if the patient sees anything. After the patient reports seeing nothing, the examiner asks "Don't you see the string?," whereupon the patient does indeed see a string stretched between the examiner's hands.

Delirium tremens.• Tactile hallucinations may accompany the visual

ones: the skin is ripped by teeth; spiders bite; bugs are felt crawling all over. The patient may complain of electric shocks or of pins being stuck into the toes.

• Auditory hallucinations are common. Patients may hear bells, whistles, or alarms. If voices are heard, they tend to be critical, persecutory, or warning of dire events. Patients hear accusations of neglecting their children; the children are starving because the patients spent their paychecks on drink. The death sentence is pronounced; the physician is revealed as the executioner.

Delirium tremens.• Delusions are common and tend to be persecutory.

Murderers are outside the door; the nurse is bringing poison to the patient; other patients talk about and conspire against the patient.

• Disorientation always occurs, often to both time and place. At times this disorientation is intensified by hallucinations. The patient refuses the bedtime medicine offered by the nurse and announces that it must be morning as the birds are chirping; if questioned as to orientation to place, the patient, seeing the clouds out the window, may report being in an airplane or perhaps an air ambulance.

Delirium tremens.

• Memory tends to be severely disturbed. The patient is unable to recall the name of the physician or of the hospital. Recall of events before admission is also often quite spotty.

• The behavior of these patients is commensurate with their symptoms. Some may sit tremulously on the bed, picking at the bed sheets or brushing away insects. They may grasp at strings in the air and mumble agitatedly about events occurring outside the window. Others may strike out at their "persecutors"; they may attempt to escape through the door or jump out the window.

• In contrast one may occasionally encounter a "quiet" delirium tremens. Here the tremor and autonomic signs and symptoms are minimal, and the patient, all the while experiencing sometimes fantastic visual hallucinations, may lie relatively quietly in bed.

Korsakoff’s syndrome

• Korsakoff's syndrome, also known as Korsakoff's psychosis, is characterized by a striking inability to form new memories, with the subsequent "blank spots" often filled in with confabulations.

• The memory loss is of the short-term variety; the patient's ability to recall anything after a few minutes (such as the physician's name) is grossly impaired. Long-term memory is relatively spared, wherein events of the distant past are better recalled than those that occurred more recently. Remarkably patients are generally unconcerned with this inability to remember things.Confabulations are typically present and may at times be quite fabulous.

Korsakoff’s syndrome

• During casual questioning, these patients may not appear ill.They may talk appropriately about their surroundings, comment on the weather as they look out the window, or compliment the physician's taste in clothing. Some may be mildly euphoric, others bland and apathetic. A few direct questions, however, disclose the memory defect and the tendency to confabulate

Alcoholic dementia

• Alcoholic dementia often presents with a personality change. Patients become coarse and heedless of social convention; they may become apathetic, and judgment is poor. Cognitive deficits eventually appear; short-term memory fails, and patients gradually have increasing difficulty in recalling events of the distant past. Thinking becomes concrete. With continued drinking the dementia may become profound. At times, minor "cortical" signs are seen such as apraxia, agnosia, and aphasia; however, these are not a prominent part of the clinical picture.

• CT or MRI studies generally demonstrate both cortical atrophy and ventricular dilitation.

Alcohol hallucinosis

• Alcohol hallucinosis, also known as alcohol-induced psychotic disorder with hallucinations, is seen only in alcoholics, and then only after one or more decades of heavy alcohol consumption. Hallucinations, generally auditory, are often accompanied by delusions of reference and persecution and appear relatively suddenly, persisting for variable periods of time.

• Auditory hallucinations constitute the principal symptom of alcohol hallucinosis. These are often extremely vivid and clear; the patient has no doubt as to their reality and does not believe that the physician does not hear them. For the most part they are critical and often persecutory. Generally more than one voice is heard, and curiously the voices often talk among themselves - about the patient. At times one may observe patients straining to overhear what the voices are saying.

Alcohol hallucinosis

• What the patients hear, or overhear, is often quite distressing or frightening. They are accused of murder; the food will be poisoned; their relatives are selling all their goods and will leave them destitute and in the street.

• Delusions of persecution and reference often accompany the auditory hallucinations and are generally congruent with them. ; Family members talk about the patient; they conspire against the patient to force her to sign documents, but she knows the documents are in fact cleverly worded confessions and refuses to sign them. Police follow the patient; they await any excuse to arrest her. Such patients are often constrained and very watchful. They tend to be irritable. Should they feel too threatened, they may turn on their supposed persecutors. Occasionally, visual hallucinations occur, but these are far less prominent than the auditory ones.

Alcoholic paranoia

• Classically, alcoholic paranoia is characterized by delusions of jealousy. The spouse is suspected of infidelity; absences from the house are seen as proof of it; the spouse's desire to keep apart from the patient during the patient's intoxicated rages is seen as a mere excuse. Rules are laid down; the spouse is neither allowed outside the house alone nor allowed to speak in private on the telephone. When drunk the patient may turn on the spouse, sometimes in a murderous fashion. In other cases the illness may be characterized by persecutory delusions: the police have begun to hound the patient. Yet another charge of driving under the influence of alcohol is trumped up; unmarked police cars cruise down the streets. The neighbors have been recruited to spy on the patient from behind their shades.

Alcoholic paranoia

• Occasionally hallucinations may occur, but they play only a minor role. Footsteps and sirens are heard at night; something moves in the attic. The food tastes spoiled, rotten, perhaps even poisoned. Strange people approach the house in the dead of night.

Alcoholic polyneuropathy

• Paresthesias begin distally, first in the feet and calves, later in the hands. Associated lancinating pains may occur. Hyperesthesia may also be present, and even the touch of a bed sheet on the soles of the feet may be more than the patient can tolerate. On examination vibratory sense is lost first, followed by other modalities; the ankle jerks are diminished or lost and the Romberg test is positive.

• With continued drinking, patients develop motor weakness; this may be seen in as few as several weeks after sensory symptoms appear. Distal musculature is affected first, the lower extremities before the upper. Foot drop with a steppage gait is common; wrist drop may also occur. Atrophy of the calves and forearms may be seen. Although motor signs are bilateral, their severity is often asymmetric.

Treatment

• Use explicit evidence; emphasize the consequences endured by the patient as a result of alcohol abuse.

• Be empathic and nonjudgmental.

• Avoid arguments about the diagnosis.

• Avoid use of the word alcoholic.

Treatment

• Treatment of alcohol withdrawal is best accomplished with benzodiazepines. Avoid fixed-dose therapy, and treat patients for symptoms. This results in use of lower doses of benzodiazepines, less patient sedation, and earlier patient discharge.

• Other agents that have been used with some success in the treatment of withdrawal include beta-blockers, phenothiazines, and anticonvulsants. All can be used with benzodiazepines, but none has been proven to be adequate as monotherapy. A number of medications have been tried in the treatment of alcoholism.

Treatment• Disulfiram (Antabuse) has been used as an adjunct to

counseling. Patients are reminded of the risks of adverse effects when tempted to drink. Disulfiram causes nausea, vomiting, and dysphoria with coincident alcohol use. In a large trial, disulfiram did not increase abstinence. If a patient asks for disulfiram and thinks it will help, it might be worth

considering. • Naltrexone blocks opiate receptors and works by decreasing

the craving for alcohol, resulting in fewer relapses. A recent positron emission tomography study demonstrated that alcoholic persons have increased opiate receptors in the nucleus accumbens of the brain and that the number of receptors correlates with craving.

Treatment• Opiate antagonists -- Alcohol has been shown to bind to

opiate receptors in the brain. Studies show that blocking opiate receptors decreases cravings for alcohol.

• Naltrexone (ReVia) -- Patients must be abstinent for 5-7 d before beginning therapy. Monitor liver function during treatment.

• Contraindications Documented hypersensitivity, acute hepatitis, liver failure

• Precautions Nausea/vomiting, abdominal pain, daytime sleepiness, and nasal congestion were more common vs placebo in largest randomized trial to date; discontinuation due to adverse effects was uncommon in most clinical trials

Treatment• Aldehyde dehydrogenase inhibitors -- Disulfiram inhibits

aldehyde dehydrogenase, and, as a result, acetaldehyde accumulates. This leads to nausea, hypotension, and flushing if a person drinks alcohol while taking disulfiram.

• Disulfiram (Antabuse) -- Decreases number of drinking days but does not increase abstinence. Directly observed therapy might be more beneficial but has not been studied in a good randomized trial.

• Contraindications Documented hypersensitivity, severe myocardial disease, coronary occlusion

• Precautions Adverse effects are uncommon, but hepatitis, optic neuritis, neuropathy, and skin rash reported

Treatment of DT• Benzodiazepines -- By acting on the GABA receptor,

benzodiazepines produce a cross-tolerance to alcohol, thus reducing the hemodynamic and peripheral symptoms of alcohol withdrawal. The dose of benzodiazepine used should be based on the patient's symptoms and signs of alcohol withdrawal, including vital signs and amount of agitation. The longer-acting agents appear to be superior compared to the short-acting agents and may result in a smoother withdrawal course with less breakthrough and rebound symptoms, although a risk of excessive sedation exists in certain patient groups (elderly patients, patients

with liver failure) with the longer-acting agents.

Treatment of DT• For the treatment of minor or moderate alcohol withdrawal (patient able to

take oral therapy), symptom-triggered therapy has been shown in prospective, randomized, controlled trials to be superior to fixed-dose drug therapy, with less medication use and a shorter duration of therapy. The dosage of benzodiazepine needs to be individualized for each patient. Successful use of symptom-triggered therapy requires motivated and

attentive nursing. • For patients with severe withdrawal symptoms, including DTs, the

benzodiazepine dose should be front-loaded. That is, large doses should be administered intravenously at short intervals until the patient is calm but easily aroused. Then additional doses are administered only as needed. Most authorities recommend intravenous diazepam as the first choice for front-loading treatment of severe alcohol withdrawal. Because of its long serum half-life, and the even longer half-life of its active metabolite (desmethyldiazepam), additional doses may not be required once the patient is calm.

Treatment of DT• Diazepam (Valium, Diazemuls, Diastat) -- Depresses all levels of CNS

(eg, limbic and reticular formation), possibly by increasing activity of GABA.Individualize dosage and increase cautiously to avoid adverse effects.

• Anesthetic agents -- Propofol, an intravenous anesthetic agent, is active on both the glutamate and GABA-A receptors, similar to the alcohol itself, whereas benzodiazepines are active only against the GABA receptors. It may be effective for patients with DTs refractory to benzodiazepines. Due to its rapid onset of hypnosis and anticonvulsant properties, propofol is an alternative treatment for intubated patients with DTs refractory to high-dose benzodiazepines. Advantages to its use are that it is easily titratable with predictable effects and has a rapid metabolic clearance

Treatment of DT• Propofol (Diprivan) -- Phenolic compound unrelated to

other types of anticonvulsants. Has general anesthetic properties when administered IV. Propofol IV produces rapid hypnosis, usually within 40 s. Effects are reversed within 30 min following discontinuation of infusion.

• THANK U FOR UR ATTENTION!

Disorders of personality and behavior due to drug abuse.

Lyudmyla T.Snovyda

Introduction

• People take various substances because they like the effects. In some, such use stays at a "recreational" or "social" level; in others, abusive use occurs; and in still others, addiction, or compulsive use, occurs. Differentiating among these three forms of use is important not only with regard to prognosis but also with regard to treatment.

• Most of these substances have the capacity to produce tolerance and withdrawal, whereas others generally do not. Those that routinely produce tolerance and withdrawal include the following: caffeine, cannabis, inhalants, nicotine, amphetamines, cocaine, opioids, sedative-hypnotics, and alcohol. Those that lack substantial capacity to produce tolerance and withdrawal include hallucinogens and phencyclidine.

Tolerance and withdrawal

• Tolerance is said to occur when the patient has to take ever increasing amounts of the substance to get the desired effect. Tolerance may also be inferred when, over time, even though the patient continues to use the same amount, the effect becomes progressively less.

• Withdrawal symptoms occurring after use is discontinued often constitute a "rebound" from the effects of intoxication.

• for example, a patient who had taken a benzodiazepine exactly as prescribed for years, without ever exceeding the dose but who accidentally left the medicine at home while going on vacation. After a sleepless night and experiencing tremulousness the next day, the patient calls the physician who explains to the patient that these constitute withdrawal symptoms. Such a patient, though desperate for relief, may nevertheless decide that "it isn't worth it," and because she has no craving may simply not take anymore, "tough out" the withdrawal, and then get on with life.

Tolerance and withdrawal

• In the past these phenomena of tolerance and withdrawal have been termed "physiologic dependence." However, because the word "dependence" often conjures up the image of addiction, another term, "neuroadaptation * has been coined. Neuroadaptation is clearly the preferred term for two reasons: first, it speaks to the underlying neuronal mechanism; and second, it is neutral with respect to addiction, thus emphasizing that tolerance and withdrawal, though ubiquitous in addiction, can also occur with abusive use, occasionally with recreational use, and also during appropriate medical treatment.

RECREATIONAL USE

• Most people, at some point or other, "experiment" with substances, such as caffeine, nicotine, alcohol, cannabis, and, with ever-increasing frequency, cocaine. A morning cup of coffee and social drinking are typical examples. In some cases the substance produces some sort of dysphoria, and the person never uses it again. An example would be the teenager who gets "paranoid" the first time he smokes marijuana. In other cases peer pressure or a certain appreciation for the effects of the substance may prompt the patient to use the substance occasionally. Here the person is in the "take it or leave it alone" mode, and going to get the substance is no more important than, say, going to a good movie. He can "walk away from it" without a second thought.

RECREATIONAL USE

• In the case of caffeine, alcohol, cannabis, and perhaps also hallucinogens and phencyclidine, substance use for many appears to stay at a "recreational" level. Although a progression to abusive use may occur with any of these, a progression from recreational to abusive use appears more common for tobacco, stimulants, and especially cocaine and opioids. The likelihood of this progression is increased with intravenous use or with smoking "crack" cocaine.

ABUSIVE USE• In a minority of those who engage in recreational use, an abusive pattern of

use will emerge. In some cases this progression is due to peer pressure, in others because neuroadaptation has occurred and "relief" use seems highly desirable, and in yet a third group abusive use may occur either because the person gets substantial enjoyment from the substance or because it helps the patient "cope" with life's problems.

• Peer pressure is particularly important among teenagers and young adults. Since "everybody" is using, say, cannabis or alcohol to be "one of the crowd," these patients go along and use more than might be the case if left to their own devices.

• The need for "relief" use may occasionally prompt use beyond that which the patient wishes. A salesperson, for example, may find daily drinking "necessary" for work as customers are entertained. Eventually, though, morning shakiness starts to occur, and though not welcoming the idea, such an individual finds it very difficult to hold off until a drink can be had with lunch.

ADDICTION• These patients experience an overpowering compulsion to use the

substance and are driven by that compulsion to repeated use despite the most disastrous consequences. Despite repeated attempts to control their use, by either moderating it or stopping it altogether, addicts find themselves again and again intoxicated.

• The appearance of craving may be gradual and insidious or at times acute. But in the history of every addict is a time when she "crosses the line" and is no longer able to stop.

• Once craving develops, denial becomes severe. Cocaine addicts driven to theft and robbery to support their "habit" may insist that they are "in charge."

• Eventually, substance use becomes the primary, if not the sole, motivating factor in the patient's life. Family, friends, and work pale by importance, and all the patient's efforts become directed to one thing: ensuring an unbroken supply of the substance.

Caffeine Related Disorders • A cup of coffee contains about 100 mg of caffeine, tea about 50

mg, and caffeinated soft drinks anywhere from 25 to 200 mg. Over-the-counter analgesic and "cold" preparations, "stimulants," anorectics, herbal products and health food products may contain anywhere from 25 to 200 mg. Caffeine is almost completely absorbed, reaching peak blood levels in from 30 to 60 minutes. Metabolism is via the cytochrome P450 1A2 hepatic enzyme system, with a half-life ranging from three to five hours.

CLINICAL FEATURES• A caffeine-naive patients, about 100 mg of caffeine produces an

increased sense of alertness and decreased fatigue. At doses between 100 and 500 mg, however, caffeine intoxication begins. Patients feel apprehensive, restless, and even agitated, and complain of headache and insomnia. Tremor and tachycardia may appear. At doses of about 1 g, intense anxiety to the point of panic occurs. Agitation may be extreme, and tremor and tachycardia are now quite prominent. Premature beats and muscle twitches may occur. Significantly higher doses (e.g., 10 g) may produce serious arrhythmias, such as,ventricular fibrillation, grand mal seizures, respiratory depression and death.

CLINICAL FEATURES• Provided that no further caffeine is ingested, symptoms of

intoxication tend to clear in a matter of hours, and recovery is generally complete within 6 to 12 hours. Neuroadaptation may develop after daily use of only 500 mg of caffeine over a couple of weeks time. Tolerance is manifest by the ability of the patient to consume, without ill effect, doses of caffeine that would cause intoxication in caffeine-naive individuals. Withdrawal tends to occur in 12 to 24 hours after the last dose and is characterized by headache, poor concentration, fatigue, anxiety, irritability, and depressed mood, all gradually clearing in from 2 days up to a week.

Cannabis Related Disorders• "Cannabis" comes from the Greek word for hemp and

refers to the flowering tops of the hemp plant, Cannabis sativa. The two most commonly available preparations of cannabis are marijuana and hashish. Marijuana (also known as "grass," "pot," "reefer," "weed," or "Mary Jane") is simply a dried collection of the flowers and nearby leaves and sprouts of the hemp plant and is usually rolled into a cigarette. Hashish, on the other hand, is more potent and is the resin that is scraped from the leaves and flowers of the plant.

CLINICAL FEATURES• Cannabis intoxication is characterized for most individuals by a

dreamy sense of well-being. The senses feel heightened; color and sounds appear unusually sharp and clear. Time seems to slow down, and minutes may seem like hours. Thinking becomes less logical, and everyday things may come to seem ridiculous and amusing. Laughter and giggling may occur, and although this may leave the unintoxicated unmoved, it often is infectious to others who are intoxicated.

• While intoxicated, most individuals have difficulty remembering things and paying attention. The mouth is dry, and most experience increased hunger, often for cookies or brownies. The conjunctivae are reddened. A mild degree of ataxia may be seen. The heart rate is generally elevated, and although the supine blood pressure is often elevated, orthostatic hypotension may occur upon standing.

CLINICAL FEATURES• In a minority of cases the intoxication may be complicated by any of a

number of events. Perhaps the most common complication is anxiety, which at times may be as severe as that seen in a panic attack. This cannabis-induced anxiety generally passes as the intoxication does. Depersonalization or derealization may also occur during intoxication.

• A less common complication is the development of a psychosis. This "cannabis-induced psychotic disorder," as it is sometimes called, is characterized by the fairly abrupt appearance during intoxication of compelling delusions of persecution, which maybe accompanied by auditory or visual hallucinations. Extreme anxiety is commonly associated with this, and although patients rarely attack their "persecutors," many will flee or seek safety in some other way. The psychosis generally outlasts the intoxication per se, and indeed may persist for 1 to 3 days.

CLINICAL FEATURES• These two complications, anxiety and psychosis, may occur after

smoking only a relatively small amount of marijuana. When much higher doses are taken, a delirium may occur. This cannabis intoxication delirium is characterized by confusion and, often, agitation. Thinking is quite illogical, and delusions and hallucinations often appear. This delirium may clear as the intoxication does or it may last for up to a few days.

• The pattern of recurrent intoxication is quite different between the "social user" and the patient with cannabis abuse or dependence. Social use is often confined to weekends and generally occurs with friends. Cannabis abusers typically smoke marijuana or hashish on a daily basis, and often do so alone. The pattern is similar for cannabis addicts, whose entire lives often center on getting and staying intoxicated and who also develop either tolerance or withdrawal.

CLINICAL FEATURES• Tolerance is manifested by a decreased euphoria and a

diminution in the tachycardia and blood pressure changes. If withdrawal occurs it tends to be mild and to appear anywhere from 3 to 12 hours after the cannabis was last used. Patients are anxious, irritable, and restless and almost always complain of some insomnia. Anorexia and increased sweating are seen, and some patients may develop a fine tremor. Symptoms generally peak in 1 to 2 days and resolve spontaneously within 4 to 5 days.

Hallucinogen Related Disorders • The hallucinogens, also known as psychedelics

or psychotomimetics, may be roughly divided into two groups: the indolealkylamines, such as LSD, and the phenylalkylamines, such as mescaline

CLINICAL FEATURES• After oral use of most hallucinogens, intoxication begins

gradually within 20 minutes to 1 hour. A certain tension or apprehension may occur, soon followed by an alteration in the state of consciousness that is difficult to describe. Although fully alert and oriented, patients describe a "cosmic" sense of unity with those around them.

• Visual illusions and hallucinations are common, and patients often relate to them as they would to a movie. Patients acknowledge that they are not real, yet they are captivated by them. Rippling colors and geometric forms may occur; bodies may appear distorted, and at times complex visual hallucinations of people or things may occur

CLINICAL FEATURES• Intoxication with MDMA ("Ecstasy") is somewhat different than that seen

with other hallucinogens, being characterized by an initial "rush," followed by a heightened sense of empathy or connectedness with others.

• Not uncommonly the intoxication may become extremely dysphoric as it evolves into a "bad trip." Anxiety sets in as the patient vainly attempts to control his thoughts and perceptions. Some fear dissolution; others are in terror that they are losing their minds and that the trip will never end. Delusions of reference and persecution may occur, and the patient, panic-stricken, may be brought to the hospital.

• On examination of the intoxicated patient one finds mild degrees of tachycardia, hypertension, mydriasis, fine tremor, poor coordination, and generalized hyperreflexia: in the case of MDMA, bruxism may also be seen. The temperature may be elevated.

• Regardless of whether the intoxication is pleasant or not, patients generally recover within 6 to 24 hours after most hallucinogens.

CLINICAL FEATURES• A minority of patients develop an hallucinogen-induced mood disorder

shortly after the intoxication resolves, usually within days. Most commonly, depression is seen with anxiety, insomnia, and an unrelenting fear that the drug has caused permanent damage. At times, patients are severely agitated, and suicide attempts have occurred. Less commonly, manic symptoms may occur, and one may see a heightened mood, hyperactivity, pressured speech, and a decreased need for sleep. These mood changes tend to be relatively brief, lasting only a few days; rarely, however, they may persist for much longer, up to weeks.

• Flashbacks (also known as "hallucinogen persisting perception disorder") may occur in up to a quarter of all patients. Here, while not intoxicated, the patient experiences one or more of the symptoms seen in the intoxication. Generally the flashback itself is quite brief, sometimes lasting only seconds. Patients may experience complex visual hallucinations, or only shapes, color, or "trailing" of after-images. Auditory and tactile hallucinations may also be seen. Flashbacks may occur spontaneously or may be precipitated by moving into a darkened area, or by the use of alcohol, marijuana, or an antipsychotic.

Amphetamine (or Amphetamine-Like)Related Disorders

• Of the many stimulants that have been abused, amphetamine, dextroamphetamine and methamphetamine are the worst offenders; methylphenidate has also been abused as have some of the "diet" drugs, such as diethylpropion, benzphetamine and phenteramine. Of all these, amphetamine and methamphetamine are the most important clinically.

• These drugs may be taken orally or crushed, dissolved, and taken intravenously. Occasionally they are also "snorted." Highly purified methamphetamine ("ice") may also be smoked. Within the central nervous system the stimulants act primarily as indirect, but also possibly as direct, sympathomimetics, releasing both norepinephrine and dopamine; the amphetamines are predominantly noradrenergic and methylphenidate predominantly dopaminergic.

CLINICAL FEATURES• Stimulant intoxication may begin almost immediately with inhalation or intravenous

use, producing an intensely pleasurable "rush," whereas an hour or more may pass after oral use before the user experiences a somewhat less profound elation or sense of intense well-being. Typically, the user feels more confident, energetic, and , active. The user is disposed to talk; there may be some grandiosity.The pupils are dilated, the blood pressure, both systolic diastolic, is increased, and the heart rate may be either increased or reflexively slowed. Such a degree of intoxication rarely brings the user to medical attention.

• A severe degree of intoxication, one seen not uncommonly in the emergency room, is characterized by agitation and at times bizarre behavior. Often a peculiar interest in things mechanical is observed, and users may spend hours taking apart and then to put back together clocks, radios, televisions. Fleeting delusions of persecution and auditory hallucinations may arise.

CLINICAL FEATURES• The temperature is raised, and extreme diaphoresis may occur. The user may

experience nausea, vomiting, abdominal cramping, and diarrhea. Occasionally, in even higher degrees of intoxication, a stimulant-intoxication delirium may occur with confusion, extreme apprehension, incoherence, and at times violent behavior. Seizures, hypertensive encephalopathy, and various arrhythmias may also occur.

• Regardless of the degree of intoxication most users recover a few hours later or perhaps in a day or more.

• In some users a stimulant-induced psychotic disorder may occur, and although this is typically restricted to chronic users, it has been reported in normal volunteers given very high oral doses. The user becomes intensely suspicious, guarded, and watchful. Delusions of persecution develop, as may both auditory and visual hallucinations. Typically these users remain free of confusion and incoherence. In extreme cases the user may attack the "persecutors." With abstinence the symptoms of the psychosis gradually fade, generally over anywhere from days to weeks.

CLINICAL FEATURES• Withdrawal symptoms typically occur after extended use of

stimulants. As the intoxication clears, users become dysphoric and fatigued. They may be irritable, and some users become agitated. Suicidal ideation, which may be intense, is not uncommon. Some users experience a dreadful insomnia, whereas others sleep excessively, at least initially. This acute withdrawal syndrome, or "crash," as it is often called, may undergo considerable clearing within days or a week or more; however, dysphoria and sleep disturbance may last for weeks or months.

Cocaine Related Disorders• Several different preparations of cocaine are available illegally.

Cocaine hydrochloride is a white powder that may be "snorted" into the nasal passages where it is absorbed through the nasal mucosa; cocaine hydrochloride is also water soluble and may be injected intravenously. Cocaine hydrochloride is destroyed by heat, and is thus not suitable for smoking; however, it may be treated with sodium bicarbonate and then either extracted with ether to yield a "free base" preparation, or warmed to create a "rock" of cocaine.

CLINICAL FEATURES• During intoxication users becomes euphoric, hyperalert,

talkative, and grandiose. Hyperactivity is common, and with higher doses agitation may occur; some patients may also experience visual hallucinations, often consisting of insects, the notorious "cocaine bugs"; some of these patients may also experience tactile hallucinations, and in such cases patients may excoriate themselves in an attempt to get rid of the "bugs." The appetite for food and sleep is routinely lost, and with mild intoxication sexual desire increases, accompanied by delayed ejaculation. With greater intoxication, however, partial or complete impotence may occur.

CLINICAL FEATURES• Users may experience tachycardia or palpitations; headache, nausea,

and vomiting may also occur. Rarely choreoathetosis ("crack dancing") may occur. Mydriasis and increased blood pressure are routinely found; occasionally the user may have fever and chills. Users often take sedatives, alcohol, or opioids to enhance the intoxication or dampen the unwanted effects; a favored combination is the "speedball," a mixture of cocaine and heroin. The duration of the intoxication, varies with the preparation. Regardless, however, of the route of administration, the autonomic and cardiovascular effects tend to persist for 20 to 60 minutes.

CLINICAL FEATURES• Most users experience a "crash" shortly after using cocaine and this tends to be

more severe after taking cocaine intravenously or smoking it. During the "crash," users experience fatigue, depression, irritability, and anxiety; the overall dysphoria may be intense. The crash may come within 15 minutes after IV use or smoking; after snorting, the crash may not appear for 30 to 60 minutes. Generally this crash resolves within hours, or a day at the most.

• After 2 years or so of cocaine use, a cocaine-induced psychotic disorder may occur during intoxication, characterized by delusions of persecution and reference, which

may at times be accompanied by auditory hallucinations. • During severe intoxication after intravenous use or smoking, some users may

develop a cocaine-induced delirium. Confusion, apprehension, and incoherence may be seen. The mood is often labile, and delusions and hallucinations are common. Users in the midst of such a delirium are prone to aggression and violence. In general the delirium clears within hours; afterward the user may be amnestic for the event.

CLINICAL FEATURES• Tolerance appears to occur much more rapidly with IV use or smoking than

if cocaine is snorted. Indeed during a "run" of IV use, tolerance may appear within a day. Unfortunately such tolerance develops only to the euphoriant effect of cocaine and not to its cardiovascular effects. Thus the progressively higher doses required to achieve the euphoria may eventually cause a lethal event, such as an arrhythmia, before the euphoria can be reached.

• Withdrawal symptoms seem in some sense to be an extension and elaboration of the frequently occurring post-intoxication "crash," described earlier. Withdrawal tends to occur only after a minimum of several days of heavy use; the withdrawal symptoms themselves tend to reach a maximum in several days and then remit gradually over days or weeks. Typically a user in withdrawal experiences depression, irritability, fatigue, anhedonia, a tense craving for more cocaine, insomnia, and occasionally hyperphagia. Suicidal ideation is not uncommon and suicide attempts may occur.

Opioid Related Disorders• An opiate is any intoxicant naturally found in opium. The term

"opioid" is more general and refers to any substance, either synthetic or naturally occurring, that has morphine-like effects.

• Opium is obtained from the juice of the poppy plant, and within opium are found two opiates, namely morphine and codeine. Synthetic and semi-synthetic derivatives include heroin, hydromorphone, merperidine, hydrocodone, oxycodone and pentazocine. Methadone and buprenorphine are derivatives used, as noted below, in the treatment of opioid addiction, but these may also be abused. Of all the opioids, heroin is by far the most commonly abused.

CLINICAL FEATURES• The intoxication produced by opioids is intensely seductive.

Within minutes after the intravenous injection of heroin, morphine, or hydromorphone the user may be rewarded by an intense rush. The body is suffused with warmth, and orgasmic sensations may be felt. In less than a minute the rush tends to pass, to be replaced by a drowsy, vaguely euphoric feeling that may last for hours. Dysarthria and difficulty with concentration may occur. The pupils are constricted, peristalsis is slowed, and constipation ensues; urinary hesitancy or retention may occur. Some experience generalized pruritus. During the intoxication most users are slowed down, and some may "nod off." Aggressiveness and sexual desire are blunted, and an opioid-intoxicated user rarely harms others during the actual intoxication.

•

CLINICAL FEATURES• In an overdose the user is stuporous or comatose. Initially the pupils are pinpoint;

however, with respiratory depression and cerebral anoxia pupillary dilatation may occur. Temperature falls, and the skin is often cold and clammy. Respirations decrease not uncommonly to less than five breaths/minute. Pulmonary edema is not uncommon. Intracranial pressure may rise, and seizures may occur. Death is usually caused by respiratory arrest.

• In those addicted to heroin or morphine, withdrawal symptoms gradually emerge anywhere from 6 to 12 hours after the last dose. The user becomes uneasy and experiences a craving for the drug. Yawning, lacrimation, and rhinorrhea appear; diaphoresis is also seen. Several hours later the user may fall into a restless sleep, known as "yen" sleep. Upon awakening, the earlier symptoms intensify, and the user soon thereafter becomes irritable, demanding, and intensely dysphoric. Insomnia may be extreme. Nausea, vomiting, intestinal cramping, and diarrhea occur, and the user begins to experience waves of goose flesh that may be so severe as to make flesh resemble that of a plucked turkey, an appearance that

•

CLINICAL FEATURES• prompted the phrase "cold turkey." Intense bone and muscle pain in the

back, arms, and legs occurs. Often, seemingly involuntary kicking movements occur, a phenomenon that prompted another proverbial phrase "kicking the habit." The pupils are dilated, and the temperature, pulse, and blood pressure are all increased. Leukocytosis may be present. Fluid loss secondary to vomiting and diarrhea may lead to dehydration and rarely circulatory collapse.

• The life of the opioid addict often becomes centered on only one thing: obtaining the drug. The restless anticipation of the rush, the deep craving for the drug, and the intense fear of withdrawal symptoms combine to irresistibly drive the addict to do whatever is necessary to maintain the supply. Prostitution and murder may occur; some may sell children.

•

Sedative, Hypnotic, or AnxiolyticRelated Disorders• The sedatives, hypnotics, and anxiolytics, including the benzodi-

azepines, barbiturates, and related drugs, comprise a large group of agents often referred to as "sedative-hypnotics," all of which have an effect that is more or less similar to that of alcohol. Although most commonly used in combination with alcohol or other substances.Among the benzodiazepines, diazepam, lorazepam, and alprazolam are currently the most popular among abusers, with

diazepam heading the list. •

Clinical features.• In intoxication the user, though often euphoric, may at times display some emotional

lability. Judgment is impaired, and sexual or aggressive urges that are normally inhibited may be acted upon. . With somewhat more severe intoxication, reaction time is markedly slowed, and the user may appear drowsy or lethargic. Dysarthria, poor coordination, ataxia, and nystagmus are common at this point. Severe intoxication may produce stupor, coma, respiratory depression and death. The onset of withdrawal symptoms varies according to the ion of the agent's effect. Roughly speaking, withdrawal may expected in less than 1 day for short-acting agents, 2 to 3 days intermediate-acting agents, and 2 to 6 days for longer-acting agents. For certain very-long-acting agents, such as diazepam or phenobarbital, a "self-tapering" process may occur as the blood level falls very slowly, so withdrawal symptoms may be relatively

mild compared with other agents. • The patient in withdrawal is anxious and irritable and generally craves the drug.

Autonomic signs, such as tremor, tachycardia, and diaphoresis, are common, and muscle weakness is a typical complaint. Nausea and vomiting may occur, as may

postural hypotension. Insomnia is common and may be quite severe.

Clinical features.• If seizures occur they generally do so in the context of the withdrawal

syndrome. They are more common in barbiturate than benzodiazepine withdrawal, and when secondary to barbiturate withdrawal they tend to be much more severe than those seen in alcohol withdrawal. Multiple seizures are not uncommon, and status epilepticus may occur.

Inhalant Related Disorders• These include airplane or model glue, paint thinner, kerosene and gasoline,

various cleaners and industrial solvents, the propellants in aerosol sprays and spray paints, fingernail polish or polish remover, and typewriter correction fluid. Each of these products contains various mixtures of aliphatic or aromatic hydrocarbons.

– Inhalant abuse is sometimes also known as solvent abuse or, more loosely, "glue sniffing." The actual prevalence of inhalant abuse is not known; however, over 10% of all high school seniors have at least "experimented" with inhalants. Inhalant abuse is more common among males than females.

• substances may be soaked in a rag and held to the face, placed in a plastic or paper bag; a tell-tale rash may indicate here the bag was positioned. Intoxication usually begins within minutes. Users often describe a euphoric dreamy "high." Often some drowsiness, dizziness, dysarthria, diplopia, nystagmus, can occur. Hallucinations, generally visual, and confusion and some experience delusions. Some users become irritable, and impulsive. In severe intoxication stupor or coma may occur. Symptoms of intoxication subside gradually after about an hour or so.

Treatment of cocaine intoxication• Benzodiazepines are the first-line therapy in treating patients who are agitated and

intoxicated from cocaine. Typically, benzodiazepines can be titrated until the patient

is calm and the pulse and blood pressure have stabilized. • Use neuroleptics with caution in acute intoxication. Acute hyperthermia syndromes

associated with acute cocaine intoxication have been reported, and the use of neuroleptics with the risk of neuroleptic malignant syndrome may confuse this situation.

• Cocaine-induced chest pain • Chest pain associated with cocaine use may be from musculoskeletal,

cardiovascular, or pulmonary etiologies.

• Obtain a chest x-ray film to exclude localized infiltrates, pneumothorax, pneumomediastinum, and pulmonary edema. An ECG and serial cardiac enzyme evaluation assist in excluding acute myocardial infarction and acute coronary syndromes.

Treatment of cocaine intoxication• If an acute coronary syndrome is suggested, then oxygen, aspirin, benzodiazepines,

and nitroglycerin can be administered. Nonselective beta-blockers are best avoided in all patients who are intoxicated with cocaine.

• Hypertension• Cocaine-induced hypertension is treated first with benzodiazepines.

Benzodiazepines decrease the cocaine-induced sympathomimetic drive from the

CNS. • If this fails, phentolamine may be considered. Phentolamine is an alpha-antagonist

and counteracts cocaine's vasoconstrictive effects. Nitroprusside and nitroglycerin also may be considered.

Treatment of cocaine intoxication• Seizures • Cocaine-induced seizures may be either generalized or partial and result from

cocaine toxicity itself or from a cocaine-induced process, such as a cerebral vascular accident.

• The first-line therapy is benzodiazepines, followed by barbiturates. Consider a head CT scan for seizures associated with the use of cocaine.

• Diazepam (Valium) -- Depresses all levels of CNS (eg, limbic and reticular formation) possibly by increasing activity of GABA. Individualize dose and increase cautiously to avoid adverse effects.

• Antipsychotic agents -- High-potency antipsychotic agents in the butyrophenone class (eg, haloperidol, droperidol) are used for rapid sedation. Easily titrated and cause less sedation and orthostasis; however, they cause extrapyramidal symptoms more often than lower-potency agents. Used short term to rapidly control psychosis.

Treatment of cocaine intoxication• Newer antipsychotics (eg, risperidone, olanzapine, quetiapine) are

used for long-term management. Improvements over earlier antipsychotics include fewer anticholinergic effects and less dystonia, parkinsonism, and tardive dyskinesia. Affect dopamine and serotonin receptors.

• Haloperidol (Haldol) -- DOC for acute psychosis. Parenteral dosage form may be admixed in same syringe with 2 mg lorazepam for better anxiolytic effects.

• Olanzapine (Zyprexa) -- May inhibit serotonin, muscarinic, and dopamine effects.

Treatment of opioid intoxication• Opioid analgesics -- Two uses for opioid analgesics are as follows:

(1) Oral substitution therapy or maintenance therapy or opioid agonist therapy (OAT) refers to substitution of an oral opioid for injected heroin, with the goal of reducing harmful behaviors associated with heroin use. (2) Detoxification, or controlled withdrawal with the goal of abstinence, is based on the principle of cross-tolerance in which one opioid is replaced with another and then slowly withdrawn.

Treatment of opioid intoxication• Naloxone is very effective in treating acute overdose, and is first-line treatment.

Give IV naloxone if necessary. Naloxone is a specific opiate antagonist with no agonist or euphoriant properties. When administered intravenously or subcutaneously, it rapidly reverses the respiratory depression and sedation caused by heroin intoxication.

• Methadone, a long-acting synthetic opioid agonist, can be dosed once daily and replaces the necessity for multiple daily heroin doses. As such, it stabilizes the drug-abusing lifestyle, reducing criminal behaviors, and also reducing needle sharing and promiscuous behaviors leading to transmission of HIV and other diseases.

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