Alcohol Intoxication
Alcohol intoxication is defined by the presence of slurred speech, incoordination, unsteady gait, nystagmus, impairment in attention or memory, stupor or coma, and clinically significant maladaptive behavioral or psychological changes (inappropriate sexual or aggressive behavior, mood lability, impaired judgment, impaired social or occupational functioning) that develop during or shortly after alcohol ingestion.

The diagnosis of alcohol intoxication must be differentiated from other medical or neurologic states that may mimic intoxication, for example, diabetic hypoglycemia; toxicity with various agents, including but not limited to ethylene glycol, lithium, and phenytoin; and intoxication with benzodiazepines or barbiturates.

The diagnosis of alcohol intoxication can be confirmed by serum toxicologic screening, including a blood alcohol level (BAL).

Alcohol Dependence
Alcohol abuse becomes alcohol dependence when effects on one’s life become more global and tolerance and withdrawal symptoms develop. The alcoholically dependent patient drinks larger amounts over longer periods of time than intended, spends a great deal of time attempting to obtain alcohol, and reduces participation in or eliminates important social, occupational, or recreational activities because of alcohol. In alcohol dependence, there also is a persistent desire or unsuccessful efforts to cut down or control alcohol intake.

Epidemiology
The percentage of Americans who abuse alcohol is thought to be high. Two thirds of Americans drink occasionally; 12% are heavy drinkers, drinking almost every day and becoming intoxicated several times a month. The Epidemiological Catchment Area study found a lifetime prevalence of alcohol dependence of 14%. The male-female prevalence ratio for alcohol dependence is 4 : 1.

Etiology
The etiology of alcohol dependence is unknown.
Adoption studies and monozygotic twin studies demonstrate a partial genetic basis, particularly for men with alcoholism. Male alcoholics are more likely than female alcoholics to have a family history of alcoholism. Compared with control subjects, the relatives of alcoholics are more likely to have higher rates of depression and antisocial personality disorder (ASP). Adoption studies also reveal that alcoholism is multidetermined: genetics and environment (family rearing) both play a role.

Clinical Manifestations
History, Physical and Mental Status Examinations, and Laboratory Tests The alcohol-dependent patient may deny and/or minimize the extent of drinking, making the early diagnosis of alcoholism difficult. The patient may present with accidents or falls, blackouts, motor vehicle accidents, or after an arrest for driving under the influence. Because denial is so prominent in the disorder, collateral information from family members is essential to the diagnosis. Early physical findings that suggest alcoholism include acne rosacea, palmar erythema, and painless hepatomegaly (from fatty infiltration).
Signs of more advanced alcoholism include cirrhosis, jaundice, ascites, testicular atrophy, gynecomastia, and Dupuytren’s contracture. Cirrhosis can lead to complications including variceal bleeding, hepatocellular carcinoma, and hepatic encephalopathy. Medical disorders with an increased incidence in alcohol-dependent patients include pneumonia, tuberculosis, cardiomyopathy, hypertension, and gastrointestinal cancers (i.e., oral, esophageal, rectal, colon, pancreas, and liver).

There are also numerous neuropsychiatric complications of alcoholism. Wernicke-Korsakoff syndrome may develop in the alcohol-dependent patient because of thiamine deficiency. The Wernicke stage of the syndrome consists of the triad of nystagmus, ataxia, and mental confusion. These symptoms remit with the injection of thiamine (lOOmg 1M). Without thiamine, Wernicke’s encephalopathy may progress to Korsakoff’s psychosis (anterograde amnesia and confabulation), which is irreversible in two thirds of patients. Other neuropsychiatric complications of alcoholism include alcoholic hallucinosis, alcohol- induced dementia, peripheral neuropathy, substance-induced depression, and suicide. In the later stages of alcoholism, significant social and occupational impairment is likely: job loss and family estrangement are typical.

Various laboratory tests are helpful in making the diagnosis. BALs quantitatively confirm alcohol in the serum. They can also provide a rough measure of tolerance. In general, the higher the BAL without significant signs of intoxication, the more tolerant the patient has become of the intoxicating effects of alcohol. Alcohol-dependent patients also develop elevated high-density lipoprotein cholesterol and decreased low-density lipoprotein cholesterol, elevated mean corpuscular volume, elevated serum glutamic-oxaloacetic transaminase, and elevated serum glutamic-pyruvic transaminase. Thirty percent of alcohol-dependent patients, compared with 1 % of control subjects, have evidence of old rib fractures on chest X ray.

Differential Diagnosis
The diagnosis of alcohol dependence is usually clear after careful history, physical and mental status examination, and consultation with family or friends.

Management
Management is specific to the clinical syndrome.
Alcohol intoxication is treated with supportive measures, including decreasing external stimuli and withdrawing the source of alcohol. Intensive care may be required in cases of excessive alcohol intake complicated by respiratory compromise. All suspected or known alcohol-dependent patients should receive oral vitamin supplementation with folate 1 mg/day and thiamine 100mg/day. If oral intake is not possible, thiamine should be injected intramuscularly before any glucose is given (because glucose depletes thiamine stores).

Alcohol withdrawal syndromes include the following.

Minor Withdrawal
“The shakes” begin 12 to 18 hours after cessation of drinking and peak at 24 to 48 hours. Untreated, uncomplicated alcohol withdrawal lasts 5 to 7 days.
It is characterized by tremors, nausea, vomiting, tachycardia, and hypertension. Minor withdrawal is treated with benzodiazepines, such as chlordiazepoxide (Librium) or oxazepam (Serax) titrated to the degree of withdrawal signs. The benzodiazepine is then tapered over a period of days. The goals of treatment are prevention of more serious complications and patient comfort.

Major Withdrawal
The risk of alcoholic seizures (“rum fits”) begins 7 to 36 hours after cessation of drinking and peaks between 24 and 48 hours. One to six generalized seizures are common but rarely lead to status epilepticus. Alcoholic seizures precede delirium tremens in 30% of cases. Seizures are treated acutely with intravenous benzodiazepines. Prophylactic phenytoin (Dilantin) may be effective when administered during the high-risk period in patients with a history of withdrawal seizures.

Alcoholic hallucinosis has an onset within 48 hours of cessation of drinking and may last more than a week. It is characterized by vivid, unpleasant auditory hallucinations in the presence of a clear sensorium. Alcoholic hallucinosis may be treated with a neuroleptic (e.g., haloperidol [Haldol] 2-5mg twice a day). On rare occasions, these hallucinations become chronic.

Alcohol withdrawal delirium (delirium tremens) is a life-threatening condition manifested by delirium (perceptual disturbances, confusion or disorientation, agitation), autonomic hyperarousal, and mild fever. It affects up to 5% of hospitalized patients with alcohol dependence and typically begins 2 to 3 days after abrupt reduction in or cessation of alcohol intake. It is treated with intravenous benzodiazepines and supportive care. Treatment may need to occur in an intensive care unit, particularly if there is significant autonomic instability (e.g., rapidly fluctuating blood pressure). The syndrome typically lasts 3 days but can persist for weeks.

Alcohol Rehabilitation
The two goals of rehabilitation are sobriety and treatment of comorbid psychopathology.

To have a lasting recovery, the patient must stop denying the illness and accept the diagnosis of alcohol dependence. Alcoholics Anonymous (AA), a worldwide self-help group for recovering alcohol-dependent patients, has been shown to be one of the most effective programs for achieving and maintaining sobriety. The program involves daily to weekly meetings that focus on 12 steps toward recovery. Members are expected to pursue the 12 steps with the assistance of a sponsor (preferably someone with several years of sobriety).

Alcohol appears to be a potent depressant, so treatment of depression should be geared to patients who remain depressed after 2 to 4 weeks of sobriety.

Anxiety is also common in withdrawing or newly sober patients and should be assessed after at least 1 month of sobriety. Inpatient and residential rehabilitation programs use a team approach aimed at focusing the patient on recovery. Group therapy allows patients to see their own problems mirrored in and confronted by others. Family therapy allows the patient to examine the role of the family in alcoholism.

Disulfiram (Antabuse) can be helpful in maintaining sobriety in some patients. It acts by inhibiting the second enzyme in the pathway of alcohol metabolism, aldehyde dehydrogenase, so that acetaldehyde accumulates in the bloodstream, causing flushing, nausea, vomiting, palpitations, and hypotension. In theory, disulfiram should inhibit drinking by making it physiologically unpleasant; however, because the effects can be fatal in rare cases, patients must be committed to abstinence and fully understand the danger of drinking while taking disulfiram. The usual dose of disulfiram is 250 mg daily.

Naltrexone (Revia) is an opiate antagonist medication that has the strongest empirical support in reducing alcohol intake among medications available in the United States. Naltrexone reduces both the amount of alcohol intake and the frequency of alcohol intake. Naltrexone is usually dosed at 50mg per day, but higher doses may potentially be more effective. Unlike disulfiram, patients can continue taking naltrexone if they relapse to alcohol intake. Naltrexone, as an opioid antagonist, may work in part by reducing the reinforcing high of alcohol ingestion.

Many studies have demonstrated benefits from rehabilitation programs, but nearly half of all treated alcohol-dependent patients will relapse, most commonly in the first 6 months.