Clinical Aspects of Alcohol Abuse

Chris Cargile, M.D.

Recommended Reading K and S pg 391-406


  1. The student will be able to describe the terms, intoxication, withdrawal, tolerance, and sensitization as they relate to alcohol and drug use.
  2. The student will be able to describe the epidemiology of alcohol abuse and dependence.
  3. The student will be able to describe the physiologic effects of alcohol on the brain .
  4. The student will be able to describe the role of genetic and environmental factors in alcohol related syndromes.
  5. The student will be able to describe the fetal alcohol syndrome.
  6. The student will be able to describe difference between alcohol abuse, dependence, intoxication, withdrawal, idiosyncratic alcohol intoxication, and alcohol hallucinosis.
  7. The student will be able to describe the treatment of alcohol withdrawal, opiate withdrawal and sedative-hypnotic withdrawal.
  8. The student will be able to describe the treatment of alcohol dependency.


Alcohol is the most common psychoactive drug used throughout the world. It is estimated that as many as 13% of the US population has had alcohol abuse(5%) or dependence(8%) at some point in their lives. 6% of US adults have had alcohol dependence or abuse in the preceding 12 months. The chart below identifies some of the epidemiologic characteristics in alcohol related disorders. Genetic factors have been shown to be related to alcoholism in twin studies and family studies. (see the handout on behavioral genetics on pages 6 and 7 for statistics).

There appears to be at least two types of alcoholics; familial vs nonfamilial. Familial alcoholism differs from the nonfamilial form in the following ways; Family history of alcoholism, alcoholism begins at an earlier age-usually in the 20's or before, more sever alcoholism, the familial load is for alcoholism and not other psychiatric disorders. Recent studies have shown that males who are at risk for familial alcoholism have different reactions to alcohol on a variety of physiologic variables. These include EEG responses, tilt, neuroendocrine responses. The end result is the finding that the at risk individuals had less of an effect from the alcohol. This is true even in alcohol naive subjects. It is postulated that these persons must drink more in the social setting to achieve the same effect as peers and thus expose themselves to a greater amount of alcohol. This greater exposure results in a greater development of tolerance and subsequent addiction.

Alcohol related disorders some interesting facts

        Lower in some Asian cultures

        Higher in low eductional levels, unemployed, and lower socioeconomic status

        African-americans and whites have nearly identical rates

        Latino males have higher rates than African-american and white males

        Latino females have lower rates than african-american and white females

        Overal male:female ratio is 5:1

        Females have an increasing rate of problems

        Females tend to begin at later ages

        Females may be at greater risk for alcohol related health consequences due to a lower percentage body wieght and a slower metabolism.

        Annual consumption in the US is 3 gallons of pure alcohol for every person over 14yr/old

        10% of the population consumes 50% of the total alcohol consumed in the US

        Alcoholism reduces life expectancy by 10 years on average

Social consequences of alcohol abuse

        Approximately 50% of highway fatalities involve either a driver or pedistrian who has been drinking

        Approximately 50% of murderers and their victims are believed to be intoxicated at the time of the murder

        Approximately 25% of suicide victims are intoxicated at the time of the event

        Approximately 50% of police activities in large cities are due to alcohol-related offenses

        Alcoholism is more prominent in the homeless

Acute intoxication with alcohol is very similar to intoxication with anxiolytic and sedative/hypnotic agents. Alcohol is distributed in total body water and is metabolized by the liver by a saturable enzymatic process involving two enzymes, alcohol dehydrogenase and aldehyde dehydrogenase.

If the aldehyde dehydrogenase is blocked the acetaldehyde accumulates and a toxic reaction occurs. Pharmacologically this can be caused by disulfiram (Antabuse). The toxic effect is quite noxious and the disulfiram can be used as a part of a negative reinforcement program to help insure abstinence. The antabuse reaction can be provoked by nonrecreational alcohol containing substances such as mouthwash. Thus care must be exercised in its use. Other drugs can also block aldehyde dehydrogenase such as metronidazole (Flagyl). In most Asian cultures the overall incidence of alcohol related disorders is considerably lower than other cultures. Of significance is the absence of aldehyde dehydrogenase in as many as 50% of Japanese, Chinese, and Korean individuals. Alcohol use by affected individuals results in an antabuse like reaction. This makes the ingestion of large quantities unlikely.

The rate of absorption also alters the effects of alcohol. Rapid absorption results in a faster 'high'. Therefore alcohol consumed on an empty stomach acts faster. Other things such as the surgical removal of the pylorus increase the absorption of the alcohol. Most alcohol is absorbed in the small intestine and not the stomach. The blood alcohol level is also the tissue level because of the uniform distribution of alcohol through the system. Measurement of alcohol blood levels can be done by measuring the concentration of alcohol in the moisture of the breath.

Because the metabolism is saturable, alcohol has zero order elimination kinetics. This means that the rate of metabolism is not dependent on the plasma concentration. This is handy because it allows you to calculate the approximate amount of alcohol consumed from knowledge of two blood alcohol levels and the time of the first and last drink. The amount of alcohol in the system can be estimated from a single level. In terms of alcohol content the chart below illustrates the amount of alcohol in beer , wine, and 80 proof spirits. A sample of estimating body content of alcohol is shown.

Beer- 3.6% alcohol-approximately 1 gram of etoh per ounce

Wine-12% alcohol-approximately 2.8 grams of alcohol per ounce

80 proof spirits-40% alcohol- approximately 9 grams per ounce

A 154 pound man presents with a BAL of 240 mg% or .240 BAL. His last drink was half an hour ago. What is the approximate body content of alcohol?

240 mg% is equal to 240 mg of alcohol per 100 cc. This is equal to 2.4 grams per liter.

Total body water is approximately 70% of body weight. The man is 70 kilograms. 70 x .7=49 kilos of water or 49 liters.

Approximate body content of alcohol= 49 liter x 2.4 grams/liter = about 118 grams.

The patient states he only had 4 beers. Is this a credible statement?

1 beer is 12 onunces; 4 beers=48 ounces

at 1 gram per ounce his maximum body content would be 48 grams.

So no. He had at least 9-10 beers.

The symptoms of alcohol intoxication progress in an orderly sequence as the plasma level increases. In the person with a long history of excessive alcohol consumption tolerance to the intoxicating effects may occur. Thus even though two people have the same BAL the effect will depend on several factors including rate of absorption and previous history of use of alcohol. Tolerance develops to alcohol following repeated exposure. The legal limit for intoxication in most states is between .08 and .100 or 80 mg% and 100mg%. The nontolerant individual will exhibit signs of intoxication at these blood levels. As the levels go up the degree of intoxication increases. Alcohol poisoning can occur with the onset of respiratory arrest and coma. The chart below shows the relationship between BAL and behavior for the typical nontolerant adult.

BAL Behavior

        50 to 75 mg% pleasant tranquillity and mild sedation

        100 to 200 mg% signs of intoxication including; sense of well being, elation, poor judgment, reduced psychomotor coordination, and judgment, reduced inhibition

        200 to 300 mg% severe intoxication and blackouts, passing out

        300 to 500 mg% alcohol poisoning, reduced respiratory drive, acidosis, sometimes fatal

        500 and above mg% usually fatal

Criteria for alcohol intoxication (DSM IV)with alcohol, sedative/hypnotic, and anxiolytic agents

A. Recent ingestion of alcohol

B. Clinically significant maladaptive behavioral or psychological changes (e.g., inappropriate sexual or aggressive behavior, mood lability, impaired judgment, impaired social or occupational functioning) that develop during, or shortly after, alcohol ingestion.

C. One or more of the following signs, developing during, or shortly after, alcohol use:

        1) slurred speech

        2) incoordination

        3) unsteady gait

        4) nystagmus

        5) impairment in attention or memory

        6) stupor or coma

D. Symptoms are not due to a general medical condition and are not better accounted for by another mental disorder

The substance specific syndromes associated with intoxication of alcohol is similar to intoxications with sedative/hypnotic agents and anxiolytic agents. The best examples of agents in these categories of drugs are the benzodiazepines and barbiturates. In fact these agents may share a common site of effect at the GABA/Chloride ionophore complex. At this complex barbiturates bind to the inside of the pore to open the chloride channel. Benzodiazepines bind at an external receptor which increases the ability of GABA to act to increase the influx of chloride through the pore. Alcohol has several effects of interest is the recent finding that a benzodiazepine antagonist reduces some of the physiologic signs of alcohol intoxication. It has been suggested that this identifies a GABA site for some of the effects of alcohol. More research is needed. The end result of all of the similarities is that there is cross tolerance between the sedative/hypnotics, alcohol, and anxiolytic agents.

A few persons experience a pathologic intoxication on a very small amount of alcohol. Such persons develop a rapid personality change and amnesia for the events which occurred. EEG studies often disclose an abnormal temporal spike. There is also a higher incidence of seizures in this population. The behavior change can be replicated in the laboratory in individuals with pathologic intoxication. It should be emphasized that it is a syndrome caused by a small amount of alcohol and accompanied by amnesia. The simple finding that a person did things they regret while under the influence or that they had a blackout does not qualify them as having pathologic intoxication. DSM IIIR described this phenomena as idiosyncratic intoxication. DSM IV has dropped this characteristic. Pathologic intoxication is recognized as an insanity defense in some jurisdictions, but it must always be distinguished from the typical intoxication.

An individual who shows few signs of intoxication at a BAL of 100mg% is likely to have significant tolerance to alcohol. In such individuals sudden decrease in BAL may result in signs of withdrawal. Physiologic signs of withdrawal appear within 12 hours after a reduction of intake. The unpleasant symptoms act as negative reinforcement for further drinking. Operationally most people develop a pattern of compulsive use without experiencing a significant bout of withdrawal. For this reason they may not recognize the dependence they have on alcohol. The stereotype of a gutter drunk is uncommon and only about 5% of alcoholic patients will ever go through a severe withdrawal. The diagram below illustrates the hypothetical functioning of a person as they progress through alcohol dependence;

As you can see from the chart the patient 'hits rock bottom' relatively late in the course of the illness. By this time they may have lost their family and jobs. The symptoms of impairment were present before they ended up in the 'gutter'. Often early in the course a good history could have disclosed the problem drinking at an earlier stage when the person has more resources to deal with it. The earliest signs of a problem with alcohol is when a person functions more normally with it than without it. For instance, alcohol is a pretty good anxiolytic. That is after all why most people begin to drink. To loosen up. To close the deal. The relief of the anxiety allows the person to function more normally. As time goes by the pattern of using alcohol to unwind or improve performance begins. At this point there may be very little to suggest that the person has a problem from a social point of view. Attempts to intervene by outsiders may be refused by the patient. I remember a particular physician who was accused of alcohol abuse by a friend at this time. The accusation was well meaning and not malicious. However, the alcohol abusing physician denied the problem by saying 'he's just jealous of my practice'. After a few years the doctor had lost his license to practice when a patient complained to the board about the doctor being drunk at the hospital. With a further passage of time more and more alcohol is needed just to prevent withdrawal. At this point performance is always subpar. This late phase is usually when interventions are made. Provided the person has not lost everything to alcohol related problems they may be treatable.

Identifying the alcohol abusing patient in the hospital

The medical complications of alcohol abuse are present on every hospital ward. The physical stigmata of alcoholism may be the first clue to the physician for an underlying alcohol abuse problem. At the prestigious Johns Hopkins Hospital between 13 and 30% of patients admitted throughout the hospital screened positive for alcoholism. Of note only 25 to 50% of those who screened positive were detected by the treatment team. Of those who are identified in the hospital between 50 and 75% will be successfully referred to an alcohol treatment program. There are four common identifiers which may help identify a patient as having a significant tolerance to alcohol; Medical stigmata, presence of alcohol withdrawal, lack of intoxication with BAL greater than 100mg%, and yes to questions on CAGE questioniare.

Medical consequences of alcohol abuse

Physical examination findings

Hypertension, jaundice, increased liver span, abdominal tenderness, easy bruisability, atrial or ventricular arrhythmias, testicular atrophy, amenorrhea in women, painful and swollen muscles, spider angioma, rhinophyma, caput medusa, ascites, dementia, lability, tremor, ataxia, peripheral neuropathy, pancreatitis.

Laboratory findings


        megaloblastic indices, thrombocytopenia, mild anemia, decreased folate, reticulocytopenia, decreased white blood cells, hyperplastic bone marrow


        Increased SGOT and SGPT, gamma-glutamyl transferase, triglycerides, increased bilirubin, increased amylase


        hyponatremia, hypokalemia, reduced B-12, chronic ulcer disease, reduced phosphates, increased uric acid, reduced magnesium, alcoholic ketoacidosis

It should be common practice to inquire about drinking habits in a patient in a nonconfrontational manner. A structured approach will allow you to identify problems quickly and make appropriate referrals. The simplest approach is known as the CAGE questions. These are four questions. A yes answer to any of them is grounds for concern. These questions are;

  1. 'Have you ever attempted or considered cutting down on your drinking?',
  2. Are you annoyed by others criticism of your drinking habits?',
  3. 'Have you ever felt guilty about your alcohol use, or things you have done while drinking?',
  4. Do you ever need an eye-opener in the morning?'.

A positive answer to any other these questions should prompt a more in-depth inquiry about quantity and frequency. It is important to inquire about specific beverages used. Some people think that as long as they don't drink 'hard liquor' everyday they don't have a problem. Once a problem is identified consideration should be given to detoxification regimens.

The alcohol withdrawal syndrome

Often the problem may not be identified until a significant withdrawal syndrome has begun. Typically alcohol withdrawal begins within hours of cessation or reduction in ethanol intake in alcohol tolerant people. The typical signs are shown in the table below:

Signs of alcohol, sedative/hypnotic, and anxiolytic withdrawal

        1) nausea or vomiting

        2) malaise or weakness

        3) autonomic arousal or hyperactivity (tachycardia, hypertension, sweating, and hyperpyrexia

        4) anxiety

        5) depressed mood or irritability

        6) transient hallucinations or illusions

        7) headaches

        8) insomnia with vivid nightmares

        9) coarse tremor of hands, tongue, or eyelids

Factors which aggravate or predispose to more serious withdrawal include fatigue, malnutrition, physical illness, depression, and neurologic disorders. Grand mal or major motor seizures are common occurrences during alcohol withdrawal. In more severe cases the withdrawal may be accompanied by delirium. The classic syndrome of alcoholic delirium tremens is such a case. Typically there is a marked autonomic arousal and clouded sensorium with disorientation, perceptual distortions which are most frequently tactile and visual hallucinations, and fluctuation of psychomotor activity. The classic description is a disoriented man with elevated blood pressure, temperature, and tremors with hallucination of bugs crawling under the skin with moderate agitation.

Alcoholic hallucinosis is different from DT's. Alcoholic hallucinosis is the situation which occurs after long term drinking. It presents as systematized hallucinations which are more often auditory in the presence of a clear sensorium. Alcoholic hallucinosis is not necessarily a withdrawal syndrome and may present even while the person continues to drink. It is usually necessary to continue antipsychotics even after detox in these patients.

Untreated DT's has a mortality rate of 20%. Usually this is the result of intercurrent medical illness such as pneumonia, renal disease, hepatic insufficiency, and heart failure. DT's commonly begins about 3 days after cessation or reduction. Binge drinkers may actually be more disposed to developing DT's than the steady drinker. It is reasonable to conclude that the majority of DT's are preventable. The best way to do this is by substituting a cross tolerant drug with a more gradual washout. Historically this has meant to prescribe diazepam or chlordiazepoxide over the first 4 or 5 days in a tapering dose. This moderates the autonomic arousal and prevents the seizures.

Alcohol withdrawal can be divided into three basic symptoms groups. In the first group the primary symptoms are related to Autonomic instability. These symptoms begin 6-24 hours after the last drink and last 24-48 hours. The second set of symptoms is characterized by the appearance of symptoms associated with neuronal excitability. Epileptiform activity can occur within 12-48 hours of abstinence. The third set of symptoms are those associated with delirium tremens.

Pathophysiologically, GABA is downregulated during chronic intoxication. With abstinence many of the symptoms of withdrawal appear and are believed to be related to the lack of GABA activity present. Also with prolonged alcohol use there is an inhibition of the NMDA receptor system. Abstinence reverses the inhibition of the NMDA receptor and results in a lower seizure threshold. Finally the catecholamines of dopamine and norepinephrine are stimulated during alcohol withdrawal. This stimulation of catecholamines results in the increased sympathetic hyperactivity and hallucinations during the alcohol withdrawal.

Alcoholics are predisposed to thiamine deficiency. Thiamine is needed in the metabolism of carbohydrates. Without adequate thiamine the sudden introduction of carbohydrates results in the 'burnout' of the mamillary bodies, and central grey areas of the brainstem. The result is a syndrome called Korsakoff syndrome. It should be emphasized that the original description of the Korsakoff syndrome was not in alcoholics but in persons with nutritional deficiencies. The Korsakoff syndrome is related to thiamine deficiency and not the alcohol necessarily. Because of the loss of the mamillary bodies there is an interruption in the loop of Papez. Memory is no longer able to be encoded. The result is a profound short term amnesia. The patient may confabulate to avoid recognizing the memory deficit. Confabulation is characteristic of short term memory disturbances. Wernicke's syndrome is the ataxia, ophthalmoplegia (CN VI-lateral rectus palsy), nystagmus, and confusion. These are potentially irreversible syndromes. They can be reliably prevented by administration of 100 mg of thiamine each day for at least 1 week in a patient undergoing detoxification.

The autonomic arousal results in a greater water loss through insensible losses. The dehydration may or may not be disclosed by electrolytes alone. Alcohol causes a free water diuresis by inhibiting ADH effects at the kidney. In addition the alcoholic may have severe emesis and subsequent loss of fluid and electrolytes on that basis. Fluid status is critical for patients with other medical conditions. For instance the alcoholic who presents following an MVA and then after surgery begins to go into withdrawal. Attention to fluid status is important even in ambulatory patients. In general if there are no contraindications oral fluids are pushed with juices and solute containing fluids, not free water. Remember before beginning dextrose or carbohydrates administer thiamine.

Typical detoxification orders for uncomplicated withdrawal

        1)Vital signs q 4 hours while awake for three days then per routine

        2)Chlordiazepoxide 25 mg po QID x 24 hours and then

        Chlordiazepoxide 25 mg po TID x 24 hours and then

        Chlordiazepoxide 25 mg po BID x 24 hours and then

        Chlordiazepoxide 25 mg po q HS x one then D/C

(the dose is variable and may be doubled for patients who have histories of difficult withdrawal syndromes or in people already in alcohol withdrawal)

        3) Chlordiazepoxide 25 mg po or 50mg IM q 2 to 4 hours PRN signs of withdrawal including;

        BP diastolic >100,

        temp >100,


        insomnia, agitation, lability

        4) hold Chlordiazepoxide if patient is sedated!

        5) thiamine 100 mg po or IM now and q day

        6) multivitamin 1 q day

        7) After #5 push fluids with juice

        8) phenergan 25 mg suppository PR q 4 hours prn emesis

        9) maalox 30 cc q 2 hours prn indigestion

        10) electrolytes, glucose, BUN, creatinine, liver enzymes, CBC, PT/PTT, amylase, EKG, CXR-P/A and lateral, RPR, TB skin test if applicable

Chlordiazepoxide is chosen in most cases but any moderate or long acting benzodiazepine can be used. The long acting benzodiazepine allows a gradual taper. The short acting benzodiazepines washout quickly and the withdrawal syndrome reemerges and necessitates more frequent dosing. One problem with the chlordiazepoxide is that it is poorly absorbed from IM injection thus in general the dose is doubled or you may substitute lorazepam which is another benzodiazepine which is well absorbed from IM. In general though make sure the fluid status is reasonable when administering drugs IM. If the patient is hypovolemic the IM shot may act as a depot and result in a more erratic absorption. Although barbiturates could be used instead of benzodiazepines I do not recommend it. If significant DTs or hallucinosis is present haloperidol or thorazine is added in a rapid titration schedule to treat the psychotic symptoms and control behavior. Patients in DT's should not be restrained physically.

Another situation in which you may want to use lorazepam is in the setting of significant liver damage. Lorazepam is conjugated and easier to excrete than chlordiazepoxide.

Other potential treatments include adrenolytic agents such as beta blockers and clonidine. Although these agents may treat the autonomic arousal they probably do not reduce the risk of delirium or seizures. Hydroxyzine is used by some of the residents but the only controlled trial showed that they are less effective than benzodiazepines and more likely to be associated with DT's and seizures. In a situation where benzodiazepines cannot be given then the addition of an anticonvulsant such as phenytoin or carbamazepine in combination with a sedating neuroleptic has been advocated. However, such situations are rare and are usually related to patients with precarious respiratory drive. The routine administration of magnesium sulfate is unnecessary unless there is a documented magnesium deficiency.

Treatment of alcohol addiction

The treatment of alcohol addiction requires the appreciation of the common comorbid conditions which might predispose the patient to a relapse. The comorbidity of psychiatric conditions with alcohol abuse is complicated by the fact that alcohol can produce a range of psychiatric symptomatology. The three most common psychiatric conditions which are associated with alcoholism are; mood disorders, anxiety disorders, and antisocial personality disorder. The treatment of the alcoholism begins after withdrawal symptoms are gone. At this point the patient is evaluated for anxiety or mood disorders which are not related to the periods of alcohol abuse. It may be necessary to evaluate the patient after a prolonged period of abstinence. Comorbid conditions should be addressed.

The denial of most alcoholic patients is the first barrier to overcome. This is done in some settings by either peer or family confrontation which address the adverse effects of the alcohol in the person's life. Of interest is a report that patients referred from the general hospital by non-psychiatric physicians accept treatment more easily than those referred from outside the hospital. If so this increases the importance of the hospital history and physical for early intervention. A successful treatment model for many persons is the AA model which is a 12 step program which emphasizes the importance of self inspection, social networks, and daily confrontation of the alcoholism. It is doubtful that insight oriented therapy is indicated in many alcoholics. Such therapy is anxiety generating and would predispose the person to drinking during treatment. Adverse conditioning is advocated by some but is not well documented.

Pharmacologic treatments include treatment of comorbid psychiatric disorders. In addition, disulfiram is used as a part of an adverse conditioning program. It is important to recognize that disulfiram is not risk free. Warnings include patients with histories of psychosis (disulfiram inhibits dopamine beta hydroxylase in the CNS), and coronary artery disease (the disulfiram reaction is essentially an autonomic storm and may precipitate an MI), and hepatitis (disulfiram can cause a nasty hepatitis). In addition, lithium and SSRI's have shown some ability to reduce drinking in depressed alcoholics. However, the studies are flawed by small numbers and a high dropout rate. Finally a recent study has suggested that the opiate antagonist naltrexone reduced alcohol intake in alcoholics who were maintained on it as outpatients. This study was based on the observation that alcohol caused the production of an endogenous opiate-like compound called Tetrahydroisoquinolones (TIQs). When TIQs are given to rats they ingest alcohol in greater amounts. It may also have implication for pharmacologic treatment of other compulsive behaviors.

By it's nature alcoholism is a recurrent condition which complicates most medical treatments. Failure to recognize and address the alcohol abuse results in poor treatment response.