Alcohol-Related Disorders.

Alcohol use disorders are common, lethal conditions that often masquerade
as other psychiatric syndromes. The average alcohol-dependent person
decreases his or her life span by 10 to 15 years, and alcohol contributes to
22.000 deaths and two million nonfatal injuries each year.
The alcohol-related disorders impact on all aspects of health care delivery
systems, especially psychiatric practice. At least 20 percent of the patients
in mental health settings have alcohol abuse or dependence, including
individuals from all socioeconomic strata and both genders.
The problems can begin early – a resent national evaluation of students on
college campuses reported a 12-month prevalence for alcohol dependence
of 6 percent and for abuse more than 20 percent – and alcohol has been
estimated to have contributed to at least 15, on deaths in students per year.
Of particular importance to the psychiatrist are the estimated 40 to 50
percent of alcoholics who develop alcohol – induced, but temporary,
clinical syndromes that resemble major depressive disorders, panic
disorders, generalized anxiety disorders, and additional mood or anxiety
conditions. In addition, men and women with several independent
psychiatric disorders have elevated risks fore the future development of
alcohol – related disorders, including those with manic – depressive
disease, schizophrenia, antisocial personality disorders, panic disorders,
and, possibly, generalized anxiety disorders. Because the optimal short-
and long-term treatments of substance-induced and independent
psychiatric conditions are often different the clinician must learn to
recognize and differentiate between these conditions.
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Definition and comparative nosology.

1. Alcohol Use Disorders.

In all diagnostic systems, the definition of alcoholism (i.e., alcohol abuse
and dependence) related to evidence of repeated impairments of alcohol in
multiple areas of life functioning, despite which the person returns to
drinking. The basic elements of this definition are present in the American
Psychiatric Associations ( APA ) third edition ( 1980 ) and revised third
edition ( 1987 ) of the Diagnostic and Statistical manual of Mental
Disorders ( DSM-111, DSM-111-R, respectively ) and have continued into
the revised fourth edition of the DSM ( DSM-1v-TR ) in 1994.
In this most recent manual, dependence is diagnosed at the repeated
presence of at least three or seven major areas of life impairment related to
alcohol that cluster together in the same 12-month period.
These difficulties include tolerance, evidence of a withdrawal syndrome
when the drug is discontinued or intake is decreased, potential interference
with life functioning associated with spending a great deal of time using
the substance, and returning to use despite evidence of physical or
psychological problems. It is the syndrome of dependence for which the
best data are available regarding the usual clinical course of problems,
appropriateness of treatment, and potential importance of genetic factors.
Although DSM-1v-TR does not require tolerance or withdrawal for
dependence, resent studies has shown that a history of these phenomene,
especially withdrawal, is associated with a more severe clinical course.
All patients with a possible alcohol use disorders should first be evaluated
for the presence of alcohol dependence. For those who do not meet for
criteria fore this disorder, however, there is a second potential syndrome to
consider, abuse. Here, an individual who is not dependent on alcohol
demonstrates repeated problems within any 12-month period in any one
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are more at four potential areas of difficulties. These include repeated legal,
interpersonal, social, or occupational impairments related to alcohol as well
as use of alcohol in physically hazardous situations.
DSM-1v-TR reformulated the concept of abuse to identify criteria that were
not just a subset of those noted for dependence. Although abuse and
dependence both correlated with similar background characteristics,
including the family history of alcoholism, dependence has been reported
to be tied to future problems for as many as 80 percent. Approximately 50
percent of those with difficulties with alcohol abuse continue to have
alcohol problems, but fewer than 10 percent go on to dependence. A similar
definition of dependence is offered in the tenth revision of the International
Statistical Classification of diseases and Related Health Problems (ICD-10).
Here, however, the threshold for diagnosis is any three of six (rather than
seven) items. The criteria for ICD-10 dependence include all the concepts in
DSM-1v_TR, although they are expressed and numbered differently, and
some concepts are combined in a single criterion. ICD-10 also lists a second
and less intense alcohol use disorder known as harmful use. The definition
of this second syndrome is quite different from DSM-1v-TR abuse because
the ICD-10 approach is based on evidence of repeated interference with
psychological and physical health functioning and does not include social
impairment, legal problems, or use in physical hazardous situations. Some
authors have called for the recognition of a more sever early-onset alcohol
dependence syndrome, often accompanied by criminality and dependence
on other drugs, which has been labeled as type 11 or type B alcoholism.
These approaches are consistent with the recognition that an earlier-onset
alcohol dependence syndrome, like most medical and psychiatric disorders
is likely to have more severe course, but it appears as if some of the
prognostic significance of type 11 or B alcoholism rests with an elevated risk
for a concomitant antisocial personality disorders in the early-onset group.
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2. Severity and Remission

The DSM-1v definition of dependence also attempts to better clarify the
concepts of severity and remission. Regarding the former, no reliable
criteria could be developed, and the manual offers the clinician the
possibility of incorporating the relatively imprecise divisions of mild (with
few symptoms), moderate (with functional impairment intermediate
between mild and sever), and sever (with many symptoms); ICD-10 has no
formal notation of severity.
Remission is a more complex phenomenon, and the diagnostic criteria
distinguish between the high-risk period in the first 12 months of recovery
and at later time points, asking the clinician to specify whether the patient
is totally free of substance-related problems. The criteria also consider
whether individual is living in a controlled environment such as prison or a
hospital; ICD-10 makes similar but not identical distinction.

Epidemiology

Psychiatrists need to be concerned about alcoholism because this condition

is common, intoxication and withdrawal mimic many major psychiatric
problems, and the usual alcoholic person does not fit the common
stereotype.
- Prevalence of Drinking
At sometime during life, 90 percent of the population in the U.S. drinks,
Table – 1
with most people beginning their alcohol intake in the early to middle
Condition Population (%)
teens.
1. Ever had a drink 90
2. Current drinker 60 – 70
3. Temporary problems 40
4. Abuse Male: 10 Female: 5
5. Dependence Male: 10 Female: 3-5
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See Table-1.
Different groups in the U.S. have different rates of drinkers.
Generally, groups with high education and high socioeconomic status have
the highest proportion of people who currently imbibe. Among religious
groups, Jews have the highest proportions who consume alcohol but the
lowest number of people with alcohol dependence. Conservative
Protestants and Catholics are less likely to use alcohol than liberal
Protestants and Catholics.
Other groups, such as the Irish, have higher rates of severe alcohol
problems, but they also have significantly higher rates of abstention. Very
high rates of alcohol problems are found among most, but not all, American
Indian and Inuit Tribes.
In the U.S. in the mid-1990, the average person older than 14 years of age
consumed 2, 2 gallons of absolute alcohol a year.

Alcohol problems

Because a high proportion of people are drinkers, especially in their middle

teens to mid-20, and because the per capita consumption of alcohol is
high, it is not surprising that a large proportion of people have alcohol-
related problems sometime in their lives. A recent 10-years follow-up study
of almost 500 men evaluated at 33 years of age found that, during the
presided decade, between one-fourth and one-third had alcohol-related
blackouts, approximately one-third admitted to driving after consuming
enough alcohol to be impaired, and 20 percent reported missing school or
work because of either a hangover or a desire to party with alcohol rather
than work. As common and costly as the problems are, most people mature
out of less severe alcohol problems with the passage of time. Thus, the
average person is likely to experience fewer alcohol-related difficulties
during their 30s than during their 20s, and even fewer difficulties in their
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40s and 50s.

Pharmacology and effects on the body

1. Properties and metabolism of alcohol

2. Alcohol as the depressant drug
3. Neurochemical effects of ethanol
4. Tolerance
5. Craving
6. Blackout
7. Sleep impairment
8. Cerebellar degeneration
9. Other effects on the Central nervous system
10. Effects on the rest of the body
11. Peripheral neuropathy
12. Gastrointestinal problems
13. Cerebrovascular and cardiovascular problems
14. Cancer
15. Fetal alcohol effect
And other problems

1. Properties and metabolism of alcohol

Ethanol (beverage alcohol) is a simple molecule that is well absorbed

through the mucosal lining of the digestive tract in the mouth, esophagus,
and stomach. The most prominent area of uptake, however, is in the
proximal small intestine, which is also the site of absorption of many of the
B vitamins.
Ethanol rapidly enters the bloodstream and, as result of its high solubility
in water, is distributed to almost every body system. As a consequence of its
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modest fat solubility, alcohol is likely to have effects on body members

which in fat, including neurons.
Wine beer, and such distilled spirits as whisky, gin and vodka differ in their
content of components other than alcohol. These congeners are responsible
for much of the characteristic taste of the beverage and consist of
combination of methanol, butanol, aldegides, phenols, tannins, lead, cobalt,
iron, and other substances. Under curtain circumstances, congeners can
have physiological effects, but their potency pales in comparison with the
effects of alcohol.
A standard drink of an alcoholic beverage is usually defined as containing
10 to 12g of ethanol.
The rate of absorption of alcohol from the digestive tract is likely to be
faster on en empty stomach than after a full meal, especially one reach of
fats and carbohydrates.
After absorption into the bloodstream from the small intestine, between 2
and 10 percent of the alcohol is then excreted unchanged from the lungs or
the kidneys or through sweat, but the majority is broken down in the liver.
Metabolism in that organ occurs mostly, through four pathways, with each
resulting in the production of acetaldehyde. Most of the process occurs
through the action of alcohol degidrogenase (ADH) in the cytosol of hepatic
cells. Especially at high blood alcohol levels, some of the alcohol is also
broken down in the microsomes of the smooth endoplasm reticulum. The
ADH process is the usual rate-limiting metabolic step, occurring relatively
slowly because of the livers need to handle the produced hydrogen ions
through use the cofactor that is in relatively short supply, nicotinamide
adenine dinucleotide (NAD).
As described later in the section on genetics of alcohol use disorders, the
aldehyde degidrogenase and ADH izoensime patterns of an individual are
related to the risk for developing alcoholism. This is especially relevant to
Asian (Japanese, Chinese, Korean) men and women, although the impact of
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genes that control ADH also extends to some other groups.

2. Alcohol as a Depressant Drug

All substances of abuse share he ability to produce changes in felling states

and subsequently increase the likely hood that a person will have a
psychological drive to continue to take the substance despite potentially
severe adverse consequences (psychological dependence). That effect is
distinct from the physical dependence that produces the withdrawal, or
abstinence syndrome, that characterizes drugs such as alcohol.
A useful shortcut is to place drugs of abuse into categories based on their
most prominent effects at the usual doses as which they are taken. In this
scheme, substances that have their most prominent usual effects the
production of somnolence and decreased neuronal activity but that are not
powerful in attenuating pain are labeled as depressants or sedative-
hypnotics. They include alcohol, all the benzodiazepines, and the
barbiturates.
These substances produce similar intoxications, are potential lethal in
overdose, produce cross-tolerance with other depressants, and are
physically addicting, with similar withdrawal syndromes.
They behavioral and physiological changes observed with any substance
differ with the dose, the patient’s history of exposure to the drug, and
clinical conditions, including physiological disorders and the patient’s state
of fatigue, with a drug like alcohol, the effects also change over time often
intake, with more pronounced symptoms observed while the blood alcohol
levels are rising than that then the blood alcohol levels are falling, a
phenomenon called acute tolerance of the Mallenby effect.
3. Neurochemical effects of ethanol

Alcohol has major effects on on most neurochemical systems, depending on

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the dose, with opposite actions during the intoxication and withdrawal.
Alcohol acutely increases dopamine and its metabolites, brain imaging
reveals enhanced activity in relevant areas of the brain, and chronic
drinking changes dopamine receptor numbers and sensitivity. Another key
neurochemical is serotonin, with alcohol causing changes in key aspects of
this transmitter and associated receptors, and levels of serotonin impact on
the amount of alcohol consumed.
Alcohol also acutely enhanced the functioning of the opioid-related brain
systems and impacts on adenosine, neurosteroids, and acetylcholine.

4. Tolerance

With repeated administration of alcohol, large and large doses of the drug
are required to produce the desired effect. This phenomenon, called
tolerance, is also the ability to tolerate higher and higher doses of the
substance and in the result of at least three processes.
- Behavioral tolerance reflects the ability of a person to learn how to
perform tasks effectively despite the effects of alcohol.
- Pharmacokinetic tolerance is an adaptation of the metabolizing
systems, including ADH and microsomal ethanol oxidizing system
(MEOS), to rid the body of alcohol rapidly.
- Pharmacodinamic or cellular tolerance is an adaptation of the
nervous systems so that it can function, despite very high blood
alcohol concentrations (e.g., as much as 600 mg/dl), by resisting the
actions of alcohol on the cell.
Once tolerance has developed for one of the brain depressants, an
individual is likely to demonstrate a similar reaction to a second drug of
that class (cross-tolerance). Therefore, a person who has been drinking
heavily has tolerance for alcohol, and then stops drinking can be expected
to require a higher dose of benzodiazepines for sleep induction. If the
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individual took two depressant drags at the same time, tolerance is not
likely to be observed, and the mixing of two substances can have lethal
effects.
Aspects of tolerance decrease and even disappear with consecutive weeks of
abstinence. In addition, some clinicians and researchers have described a
phenomenon of reveals tolerance, increased sensitivity, or sensitization.
This is a complex situation that might relate to neurochemical adaptation
or other mechanisms.

5. Craving

The state of motivation to seek out an alcohol is an important component of

drinking behavior.
This phenomenon of craving, however, fluctuates with time and can be
different to measure.
Aspects of the drive to drink are believed to relate to classical conditioning
and to also reflect neurochemical changes. On neuroimaging, presenting
substance-dependent subjects with images of their drag or autobiographical
stories about their substance use results in activation in the limbic system
and orbitofrontal, insular cortex, and cerebellum.

6. Blackout

Blackout indicates a memory impairment (anterograde amnesia) for the

period when the person was drinking heavily but remained awake.
This common phenomenon is related to the ability of any brain depressant
at high enough doses to interfere with the acquisition of memory.
The blackout, which is temporary and limited to memory problems
involving a short period, is not part of the DSM-1v-TR diagnosis and is
distinct from alcohol-induced persisting amnestic disorders, formerly
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known as Wernicke-Korsakoff syndrome.

7. Sleep impairment

Alcohol intoxication can help a person fall asleep more quickly, but intake
in an evening is more than one or two drinks, the sleep pattern can be
significantly impaired. Most heavy drinkers awake after several hours and
can have problems falling back asleep.
Alcohol also tends to depress rapid eye movements and inhibit stage 4 sleep
and, thus, is likely to be associated with frequent alternations between sleep
stages (sleep fragmentation) and with more dreams late in the night as the
blood alcohol level falls.

8. Cerebellar Degeneration

Characterized by unsteadiness of gait, problems with standing, and mild

nistagmus, cerebellar degeneration is probably caused by a combination of
the effects of ethanol and acetaldehyde along with vitamin deficiencies.
Treatment is usually consists of total abstinence and vitamin
supplementation, although complete recovery is not usual.

9. effects on the Rest of the Body

Under certain circumstances, one to two drinks per day can have some
beneficial effects.
Low doses of ethanol appear to decrease the risk for myocardial infarction
and thrombotic stake, probably through decreasing platelet aggregation
and enhancing the beneficial impact of high-density lipoprotein cholesterol.
Low doses of alcohol have also been reported to decrease the risk of some
old age dementias, peripheral arterial disease, and gallstones.
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However, any amount of alcohol is considered harmful to the developing

fetus, recovering alcoholics, people taking medications that may adversely
interact with alcohol, and individuals with certain medical disorders or
psychiatric symptoms ( such as major depressive disorder or
schizophrenia) that might be intensified by alcohol.

10. Effects for the Central Nervous System and Peripheral

Neuropathy

Several rare but serious neurological and cognitive syndromes ca also be

observed in alcohol-dependent men and women. A thiamine deficiency,
especially in the context of a preexisting vulnerability, such as transketolase
deficiency, can present as any of several neurological syndromes, including
a sixth cranial nerve palsy (Wernicke’s) and a severe anterograde amnesia
that is out of proportion to the alcohol level of confusion (Korsakoff’s).
Approximately 10 percent of alcoholic people develop a deterioration of
nerve functioning to the hands and feet, often bilateral, frequently
accompanied by tingling and paresthesias. Although the condition is
usually relatively mild and often improves with abstinence, the pain and the
numbness can result in a permanent impairment.

11. Gastrointestinal, cerebrovascular and cardiovascular and other

problems.

The gastrointestinal system can be severely affected by heavy drinking, with

a relatively common problem of an acute and at times severe inflammation
of the esophagus or the stomach, often accompanied by vomiting and
bleeding. If gastritis occurs in the presence of dilated esophageal veins, as
seen with cirrhosis, it can induce potentially lethal bleeding.
The liver and the pancreas are especially vulnerable to alcohol. In the liver,
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increasing alcohol doses result in the accumulation of fats in proteins cells,

producing a reversible swelling often descriled as a fatty liver.
Perhaps 10 percent of alcoholic people develop an inflammation of the
pancreas that can present as the abdominal emergency of acute
pancreatitis, which can lead to a chronic irreversible condition with
associated sings of insufficiency of both sugar metabolism (a form of
diabetes) and digestive enzymes.
Heavy intake of alcohol increases the blood pressure and elevates both LDL
cholesterol and triglycerides, thus enhancing the risk for myocardial
infarction and thrombosis.