344 Therapy of Selected Diseases

function (danger of hepatic coma). Collat-

‡ Alcohol Abuse
Since prehistoric times, ethanol-containing
beverages have enjoyed widespread use as
a recreational luxury. What applies to any
medicinal substance also holds for alcohol:
the dose alone makes the poison (see p. 2).
Excessive, long-term consumption of alco-
holic drinks, or alcohol abuse, is harmful
to the affected individual. Alcoholism must
be considered a grave disorder that plays a
major role in terms of numbers alone; for
instance, in Germany 1 000 000 people are
affected by this self-inflicted illness.
Ethanol is miscible with water and is well
lipid-soluble, enabling it to penetrate easily
through all barriers in the organism; the
blood–brain barrier and the placental barrier
are no obstacles. In liver cells, alcohol is bro-
ken down to acetic acid via acetaldehyde (A).
Ethyl alcohol is never ingested as a chemi-
cally pure substance but in the form of an
alcoholic beverage that contains flavoring
agents and higher alcohols, depending on
its origin. The effect desired by the consumer
takes place in the brain: ethanol acts as a
stimulant, it disinhibits, and it enhances so-
ciability, as long as the beverage is enjoyed
in moderate quantities. After higher doses,
self-critical faculties are lost and motor func-
tion is impaired–the familiar picture of the
drunk. Still higher doses induce a comatose
state (caution: hypothermia and respiratory
paralysis). The complex effects on the CNS
cannot be ascribed to a simple mechanism of
action. An inhibitory effect on the NMDA
subtype of glutamate receptor appears to
predominate.
In chronic alcohol abuse, mainly two or-
gans are damaged:
1. In the liver, hepatocytes may initially
undergo fatty degeneration, this process
being reversible. With continued expo-
sure, liver cells die and are replaced by
connective tissue newly formed from my-
ofibroblasts: liver cirrhosis. Hepatic blood
flow is greatly reduced; the organ be-
comes unable to fulfill its detoxification
Luellmann, Color Atlas of Pharmacology © 2005 Thieme
All rights reserved. Usage subject to terms and conditions of license.
eral circulation routes develop (bleeding
from esophageal varicose veins) with pro-
duction of ascites. Alcoholic liver cirrhosis
is a severe, mostly progressive disease that
permits only symptomatic therapy (B).
2. The functional capacity of the brain is
impaired. Irreversible damage may mani-
fest in a measurable fallout of neuronal cell
bodies. Often delirium tremens develops
(usually triggered by alcohol withdrawal),
which can be managed with intensive ther-
apy (clomethiazole, haloperidol, among
others). In addition, alcoholic hallucina-
tions and Wernicke–Korsakow syndrome
occur. All of these are desolate states.
It must be pointed out specifically that alco-
hol abuse during pregnancy leads to (em-
bryo–fetal alcohol syndrome (malforma-
tions, persistent intellectual deficits). This
intrauterine intoxication is relatively com-
mon: one case per 1000 births (C).
Chronic alcohol abuse is an expression of
true dependence. Thus, therapy of this ad-
diction is dif cult and frequently without
success. There is no pharmacotherapeutic
silver bullet (the NMDA receptor antagonist
acamprosate may be worth trying). Above
all, psychotherapeutic care, a change in mi-
lieu, and supportive treatment with benzo-
diazepines are important.
 Alcohol Abuse 345

A. Alcoholism

Ethanol Acetaldehyde Acetic acid Quotient NADH/NAD+

Fatty acid oxidation

H3C H3C H3C Fatty acid synthesis
Triglyceride synthesis

H2COH HC=O COOH

Fatty liver

Cell necroses
NAD+ NADH NAD+ NADH

Main catabolic pathway of ethanol in liver cell Cirrhosis

B. Liver cirrhosis
Hepatic Esophageal and Ascites
encepha- gastric varices
lopathy
Insufficient Portal
presystemic hypertension
elimination
of NH3
Liver cirrhosis

C. Embryo-fetal alcohol syndrome

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