Any alcohol (hydroxylated hydrocarbon) has the potential for
toxicity. The term toxic alcohols is generally
used to refer to methanol and ethylene glycol. All alcohols cause
clinical inebriation, with the strength of the inebriating effects
directly proportional to the alcohol’s molecular weight;
hence, at the same concentration, isopropanol is more intoxicating
than ethanol (Figure 179-1).
Chemical structures of toxic alcohols.
It is useful to categorize the alcohols based on whether the
primary toxicity is due to the parent compound (ethanol and isopropanol)
or to toxic metabolites (ethylene glycol and methanol). Ethanol
and isopropanol are the most common alcohols ingested, and do not
in and of themselves cause metabolic acidosis. Their principal acute
toxicities are due to the GI irritant and intoxicating effects of
the parent compounds, and both are significantly less toxic than
methanol and ethylene glycol.
Ethanol (CH3CH2OH, molecular weight 46.07)
is a colorless, volatile liquid and is the most frequently used
and abused drug in the world. Ethanol is unique among drugs of potential
abuse because its use is legal and culturally acceptable in many
societies. Most morbidity from acute ethanol intoxication is related
to secondary injuries rather than direct toxic effects. Toxicity
most commonly results from ingestion, but ethanol may also be absorbed
via inhalation or percutaneous exposure.
Ethanol is readily available in many different forms. A standard
alcoholic beverage—such as 12 oz (355 mL) of beer (2% to
6% ethanol by volume), 5 oz (148 mL) of wine (10% to
20% ethanol by volume), or 1.5 oz (44 mL) of 80-proof spirits
(40% ethanol by volume)—contains about 15 grams of
ethanol. Ethanol may be found in high concentrations in many other common
household products such as mouthwash (may contain up to 75% ethanol
by volume) and colognes and perfumes (up to 40% to 60%) and
as a diluent or solvent for medications (concentration varies widely between
0.4% and 65.0%). Such products are often flavored
or brightly colored and may be attractive to children.
Ethanol use contributes to the number of patients seen in the
ED.1 Depending on the locale, ethanol is detected
in the blood of 15% to 40% of ED patients.2
In 2006, 32% of motor vehicle accident fatalities in
the U.S. involved an alcohol-impaired driver.3 One
quarter of the victims of interpersonal trauma report alcohol use
by their assailants, and alcohol abuse reported by the injured woman
is the strongest predictor for acute injury related to domestic
violence.4,5 From data collected in 2001 and 2002,
the lifetime prevalence of alcohol abuse and dependence in the U.S.
was estimated to be 17.8% and 12.5%, respectively.6
Ethanol is rapidly absorbed after oral administration, and blood
levels peak about 30 to 60 minutes after ingestion. The presence
of food in the stomach prolongs absorption and delays the peak blood
level. Also, high concentrations of ethanol in the stomach may cause
pylorospasm and delay gastric emptying. Some ethanol is broken down
in the stomach by gastric alcohol dehydrogenase, which lowers the
amount available for absorption. This enzyme is present at higher
levels in men than in women, which may account for the fact that
women usually develop a higher blood ethanol level than men after
consuming the same dose per kilogram of body weight. The volume
of distribution of ethanol is also gender dependent due to different
average body fat percentages: 0.6 L/kg in men and 0.7 L/kg
Ethanol is a central nervous system depressant. The mechanism
of action is complex and incompletely understood. Major actions
of ethanol include enhancement of the effects of the inhibitory
neurotransmitter γ-aminobutyric acid receptors
and blockade of excitatory N-methyl-d-aspartic
acid receptors. Ethanol also interacts with other neurotransmitters
and signaling pathways. Modulation of these systems, including upregulation
or downregulation of receptors, leads to the development of tolerance,
dependence, and a dangerous withdrawal syndrome when ethanol intake
ceases in dependent individuals.
Because of the phenomenon of tolerance, blood ethanol levels
correlate poorly with degree of intoxication. Although death from
respiratory depression may occur in nonhabituated individuals at
concentrations of 400 to 500 milligrams/dL, it is not uncommon
for some alcoholic individuals to appear minimally intoxicated at
blood concentrations as high as 400 milligrams/dL.7 Although
Canada, Mexico, and the U.S. have adopted 80 milligrams/dL
as the legal definition of intoxication for the purposes of driving
a motor vehicle, there is considerable evidence to suggest that
impairment may be seen with levels as low as 5 milligrams/dL,
especially in nonhabituated individuals.
Ethanol is predominantly eliminated via hepatic metabolism, with about
10% excreted in the urine, exhaled breath, and sweat. Metabolism to acetaldehyde by alcohol
dehydrogenase (Figure 179-2) is the main rate-limiting
step. At low concentrations, this metabolism follows first-order
kinetics, but as concentrations rise, alcohol dehydrogenase becomes
saturated and metabolism switches to zero-order kinetics. Also, as
ethanol concentrations rise, the hepatic microsomal oxidizing system (specifically,
cytochrome P-450 2E1) plays a more important role in metabolism.
Metabolism of ethanol. CoA = coenzyme A.
Both alcohol dehydrogenase and cytochrome P-450 2E1 are inducible and
thus are more active in chronic ethanol users. Therefore, rates
of ethanol elimination from the blood vary from about 15 to 20 milligrams/dL/h
in nonhabituated individuals to up to 30 milligrams/dL/h
in individuals with chronic alcoholism.
The hallmark of ethanol toxicity is clinical inebriation.8 Behavioral
disinhibition may initially appear as euphoria or agitation and
combativeness. As intoxication becomes more severe, central nervous
system depression develops. ...