DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

other factors such as age, nicotine use, and chronic illness.
Heavy doses of alcohol also can cause irreversible damage
to muscle, reflected by a marked increase in the activity of
creatine kinase in plasma.
Muscle biopsies from heavy drinkers also reveal decreased
glycogen stores and reduced pyruvate kinase activity (Vernet et al.,
1995). Approximately 50% of chronic heavy drinkers have evidence
of type II fiber atrophy. These changes correlate with reductions in
muscle protein synthesis and serum carnosinase activities (Wassif
et al., 1993). Most patients with chronic alcoholism show electromyographical
changes, and many show evidence of a skeletal
myopathy similar to alcoholic cardiomyopathy.
Body Temperature
Ingestion of ethanol causes a feeling of warmth because
alcohol enhances cutaneous and gastric blood flow.
Increased sweating also may occur. Heat, therefore, is
lost more rapidly, and the internal body temperature
falls. After consumption of large amounts of ethanol,
the central temperature-regulating mechanism becomes
depressed, and the fall in body temperature may
become pronounced. The action of alcohol in lowering
body temperature is greater and more dangerous when
the ambient environmental temperature is low. Studies
of deaths from hypothermia suggest that alcohol is a
major risk factor in these events. Patients with ischemic
limbs secondary to peripheral vascular disease are
particularly susceptible to cold damage.
Diuresis
Alcohol inhibits the release of vasopressin (antidiuretic
hormone) from the posterior pituitary gland, resulting in
enhanced diuresis. The volume loading that accompanies
imbibing complements the diuresis that occurs as a result
of reduced vasopressin secretion.
Alcoholics have less urine output than do control subjects in
response to a challenge dose with ethanol, suggesting that tolerance
develops to the diuretic effects of ethanol (Collins et al., 1992).
Alcoholics withdrawing from alcohol exhibit increased vasopressin
release and a consequent retention of water, as well as dilutional
hyponatremia.
Gastrointestinal System
Esophagus. Alcohol frequently is either the primary etiologic
factor or one of multiple causal factors associated
with esophageal dysfunction. Ethanol also is
associated with the development of esophageal reflux,
Barrett’s esophagus, traumatic rupture of the esophagus,
Mallory-Weiss tears, and esophageal cancer.
When compared with nonalcoholic nonsmokers, alcoholdependent
patients who smoke have a 10-fold increased risk of
developing cancer of the esophagus. There is little change in
esophageal function at low blood alcohol concentrations, but at
higher blood alcohol concentrations, a decrease in peristalsis and
decreased lower esophageal sphincter pressure occur. Patients with
chronic reflux esophagitis may respond to proton pump inhibitors
and abstinence from alcohol.
Stomach. Heavy alcohol use can disrupt the gastric
mucosal barrier and cause acute and chronic gastritis.
Ethanol appears to stimulate gastric secretions by exciting
sensory nerves in the buccal and gastric mucosa and
promoting the release of gastrin and histamine.
Beverages containing more than 40% alcohol also have
a direct toxic effect on gastric mucosa. While these
effects are seen most often in chronic heavy drinkers,
they can occur after moderate and short-term alcohol
use. The diagnosis may not be clear because many
patients have normal endoscopic examinations and
upper gastrointestinal radiographs. Clinical symptoms
include acute epigastric pain that is relieved with antacids
or histamine H 2
receptor blockers.
Alcohol is not thought to play a role in the pathogenesis of
peptic ulcer disease. Unlike acute and chronic gastritis, peptic ulcer
disease is not more common in alcoholics. Nevertheless, alcohol
exacerbates the clinical course and severity of ulcer symptoms. It
appears to act synergistically with Helicobacter pylori to delay healing
(Lieber, 1997). Acute bleeding from the gastric mucosa, while
uncommon, can be a life-threatening emergency. Upper GI bleeding
is associated more commonly with esophageal varices, traumatic
rupture of the esophagus, and clotting abnormalities.
Intestines. Many alcoholics have chronic diarrhea as a
result of malabsorption in the small intestine (Addolorato
et al., 1997). The major symptom is frequent loose stools.
The rectal fissures and pruritus ani that frequently are
associated with heavy drinking probably are related to
chronic diarrhea. The diarrhea is caused by structural and
functional changes in the small intestine (Papa et al.,
1998); the intestinal mucosa has flattened villi, and digestive
enzyme levels often are decreased. These changes
frequently are reversible after a period of abstinence.
Treatment is based on replacing essential vitamins and
electrolytes, slowing transit time with an agent such as
loperamide, and abstaining from all alcoholic beverages.
Patients with severe magnesium deficiencies (serum Mg 2+
< 1 mEq/L) or symptomatic patients (a positive
Chvostek’s sign or asterixis) should receive 1 g MgSO 4
intravenously or intramuscularly every 4 hours until the
serum [Mg 2+ ] > 1 mEq/L.
Pancreas. Heavy alcohol use is the most common cause
of both acute and chronic pancreatitis in the U.S. While
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CHAPTER 23
ETHANOL AND METHANOL