This document discusses the toxicity of ethanol. It is a colorless, volatile liquid that readily diffuses through membranes and is metabolized in the liver. Chronic ethanol consumption can lead to malnutrition, oxidative stress, production of toxic metabolites like acetaldehyde, and increased risk of cancer. Clinical effects include inebriation, respiratory depression, hypothermia, and dysrhythmias. Blood tests can assess electrolyte abnormalities. Treatment involves stabilization, fluid/electrolyte correction, and occasionally hemodialysis. Ethanol metabolism can also cause hypoglycemia or alcoholic ketoacidosis in malnourished chronic drinkers.

1. Ethanol Toxicity

2.  A colorless, odorless, volatile liquid. It is fully
miscible in water and is lipid soluble.
 Readily diffuses across lipid membranes,
accounting for its ubiquitous multiorgan effects.
 Heavily consumed in intoxicating beverages.
 Used as an additive in gasoline, as a diluent or
solvent, in many household products, and in
pharmaceuticals
 Its metabolism follows first-order, then after
saturation, Zero-order kinetics.
Introduction

3.  CNS depression.
 Malnutrition by decreasing intake or by
altering absorption, metabolism and/or
utilization of nutrients.
 Elevation of endotoxin in the bloodstream.
 Induction of microsomal enzymes.
 Change in the redox potential of the cell.
 Production of toxic metabolite
(acetaldehyde).
 Oxidative stress.

5.  The unfavorable change in redox potential as a
consequence of ethanol metabolism contributes to the
development of metabolic disorders, increased collagen
and scar tissue formation associated with alcoholism, and a
clinical syndrome of alcoholic ketoacidosis.
 Acetaldehyde directly affects cardiac function, interferes
with phosphorylation, causes structural and functional
alterations in mitochondria and hepatocytes, and
inactivates coenzyme A.
 Acetaldehyde can react with intracellular proteins to
generate adducts.
 Ethanol metabolism through the hepatic CYP2E1 pathway
generates highly reactive oxygen radicals.
 The induction of hepatic enzymes by ethanol may increase
the toxicity of some substances like CCl4.

6.  chronic ethanol consumption may promote carcinogenesis
by:
 Production of acetaldehyde, a weak mutagen and
carcinogen.
 Induction of CYP2E1 and its associated oxidative
stressors and conversion of procarcinogens to
carcinogens.
 Depletion of S-adenosylmethionine and, consequently,
induction of global DNA hypomethylation.
 Increased production of inhibitory guanine nucleotide
regulatory proteins and components of extracellular
signal-regulated kinase-mitogen-activated protein
kinase signaling.
 Accumulation of iron and associated oxidative stress.
 Inactivation of the tumor suppressor gene BRCA1 and
increased estrogen responsiveness (primarily in the
breast).
 Impairment of retinoic acid metabolism.

7. Clinical Features
 Inebriation with variable signs that differ
according to the degree of intoxication.
 Loss of respiratory reflexes with increased
intoxication, coma and maybe death.
 Flushed facies, hypothermia, diaphoresis,
vomiting and hypotension.
 Dysrhythmias .
 Diplopia, visual disturbances, and nystagmus.
 decreased serum ionized magnesium
concentrations.
 Myocardial ischemia in susceptible patients.
 Ethanol-induced seizures.

8.  Immunoassay or gas chromatography is
commonly used for determination of ethanol in
liquid specimens in most hospitals.
 The usual sample is serum, rarely plasma. Whole
blood is used in forensic determination of BAL.
 Breath ethanol analyzers make use of
electrochemical sensors for ethanol oxidation
or infrared spectral analysis for ethanol
determination.
 Ethanol-saliva testing is a promising alternative
to breath ethanol analysis in the rapid
assessment of blood ethanol levels in patients.

9.  Blood tests that should be considered for patients
with ethanol intoxication or alcoholic ketoacidosis:
 CBC.
 Electrolytes.
 BUN.
 Creatinine.
 Ketones.
 Acetone.
 Lipase.
 Liver enzymes.
 Prothrombin time.
 Ammonia.
 Calcium.
 Magnesium.

10.  gastrointestinal decontamination may be considered in
case of delayed absorption or recent ingestion.
 endotracheal intubation and ventilatory support in
case of severe respiratory depression.
 Abnormal vital signs should be addressed and
stabilized.
 Patients who are combative and violent should be both
physically and then chemically restrained with a
benzodiazepine.
 The patient's fluid and electrolyte status should be
assessed and abnormalities corrected.
 Hemodialysis is an effective means of enhancing the
systemic elimination of ethanol .

11. Indications for hospital admission:
 persistently abnormal vital signs.
 persistently abnormal mental status, with
or without an obvious cause.
 mixed overdose with other concerning
xenobiotics.
 concomitant serious trauma.
 consequential ethanol withdrawal.
 associated serious disease process, such
as pancreatitis or gastrointestinal
hemorrhage.

12. Ethanol-induced
Hypoglycemia
 Occurs when ethanol metabolism
provides a high cellular reduction-to-
oxidation (redox) ratio. This redox state
favors the conversion of pyruvate to
lactate, diverting pyruvate from
gluconeogenesis.
 Hypoglycemia associated with ethanol
consumption usually occurs in
malnourished chronic alcoholics and
children

14.  Clinical features include: altered
consciousness, hypothermia and
tachypnea, positive blood ethanol
concentration, ketonuria without
glucosuria, and mild acidosis.
 Management of ethanol-induced
hypoglycemia is similar to other causes
of hypoglycemia.

15. Alcoholic Ketoacidosis
 Ethanol metabolism generates NADH, resulting
in an excess of reducing potential. This high
redox state favors the conversion of pyruvate
to lactate.
 The body increases fatty acid metabolism as
an alternative source of energy
 This response is mediated by a decrease in
insulin and an increased secretion of glucagon,
catecholamines, growth hormone, and cortisol.

16.  Most of the acetoacetate is reduced to
β-hydroxybutyrate as a consequence of
the excess reducing potential.
 Volume depletion contributes to the
acidosis.
 Lactic acidosis caused by hypoperfusion
or infection may coexist with the
underlying ketoacidosis.

18.  Patients are typically chronic ethanol
users, presenting after a few days of
“binge” drinking.
 starved because of cessation in oral
intake as a consequence of binging
itself, or because of:
Nausea.
 Vomiting.
 Abdominal pain from gastritis, hepatitis,
pancreatitis, or a concurrent acute illness.

19.  Underlying medical conditions may be present.
 Alcohol withdrawal may develop.
 Diagnosis of AKA is a diagnosis of exclusion.
 blood ethanol concentration is usually low or
undetectable.
 elevated anion gap metabolic acidosis with a
serum lactate concentration insufficient to
account for the gap.
 some patients will have a normal arterial pH or
be alkalemic.
 Reliance on the nitroprusside test alone may
underestimate the severity of ketoacidosis.

20.  Treatment should begin with adequate
crystalloid fluid replacement dextrose
and thiamine.
 Supplemental multivitamins, potassium,
and magnesium should be instituted on
an individual basis.
 During the recovery, β-hydroxybutyrate is
converted to acetoacetate.
 Mortality is rare from either ethanol-
induced ketoacidosis or hypoglycemia.