3. • After oral administration, it is absorbed rapidly into the
bloodstream and distributes into total-body water (0.5–0.7
L/kg).
• Peak blood levels occur ∼30 minutes after ingestion of
ethanol when the stomach is empty.
delays in gastric emptying slow ethanol absorption.
• Because of first-pass metabolism by gastric and liver alcohol
dehydrogenase (ADH), oral ingestion of ethanol leads to lower
.
• Gastric metabolism of ethanol is lower in women than in
men, which may contribute to the greater susceptibility of
women to ethanol intoxication.
• Aspirin increases ethanol bioavailability by inhibiting
gastric ADH.
4. • Small amounts of ethanol are excreted in urine, sweat, and
breath,
• metabolism to acetate accounts for 90–98% of ingested
ethanol, mostly owing to hepatic metabolism by ADH and ADLH.
• CYP2E1 also can contribute at higher ethanol concentrations .
• Although CYP2E1 usually is not a major factor in ethanol
metabolism, it can be an important site of interactions of ethanol
with other drugs.
• CYP2E1 is induced by chronic consumption of ethanol, increasing
the clearance of its substrates and activating certain toxins such
as CCl4.
5. Acute Intoxication
• Alcohol perturbs the balance between excitatory and inhibitory
influences in the brain, resulting in Anxiolysis , ataxia , and
sedation.
• This is accomplished by either enhancing inhibitory or
antagonizing excitatory neurotransmission.
• Although ethanol was long thought to act non-specifically by
disordering lipids in cell membranes, ethanol likely produces its
effects by simultaneously altering the functioning of a
number of proteins that can affect neuronal excitability.
• A key issue has been to identify proteins that determine
neuronal excitability and are sensitive to ethanol at the
concentrations (5–20 mM) that produce behavioral effects.
6. Candidate proteins include ion channels in the CNS, and cell
signaling enzymes such as protein kinase C- g and components of
signaling pathways such as the MAP kinase and cAMP /PKA
pathways.
• The best studied of these include ligand-gated g-aminobutyric
acid A (GABAA) receptors, whose function is markedly
enhanced by a number of classes of sedative, hypnotic, and
anesthetic agents, including barbiturates, benzodiazepines,
and volatile anesthetics , neuronal nicotinic acetylcholine
receptors , and excitatory ionotropic glutamate receptors,
including N-methyl-D-aspartate (NMDA) and non- NMDA
receptor classes .
7. • ACUTE ETHANOL INTOXICATION
• An increased reaction time, diminished fine motor control,
impulsivity, and impaired judgment
become evident when the concentration of ethanol in the blood is 20–
30 mg/dL.
More than 50% of persons are grossly intoxicated by a concentration
of 150 mg/dL.
In fatal cases, the average concentration
• is 400 mg/dL, although alcohol-tolerant individuals often can
withstand comparable BALs.
The definition of intoxication varies by state and country.
• In the U.S., most states set the ethanol level defined as intoxication
at 80 mg/dL.
• There is increasing evidence that lowering the
• limit to 50–80 mg/dL can reduce motor vehicle injuries and fatalities
significantly.
• While alcohol can be measured in saliva, urine, sweat, and blood,
measurement of levels in exhaled air remains the primary method of
assessing the level of intoxication.
8. Factors affecting intoxication risk
body weight and composition
rate of absorption from the GI tract
• On average, the ingestion of three standard drinks (42 g
ethanol) on an empty stomach results in a maximum blood
concentration of 67–92 mg/dL in men.
• After a mixed meal, the maximal blood concentration from
three drinks is 30–53 mg/dL in men.
Concentrations of alcohol in blood will be
higher in women because, on average, women
are smaller than men, have less body water per unit of weight
into which ethanol can distribute, and have less gastric ADH
activity than men.
9. DD :
Diabetic coma, for example, may be mistaken for severe alcoholic
intoxication. Drug intoxication, cardiovascular accidents, and skull
fractures
BALs are necessary to confirm the presence or absence of alcohol
intoxication.
10. Tx
The treatment of acute alcohol intoxication is based on the severity of
respiratory and CNS depression.
Acute alcohol intoxication can be a medical emergency.
Patients who are comatose and who exhibit evidence of
respiratory depression should be intubated to protect the airway and
to provide ventilatory assistance.
• The stomach may be lavaged, but care must be taken to prevent
pulmonary aspiration of the return flow.
• ethanol can be removed from blood by hemodialysis.
11. Acute alcohol intoxication is not always associated with coma, and
careful observation is the primary treatment.
Usual care involves observing the patient in the emergency room for
4–6 hours while the patient metabolizes the ingested ethanol.
BALs will be reduced at a rate of ∼15 mg/dL/hr.
During this period, some individuals may display extremely violent
behavior.
Sedatives and antipsychotic agents have been employed to quiet such
patients, but great care must be taken when
using sedatives to treat these patients because of possible synergistic
CNS depressant effects.
12. Signs and symptoms
• Whole body: blackout, dehydration, fainting, flushing, or nausea
• Speech: slurred speech
• Behavioral: aggression ,Disinhibition
• Cognitive: amnesia or mental confusion
• Also common: depression, euphoria, low blood sugar, problems
with coordination, rapid involuntary eye movement, slow
breathing, stupor, or vomiting
