Alcohol Intoxication

Molecular structure

• 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.

• 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.

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.

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 .

• 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.

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 behigher in women because, on average, womenare smaller than men, have less body water per unit of weight into which ethanol can distribute, and have less gastric ADH activity than men.

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.

TxThe 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 ofrespiratory 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.

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 whenusing sedatives to treat these patients because of possible synergistic CNS depressant effects.

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