Withdrawal syndrome primarily affects persons who are habituated (tolerant) to chronic ethanol ingestion who either cease their drinking or markedly reduce their consumption
Symptoms of alcohol withdrawal occur because alcohol is a central nervous system depressant; abrupt withdrawal unmasks compensatory overactivity of certain parts of the nervous system, including sympathetic autonomic outflow.
Altered levels of several neurotransmitters have been noted, and may be important in the pathophysiology of alcohol withdrawal:
Gamma-aminobutyric acid: Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain.
Its receptor is downregulated and its neuronal activity decreased in alcohol withdrawal, resulting in hyperarousal
Norepinephrine: Elevated levels of norepinephrine are found in the cerebrospinal fluid of patients withdrawing from alcohol and are believed due to a decrease in the alpha-2 receptor-mediated inhibition of presynaptic norepinephrine release
Serotonin: Serotonin and its degradation products have been implicated in both tolerance and craving for alcohol
Characterized by a hyperadrenergic state that develops 6-8 hours after the cessation of drinking and may last up to 5 days
Enhanced excitatory neurotransmission
Increased levels of plasma and urine catecholamines
Decreased inhibitory activity of presynaptic 2 receptors
Symptom severity determined by the amount of endogenous norepinephrine released during withdrawal
Diagnosis
DSM-IV Diagnosis
The essential feature of Alcohol Withdrawal is the presence of a characteristic withdrawal syndrome that develops after the cessation of (or reduction in) heavy and prolonged alcohol use
The withdrawal syndrome includes two or more of the following symptoms:
Autonomic hyperactivity (e.g. sweating or pulse rate greater than 100)
Increased hand tremor
Insomnia
Psychomotor agitation
Anxiety
Nausea or vomiting
Grand mal seizures
Transient visual, tactile, or auditory hallucinations or illusions
Withdrawal symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning (Criterion C)
The symptoms must not be due to a general medical condition and are not better accounted for by another mental disorder (e.g., Sedative, Hypnotic, or Anxiolytic Withdrawal or Generalized Anxiety Disorder) (Criterion D).
Treatment
Basic principles
The major objective of drug therapy in the alcohol withdrawal period is prevention of seizures, delirium, and arrhythmias
Specific drug treatment for detoxification in severe cases involves two basic principles: substituting a long-acting sedative-hypnotic drug for alcohol and then gradually reducing ("tapering") the dose of the long-acting drug.
Because of their wide margin of safety, benzodiazepines are preferred for treatment of alcohol withdrawal syndrome
After the alcohol withdrawal syndrome has been treated acutely, sedative-hypnotic medications must be tapered slowly over several weeks.
Initial stabilization
ABCs
Correct hypoglycemia
IV fluids
Initiate tranquilization to prevent the progression of the syndrome to more severe levels and to relieve the symptoms
Administer thiamine
Restore Inhibitory Tone to the CNS
Benzodiazepines:
Examples: diazepam, lorazepam, chlordiazepoxide
Uses: Standard therapy, high doses required owing to cross-tolerance with chronic ethanol ingestion, anticonvulsant effect and may halt progression to DTs
Dosage: Diazepam: 5-20 mg PO for mild reactions; 5-10 mg i.v.
Diazepam is administered 10 to 20 mg po every hour until the patient's symptoms are relieved and the patient is sedated.
Chlordiazepoxide (Librium): 25-100 mg, PO or i.v. q6h
Barbiturates (phenobarbital)
Uses: Cross-tolerant with alcohol, anticonvulsant effect, and useful if severe withdrawal or DTs refractory to large doses of benzodiazepines
Butyrophenone antipsychotics
Examples: Haloperidol (low doses)
Uses: Indicated as adjuncts in the hallucinating patient
Dosage: Haloperidol: 2-10 mg PO, i.v., or i.m.
Thiamine: 100 mg i.v.
Folate: 1 mg i.v. or PO
Major tranquilizer: SYN: antipsychotic agent.
Disulfiram
Disulfiram (tetraethylthiuram), a widely used antioxidant in the rubber industry, causes extreme discomfort to patients who drink alcoholic beverages.
Disulfiram causes: flushing, throbbing headache, nausea, vomiting, sweating, hypotension, and confusion occur within a few minutes after drinking alcohol
The effect may last 30 minutes in mild cases or several hours in severe ones
After the symptoms wear off, the patient is usually exhausted and may sleep for several hours.
Disulfiram acts by inhibiting aldehyde dehydrogenase.
Thus, alcohol is metabolized as usual, but acetaldehyde accumulates.
The symptoms resulting from disulfiram plus alcohol are typical of acetaldehyde toxicity: the reaction is reproduced by acetaldehyde infusion in humans.
The usual oral dose is 250 mg daily taken at bedtime.
Naltrexone
Naltrexone is an orally available opioid receptor antagonist that blocks the effects of exogenous and, presumably, endogenous opioids.
Naltrexone is taken once a day in a dose of 50 mg for treatment of alcoholism.
