Page 417 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 23 The Alcohols 403

fatal cases is above 400 mg/dL; however, the lethal dose of alcohol agitation, autonomic nervous system instability, low-grade fever,
varies because of varying degrees of tolerance. and diaphoresis.
Electrolyte imbalances often need to be corrected, and meta- The major objective of drug therapy in the alcohol withdrawal
bolic alterations may require treatment of hypoglycemia and period is prevention of seizures, delirium, and arrhythmias. Potas-
ketoacidosis by administration of glucose. Thiamine is given to sium, magnesium, and phosphate balance should be restored as
protect against Wernicke-Korsakoff syndrome. Patients who are rapidly as is consistent with renal function. Thiamine therapy is
dehydrated and vomiting should also receive electrolyte solutions. initiated in all cases. Individuals in mild alcohol withdrawal do
If vomiting is severe, large amounts of potassium may be required not need any other pharmacologic assistance.
as long as renal function is normal. Specific drug treatment for detoxification in more severe
cases involves two basic principles: substituting a long-acting
sedative-hypnotic drug for alcohol and then gradually reducing
MANAGEMENT OF ALCOHOL (“tapering”) the dose of the long-acting drug. Because of their
WITHDRAWAL SYNDROME wide margin of safety, benzodiazepines are preferred. Long-acting
benzodiazepines, including chlordiazepoxide and diazepam,
Abrupt alcohol discontinuation in an individual with alcohol have the advantage of requiring less frequent dosing. Since their
dependence leads to a characteristic syndrome of motor agita- pharmacologically active metabolites are eliminated slowly, the
tion, anxiety, insomnia, and reduction of seizure threshold. The long-acting drugs provide a built-in tapering effect. A disadvantage
severity of the syndrome is usually proportionate to the degree of the long-acting drugs is that they and their active metabolites
and duration of alcohol abuse. However, this can be greatly modi- may accumulate, especially in patients with compromised liver
fied by the use of other sedatives as well as by associated factors function. Shorter-acting drugs such as lorazepam and oxazepam
(eg, diabetes, injury). In its mildest form, the alcohol withdrawal are rapidly converted to inactive water-soluble metabolites that
syndrome of increased pulse and blood pressure, tremor, anxiety, will not accumulate, and for this reason the short-acting drugs are
and insomnia occurs 6–8 hours after alcohol consumption is especially useful in alcoholic patients with liver disease. Benzodi-
stopped (Figure 23–2). These effects usually lessen in 1–2 days, azepines can be administered orally in mild or moderate cases, or
although some, such as anxiety and sleep disturbances, can be parenterally for patients with more severe withdrawal reactions.
seen at decreasing levels for several months. In some patients, After the alcohol withdrawal syndrome has been treated
more severe acute reactions occur, with withdrawal seizures or acutely, sedative-hypnotic medications must be tapered slowly
alcoholic hallucinations during the first 1–5 days of withdrawal. over several weeks. Complete detoxification is not achieved
Alcohol withdrawal is one of the most common causes of seizures with just a few days of alcohol abstinence. Several months may
in adults. Several days later, individuals can develop the syn- be required for restoration of normal nervous system function,
drome of delirium tremens, which is characterized by delirium, especially sleep.

Anxiety, insomnia,
tremor, palpitations,
nausea, anorexia
Withdrawal
seizures
Alcoholic
hallucinations
Delirium tremens
(tachycardia, hypertension, low-grade fever,
tremor, diaphoresis, delirium, agitation)

0 1 2 3 4 5 6 7 8 9 30-90
Days since alcohol discontinuation

FIGURE 23–2 Time course of events during the alcohol withdrawal syndrome. The signs and symptoms that manifest earliest are anxiety,
insomnia, tremor, palpitations, nausea, and anorexia as well as (in severe syndromes) hallucinations and seizures. Delirium tremens typically
develops 48–72 hours after alcohol discontinuation. The earliest symptoms (anxiety, insomnia, etc) can persist, in a milder form, for several
months after alcohol discontinuation.