Benzodiazepines ethanol withdrawal

The withdrawal syndrome from ethanol includes anxiety, insomnia, possibly convulsions and visual hallucinations (delirium tremens - the Dts). It is treated or better still prevented by a calm environment, adequate (but not excessive) hydration, and careful monitoring, with the added use of anticon-vulsive/sedative agents, mainly benzodiazepines to prevent or treat convulsions. The preventive effects of benzodiazepines on withdrawal morbidity has been clearly demonstrated. There do not seem to be major differences between benzodiazepines, such as chlordiazepoxide or diazepam or others. Because of the abuse potential in these highly susceptible patients, these should be rapidly weaned, and proper prevention of relapse instituted. Other drugs such as meprobamate and clomethiazole (Hemineurin) are commonly used in some countries. The effectiveness... 

Treatment of ethanol withdrawal is supportive and relies on benzodiazepines, taking care to use compounds such as oxazepam and lorazepam, which are not as dependent on hepatic metabolism as most other benzodiazepines. In patients in whom monitoring is not reliable and liver function is adequate, a longer-acting benzodiazepine such as chlordiazepoxide is preferred. 

Tiapride appears to be useful in alcohol withdrawal as an alternative to the benzodiazepines (2). It facilitates the management of ethanol withdrawal, but its use in patients at risk of severe reactions in acute withdrawal should be accompanied by adjunctive therapy for hallucinosis and seizures. Since it may prove difficult to identify such patients and since there is also a small risk of the neuroleptic malignant syndrome (particularly with parenteral administration), the usefulness of tiapride in this setting is likely to be limited. The potential risk of tardive dyskinesia at the dosage used in alcoholic patients following detoxification (300 mg/day) requires evaluation and necessitates medical supervision. It is unlikely to produce problems of dependence or abuse. 

Experimentally, benzodiazepines inhibit some types of seizure activity. Clonazepam, nitrazepam, and nordazepam have more selective anticonvulsant activity than most other benzodiazepines. Benzodiazepines also suppress ethanol-withdrawal seizures in human beings. However, the development of tolerance to the anticonvulsant effects has limited the usefulness of benzodiazepines in the treatment of recurrent seizure disorders (see Chapter 19). 

Lejoyeux et al. 1998). Similar to opioid-dependent persons, these patients reported that they use benzodiazepines to self-medicate anxiety, insomnia, and alcohol withdrawal and, less commonly, to enhance the effects of ethanol. Approximately l6%-25% of patients presenting for treatment of anxiety disorders abuse alcohol (Kushner et al. 1990 Otto et al. 1992). Controversy exists concerning appropriate benzodiazepine prescribing in this population (Cir-aulo and Nace 2000 Posternak and Mueller 2001). 

Changes have also been reported to occur in the sub-unit composition of the GABA-A receptor following chronic exposure to barbiturates, neurosteroids, ethanol and benzodiazepine agonists. These changes may underlie the development of tolerance, physical dependence and the problems which are associated with the abrupt withdrawal of such drugs. 

Barbiturates, which preceded benzodiazepines as the most commonly abused sedative hypnotics (after ethanol), are now rarely prescribed to outpatients and therefore constitute a less common prescription drug problem than they did in the past. Street sales of barbiturates, however, continue. Management of barbiturate withdrawal and addiction is similar to that of benzodiazepines. 

Answer B. Buspirone has selective anxiolytic activity that is slow in onset The drug has no abuse liability and will not suppress withdrawal symptoms in patients who have become physically dependent on barbiturates, benzodiazepines, or ethanol. Bupropion is an antidepressant, also approved for management of dependence on nicotine. Baclofen is a spinal cord muscle relaxant that activates GABAfi receptors. Buprenorphine is a long-acting opioid analgesic with no effectiveness in GAD, and butabarbital is a barbiturate that may cause dependence. 

Other uses Thiopental is commonly used for the induction of anesthesia, and certain benzodiazepines (eg, diazepam, midazolam) are used as components of anesthesia protocols. Special uses include the management of seizure disorders (eg, clonazepam, phenobarbital) and muscle spasticity (diazepam). Longer-acting dmgs (eg, chlordiazepoxide, diazepam) are used in the management of withdrawal states in persons physiologically dependent on ethanol and other sedative-hypnotics. 

Even normal therapeutic doses of benzodiazepines may lead to physiologic dependence with withdrawal symptoms. These can include increases in REM sleep (REM rebound), increased anxiety, agitation, and insomnia. The severity of withdrawal symptoms depends on the dose used and on the concomitant use of other sedative-hypnotics, including ethanol. In general, withdrawal symptoms are more severe with the use of shorter-acting sedative-hypnotics. The answer is (E). 

Opioids (especially methadone and heroin) are the most common cause of serious neonatal drug withdrawal symptoms. Other dmgs for which a withdrawal syndrome has been reported include phencyclidine (POP), cocaine, amphetamines, tricyclic antidepressants, phenothiazines, benzodiazepines, barbiturates, ethanol, clonidine, diphenhydramine, lithium, meprobamate, and theophylline. A careful dmg history from the mother should include illicit drugs, alcohol, and prescription and over-the-counter medications, and whether she is breast-feeding. 

---