Benzodiazepines

Benzodiazepines are anti-anxiety and sedative-hypnotic medications that enhance gamma-amino butyric acid (GABA) activity in the central nervous system. A wide variety of benzodiazepines have been used for alcohol withdrawal. In general, long-acting benzodiazepines with a rapid onset of action (particularly important in seizure prophylaxis) are most commonly recommended. 

Diazepam is the benzodiazepine of choice. Diazepam is well absorbed orally, has a rapid onset of action (within one hour), and has prolonged duration of effects (up to several days), important in preventing symptom recurrence between doses. Chlordiazepoxide, a long-acting and rapid-onset benzodiazepine, is widely used internationally but is not registered in Australia. 

In certain clinical circumstances, long-acting benzodiazepines such as diazepam may be problematic. Shorter acting benzodiazepines (such as midazolam, lorazepam, oxazepam) should be used where there is concern about prolonged sedation, such as in the elderly, recent head injury, liver failure, respiratory failure, other serious medical illness or in severely obese patients (due to accumulation of lipophilic diazepam and active metabolites). Short acting benzodiazepines have a simpler hepatic metabolism (conjugation that is less affected by liver disease or aging) without active metabolites, and can be more easily discontinued in the event of clinical deterioration such as head injury. 

• Lorazepam is the preferred benzodiazepine under these circumstances as it has rapid onset after oral administration (within 2 hours) and has short to medium duration of action (half life of 10 to 20 hours); 2 mg oral lorazepam is equipotent to 10 mg oral diazepam. 
• Oxazepam has also been used in Australia under these circumstances (onset of action within 2 hours, half-life of 5 to 10 hours); 15 to 30 mg oxazepam is approximately equipotent to 5 mg diazepam. 
• Midazolam by intravenous bolus or infusion is preferred where rapid, but easily reversible, sedation is required (for example, in patient with recent seizure and with suspected head injury). It is used in acute care settings such as Emergency Departments or Intensive care units. 

The three most commonly used benzodiazepine regimens are symptom-triggered therapy, loading dose therapy and fixed-schedule therapy. Figure 8.2 shows a schematic for use of the different benzodiazepine regimens. In practice, hybrid regimens that combine these approaches are commonly used.