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Author: Admin | 2025-04-28
Benzodiazepines are prescribed to over 5% of the United States population and that number continues to grow. This class of medications is responsible for facilitating the binding of the inhibitory neurotransmitter GABA-A at various GABA receptors throughout the central nervous system. GABA is the most common neurotransmitter in the central nervous system, found in high concentrations in the cortex and limbic systems. Benzodiazepines have been used for a variety of indications including anxiety, insomnia, muscle relaxation, seizures, and alcohol withdrawal syndrome. As displayed in the benzodiazepine comparison table below, diazepam and midazolam are also used as sedatives prior to or during medical operations. IV and Oral Benzodiazepine Comparison TableDrug (Brand)Approved Formulations Primary Metabolic PathwayOnsetHalf-life (hrs)Alprazolam (Xanax) Tablet: 0.25mg, 0.5mg, 1mg, 2mgOrally Disintegrating Tablet: 0.25mg, 0.5mg, 1mg, 2mgCYP3A4Intermediate (1-1.5 hours)16-20(intermediate)Midazolam (Versed)Injection: 1mg/mL, 5mg/1 mLCYP3A4Fast (Injectable only)(1-15 minutes)3-8 (short)Clonazepam (Klonopin)Tablet: 0.5mg, 1mg, 2mgOrally Disintegrating Tablet: 0.125mg, 0.25mg, 0.5mg, 1mg, 2mgCYP3A4 NAT2Intermediate(1-4 hours)30-50 (long)Temazepam (Restoril)Capsule: 7.5mg, 15mg, 22.5mg, 30mgCYP3A4CYP2C19Intermediate(45 minutes-1.5 hours)3.5-18(Short)Diazepam (Valium) Tablet: 2mg, 5mg, 10mgInjection: 5mg/1mLCYP3A4 CYP2C19Fast (oral)(30 minutes-1.5 hours)Injectable – rapid20-100(long)Lorazepam (Ativan)Tablet: 0.5mg, 1mg, 2mgInjection: 2mg/1mL, 4mg/1mLUGT2B15Intermediate (oral)(2-3 hours)Injectable – rapid11-20 (intermediate)Oxazepam (Serax)Capsule: 10mg, 15mg, 30mgUGT2B15UGT1A9UGT2B7Intermediate(2-3 hours)5-15 (short)Triazolam (Halcion)Tablet: 0.125mg, 0.25mgCYP3A4Fast(15-30 minutes)1.5-5.5(short)Chlordiazepoxide (Librium)Capsule: 5mg, 10mg, 25mgCYP3A4Variable(30 minutes- 6 hours)24-48 (long)The benzodiazepine class of medications are considered to have a tranquilizing effect in patients, so it is important patients understand how it affects them before operating heavy machinery or driving a vehicle. Some common adverse effects that can be seen with these medications include sedation, drowsiness, confusion, dizziness, impaired balance and coordination, memory impairment, blurred vision, insomnia, and anxiety.All benzodiazepines besides lorazepam, oxazepam, and temazepam are primarily metabolized by CYP3A4 leading to the potential for drug-drug interactions. The inhibition of CYP3A4 leads to an increase in benzodiazepine concentration in the body and increases the risk for adverse events or toxicity. Examples of CYP3A4 inhibitors include erythromycin, amiodarone, grapefruit juice, oral contraceptives, and fluvoxamine. If taken simultaneously with any of the listed medications patients may need a decreased dose of benzodiazepine to avoid the potential for adverse events. Oppositely, the induction of CYP3A4 by medications like carbamazepine, phenytoin, rifampin, and St. John’s wort can lead to decreased levels of benzodiazepines and need for increased doses to potentiate the desired effectiveness.It is important to understand that benzodiazepines are schedule 4 controlled substances and have the potential for not only dependence but also severe withdrawal if used for extended periods of time. It is generally recommended that these medications are used on an as-needed basis and for a short period of time (2-4 weeks). If patients need to be on these medications longer than this duration, tapering needs to be considered to prevent the potential for severe withdrawal symptoms (rebound anxiety, insomnia, restlessness, twitches, sweating, GI complaints, and seizure). Clinical Pearls: Comparing The BenzodiazepinesThe most commonly prescribed benzodiazepines are clonazepam, lorazepam, diazepam, and alprazolam. As noted in the benzodiazepine comparison table above, lorazepam is not metabolized by CYP3A4. This medication may be used preferentially when patients are on medications that either induce or inhibit CYP3A4
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