Benzodiazepines, commonly known as benzos, are a class of psychoactive drugs primarily used for their sedative, anxiolytic (anxiety-reducing), muscle relaxant, and anticonvulsant properties. Benzodiazepines, like Xanax (alprazolam) and Valium (diazepam) function by enhancing the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABA_A receptor, leading to a calming effect on the nervous system. The answer to how long does benzodiazepine stay in system is that it varies, depending on what therapeutic area it is being used for, the potency, and the type of metabolizer you are.

Common Uses of Benzodiazepines

Benzodiazepines are prescribed to treat a variety of conditions, including:

• Anxiety Disorders: They help reduce the symptoms of anxiety and panic attacks. Common benzodiazepines include, Xanax, Valium, Ativan (lorazepam), and Librium (chlordiazepoxide).
• Insomnia: Due to their sedative properties, they are used to aid sleep. Commonly prescribed benzodiazepines include Dalmane (flurazepam), Restoril (temazepam), and Halcion (triazolam).
• Seizure Disorders: They possess anticonvulsant properties beneficial in managing seizures. Common ones include Ativan, Klonopin (clonazepam), and Valium.
• Muscle Spasms: Benzodiazepines like Valium are used for their muscle relaxant effects which help ease muscle tension and spasms.

Duration of Benzodiazepines in the System

The duration benzodiazepines remain in the body varies based on factors such as the specific drug’s half-life, dosage, frequency of use, and individual metabolism. Generally, benzodiazepines can be categorized as:

• Short-acting: Effects of Benzos such as triazolam last for a few hours.
• Intermediate-acting: Effects of Benzos such as alprazolam and lorazepam last up to 24 hours.
• Long-acting: Effects of Benzos such as diazepam and clonazepam can last over 24 hours.

For instance, diazepam has a long half-life, and its effects can persist for several days. In contrast, drugs like triazolam are eliminated more quickly. Individual factors such as age, liver function, and genetic variations can also influence how long these drugs stay in one’s system.

Warning:

As per the boxed warning, “Concomitant use of benzodiazepines, including Halcion, and opioids may result in profound sedation, respiratory depression, coma, and death.”

Active Ingredients in Benzodiazepines

The active ingredients in benzodiazepines are the specific chemical compounds that produce their therapeutic effects. Each benzodiazepine has a unique chemical structure, but they all share a core benzene ring fused to a diazepine ring. Examples include:

• Diazepam: Its active ingredient is Valium and it is sold under the brand name Valium. The liver’s cytochrome P450 (CYP) enzymes metabolize Valium (diazepam). CYP3A4 and CYP2C19 are the primary enzymes responsible for metabolizing diazepam.
• Alprazolam: Its active ingredient is Xanax and it is sold under the brand name Xanax. CYP3A4 is primarily responsible for metabolizing Xanax in the liver.
• Clonazepam: The active ingredient is Clonazepam and it is sold under the brand name Klonopin. CYP3A4 plays a major role in breaking down (metabolizing) clonazepam in the body.

According to the AAFP, “Cytochrome P450 enzymes are essential for the metabolism of many medications. Although this class has more than 50 enzymes, six of them metabolize 90 percent of drugs, with the two most significant enzymes being CYP3A4 and CYP2D6.”

Check out if you are rapid, intermediate, poor, or normal metabolizer of CYP3A4 and CYP2D6 with a non-invasive at-home pharmacogenetic test by RPh LABS.

Enzymes Involved in Benzodiazepine Metabolism

Except for lorazepam, oxazepam, and temazepam, which are primarily metabolized by glucuronidation in the liver, most benzodiazepines are primarily metabolized in the liver by the cytochrome P450 enzyme system. The specific enzymes involved include:

• CYP3A4: Plays a significant role in the metabolism of many benzodiazepines.
• CYP2C19: Involved in the metabolism of certain benzodiazepines, such as diazepam.

Genetic polymorphisms in these enzymes can lead to variations in drug metabolism among individuals. For example, polymorphisms in CYP2C19 can decrease diazepam clearance, increasing its half-life up to four times the typical duration.

Important:

Lorazepam, oxazepam, and temazepam are often preferred over other benzodiazepines for patients with liver disease because they are less likely to cause toxicity.

Individual Variations in Benzodiazepine Effects

Individuals may experience different effects from benzodiazepines due to factors such as:

• Genetic Variations: Differences in genes encoding metabolizing enzymes can affect drug levels and responses.
• Age: Older adults may metabolize benzodiazepines more slowly, leading to prolonged effects.
• Liver Function: Impaired liver function can reduce the metabolism and clearance of these drugs.
• Drug Interactions: Concomitant use of other medications can influence benzodiazepine metabolism.

PGx Testing and Benzodiazepine Dosage Assessment

Pharmacogenetic testing, commonly known as PGx testing, involves analyzing your genome (set of all DNA) to predict response to specific medications. By identifying genetic variations in drug-metabolizing enzymes, such as CYP2C19 and CYP3A4 healthcare providers can tailor benzodiazepine therapy as per your genetic profile. The personalized approach in medication improves the efficacy and reduces trial and error in your treatment. For example, if a patient is found to have a CYP2C19 polymorphism that reduces enzyme activity, a lower dose of diazepam might be recommended to avoid excessive sedation.

Conclusion
Usually prescribed for anxiety disorders, sleep issues, and certain seizure disorders, benzodiazepines belong to Schedule IV controlled substances. How long does benzodiazepine stay in the system is based on numerous factors such as the potency, exact drug, age, sex, and other medical conditions of the patient who is being administered benzodiazepine. While most of the benzos are metabolized by CYP2C19 and CYP3A4 enzymes, lorazepam, oxazepam, and temazepam, are primarily metabolized by glucuronidation in the liver and are usually prescribed to patients who have liver issues or to the elderly individuals. Metabolism plays a crucial role in breaking down drugs in our system. Some people are rapid metabolizers of a certain drug, while others may be poor, intermediate, or normal metabolizers. Knowing what type of metabolizer, you are can help your doctor prescribe the right drug and dosage, resulting in fewer chances of adverse reactions and increased drug efficacy. A simple at-home PGx test by RPh LABS can show you how your body may respond to 250+ medications.

References:

https://www.pharmgkb.org/pathway/PA165111375
https://wikianesthesia.org/wiki/Pharmacogenetics_and_pharmacogenomics
https://www.pharmgkb.org/pathway/PA165111375

Disclaimer:  This blog is only for informational purposes. Always consult a doctor before taking any medical action.