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benzodiazepines

Benzodiazepines are central nervous system (CNS) depressants. 

 

Benzodiazepines are effective in treating anxiety, insomnia, and seizures due to their sleep-inducing, sedative, and muscle-relaxing properties. 

Diazepan (Valium®), alprazolam (Xanax®), clonazepam (Klonopin®), and lorazepam (Ativan®) are all types of benzodiazepines ("benzos").

While considered safe for short-term treatment, long-term use can lead to tolerance and dependence. 

Bezodiazepines are often implicated in overdose deaths, as they are especially dangerous when combined with other CNS depressants like alcohol and opioids that also slow respiration (breathing).

Pharmacology

Pharmacology is a branch of science that deals with the study of drugs and their actions on living systems - that is, the study of how drugs work in the body.

Benzodiazepines (BZD) are a class of hypnotic anxiolytic medications that are commonly used without a prescription and frequently implicated in polysubstance use (1).

 

There are several dozen individual medications. Some of the more commonly known are diazepam (Valium®), alprazolam (Xanax®), lorazepam (Ativan®), clonazepam (®), chlordiazepoxide (Librium®), and midazolam (Versed®).

 

BZDs bind to the GABA type A receptor, causing central nervous system depression, with the result of sedation, skeletal muscle relaxation, decreased anxiety, decreased seizure activity, and respiratory depression.

 

Benzodiazepines and opiates have a synergistic effect, and concurrent use of BZD may lower or eliminate buprenorphine’s respiratory depression ceiling effect (1, 2).

 

Side effects are drowsiness, fatigue, sedation, decreased attention, physiological dependence, hypotonia, ataxia, and “hangover” (2, 3).

 

What Does Xanax Really Do To Your Body?
Treatment

Treatment involves gradual decreased doses with medical supervision over 1-2 months. This can be accomplished on an outpatient basis, but for extremely high doses, initial hospitalization may be beneficial.

 

There is no evidence-based medication to assist withdrawal, but medications for rebounding conditions such as anxiety or depression may be useful (2).

 

Pregnancy

The FDA places most BZD medications in pregnancy category D or X.

 

There is some evidence of increased risk of congenital malformations and low birth weight (3, 4, 5). It is unclear whether or not these possible effects are due to BZD use, or sleep disturbances, for which BZDs are often prescribed (6).

 

Withdrawal signs have been reported in newborns prenatally exposed to BZD (7).


Infants exposed to BZD via breastmilk may exhibit signs of sedation such as apnea (8).

 

Lactation

Infants exposed to BZD via breastmilk may exhibit signs of sedation such as apnea (8).

 

Overdose

BZD medications cause respiratory depression and can cause monodrug overdose at very high doses, but more commonly with concurrent use of other respiratory suppressants such as opiates (1, 2, 9).

 

Treatment is supportive, with supplemental oxygen or positive pressure ventilation. Flumazenil may be used to reverse BZD overdose, but its use may precipitate withdrawal symptoms such as seizures (1).

 

Withdrawal

Physiological dependence can occur in the absence of tolerance.

 

Length of time from last dose varies depending on the half-life of the medication used.

 

Symptoms of withdrawal are muscle tension, weakness, spasms, pain, malaise, anxiety, depression, tremor, sleep disturbances, nightmares, anorexia, tachycardia, blurred vision, dry mouth, tinnitus, seizures, delirium, and psychosis.

 

In rare instances, unsupervised withdrawal can be fatal (2).

 

References:

1.    Jones, J. D., Mogali, S., & Comer, S. D. (2012). Polydrug abuse: a review of opioid and benzodiazepine combination use. Drug and alcohol dependence, 125(1-2), 8–18. https://doi.org/10.1016/j.drugalcdep.2012.07.004
2.    Soyka, M., & München, B. (2019). Therapie der Benzodiazepinabhängigkeit [Treatment of benzodiazepine dependence]. Fortschritte der Neurologie-Psychiatrie, 87(4), 259–270. https://doi.org/10.1055/a-0836-7514
3.    Okun, M. L., Ebert, R., & Saini, B. (2015). A review of sleep-promoting medications used in pregnancy. American journal of obstetrics and gynecology, 212(4), 428–441. https://doi.org/10.1016/j.ajog.2014.10.1106
4.    Zwink, N., & Jenetzky, E. (2018). Maternal drug use and the risk of anorectal malformations: systematic review and meta-analysis. Orphanet journal of rare diseases, 13(1), 75. https://doi.org/10.1186/s13023-018-0789-3
5.    Ogawa, Y., Takeshima, N., & Furukawa, T. A. (2018). Maternal exposure to benzodiazepine and risk of preterm birth and low birth weight: A case-control study using a claims database in Japan. Asia-Pacific psychiatry : official journal of the Pacific Rim College of Psychiatrists, 10(3), e12309. https://doi.org/10.1111/appy.12309
6.    Reichner C. A. (2015). Insomnia and sleep deficiency in pregnancy. Obstetric medicine, 8(4), 168–171. https://doi.org/10.1177/1753495X15600572
7.    Hudak, M. L., Tan, R. C., COMMITTEE ON DRUGS, COMMITTEE ON FETUS AND NEWBORN, & American Academy of Pediatrics (2012). Neonatal drug withdrawal. Pediatrics, 129(2), e540–e560. https://doi.org/10.1542/peds.2011-3212
8.    Sachs, H. C., & Committee On Drugs (2013). The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics, 132(3), e796–e809. https://doi.org/10.1542/peds.2013-1985. 
9.    Martins, S. S., Sampson, L., Cerdá, M., & Galea, S. (2015). Worldwide Prevalence and Trends in Unintentional Drug Overdose: A Systematic Review of the Literature. American journal of public health, 105(11), e29–e49. https://doi.org/10.2105/AJPH.2015.302843

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