Anxiolytics

Abstract

Anxiolytics are also known as minor tranquilizers and are prescribed to treat and prevent symptoms of anxiety or for the management of anxiety disorders. The term tranquilizer is no longer popular; the term ‘anxiolytics’ is frequently used because they diminish the feelings of anxiety. Benzodiazepines (BZD) are prescribed in the millions every year. Some of the frequently prescribed BZDs are diazepam (Valium®; CASRN: 439-14-5), chlordiazepoxide (Librium®, CASRN: 58-25-3); flurazepam (Dalmane®, CASRN: 17617-23-1); clonazepam (Klonopin®, CASRN: 1622-61-3); midazolam (Versed®, CASRN: 59467-70-8); and alprazolam (Xanax®, CASRN: 28981-97-7). According to 2011 American Association of Poison Control Centers' report, sedative-hypnotics ranked No. 1 in the top-25 fatality list. A pure oral BZD overdose rarely results in morbidity (e.g., aspiration pneumonia, rhabdomyolysis) or mortality; those usually occur when BZDs are combined with alcohol or other sedative-hypnotics. Ethanol and BZD combination is considered a lethal combination. In addition, intravenous administration of BZDs is associated with greater degrees of hypotension and occasional cardiac and respiratory arrest. BZDs act by potentiating the activity of γ-aminobutyric acid (GABA)-mediated chloride channels. BZDs bind to the GABAA receptor complex, consequently increasing frequency of opening of the chloride channel. Enhanced GABA neurotransmission results in sedation, striated muscle relaxation, anxiolysis, and anticonvulsant effects. BZDs are metabolized predominantly in the liver by oxidation and/or conjugation. Most BZDs are broken down into pharmacologically active metabolites, which may have longer half-lives than the parent compounds. BZD toxicity may result from overdose or from abuse. Cigarette smoking may decrease the sedative effects of usual doses of BZDs. It is assumed that alprazolam undergoes transplacental passage and that it is excreted in human milk. All BZDs are classified as schedule IV controlled substances, capable of causing dependence, tolerance, and abuse. Liver and kidney function tests and blood counts should be performed regularly during long-term BZD therapy. BZD used solely as hypnotics (flurazepam, temazepam, triazolam) are contraindicated during pregnancy. Treatment of BZD overdose involves supportive care, single-dose activated charcoal, airway protection, and monitoring. Flumazenil (Romazicon®) is a specific antidote for BZDs. Isolated BZD overdose in BZD-naive patients is the ideal indication for flumazenil use. Flumazenil may precipitate withdrawal in long-term BZD users, whereas it may result in exacerbation of the condition in patients taking BZDs for a life-threatening condition.